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science.medmentions_ner
science.medmentions_ner.325
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"HealthCareActivity\", \"InjuryOrPoisoning\", \"BodySubstance\", \"IntellectualProduct\", \"AnatomicalStructure\", \"SpatialConcept\", \"Chemical\", \"Bacterium\", \"MedicalDevice\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Finding\", \"BiologicFunction\", \"Virus\", \"ResearchActivity\", \"ClinicalAttribute\", \"PopulationGroup\", \"Eukaryote\", \"BodySystem\", \"Food\", \"ProfessionalOrOccupationalGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nSlow-Growing Large Irritation Fibroma of the Anterior Hard Palate: A Case Report Using Immunohistochemical Analysis Irritation fibromas are recognized as fibrous lesions, usually reactive hyperplasias; however, the mechanism of enlargement is unclear. This paper reports on an abnormally large irritation fibroma of extremely gradual growth. The immunohistochemical features (CD34, α-SMA, vimentin, Ki-67, and TGF-α) of this irritation fibroma are presented to distinguish reactive hyperplasia from other true fibrous neoplasm diseases. In the only previous study, it was reported that the expression of TGF-α might be associated with the development of oral fibromas. Therefore, we investigated the relationship between this exceptionally-large fibrous lesion of extremely slow growth and the immunohistochemical reactivity of TGF-α, finding that, in contrast to the previous study, TGF-α was not expressed. This is the first study to evaluate the enlargement mechanism of such a large irritation fibroma using the approach of immunohistochemical analysis, and it indicates that such analysis can help elucidate the diverse causes and enlargement mechanisms of irritation fibromas." }, { "role": "assistant", "content": "{\"AnatomicalStructure\": [\"Irritation Fibroma\", \"Irritation fibromas\", \"irritation fibromas\", \"irritation fibroma\"], \"Bacterium\": [], \"BiologicFunction\": [\"hyperplasia\", \"expressed\", \"true fibrous neoplasm diseases\", \"expression\", \"oral fibromas\", \"reactive hyperplasias\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"CD34\", \"Ki-67\", \"TGF-\\u03b1\", \"vimentin\", \"\\u03b1-SMA\"], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"gradual growth\", \"lesions\", \"lesion\", \"Slow-Growing\", \"slow growth\", \"abnormally\"], \"Food\": [], \"HealthCareActivity\": [\"reported\", \"enlargement mechanism\", \"mechanism of enlargement\", \"enlargement mechanisms\", \"evaluate\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"Case Report\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"Anterior Hard Palate\"], \"Virus\": []}" } ]
science.chemdner_ner
science.chemdner_ner.2296
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nArraying Cell Cultures Using PEG-DMA Micromolding in Standard Culture Dishes. A robust and effortless procedure is presented, which allows for the microstructuring of standard cell culture dishes. Cell adhesion and proliferation are controlled by three-dimensional poly(ethylene glycol)-dimethacrylate (PEG-DMA) microstructures. The spacing between microwells can be extended to millimeter size in order to enable the combination with robotic workstations. Cell arrays of microcolonies can be studied under boundary-free growth conditions by lift-off of the PEG-DMA layer in which the growth rate is accessible via the evolution of patch areas. Alternatively, PEG-DMA stencils can be used as templates for plasma-induced patterning." }, { "role": "assistant", "content": "{\"Chemical\": [\"PEG-DMA\", \"poly(ethylene glycol)-dimethacrylate\"]}" } ]
science.scientific_lay_summarisation_plos_single_doc_summ
science.scientific_lay_summarisation_plos_single_doc_summ.2460
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: A nanobody targeting the translocated intimin receptor inhibits the attachment of enterohemorrhagic E. coli to human colonic mucosa}\nArticle:\nAbstract:\nEnterohemorrhagic E. coli( EHEC) is a human intestinal pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. No vaccines or specific therapies are currently available to prevent or treat these infections. EHEC tightly attaches to the intestinal epithelium by injecting the intimin receptor Tir into the host cell via a type III secretion system( T3SS). In this project, we identified a camelid single domain antibody( nanobody), named TD4, that recognizes a conserved Tir epitope overlapping the binding site of its natural ligand intimin with high affinity and stability. We show that TD4 inhibits attachment of EHEC to cultured human HeLa cells by preventing Tir clustering by intimin, activation of downstream actin polymerization and pedestal formation. Furthermore, we demonstrate that TD4 significantly reduces EHEC adherence to human colonic mucosa in in vitro organ cultures. Altogether, these results suggest that nanobody-based therapies hold potential in the development of much needed treatment and prevention strategies against EHEC infection.\nIntroduction:\nEnterohemorrhagic E. coli( EHEC) is a major public health concern in industrial countries with most severe infections linked to serotype O157:H7. In addition to diarrhoea, EHEC can cause hemorrhagic colitis as well as life-threatening hemolytic uremic syndrome( HUS) damaging the kidneys and central nervous system[1–4]. EHEC naturally resides in the intestinal tract of cattle, and most infections are acquired by consumption of undercooked beef products or cross-contaminated vegetables or sprouts[5]. Upon infection, EHEC adheres to the epithelium of the distal ileum and colon by forming attaching and effacing( A/E) lesions, which are characterized by intimate bacterial attachment and effacement of the brush border microvilli[6, 7]. This is mediated by the Locus of Enterocyte Effacement( LEE)[8], a pathogenicity island encoding a filamentous type III secretion system( T3SS)[9, 10], the outer membrane adhesin intimin and the translocated intimin receptor( Tir), and other effector proteins involved in pathogenesis[11, 12]. After formation of the translocation filament consisting of EspA proteins, Tir is injected into intestinal epithelial cells( IECs), where it integrates into the plasma membrane in a hairpin loop topology, presenting an extracellular domain of about 100 residues( TirM)[13, 14] that serves as a binding site for the C-terminal lectin-like domain of intimin[15–17]. Binding of intimin to Tir leads to intimate bacterial attachment, Tir clustering, activation of actin polymerization pathways and subsequent formation of actin pedestals and A/E lesions[7, 18–22]. Other key virulence factors of EHEC are the phage-encoded Shiga toxins( Stx) which are released into the bloodstream and cause the systemic effects associated with HUS[23, 24]. So far, there is no specific treatment for HUS, and application of antibiotics is discouraged as it induces Stx expression and thereby increases the risk of developing HUS[25, 26]. Therefore, there is a need to develop alternative therapies, and the use of antibodies( Abs) has been proposed for treatment of infectious diseases[27]. In particular, members of the family Camelidae( e. g. dromedaries, llamas) produce a class of Abs devoid of light chains[28, 29]. In these heavy-chain-only Abs, the antigen-binding site is formed by a single variable domain termed VHH[30]. The recombinant expression of camelid VHHs yields single domain Ab fragments, which are also referred to as nanobodies( Nbs)[31]. The VHHs have extended complementarity determining regions( CDRs) capable of adopting novel conformations and recognizing epitopes located in otherwise non-accessible clefts or protein cavities, such as active sites of enzymes[32, 33] and inner regions of surface proteins from pathogens[34]. They also show strict monomeric behavior, reversible folding properties, higher resistance to proteolysis and thermal degradation, when compared with the variable domains of conventional antibodies[31, 35, 36]. In addition, the high similarity between VHHs and human VH3 sequences opens their potential use in therapeutic applications[31]. These beneficial properties offer opportunities to use Nbs for the development of therapeutic inhibitors against extracellular pathogens[37, 38]. We have previously isolated a set of Nbs binding to EspA, the C-terminal receptor-binding domain of intimin( Int280) and the TirM domain from a library of VHHs obtained after immunization of a dromedary( Camelus dromedarius). Nanobodies were secreted to the extracellular medium using the hemolysin( Hly) transport system of E. coli and purified from the culture supernatants[39]. Here, we have investigated the ability of the selected Nbs to inhibit EHEC adhesion to HeLa cells and human colonic mucosa. We have identified a Nb clone that binds TirM, named TD4, which reduces the interaction of TirM with Int280 and interferes with actin pedestal formation and the intimate attachment of EHEC to human cells. Importantly, using infection of human in vitro organ cultures( IVOC), we demonstrate that Nb TD4 can also inhibit the attachment of EHEC to human colonic tissue.\nDiscussion:\nEHEC infections are associated with severe diseases such as bloody diarrhoea and HUS[1, 2]. Efficient therapies against EHEC infections are lacking, and current treatment is based on fluid replacement and supportive care[43]. However, increasing knowledge on EHEC virulence factors and infection mechanisms is contributing to the development of new treatment strategies[44], such as inhibition of quorum sensing[45], use of EHEC LPS-specific bacteriocins[46] and inhibition of Stx binding to its host receptor globotriaosylceramide( Gb3) with antibodies[47, 48] or other ligands[49]. In this work, we tested the possibility of using specific Nbs against the EHEC proteins EspA, intimin and Tir as an alternative approach to interfere with EHEC infection. Nb clones binding Int280( IB10) or EspA( EC7) did not interfere with EHEC infection. Since intimin covers the entire surface of EHEC, binding of Nb IB10 in the concentration used might not be sufficient to mask all the Tir-binding sites, despite some inhibitory activity of this Nb in the in vitro Int280:TirM binding assay. Similarly, binding of Nb EC7 to EspA, which forms the translocation filament, did not affect EHEC infection nor inhibit Tir translocation. In contrast, a Nb binding TirM( TD4) reduced the attachment of EHEC and actin pedestal formation in HeLa cells. As the TirM domain is exposed on the host cell surface after Tir translocation[13, 14], binding of TD4 appears to block intimin binding. The fact that TirM is only presented on infected cells, suggests that a relatively low Nb concentration is needed for inhibition. Staining of Tir after EHEC infection showed that TD4 hindered the formation of actin pedestals by preventing the characteristic Tir clustering produced at the bacterial:host interface[19, 50], which is achieved even after its addition 2 h post infection and is maintained for 6 h. In vitro protein interaction assays confirmed a strong inhibition of Int280:TirM interaction by the presence of TD4, which prevents Tir clustering by binding to TirM. SPR analysis of this interaction demonstrated an extremely slow dissociation rate of TD4. This analysis also revealed that the affinity for TD4 to TirM( KD ≤ 4 nM) is at least 10 times higher than the affinity of Int280 to TirM( KD ~40 nM). Strikingly, Int280 showed a fast dissociation of TirM, suggesting a dynamic interaction. SPR experiments also determined that the TirM epitope recognized by TD4 could partially overlap with the binding region of Int280 as the addition of TD4 reduces the binding of Int280 to TirM. We mapped two TirM consecutive non-overlapping peptides bound by TD4: VNIDELGNAIPS( 296–307) and GVLKDDVVANIE( 308–319). It may be possible that each of these peptides is recognized by different CDRs of the Nb TD4, but this experiment does not exclude that TD4 may recognize a conformational structure of TirM. Its CDRs could still bind to the primary structure of these peptides, albeit with reduced affinity. Importantly, these recognized peptides are fully conserved in all Tir sequences from EHEC strains. We also determined that TD4 does not bind to TirMEPEC and has a weak interaction with TirMCR, which are highly similar but not identical to TirMEHEC. This information helped us to narrow the interaction site of TD4 and TirMEHEC by comparing the TirM sequences of the three pathogens. Differences between TirM of EHEC and CR—i. e. V309, N317 and E319- reduce but do not abolish the interaction with TD4. On the other hand, differences with TirM of EPEC—i. e. E300, L301, V314 and A316—could be critical for the binding of TD4, likely representing energetic hotspots of protein-protein interaction[51, 52]. We could further localize the residues that may participate in the interaction of TD4 with TirM based on the crystal structure of Int280 and Tir of EPEC[15]. Within the TirM sequence, it has been identified the so-called Int280-binding domain( IBD)[13], composed of two long alpha-helices( HA, residues 271–288, and HB, residues 312–331) separated by a ß-hairpin( residues 294–308). The described complex of EPEC reveals that the Int:Tir interaction is primarily mediated by the lectin-like D3 domain of Int280 and the ß-hairpin and the N-terminal part of the HB of Tir IBD, corresponding to residues 294–313 of TirMEHEC. The peptides identified to which TD4 binds( residues 296–319 of TirMEHEC), are enclosed within the IBD of Tir, indicating that TD4 is directly interfering with the Int:Tir interaction. Importantly, we have shown that TD4 can also block the interaction of EHEC to intestinal human colonic tissue ex vivo[7], as the number of bacteria bound to the epithelium was significantly reduced in the presence of this Nb. This result opens the possibility of testing TD4 protection in humans, which could be administered using a passive immunization strategy. The fact that TD4 shows inhibitory activity once EHEC infection has already begun opens also the possibility of using this Nb as a therapeutic Ab to treat infections. Nbs can be overproduced in bacteria, yeast, plants and mammalian cells to obtain highly concentrated purified proteins[53–56]. A purified Nb recognising EHEC toxins Stx1 and Stx2 has been administered, in combination with IgG, for the treatment of HUS[57]. However, the use of purified antibodies is a costly strategy for therapy development. To circumvent this problem, some studies describe the production of Abs and Nbs in edible plants and seeds. The production of Abs in edible tissues allows oral passive immunization at the gastric mucosal surface. For instance, a Nb against rotavirus infection has been expressed in rice and shown to protect infant mice from severe diarrhoea[58]. Abs contained in seeds enable long-term storage and the direct use for passive immunization with oral administration, which is particularly advantageous. Interestingly, a Nb against enterotoxigenic E. coli( ETEC) has been fused to the constant region( Fc) of immunoglobulins and produced in seeds. Piglets fed with these seeds were protected against ETEC infection[59, 60]. Alternatively, probiotic strains such as E. coli Nissle 1917( EcN)[61] could be used for delivery of TD4 to the gastrointestinal tract. EcN is known to compete with EHEC for colonisation of the mouse intestine[62] through specific mechanisms including the secretion of microcins[61, 63]. Hence, secretion of TD4 by EcN could enhance its natural anti-microbial activity and leads to the development of a superior therapeutic strain against EHEC infection. Other probiotic bacteria can be considered for local delivery of Nb TD4. For instance, Gram-positive Lactobacillus strains producing surface-bound or secreted Nbs against rotaviruses have been shown to reduce the severity and duration of rotavirus-induced diarrhoea in mice[64–66]. Overall, this study demonstrates that a Nb recognising Tir reduces intimate attachment of EHEC to human cells and colonic tissue by competing with its natural partner, intimin, thereby preventing colonization of the epithelium. These results open the possibility for passive immunization and therapeutic strategies that could prevent EHEC adhesion to intestinal tissues during infection. This could also be applied to reduce the prevalence of EHEC in its natural bovine host and minimize the risk of EHEC contamination into the food chain." }, { "role": "assistant", "content": "Currently , there is no effective treatment or vaccine against enterohemorrhagic E . coli ( EHEC ) , a bacterial pathogen that infects human colon after the ingestion of contaminated food . It thrives in the colon thanks to its ability to attach intimately to the intestinal epithelium . Here , we have identified and characterised a small antibody fragment ( nanobody ) that recognises Tir , a receptor injected by the bacterium into the host cell to mediate intimate attachment . This nanobody shows higher affinity against Tir than its natural bacterial ligand ( intimin ) and , most importantly , blocks the intimate attachment of the pathogen to the human colonic tissue . Our results show the potential of this nanobody to prevent and treat EHEC infection ." } ]
science.data_reco_mcq_mc
science.data_reco_mcq_mc.1688
[ { "role": "user", "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I am trying to align faces using the proposed method, which performs well on publicly available datasets.\n\nKeyphrases: face alignment image\n\nDataset description:\nSpeakingFaces: SpeakingFaces is a publicly-available large-scale dataset developed to support multimodal machine learning research in contexts that utilize a combination of thermal, visual, and audio data streams; examples include human-computer interaction (HCI), biometric authentication, recognition systems, domain transfer, and speech recognition. SpeakingFaces is comprised of well-aligned high-resolution thermal and visual spectra image streams of fully-framed faces synchronized with audio recordings of each subject speaking approximately 100 imperative phrases.\nKTH: The efforts to create a non-trivial and publicly available dataset for action recognition was initiated at the KTH Royal Institute of Technology in 2004. The KTH dataset is one of the most standard datasets, which contains six actions: walk, jog, run, box, hand-wave, and hand clap.\nAFW: AFW (Annotated Faces in the Wild) is a face detection dataset that contains 205 images with 468 faces. Each face image is labeled with at most 6 landmarks with visibility labels, as well as a bounding box.\n300W: The 300-W is a face dataset that consists of 300 Indoor and 300 Outdoor in-the-wild images. It covers a large variation of identity, expression, illumination conditions, pose, occlusion and face size.\nACDC: The goal of the Automated Cardiac Diagnosis Challenge (ACDC) challenge is to: compare the performance of automatic methods on the segmentation of the left ventricular endocardium and epicardium as the right ventricular endocardium for both end diastolic and end systolic phase instances; compare the performance of automatic methods for the classification of the examinations in five classes (normal case, heart failure with infarction, dilated cardiomyopathy, hypertrophic cardiomyopathy, abnormal right ventricle). The overall ACDC dataset was created from real clinical exams acquired at the University Hospital of Dijon.\n\nOptions:- A: SpeakingFaces B: KTH C: AFW D: 300W E: ACDC" }, { "role": "assistant", "content": "[\"AFW\", \"300W\"]" } ]
science.chia_ner
science.chia_ner.828
[ { "role": "user", "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Observation\", \"Condition\", \"Procedure\", \"Drug\", \"Temporal\", \"Multiplier\", \"Qualifier\", \"Negation\", \"ReferencePoint\", \"Scope\", \"Value\", \"Mood\", \"Device\", \"Visit\", \"Measurement\", \"Person\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\" : [\"breast cancer\", ...], \"Device\" : [\"ports\", ...], \"Drug\" : [\"Atenolol\", ...], \"Measurement\" : [\"blood pressure\", ...], \"Mood\" : [\"suspected\", ...], \"Multiplier\" : [\"more than two\", ...], \"Negation\" : [\"no\", ...], \"Observation\" : [\"history\", ...], \"Person\" : [\"male\", ...], \"Procedure\" : [\"surgery\", ...], \"Qualifier\" : [\"severe\", ...], \"ReferencePoint\" : [\"enrollment\", ...], \"Scope\" : [\"infection\", ...], \"Temporal\" : [\"one day\", ...], \"Value\" : [\"50%\", ...], \"Visit\" : [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPrior treatment with Acthar in the past 2mos\nMeet one of the above RA flare requirements\nSubjects who have received live or live attenuated vaccines within 6 weeks prior to the first dose of study drug (or the zoster vaccine)" }, { "role": "assistant", "content": "{\"Condition\": [\"RA flare requirements\"], \"Device\": [], \"Drug\": [\"zoster vaccine\", \"Acthar\", \"ve o ccines w\", \"live attenuated vaccines\", \"study drug\"], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [\"one of\", \"first dose\"], \"Negation\": [], \"Observation\": [], \"Person\": [], \"Procedure\": [\"treatment\"], \"Qualifier\": [], \"ReferencePoint\": [\"the first dose of study drug\"], \"Scope\": [\"live or live attenuated vaccines\"], \"Temporal\": [\"in the past 2mos\", \"within 6 weeks prior to the first dose of study drug\", \"Prior\"], \"Value\": [], \"Visit\": []}" } ]
science.drug_combo_extraction_re
science.drug_combo_extraction_re.967
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Ribosomal protein S6 is a selective mediator of TRAIL-apoptotic signaling. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis in tumor cells and holds a promise as a therapeutic agent against cancer. To elucidate the death signaling evoked by TRAIL, we performed a functional genetic screening and rescued TRAIL-resistant Jurkat clones harboring ribosomal protein S6 (rpS6) cDNA in anti-sense frame. Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL , but not those by other cell death signals , including tumor necrosis factor-alpha and cycloheximide , etoposide , doxorubicin , tunicamycin and staurosporine . Death receptor (DR) 4, but not DR5, was downregulated in rpS6 knockdown cells. Conversely, the sensitivity to TRAIL was increased by the ectopic expression of wild-type rpS6 and further by phospho-defective rpS6 mutant (S6-SS235,6AA), but not by phospho-mimic rpS6 mutant (S6-SS235,6DD). Also, unphosphorylatable rpS6 knock-in mouse embryo fibroblasts (rpS6(P-/-) MEFs) were more sensitive to TRAIL than control MEFs. In addition, SKHep-1 tumor cells, which express less phospho-rpS6 and are more sensitive to TRAIL than other tumor cells, became effectively desensitized to TRAIL after rpS6 knockdown. These results suggest that rpS6, especially in its unphosphorylated form, is a selective mediator of TRAIL-induced apoptosis.\n\nsentence: Reduction of rpS6 expression in Jurkat and HeLa cells attenuated apoptosis induced by TRAIL , but not those by other cell death signals , including tumor necrosis factor-alpha and cycloheximide , etoposide , doxorubicin , tunicamycin and staurosporine ." }, { "role": "assistant", "content": "[]" } ]
science.scierc_re
science.scierc_re.320
[ { "role": "user", "content": "Below is an abstract from a computer science research paper. Given this abstract, your task is to extract all unique relationships between entities of the following types:\n\n- \"USED-FOR\": For instance, \"Our method models user proficiency\" -> [\"method\", \"user proficiency\", \"USED-FOR\"].\n- \"EVALUATE-FOR\": For instance, \"We evaluate our method using F1-measure\" -> [\"F1-measure\", \"method\", \"EVALUATE-FOR\"].\n- \"FEATURE-OF\": For instance, \"prior knowledge of the model\" -> [\"prior knowledge\", \"model\", \"FEATURE-OF\"].\n- \"HYPONYM-OF\": For instance, \"TUIT is a software library\" -> [\"TUIT\", \"software library\", \"HYPONYM-OF\"].\n- \"PART-OF\": For instance, \"We incorporate NLU module into the system.\" -> [\"NLU module\", \"system\", \"PART-OF\"].\n- \"COMPARE\": For instance, \"Unlike the quantitative prior, the qualitative prior is often ignored\" -> [\"quantitative prior\", \"qualitative prior\", \"COMPARE\"].\n- \"CONJUNCTION\": For instance: \"obtained from human expert or knowledge base\" -> [\"human expert\", \"knowledge base\", \"CONJUNCTION\"].\n\nFormat your output as a json array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<Entity_B>\", \"<RELATION_A_B>\"]. An example output might look like:\n\n[[\"neural networks\", \"classification\", \"USED-FOR\"], [\"neuron\", \"neural network\", \"PART-OF\"]].\n\nIf no relations are found, please return an empty array [].\n\nAbstract:\n\nIn this paper we present ONTOSCORE, a system for scoring sets of concepts on the basis of an ontology. We apply our system to the task of scoring alternative speech recognition hypotheses (SRH) in terms of their semantic coherence. We conducted an annotation experiment and showed that human annotators can reliably differentiate between semantically coherent and incoherent speech recognition hypotheses. An evaluation of our system against the annotated data shows that, it successfully classifies 73.2% in a German corpus of 2.284 SRHs as either coherent or incoherent (given a baseline of 54.55%)." }, { "role": "assistant", "content": "[[\"ONTOSCORE\", \"speech recognition hypotheses (SRH)\", \"USED-FOR\"], [\"ontology\", \"ONTOSCORE\", \"USED-FOR\"]]" } ]
science.scireviewgen_multidoc_summarization
science.scireviewgen_multidoc_summarization.79241
[ { "role": "user", "content": "You are presented with multiple paper abstracts, alongside the associated literature review and chapter titles. Given the provided information, you are going to do a literature review. Please generate a coherent literature review that synthesizes the content, draws connections between different works, highlights major findings, and identifies any gaps in the existing research.\n\nLiterature Review Title: A Review of the Capacitive MEMS for Seismology \nChapter Title: Capacitive MEMS \n1. Abstract of Cited Paper (BIB001): Lumped-parameter electromechanical transducers are examined theoretically with special regard to their dynamic electromechanical behaviour and equivalent circuits used to represent them. The circuits are developed starting from basic electromechanical transduction principles and the electrical and mechanical equations of equilibrium. Within the limits of the assumptions on boundary conditions, the theory presented is exact with no restrictions other than linearity. Elementary electrostatic, electromagnetic, and electrodynamic transducers are used to illustrate the basic theory. Exemplary devices include electro-acoustic receivers (e.g., a microphone) and actuators (e.g., a loudspeaker), electromechanical filters, vibration sensors, devices employing feedback, and force and displacement sensors. This paper forms part I of a set of two papers. Part II extends the theory and deals with distributed-parameter systems. \n2. Abstract of Cited Paper (BIB002): Space exploration in the coming century will emphasize cost effectiveness and highly focused mission objectives, which will result in frequent multiple missions that broaden the scope of space science and to validate new technologies on a timely basis. Micro Electro Mechanical Systems (MEMS) is one of the key enabling technology to create cost-effective, ultra-miniaturized, robust, and functionally focused spacecraft for both robotic and human exploration programs. Examples of MEMS devices at various stages of development include microgyroscope, microseismometer, microhygrometer, quadrupole mass spectrometer, and micropropulsion engine. These devices, when proven successful, will serve as models for developing components and systems for new-millennium spacecraft. \n3. Abstract of Cited Paper (BIB003): This paper presents a new method for wideband force balancing a proof-mass in multiple axes simultaneously. Capacitive position sense and force feedback are accomplished using the same air-gap capacitors through time multiplexing. Proof of concept is experimentally demonstrated with a single-mass monolithic surface micromachined 3-axis accelerometer. \n4. Abstract of Cited Paper (BIB004): This paper presents a review of silicon micromachined accelerometers and gyroscopes. Following a brief introduction to their operating principles and specifications, various device structures, fabrication, technologies, device designs, packaging, and interface electronics issues, along with the present status in the commercialization of micromachined inertial sensors, are discussed. Inertial sensors have seen a steady improvement in their performance, and today, microaccelerometers can resolve accelerations in the micro-g range, while the performance of gyroscopes has improved by a factor of 10/spl times/ every two years during the past eight years. This impressive drive to higher performance, lower cost, greater functionality, higher levels of integration, and higher volume will continue as new fabrication, circuit, and packaging techniques are developed to meet the ever increasing demand for inertial sensors. \n5. Abstract of Cited Paper (BIB005): Micromachining and micro-electromechanical system (MEMS) technologies can be used to produce complex structures, devices and systems on the scale of micrometers. Initially micromachining techniques were borrowed directly from the integrated circuit (IC) industry, but now many unique MEMS-specific micromachining processes are being developed. In MEMS, a wide variety of transduction mechanisms can be used to convert real-world signals from one form of energy to another, thereby enabling many different microsensors, microactuators and microsystems. Despite only partial standardization and a maturing MEMS CAD technology foundation, complex and sophisticated MEMS are being produced. The integration of ICs with MEMS can improve performance, but at the price of higher development costs, greater complexity and a longer development time. A growing appreciation for the potential impact of MEMS has prompted many efforts to commercialize a wide variety of novel MEMS products. In addition, MEMS are well suited for the needs of space exploration and thus will play an increasingly large role in future missions to the space station, Mars and beyond. (Some figures in this article are in colour only in the electronic version) \n6. Abstract of Cited Paper (BIB006): 1. Introduction 2. Circuit-based modeling 3. Capacitive lumped parameter electromechanics 4. Small-signal capacitive electromechanical systems 5. Capacitive sensing and resonant drive circuits 6. Distributed 1-D and 2-D electromechanical structures 7. Practical MEMS devices 8. Electromechanics of piezoelectric elements 9. Electromechanics of magnetic MEMS devices A. Review of quasistatic electromagnetics B. Review of mechanical resonators C. Micromachining D. A brief review of solid mechanics. \n7. Abstract of Cited Paper (BIB007): 3D printing has emerged as a valuable approach for the fabrication of fluidic devices and may replace soft-lithography as the method of choice for rapid prototyping. The potential of this disruptive technology is much greater than this – it allows for functional integration in a single, highly automated manufacturing step in a cost and time effective manner. Integration of functionality with a 3D printer can be done through spatial configuration of a single material, inserting pre-made components mid-print in a print-pause-print approach, and/or through the precise spatial deposition of different materials with a multimaterial printer. This review provides an overview on the ways in which 3D printing has been exploited to create and use fluidic devices with different functionality, which provides a basis for critical reflection on the current deficiencies and future opportunities for integration by 3D printing.\n\nLiterature Review:" }, { "role": "assistant", "content": "The manufacturing of MEMS accelerometers is made using the crystalline Si and a dry reactive ion attachment process. This construction technique was initially borrowed form the ones employed in the realization of the integrated circuits and it is nowadays fairly simple and economical. Only later, some MEMS-specific fabrication processes have been developed. The basic production process is the photolithographic process which involves the \"printing\" of the pattern of the circuit on the crystalline silicon wafer. Consecutive and repeated steps of substrate carving and etching, together with ion doping to alter the materials' properties, allow for creating the three-dimensional structure. These processes allow for achieving the complex mechanical pattern of the MEMS geometry which include both fixed and mobile elements. Probably, in the next future, the 3D printing will represent the new approach for the fabrication of miniaturized devices, replacing the other methods, at least for rapid prototyping BIB008 . For a complete review of the fabrication technologies and materials used for MEMS production, refer to BIB006 . The mechanical stiffness of the various elements is ensured by a truss structure. The gap between the elements is in the order of few µm and is small if compared to the width of the trusses. The trusses of the mobile elements are electrically conductive, while those of the stationary electrodes are isolated on both sides. The capacitance between a single truss and the Si substrate is very small, so that parasites and contributions of stray are much larger than transducer capacitance. Complex structures that involve higher capacity are preferred because they are less susceptible to parasites. The sensing part of a MEMS device is interconnected to the circuitry using metal traces that are patterned on the thin dielectric layer. The estimation of the capacitance of the traces is important to counteract their contribution in the parasitic effects and improve the sensitivity. The adjacent electrodes are designed for a given capacitance, but they could interact with the surrounding elements and in particular with substrate. The resulting effect is the lowering of resolution and accuracy. The capacitive MEMS transducers can be classified into two types according to the different designs of their geometry: variable gap and variable area transducers BIB007 (Figure 6 ). The first type is characterized by fixed area and variable gap between the capacitors. The electrical constraints imposed on a variable-gap capacitive transducer are the constant charge and the constant voltage. The constant charge constraint gives constant electrical force. The constant voltage constrains the electrical force to have a strong dependence on gap. The second type is characterized by fixed gap and variable area. The constant voltage constraints the electrical force to be constant. The constant charge constrains the electrical force to have a strong dependence on the area. The two types of transducers have different behaviours and they exploit constant charge and constant voltage respectively, to counteract the distribution of the surface charge on the electrodes. The comb-drives are electrodes with interdigitated structure which are used in a variety of MEMS actuators. They have high aspect-ratio geometry and are specifically designed to maximize the useable working area. Such geometry is usually adopted for variable area capacitors. In the comb-drive electrodes with single polarity excitation, the moving electrodes undergo a direct force perpendicular to the plane of combs. The main limitation of comb-drive geometry is an unwanted electrostatic force component that pulls the moving electrodes out of alignment. To reduce such parasitic effect, the devices may be operated as three-plates systems in which the middle electrode moves back and forth ( Figure 7 ) using the bipolar voltage excitation BIB003 . The advantage of the tree-plate systems, operated in a differential mode, is the excellent response linearity between displacement and capacitance charge over a large dynamic range. Moreover, they are immune to the parasitic cable capacitance and most of the three-plates geometries are inherently self shielding, which reduces stray coupling noise. The performance depends on the difference between the two capacitances and improvements in the linear dynamic range of such sensor can be achieved through the cancellation of the second-order terms arising from the capacitance design. For both the variable-gap and variable-area transducers, the electromechanical force always acts to increase the overall capacitance of the system; this general rule of thumb is always valid and applies to all capacitive electromechanical couplings, irrespective of the geometry. The only way to overcome the tendency of force to increase is to introduce an external constraint such as feedback BIB007 . The negative feedback is a system designed with the aim to exert a force which opposes the movement of the oscillating mass. The negative feedback affords benefits to the sensor, reducing the nonlinearity of transducers [16] . The force feedback uses the electrostatic force to maintain the moving element at the equilibrium position: when the mass oscillates, it drives the moving element back to the equilibrium. Moreover, the force feedback attenuates the effects imparted by eventual mechanical shocks, when the signal is far larger compared with the normally expected one. To be effective, the feedback response must be sufficiently fast and the feedback voltage must have sufficient voltage range BIB004 BIB001 . The feedback force balance is realized exactly adopting the comb geometry described above which entails a high aspect ratio; they are usually designed as variable area capacitors. The electric field in the coplanar comb-drive structures is highly non-uniform, meaning that the uniform field approximation cannot be used. The comb-drive and variable-area geometries have electrical force independent of displacement for fixed voltage. The mathematical treatment used to model a capacitive sensor is the coenergy; for a complete review, refer to [19, BIB002 . The electronic circuitry for commercial accelerometers is quite sophisticated. An application-specific integrated circuit (ASIC) is designed to handle not only sensing, but also ratio metric and temperature compensation. It often converts output into various digital formats. Switched capacitance is used to mimic resistors and a modulation scheme suppress noise with constant 1/ f . Electronics can be simplified for an analysis with op-amp circuit with feedback capacitance and resistor. The transfer function relating the currentî to the output voltagev 0 is: The transfer function of the sensor is calculated as the product of the subsystems' transfer functions. The equivalent circuit of the whole system is shown in Figure 8 . The transfer function acceleration a to output voltage v 0 is: In International System (SI) units, the termĤ v 0 /a 0 in Equation (9) is in V/(m/s 2 ) , while in the commercial MEMS accelerometers the sensitivity is usually specified in mV/g where g is the gravitational force due to gravity and is g = 9.81 m/s 2 . To convert the units from standard SI units to this most common convention, the termĤ v 0 /a 0 (ω) is multiplied by a factor of 10 3 /9.81 ≈ 101.94. Since the mechanical transfer function is dependent on air density, the packaging is an integral part of MEMS design. This imposes a design trade-off between the requirements of good sensitivity and a large bandwidth. The mechanical white noise of thermal origin influences the resolution of accelerometers BIB004 BIB001 . This noise can be represented as an external force contribution related to an integral of the noise density over the bandwidth of the accelerometer. The selection of the type of electrode (variable-gap or variable-area) imposes the design rules of the MEMS fabrication process. The design rules prescribe a certain minimum value for the gap spacing d and a maximum value for h (height of the electrode). Assuming the same values both for d and h in the two design alternatives, the variable-gap configuration is L/d times more sensitive than the variable-area configuration (L is the length of the electrode). The typical accelerometer structure features a large number of electrodes and a correspondingly large effective length ( Figure 9 ). Thus, for high-sensitivity (low-g) applications, the variable-gap configuration may be the best choice. Conversely, for low-sensitivity (high-g) applications (e.g., detection of mechanical jolts and shocks), the variable-area structure may be preferred because sensitivity can be traded in favour of a larger bandwidth. The variable-gap configuration is subject to pull-in problems which can be avoided by designing mechanical stops to prevent the distance to be too small if compared to the traction spacing: d > d bs < d * where d * is the traction spacing. The shocks result in small contact areas and the van der Waals forces cannot prevent the spring from restoring the moving electrode around its equilibrium. For this reason, the springs are built with bent beam structures so that the moving test mass is kept in balance. The sensitivity of the accelerometers is directly proportional to dC/dx and to the bias voltage V B ; it is inversely proportional to the squared resonant frequency and to the feedback capacitance C f . A practical constraint imposed on the MEMS manufactures is that, for any given fabrication process and the associated design rules, the nominal capacitive air gap is fixed. Thus, the only way to increase the derivative dC/dx to increase the net area of the capacitive element, which increases the proof mass. The increasing of the mass decreases the resonant frequency, which, in turn, further increases the sensitivity, to the detriment of the bandwidth. The study of the stability of capacitive MEMS devices is aimed to the prevention of their failures. It is convenient to look for general criteria to assess the instability of the system. Table 1 summarizes the instability thresholds for both types of transducers. Considering the definition of capacity, it is possible to deduce that only the variable-gap devices can become unstable and only when the voltage is fixed. The instability consists of pull-in phenomena when a threshold value of a voltage between the electrodes is overcome, causing their permanent instability. Pull-in instability can even permanently disable the in variable-gap MEMS devices. Finally, high order effects, noise sources, and distortions may affect the signal. For this reason, it is important to consider the following parameters accordingly to the specific objectives: offset, sensitivity, resolution, nonlinearity, cross-axias sensitivity, temperature sensitivity, ASIC, ratiometricity, and self-test. The treatise of these topics is out of the aim of this review; we therefore refer to the specific literature BIB005 BIB007 16, 19, BIB002 . In this review, we will only report the range of values of some generic parameters desirable for application in seismology." } ]
science.scierc_re
science.scierc_re.49
[ { "role": "user", "content": "Below is an abstract from a computer science research paper. Given this abstract, your task is to extract all unique relationships between entities of the following types:\n\n- \"USED-FOR\": For instance, \"Our method models user proficiency\" -> [\"method\", \"user proficiency\", \"USED-FOR\"].\n- \"EVALUATE-FOR\": For instance, \"We evaluate our method using F1-measure\" -> [\"F1-measure\", \"method\", \"EVALUATE-FOR\"].\n- \"FEATURE-OF\": For instance, \"prior knowledge of the model\" -> [\"prior knowledge\", \"model\", \"FEATURE-OF\"].\n- \"HYPONYM-OF\": For instance, \"TUIT is a software library\" -> [\"TUIT\", \"software library\", \"HYPONYM-OF\"].\n- \"PART-OF\": For instance, \"We incorporate NLU module into the system.\" -> [\"NLU module\", \"system\", \"PART-OF\"].\n- \"COMPARE\": For instance, \"Unlike the quantitative prior, the qualitative prior is often ignored\" -> [\"quantitative prior\", \"qualitative prior\", \"COMPARE\"].\n- \"CONJUNCTION\": For instance: \"obtained from human expert or knowledge base\" -> [\"human expert\", \"knowledge base\", \"CONJUNCTION\"].\n\nFormat your output as a json array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<Entity_B>\", \"<RELATION_A_B>\"]. An example output might look like:\n\n[[\"neural networks\", \"classification\", \"USED-FOR\"], [\"neuron\", \"neural network\", \"PART-OF\"]].\n\nIf no relations are found, please return an empty array [].\n\nAbstract:\n\nThis paper introduces a method for computational analysis of move structures in abstracts of research articles. In our approach, sentences in a given abstract are analyzed and labeled with a specific move in light of various rhetorical functions. The method involves automatically gathering a large number of abstracts from the Web and building a language model of abstract moves. We also present a prototype concordancer, CARE, which exploits the move-tagged abstracts for digital learning. This system provides a promising approach to Web-based computer-assisted academic writing." }, { "role": "assistant", "content": "[[\"abstracts of research articles\", \"computational analysis of move structures\", \"USED-FOR\"], [\"CARE\", \"prototype concordancer\", \"HYPONYM-OF\"], [\"Web\", \"abstracts\", \"USED-FOR\"], [\"abstract moves\", \"language model\", \"USED-FOR\"], [\"CARE\", \"move-tagged abstracts\", \"USED-FOR\"], [\"move-tagged abstracts\", \"digital learning\", \"USED-FOR\"], [\"method\", \"Web-based computer-assisted academic writing\", \"USED-FOR\"], [\"method\", \"computational analysis of move structures\", \"USED-FOR\"], [\"CARE\", \"method\", \"USED-FOR\"]]" } ]
science.data_reco_mcq_sc
science.data_reco_mcq_sc.11104
[ { "role": "user", "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from options provided. A short description of the datasets is also provided to help you.\n\nQuery: I want to use a deep convolutional neural network to learn augmented attributes for person Re-ID\n\nKeyphrases: person re-id images\n\nDataset description:\nGoPro: The GoPro dataset for deblurring consists of 3,214 blurred images with the size of 1,280×720 that are divided into 2,103 training images and 1,111 test images. The dataset consists of pairs of a realistic blurry image and the corresponding ground truth shapr image that are obtained by a high-speed camera.\nMarket-1501: Market-1501 is a large-scale public benchmark dataset for person re-identification. It contains 1501 identities which are captured by six different cameras, and 32,668 pedestrian image bounding-boxes obtained using the Deformable Part Models pedestrian detector.\nCOVIDx: An open access benchmark dataset comprising of 13,975 CXR images across 13,870 patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge.\nBraTS 2017: The BRATS2017 dataset. It contains 285 brain tumor MRI scans, with four MRI modalities as T1, T1ce, T2, and Flair for each scan.\n\nOptions:- A: GoPro B: Market-1501 C: COVIDx D: BraTS 2017" }, { "role": "assistant", "content": "Market-1501" } ]
science.scicite_classification
science.scicite_classification.1601
[ { "role": "user", "content": "You will be presented with a citation segment from the section of a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nKinocilial links are, like tip links, BAPTA-sensitive/ subtilisin-resistant structures (Goodyear and Richardson, 2003)." }, { "role": "assistant", "content": "Background" } ]
science.craftchem_ner
science.craftchem_ner.8485
[ { "role": "user", "content": "You will be presented a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nCox11inhibitsnoncompetitivelytheactivityofHKIwith~2-3moleculesofCox11(assumingformationofCox11dimer)requiredtoinhibitcompletelytheactivityofamoleculeofHKI(Figure2Aand2B)." }, { "role": "assistant", "content": "[\"molecules\", \"molecule\"]" } ]
science.data_reco_mcq_sc
science.data_reco_mcq_sc.12380
[ { "role": "user", "content": "Given a short query with keyphrases about a research idea in 2020 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from options provided. A short description of the datasets is also provided to help you.\n\nQuery: We propose an architecture for action recognition from wearable cameras which jointly models the object appearance and the context motion\n\nKeyphrases: manipulation action recognition videos\n\nDataset description:\nGTEA: The Georgia Tech Egocentric Activities (GTEA) dataset contains seven types of daily activities such as making sandwich, tea, or coffee. Each activity is performed by four different people, thus totally 28 videos.\nMSR ActionPairs: This is a 3D action recognition dataset, also known as 3D Action Pairs dataset. The actions in this dataset are selected in pairs such that the two actions of each pair are similar in motion (have similar trajectories) and shape (have similar objects); however, the motion-shape relation is different.\nRareAct: RareAct is a video dataset of unusual actions, including actions like “blend phone”, “cut keyboard” and “microwave shoes”. It aims at evaluating the zero-shot and few-shot compositionality of action recognition models for unlikely compositions of common action verbs and object nouns.\nDrive&Act: The Drive&Act dataset is a state of the art multi modal benchmark for driver behavior recognition. The dataset includes 3D skeletons in addition to frame-wise hierarchical labels of 9.6 Million frames captured by 6 different views and 3 modalities (RGB, IR and depth).\n\nOptions:- A: GTEA B: MSR ActionPairs C: RareAct D: Drive&Act" }, { "role": "assistant", "content": "GTEA" } ]
science.bioasq_general_qa
science.bioasq_general_qa.290
[ { "role": "user", "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: How does Rif1 regulate DNA replication?\n\nContext: Protein phosphatase 1 recruitment by Rif1 regulates DNA replication origin firing by counteracting DDK activity\nYeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in ALT cells, a pattern of telomere association typical of DNA-damage-response factors.\nAfter induction of double-strand breaks (DSBs), Rif1 formed foci that colocalized with other DNA-damage-response factors.\nThese data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.\nMammalian Rif1 contributes to replication stress survival and homology-directed repair.\nRif1 deficiency leads to failure in embryonic development, and conditional deletion of Rif1 from mouse embryo fibroblasts affects S-phase progression, rendering cells hypersensitive to replication poisons\nRif1 deficiency does not alter the activation of the DNA replication checkpoint but rather affects the execution of repair.\nConsistent with a role in S-phase progression, Rif1 accumulates at stalled replication forks, preferentially around pericentromeric heterochromatin. Collectively, these findings reveal a function for Rif1 in the repair of stalled forks by facilitating HDR.\nRif1 regulates the replication timing domains on the human genome\nRif1 (Rap1-interacting-factor-1), originally identified as a telomere-binding factor in yeast, is a critical determinant of the replication timing programme in human cells\nDepletion of Rif1 results in specific loss of mid-S replication foci profiles, stimulation of initiation events in early-S-phase and changes in long-range replication timing domain structures\nRif1 tightly binds to nuclear-insoluble structures at late-M-to-early-G1 and regulates chromatin-loop sizes.\nRif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early-S-phase. Our results indicate that Rif1 plays crucial roles in determining the replication timing domain structures in human cells through regulating higher-order chromatin architecture.\nmouse Rif1 as a key player in the regulation of DNA replication timin\nMouse Rif1 is a key regulator of the replication-timing programme in mammalian cells\nRif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication\nRif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin.\nRif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication\nRif1 is a global regulator of timing of replication origin firing in fission yeast\nWe identified rif1Δ, a null mutant of rif1(+), a conserved telomere-binding factor, as an efficient bypass mutant of fission yeast hsk1\nAt the same time, many early-firing, efficient origins are suppressed or delayed in firing timing in rif1Δ\nRif1 binds not only to telomeres, but also to many specific locations on the arm segments that only partially overlap with the prereplicative complex assembly sites, although Rif1 tends to bind in the vicinity of the late/dormant origins activated in rif1Δ\nRif1 is a critical determinant of the origin activation program on the fission yeast chromosomes.\nRif1 as a global regulator of replication timing\nRif1 which plays crucial roles in the regulation of the replication timing program in yeast as well as in higher eukaryotes\nIn mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures. Regulation of chromatin architecture by Rif1 may be linked to other chromosome transactions including recombination, repair, or transcription.\nRif1 has recently been identified as a genome-wide regulator of replication timing in fission yeast and in mammalian cells\nHowever, previous studies in budding yeast have suggested that Rif1's role in controlling replication timing may be limited to subtelomeric domains and derives from its established role in telomere length regulation\nWe have analyzed replication timing by analyzing BrdU incorporation genome-wide, and report that Rif1 regulates the timing of late/dormant replication origins throughout the S. cerevisiae genome\nRif1 regulates replication timing through a mechanism independent of this checkpoint.\nthe Rif1 mechanism regulates origin timing irrespective of proximity to a chromosome end, and suggest instead that telomere sequences merely provide abundant binding sites for proteins that recruit Rif1. Still, the abundance of Rif1 binding in telomeric domains may facilitate Rif1-mediated repression of non-telomeric origins that are more distal from centromeres.\nRif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex\nMammalian Rif1 is a key regulator of DNA replication timing, double-stranded DNA break repair, and replication fork restart. Dissecting the molecular functions of Rif1 is essential to understand how it regulates such diverse processes. However, Rif1 is a large protein that lacks well defined functional domains and is predicted to be largely intrinsically disordered; these features have hampered recombinant expression of Rif1 and subsequent functional characterization.\nthe first structural study of the mammalian Rif1, identifying a domain that directly links its function to DNA binding. The high specificity of Rif1 for cruciform structures is significant given the role of this key protein in regulating origin firing and DNA repair.\nRIF1: a novel regulatory factor for DNA replication and DNA damage response signaling.\nRif1 is conserved from yeast to humans but its function has evolved from telomere length regulation in yeast to the maintenance of genome integrity in mammalian cells.\nRecently its role in the maintenance of genomic integrity has been expanded to include the regulation of chromatin structure, replication timing and intra-S phase checkpoint\nbudding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs).\nThe Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans\nRif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7\nRif1 also interacts with Dbf4 in yeast two-hybrid assays, further implicating this protein in direct modulation of pre-RC activation through the DDK. Finally, we demonstrate Rif1 RVxF/SILK motif-dependent recruitment of Glc7 to telomeres and earlier replication of these regions in cells where the motifs are mutated. Our data thus link Rif1 to negative regulation of replication origin firing through recruitment of the Glc7 phosphatase.\nRif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases\nOur data suggest that the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK. These findings elucidate the mechanism of action of Rif1 in the control of DNA replication and demonstrate a role of PP1 phosphatases in the regulation of origin firing.\nRecent studies have identified factors that regulate the timing of origin activation, including Rif1 which plays crucial roles in the regulation of the replication timing program in yeast as well as in higher eukaryotes. In mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures." }, { "role": "assistant", "content": "Rif1 (Rap1-interacting-factor-1), originally identified as a telomere-binding factor in yeast, is a critical determinant of the replication timing programme in human cells. Rif1 tightly binds to nuclear-insoluble structures at late-M-to-early-G1 and regulates chromatin-loop sizes. Furthermore, Rif1 colocalizes specifically with the mid-S replication foci. Thus, Rif1 establishes the mid-S replication domains that are restrained from being activated at early-S-phase. Overall, Rif1 plays crucial roles in determining the replication timing domain structures in human cells through regulating higher-order chromatin architecture. This function of Rif1 depends on its interaction with PP1 phosphatases and the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK." } ]
science.bioasq_factoid_qa
science.bioasq_factoid_qa.742
[ { "role": "user", "content": "You will be shown biomedical passages and your task is to the answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: In which syndrome is the RPS19 gene most frequently mutated?\n\nContext: The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups.\nTwenty-one cases of DBA admitted in our hospital from Dec 2008 to Aug 2012 were screened by PCR for mutations in the nine known genes associated with DBA: RPS19, RPS24, RPS17, RPL5, RPL11, RPS7, RPL35a, RPS10 and RPS26\nThe results found that 8 patients (38.1%) with DBA had mutations in the genes coding for ribosomal protein, in which RPS19 mutation was identified in 3 patients, RPS24, RPS7, RPL5, RPL11 and RPL35A mutations were identified respectively in 1 of the patient.\nThe hypospadias can be observed in some patients with RPS19 mutation and some dactyl anomalies are associated with RPL11 and RPL5 mutations.\nA transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia.\nMutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families.\nDiamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands.\nRibosomal protein S19 (RPS19), currently the only gene associated with DBA, is mutated in 25% of DBA patients, but its role in erythropoiesis is unknown.\nSince a fraction of DBA patients have a deficiency in ribosomal protein S19 (RPS19), we constructed lentiviral vectors containing the RPS19 gene for overexpression in hematopoietic progenitors from RPS19-deficient DBA patients.\nDBA is a heterogeneous disorder, caused in about 25% of cases by heterozygous mutations in the RPS19 gene (DBA1)\nMutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations.\nThe gene encoding the small subunit ribosomal protein 19 (RPS19) is mutated in about 25% of cases of the bone marrow failure syndrome Diamond Blackfan Anemia (DBA), a childhood disease characterized by failure of red cell production.\nDiamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome that is characterized by pure red-cell aplasia and associated physical deformities.\nNonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia.\nMutations in the ribosomal protein (RP)S19 gene have been found in about 25% of the cases of Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia that includes variable physical malformations.\nThe gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia.\nBACKGROUND Mutations in the ribosomal protein S19 gene (RPS19) have been found in 25% of patients with Diamond-Blackfan anemia, a rare syndrome of congenital bone marrow failure characterized by erythroblastopenia and various malformations.\nRibosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia.\nBy applying EMSA and ChIP methodologies in mouse erythroleukemia cells we show that GATA1 and PU.1 bind in vitro and in vivo the proximal promoter region of the RPS19 gene which is frequently mutated in Diamond-Blackfan Anemia.\nDiamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by a specific deficiency in erythroid progenitors.\nDiamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer." }, { "role": "assistant", "content": "Diamond-Blackfan Anemia, or DBA" } ]
science.drug_combo_extraction_re
science.drug_combo_extraction_re.1321
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Human Herpesvirus Type 8-associated Large B-cell Lymphoma: A Nonserous Extracavitary Variant of Primary Effusion Lymphoma in an HIV-infected Man: A Case Report and Review of the Literature. Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma subtype primarily seen in human immunodeficiency virus (HIV)-infected individuals with low CD4(+) cell counts and elevated HIV viral loads. It has always been associated with human herpesvirus type 8 (HHV-8) and in 80% of cases has also been associated with Epstein-Barr virus (EBV). Less commonly, PEL has presented in patients with advanced age and other conditions associated with an altered immunity, including malignancy, liver cirrhosis, and immunosuppressive medications. It is a tumor of B-cell lineage; however, it shows a \"null\" phenotype, rarely expressing pan-B cell surface antigens. It will usually express CD45, CD30, CD38, CD138, and MUM1 and is characterized by lymphomatous effusions in body cavities but not lymphadenopathy. It is an aggressive lymphoma, with an average median survival of < 1 year. HHV-8-associated large B-cell lymphoma (HHV-8-LBL) is a second variant of PEL that is both solid and extracavitary. It has immunoblastic and/or anaplastic morphologic features and a distinct immunohistochemical staining pattern. It could also have a different clinical presentation than that of classic PEL. ### Materials And Methods We describe the case of a 57-year-old HIV-infected man who presented with a slow-growing and asymptomatic abdominal mass. Examination of an excisional biopsy specimen showed malignant large cells with prominent cytoplasm that were positive for pan-B cell antigen CD20, HHV-8, and EBV and negative for CD138, CD10, BCL-6, CD3, and CD30. The Ki-67 labeling index was 90%. The diagnosis was stage IIIA HHV-8-LBL , and he was treated with 6 cycles of R-EPOCH ( rituximab , etoposide , vincristine , doxorubicin , cyclophosphamide , and prednisone ) infusion chemotherapy . At 12 months after treatment, he was in complete remission. We also performed a Medline and Embase search to better understand the clinical findings of our patient and the unique attributes of HHV-8-LBL. Focusing our search on English language studies, we identified 83 cases of HHV-8-LBL without an effusion component. We compared these 83 cases with 118 reported cases of classic PEL. ### results The median age of the patients with HHV-8-LBL was 41 years (range, 24-77), and 96% of the cases were associated with HIV. The median age of the patients with classic PEL was 41 years (range, 26-86), and 96% of the cases were associated with HIV. Of those with HHV-8-LBL, 31 of 61 (51%) had a pre-existing diagnosis of acquired immunodeficiency syndrome (AIDS) and 47 of 63 (75%) were coinfected with EBV. In contrast, 69 of 96 patients (72%) with classic PEL had a pre-existing AIDS diagnosis and 40 of 49 (82%) were coinfected with EBV. The mean CD4(+) count of the HHV-8-LBL patients was 256 cells/μL (range, 18-1126 cells/μL) compared with 139 cells/μL (range, 2-557 cells/μL) in the classic PEL patients. The median survival time for both groups was similar at 5.5 months (range, 25 days to ≥ 25 months) for patients with HHV-8-LBL and 4 months (range, 2 days to ≥ 113 months) for those with classic PEL. More patients with HHV-8-LBL were alive at the last follow-up point (59% vs. 18%). The percentage of patients achieving complete remission was 54% (30 of 56) and 36% (32 of 89) for HHV-8-LBL and classic PEL, respectively. ### conclusion Our patient's high CD4(+) cell count, the lack of a pre-existing AIDS diagnosis, and the excellent response to chemotherapy highlights that HHV-8-LBL might have distinct clinical features and possibly a better response to chemotherapy than classic PEL. HHV-8-LBL should be included in the differential diagnosis of HIV patients with solid lesions. It is essential that patients' Centers for Disease Control and Prevention HIV clinical status and HIV viral load at the diagnosis of PEL and HHV-8-LBL be reported and that the reported clinical results include longer term follow-up data. Only then will a more complete clinical picture of this little-appreciated and little-understood PEL variant be defined.\n\nsentence: The diagnosis was stage IIIA HHV-8-LBL , and he was treated with 6 cycles of R-EPOCH ( rituximab , etoposide , vincristine , doxorubicin , cyclophosphamide , and prednisone ) infusion chemotherapy ." }, { "role": "assistant", "content": "[[\"rituximab\", \"etoposide\", \"vincristine\", \"doxorubicin\", \"cyclophosphamide\", \"prednisone\", \"POS\"]]" } ]
science.scientific_lay_summarisation_elife_single_doc_summ
science.scientific_lay_summarisation_elife_single_doc_summ.1661
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration}\nArticle:\nAbstract:\nMorphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly understood. Here, we show this collective cell behavior is regulated by non-canonical Wnt signaling. We identify that Wnt5a specifically activates Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. We show that Wnt5a signaling stabilizes vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro leads to uncoordinated polarity and deficient sprouting angiogenesis in Mus musculus. Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.\nIntroduction:\nMorphogenesis is driven by coordinated and dynamic cell movements, which are regulated by a combination of chemical and physical cues( Jaalouk and Lammerding, 2009). Morphogenic cues are sensed and read at the single cell-level, yet biomechanical information is relayed to and integrated by neighboring cells leading to tissue-level collective cell behaviors. These emergent collective behaviors arise by mechanically coupling cadherin-based adhesion and actomyosin-based contraction, allowing propagation of cell-cell interactions across large cell populations( Friedl and Mayor, 2017; Lecuit and Yap, 2015; Yap et al., 2018). One of such morphogenic processes is the formation of blood vessels. Vascular morphogenesis occurs mainly through sprouting angiogenesis, a process where endothelial tip cells lead the vascular sprout, migrate and invade into avascular tissues in response to pro-angiogenic molecules. Endothelial stalk cells follow tip cells contributing to sprout elongation and branch formation through proliferation and migration( Potente and Mäkinen, 2017). Although sprouting angiogenesis is considered a collective cell migration process( Friedl and Gilmour, 2009; Vitorino and Meyer, 2008), little is known about the mechanisms regulating this collective behavior. Recently, endothelial cell front-rear polarity has emerged as a crucial regulator of collective behavior in sprouting angiogenesis. In fact, endothelial cell( EC)-specific deletion of NCK1/2 and Cdc42 impairs cell polarity, which correlates with decreased sprouting efficiency( Dubrac et al., 2016; Laviña et al., 2018). However, the mechanisms controlling and coordinating polarity patterns of endothelial cells during sprouting angiogenesis remain elusive. Recent reports showed that non-canonical Wnt signaling, a known regulator of cell migration and cell polarity in key morphogenic events such as gastrulation, neural tube closure, fur orientation, and ureteric bud formation( Gray et al., 2011; Yang and Mlodzik, 2015), also controls sprouting angiogenesis and vascular remodeling( Franco et al., 2016; Korn et al., 2014). Non-canonical Wnt signaling was shown to control vascular remodeling by blocking excessive vessel regression in a flow-dependent manner( Franco et al., 2016; Korn et al., 2014). In this context, non-canonical Wnt signaling modulates the threshold for flow-dependent EC polarization, inducing premature vessel regression, and leading to a decrease in vessel density( Franco et al., 2016). In parallel, abrogation of endothelial non-canonical Wnt ligands also leads to reduce sprouting efficiency( Franco et al., 2016; Korn et al., 2014). Yet, it remains unresolved how mechanistically non-canonical Wnt signaling regulates sprouting angiogenesis. Here, we have established a simple assay to measure endothelial collective cell behavior in vivo and in vitro using axial polarity histograms. Using this assay, we uncovered a novel Wnt5a pathway that stabilizes the binding of vinculin to ɑ-catenin at adherens junctions, and consequently the efficient coupling between adherens junctions and the actin cytoskeleton in endothelial cells. We showed that vinculin loss-of-function impairs collective polarity in vivo and in vitro, leading to deficient sprouting angiogenesis. Overall, we propose that non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.\nDiscussion:\nSprouting angiogenesis requires efficient coordination of cell specification, cell proliferation, cell migration, and cell rearrangements. Previous work has elucidated the basic cellular and molecular mechanisms leading to endothelial tip/stalk cell specification and proliferation( Potente and Mäkinen, 2017). Yet, the mechanisms controlling collective cell polarity, migration and cell rearrangements at the vascular sprouting front are still poorly understood. Here, we identify a novel signaling pathway that reinforces mechanocoupling between endothelial cells to coordinate collective cell polarity and migration during sprouting angiogenesis. We uncover that Wnt5a, through ROR2, activates Cdc42 at adherens junctions, which is necessary for stable binding of vinculin to ɑ-catenin, and efficient mechanocoupling between endothelial cells( Figure 10). Low non-canonical Wnt signaling weakens adherens junctions, impairs force propagation, and disrupts collective behavior of endothelial cells, which in turn affects angiogenic sprouting efficiency. We identify that Cdc42 plays an important role downstream of Wnt5a-ROR2 signaling in the regulation of vinculin’s stabilization and activation at adherens junctions. Cdc42 is a well-known regulator of cell polarity, playing important roles in yeast budding, epithelial polarity, migratory polarity and fate specification during cell division( Heasman and Ridley, 2008). In this context, Cdc42 frequently interacts with the PAR complex( PAR6–PAR3–aPKC) to mediate both front-rear polarity and apical-basal polarity( Etienne-Manneville and Hall, 2001; Etienne-Manneville and Hall, 2003; Wu et al., 2007). In endothelial cells, Cdc42 was previously implicated in filopodia formation( Barry et al., 2015; Fantin et al., 2015; Wakayama et al., 2015), adherence, junction stability( Broman et al., 2006), cell migration( Vitorino and Meyer, 2008; Wakayama et al., 2015), and more recently on collective polarity( Laviña et al., 2018). Yet, Cdc42 seems to be dispensable for apical-basal but essential for front-rear polarization( Laviña et al., 2018). Interestingly, non-canonical Wnt pathway was shown to cooperate with Cdc42/PAR complex to regulate front-rear polarity in migrating fibroblasts at the leading edge( Schlessinger et al., 2007), evoking two parallel mechanisms regulating polarity of leader cells. This fits with our own results, as leader cells were mildly affected by Wnt5a KD. In endothelial cells, we show that Wnt5a regulates Cdc42 activity at cell-cell boundaries but not at the leading edge of leader cells. This signaling spatial regulation could explain why leader cells are less affected by deficient Wnt5a signaling. Indeed, Cdc42 inhibition or LOF in vitro or in vivo gives to a stronger polarity phenotype than non-canonical Wnt signaling LOF experiments( Laviña et al., 2018). This suggests that Cdc42 is regulated by multiple inputs to control cell polarity, and that Wnt5a signaling fine-tunes Cdc42 activity at cell-cell junctions. Our data further shows that the role of non-canonical Wnt signaling on mechanocoupling relies on vinculin stabilization at adherens junctions. The biological function of vinculin at adherens junctions has been a theme of controversy. Despite being present at high-tension junctions in several model organisms, vinculin is dispensable for zebrafish and fruitfly normal development( Alatortsev et al., 1997; Han et al., 2017). However, its absence during mouse embryonic development results in lethal cardiovascular and neuronal defects( Xu et al., 1998). To explain these differences, it has been proposed that mechanical and molecular properties of proteins from the adherens junctions might have diverged during evolution( Han et al., 2017). For instance, zebrafish ɑ-catenin is monomeric and can form a complex with β-catenin and F-actin simultaneously, whilst the murine orthologue forms dimers and cannot bind simultaneously to F-actin and β-catenin in solution( Buckley et al., 2014; Miller et al., 2013). Thus, vinculin is required to promote efficient coupling between ɑ-catenin and F-actin in mouse. However, the factors that would regulate these interactions are so far elusive. Our results are compatible with the idea that a Wnt5a-ROR2-Cdc42 signaling axis could have evolved in mammals to enhance cadherin mechanoproperties through vinculin. Moreover, the ability to rescue the collective cell polarity defects on Wnt5a-deficient cells by re-expression of Vinc-T12 or ɑCat-Vinc fusion protein further suggests that Wnt5a modulates mechanocoupling efficiency by regulating vinculin’s actin-binding properties. How Wnt5a affects the dynamics or affinity of vinculin to actin filaments shall be investigated in future work. In addition, our results strongly suggest that Wnt5a acts as a permissive rather than an instructive cue regarding cell polarity. The ability to rescue the collective polarity phenotype of siWNT5a cells by re-expression of either Vinc-T12 or ɑCat-Vinc fusion protein implies that the polarity cue organizing collective cell polarity does not depend on Wnt5a. In this context, Wnt5a seems to be mainly necessary to potentiate mechanocoupling between cells via vinculin activation, a condition sufficient to propagate the external polarity cue in the system. This is also concordant with our previous observations that overexpression of Wnt5a in endothelial cells in vivo led to normal vascular sprouting and remodeling phenotypes( Franco et al., 2016). Interestingly, a similar debate regarding a permissive or instructive role involves non-canonical Wnt signaling in planar cell polarity( PCP) establishment( Humphries and Mlodzik, 2018), where conflicting evidences exists in favor of each role. Our results suggest that non-canonical Wnt signaling plays a role in force transmission within cell populations. As mechanical cues were shown to play a contributing role in PCP establishment( Humphries and Mlodzik, 2018), a mechanobiology perspective into the function of non-canonical Wnt signaling in PCP could in part conciliate the possibility that non-canonical Wnt signaling can be seen as instructive or permissive, depending on the experimental setting. Non-canonical Wnt signaling was previously implicated in the regulation of vessel regression( Franco et al., 2016; Korn et al., 2014). Intriguingly, Vinculin EC-KO shows a very similar phenotype, with an increase in vessel regression, and a decrease in vessel density and radial expansion. It was suggested that non-canonical Wnt signaling regulates vessel regression by controlling a mechanosensitive threshold, based on wall shear stress, that induces endothelial cell polarization and migration( Franco et al., 2016). The mechanisms controlling this threshold are still unclear. Given the well-known mechanoresponsive properties of vinculin, it is tempting to speculate that vinculin could also play a relevant role in establishing this threshold. Further work is necessary to clarify this question. Nevertheless, it is relevant to note that Wnt5a and vinculin regulates a different mechanosensitive pathway in flow-independent conditions. This also raises the question of how shear stress and junctional mechanotransduction pathways are regulated and coordinated by non-canonical Wnt signaling in space and time within the vascular network. Taken together, our results show that Wnt5a signaling fine-tunes junctional mechanocoupling between endothelial cells to promote collective cell behavior during vascular morphogenesis." }, { "role": "assistant", "content": "When a new blood vessel is created , a leader cell branches out from the lining of an existing vessel before being joined by other cells moving together in the same direction . A protein called Wnt5a regulates this process by helping the cells to orient themselves and finely coordinating their migration , but the exact details of this mechanism are still unclear . One way that cells can communicate is by touching and physically exerting forces on each other . This is made possible by structures called cellular junctions , which are present at the interface between cells . These can transmit forces within a tissue because they are connected with elements that form the cells’ internal skeletons . A protein known as vinculin is involved in these connections . To find out what role Wnt5a plays in cell migration , Carvalho et al . prevented blood vessel cells from creating the protein . The results showed that Wnt5a helps cells to move together by stabilizing vinculin at cell junctions . This strengthens the physical communication between cells and allows them to efficiently coordinate their movements . Indeed , in the mouse retina , deleting vinculin from cells that make blood cells impaired the formation of new blood vessels . Problems in the way that blood vessels grow are very common in the human population . In addition , Wnt5a is linked to cancer progression , which also relies on coordinated movement of cells . A better grasp of the role of this protein could therefore be relevant to understand how blood vessels are formed , but also how certain cancers invade surrounding tissues ." } ]
science.scientific_papers_summarization_single_doc_arxiv
science.scientific_papers_summarization_single_doc_arxiv.20940
[ { "role": "user", "content": "You will be presented with the full text of a science research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\ncomputer visualization is nowadays an important field of scientific research , because it often allows a better understanding of natural phenomena . gravitational lenses ( hereafter gl ) , predicted by einstein s general relativity theory ,\ndeflect the light rays coming from a distant object .\ngl s allow the formation of mutiple images of the same source object .\nmoreover this gravitational effect opens the possiblity of determining the mass of the deflector and the computation of the age of the universe ( hubble s constant ) , as well as other lens parameters and cosmological parameters .\nan interactive computer program to visualize this gravitational effect has been developed .\nthe program was written in the c programming language and uses the _ xforms _ ( tool kit ) , _ mesa _ ( graphic library ) and _ imlib _ ( image library ) .\nthe program runs on systems with linux or unix .\nan sgi version of this program is also available . in the first section the gravitational lens effect is briefly reviewed .\nthe visualization program is presented in the second section . in the third section\nsome applications are shown : image sequences and easy visual modelling .\nimproved versions of this program can be produced and the author wishes to invite the interested reader to participate in this process .\nthe author is preparing a website for downloading this program : http://lia.efis.ucr.ac.cr/~frutos/\ndue to the curvature of space - time , light rays coming from a distant source object ( quasar , star or galaxy ) are deflected when passing close to a lens or deflector ( star , galaxy or cluster of galaxies ) . for weak gravitational fields\nthe _ post - newtonian _ approximation is applicable . under this approximation\nthe deflection angle or einstein s angle does not depend on the direction of propagation and the trayectory are approximated by straight lines .\nthis gravitational light deflection is depicted in figure 1 . from this figure\nan equation , the _ gl equation _ or the _ ray tracing equation_which is obeyed by light rays passing near a lens object can be deduced : @xmath0 where @xmath1 @xmath2 and @xmath3 is the length scale on the lens surface . the angle @xmath4 is called the einstein s angle .\nthe surface density of the lens is given by @xmath5 where @xmath6 represents the _ critical density _ : @xmath7 a generalization of equation ( [ ecgl ] ) which considers the perturbation of a _ macrolens _ ( a galaxy or cluster of galaxies ) is given by @xmath8 where the matrix @xmath9 is given by the expression @xmath10 the components of the matrix depend upon the parameters @xmath11 and @xmath12 and @xmath13 which are respectively the dimensionless constant surface mass density , the dimensionless shear of the macrolens and the shear angle .\nthe microlens ( a star in a galaxy or a galaxy in a cluster of galaxies ) is represented by means of the einstein s angle @xmath4 .\n[ fig1 ] = 0.9 to simulate einstein s angle there are several models for the lens mass distribution .\nthe gravitational lens models are divided as follows : * parametric models * non - parametric models . at the present time the program has only parametric models@xmath14 .\nthe non - parametric models are lately used to model gravitational lenses@xmath14 . for weak lensing the _ kaiser - squires _ method can be applied to model lenses @xmath14 . in the program\nthese techniques have not been implemented .\nthe program includes the following parametric models : * chang refsdal model , * double plane lens , * transparent sphere , * singular isothermal sphere , * nonsingular isothermal sphere , * elliptical model , * king model , * truncated king model , * hubble model , * de vaucouleur model , * spiral model , * multipole lens , * rotation lens and * uniform ring .\nthe interested reader is refered to the literature for a discussion of these models@xmath14 .\nthe program was written in c and the _ mesa graphic libraries _ ( free version of the open gl ) have been used .\nthese graphic subroutines are available for unix or linux systems .\nthe _ xforms library _ was used to designed the control panel program(see fig .\nthe _ image library _ permits to load an image file on the program .\nthese libraries can be found at the following addresses : + http://bragg.phys.uwm.edu/xform + http://www.mesa3d.org/ + ftp://ftp.enlightenment.org/pub/enlightenment/imlib/ the program creates a window : the _ control panel _ ( see fig .\n2 ) . the user can control all item on it by clicking . a second window , the _ image window _\n, appears when the image window button is clicked on this panel ( see fig .\nthe help button on the panel give the user a concise program guide .\na version of this program which employs the sgi _\ngraphic libraries_is also available .\n[ general ] [ images2 ] all the objects are adjusted interactively with the mouse . this control panel interface has the following items : * source menu ( filled circle , coloured rings and image file ) * model menu ( the aforementioned models ) * source positioner * three counters , two for source positioning ( x , y ) and one for adjusting the pixel resolution ( n ) * two inputs for positioning the observed lense images ( x , y ) * buttons ( model paramters , image window , source , images , smooth , grid , r plot , r_e , file , add , replace , remove , clear , obip , save , help , exit ) , * sliders ( if one chooses a model , then the corresponding sliders appear ) * a browser for showing the observed lense images for a detailed discussion of these items see the manual program ( to get the program manual send an email to the author or click the help button on the control panel ) . on this window the events ( images , ray plot , etc .\nall variations of the parameters on the control panel are shown immediately on this window . to show the images of a chosen gravitational lens model\nthe _ ray tracing method _ has been used .\nthe caustic is represented by means of the _ ray plot method_.\nin this section two of many applications of the program are discussed : * _ image sequences _ * _ easy visual modeling _ an image sequence for an elliptical model and a visual modeling of the gravitational lens @xmath15 will be shown .\nan image sequence is easy to generate with this program .\nthe structure of the images for different positions of the source can be investigated by means of such an image sequence .\n_ an elliptical lens _ a sequence of images is shown in figure 4 .\nthe sequence begins on the top left - hand - side panel of the sequence .\nthe source , concentric rings , moves from left to right .\nthe source is not shown , only the images .\nthe best possible resolution given by the control panel was used . in this sequence the shear @xmath16 and the constant surface mass density @xmath17 are non zero and the shear angle @xmath18 .\nthere are two circles : the einstein ring or lens scale and the core radius\n. the formation of a small and a large arc can be seen . in the middle of the sequence one can recognize the deformation of the einstein ring in an ellipse . due to the core radius\nan image appears in the centre , which fuses with an arc , in the case that the source moves away .\n[ ellipt ] ( 11.4 , 17.2)[p]elliptical.gif [ gl2237 ] ( 12.8 , 13.2)[p]gl2237.gif [ m2237el ] ( 12.8 , 13.2)[p]m2237e.gif here an easy visual modeling of the gravitational lens system @xmath15 is shown .\nthe model images are considered well - fit when they overlap most of the area of the observed images ( represented through concentric circles ) , as visually estimated . at the present time a fitting subroutine is not implemented .\nwhen such a subroutine is included , this program would become an excellent tool to model gravitational lenses . _ visual model for the gravitational lens @xmath15 _ the system @xmath15 [ see fig .\n5 ] was discovered in 1985 . due to its unusual shape\nthis lens is called _\neinstein cross_. attempts to model this lens have been carried out@xmath14 the data used in tables [ tab1 ] and [ tab2 ] , was taken from kent and falco , and schneider et al.@xmath14the cosmological distances of table [ tab2 ] were calculated using the equations from schneider et al .\n( @xmath19 and @xmath20 ) .\n[ tab1 ] .image positions for the lens @xmath15 [ cols=\"^,^,^ \" , ]\nfrom both the didactical and scientific point of view a program to visualize the gravitational lenses is useful .\nthis versatile program works quickly and interactively with the mouse .\nthe user can produce sequences of images for a chosen gravitational lens model . through the variation of model parameters\nhe or she can investigate the structure of the images . the user can also attempt to visually model observed gravitational lenses .\nthe observed position data can be used as input data and the model parameters can be easily varied in order to approximate the observed images .\nso the user can quickly obtain model parameter estimations .\nsome observed lenses have already been modeled and the user can compare those results with the output from a chosen model of the control panel . * _ contour subroutine for the isochrones ( time delay ) _ * _ light curves subroutine ( dependence of brightness with time ) _ * _ subroutine for computing the image magnification _ * _ subroutine to calculate critical curves and caustics _ * _ fitting subroutine _ * _ root finder subroutine _ * _ subroutine to load images of observed gravitational lenses _ * _ subroutine with more complex ( elliptical ) models _ * _ subroutine for superposition of models in different lens planes _ * _ subroutine with cosmic string lens models _ * _ subroutine for non - parametric reconstruction _ * _ kaiser - squires subroutine _" }, { "role": "assistant", "content": "gravitational lenses are presently playing an important role in astrophysics . by means of these lenses the parameters of the deflector such as its mass , ellipticity , etc . and \n hubble s constant can be determined . \n using c , _ xforms _ , _ mesa _ and _ imlib _ a computer program to visualize this lens effect has been developed . \n this program has been applied to generate sequences of images of a source object and its corresponding images . \n it has also been used to visually test different models of gravitational lenses . \n epsf \n = 11 = 12" } ]
science.gnormplus_ner
science.gnormplus_ner.384
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Gene\"].\n\nPlease return the output as a JSON object of the format: {\"Gene\": [\"SSX\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. Multiple pterygium syndromes (MPS) comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). MPS are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal and nonlethal (Escobar) types. Previously, we and others reported that recessive mutations in the embryonal acetylcholine receptor g subunit (CHRNG) can cause both lethal and nonlethal MPS, thus demonstrating that pterygia resulted from fetal akinesia. We hypothesized that mutations in acetylcholine receptor-related genes might also result in a MPS/fetal akinesia phenotype and so we analyzed 15 cases of lethal MPS/fetal akinesia without CHRNG mutations for mutations in the CHRNA1, CHRNB1, CHRND, and rapsyn (RAPSN) genes. No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. Previously, RAPSN mutations have been reported in congenital myasthenia. Functional studies were consistent with the hypothesis that whereas incomplete loss of rapsyn function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype." }, { "role": "assistant", "content": "{\"Gene\": [\"RAPSN\", \"acetylcholine receptor-related genes\", \"embryonal acetylcholine receptor g subunit\", \"CHRNA1\", \"rapsyn\", \"CHRNG\", \"CHRND\", \"CHRNB1\"]}" } ]
science.chemsum_single_document_summarization
science.chemsum_single_document_summarization.85449
[ { "role": "user", "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nRapid Discrimination of the Geographical Origins of an Oolong Tea (Anxi-Tieguanyin) by Near-Infrared Spectroscopy and Partial Least Squares Discriminant Analysis\n\nPaper sections:\n1. Introduction\n<p>Oolong tea has been one of the most popular traditional beverages in the world. As a semifermented tea, Oolong tea is somewhere between the green and black tea with pleasurable aroma and taste for its particular processing. Moreover, a lot of people regard oolong tea as a functional drink for its high content of antioxidative substracts like epigallocatechin gallate (EGCG) and catechins [1]. And oolong tea is reported to have effect on antiobesity, preventing decayed tooth, disinfecting and hypolipidemic actions [2, 3].</p><p>The special aroma and taste of a tea depend largely on geographical and natural conditions of tea tree growing as well as on tea cultivar, cultivation traditions, and processing procedures. Therefore, most of the famous teas in China are named after their origins. Anxi-Tieguanyin tea (ATT) is one of the most famous Oolong teas with protected geographical indication (PGI), produced from Anxi County, a small town in Fujian province. Due to individual climate and edatope in Anxi County, ATT has a long-lasting fragrance and a strong aftertaste. It has been exported to many places all over the world. As the Tieguanyin tea with different provenances has similar appearance, some merchants fraudulently label ATT indication to non-Anxi-Tieguanyin teas (NATT) for illegal profits [4]. These actions do damage the reputation of ATT [5]. Therefore, it is important and urgent to employ quality control of ATT against various counterfeits. Until now, sensory analysis is the usually used method in distinguishing specific ATT geographical origin, which depends basically on the experience and personal emotion of tea tasters. For this application, a more stable and effective tool is worthwhile and necessary to be developed.</p><p>Different cultivating places had varied growing conditions including altitude, climate, soil, microelement, fertilizer, and processing [6, 7]. All these factors contribute to the different chemical components in teas. Although varied pattern of several chemical components could partially indicate the characters of specific teas, making errorless discriminations just by several chemical components proved difficult because the components in teas are really complicated [8, 9]. In recent years, instrumental methods coupled with chemometrics have provided promising alternative approaches in food components analysis [10–12]. As one of the rapid and effective measuring instruments, the near-infrared (NIR) spectroscopy has been widely performed in food multivariate quality control [13, 14]. Depending on individual vibrational frequency of molecular structure, NIR could characterize multiple chemical components of samples, which can help researchers discriminate the provenances of tea products. NIR has the following advantages over chemical analysis: (1) less money and time cost in analysis; (2) being nondestructive for samples; and (3) the ability in online analysis [15].</p><p>For automatic identification, some researchers have successfully used NIR spectroscopy and class models to discriminate the provenances of green teas [16, 17]. However, as a semifermented tea, the chemical components in Tieguanyin tea are far more complicated; it requires higher sensitivity in measuring process and classification. This paper aims to provide an effective way to discriminate the geographical origin of ATT by NIR spectroscopy and PLADA.</p>\n\n2.1. Tea Samples\n<p>450 authentic ATT samples were collected from 30 main Tieguanyin-producing areas of Anxi County with official certifications. 120 NATT samples were collected from Yongchun, Huaan, Xiandu, and so forth. All these samples were spring teas of 2013 (bought in the local tea markets of Anxi County before May 23, 2013) and were preserved in cold storage (4°C) before measuring analysis. The detailed information concerning samples was presented in Table 1.</p>\n\n2.2. NIR Spectrometric Analysis\n<p>All of the samples were scanned by TENSOR37 Fourier transform NIR spectrometer (Bruker, Ettlingen, Germany) and OPUS 7.2 software. Each sample was packed in a quartz cuvette and detected with a PbS detector. Each reported spectrum is the average of 64 scanning spectra in the spectral range from 4000 cm−1 to 12000 cm−1. Here the resolution was 8 cm−1 and the scanning interval was 1.928 cm−1, so 4148 individual data points were acquired from each spectrum for multivariate analysis.</p>\n\n2.3. Data Preprocessing and Splitting\n<p>Data analysis is performed on MATLAB 7.14.0.739 (Mathworks, Sherborn, MA). Aberrant spectra (outliers) are usually caused by abnormal samples or measuring faults. For class models, outliers make negative influence, sometimes even leading to model bias. Therefore, the Stahel-Donoho estimates (SDE) were used to detect abnormal spectra. SDE can detect the multiple outliers by calculating the values of outlyingness [18]. In addition, to ensure the sensitivity and the specificity, spectra need to be preprocessed. Three preprocessing methods were investigated in this study, including standard normal variate (SNV) transformation [19], taking second-order derivatives (D2), and smoothing [20].</p><p>With the spectra preprocessed, the data were split into a training set and a prediction set by the Kennard and Stone (K-S) algorithm [21]. K-S algorithm can ensure that the prediction objects are uniformly distributed in the range of training objects. In this paper, K-S algorithm was performed separately for ATT and NATT samples. Then two training sets were put together as a total training set and two prediction sets formed a total prediction set.</p>\n\n2.4. PLSDA\n<p>As a key method in chemometrics, partial least square has various applications [22–24]. The spectra of training set can be represented as an n × p matrix X (with n training objects and p wavelength points). s is the value of sorted number, in this paper, s = 2 (the ATT class and the NATT class), and an n × s matrix Y is then designed. The value of each element in Y is the corresponding category of the object in X. If an object i (i = 1 : n) is from class j (j = 1 : s), then element at ith row and jth column in Y is given a value 1; all other elements in Y are set −1. For prediction, a new sample is classified into class j (j = 1 : s) when the jth element of its predicted response is above zero. Because s = 2, we just need to consider the first column of predicted responses. If the value of the first column is above zero, it will be classified into ATT class; otherwise, it is NATT class. For PLSDA, the number of latent variables is a key parameter. Too many latent variables will cause the risk of overfitting. So in this model, Monte Carlo cross-validation (MCCV) [25] was performed to estimate the parameter. The number of latent variables was selected to calculate the minimal misclassification rate of MCCV (MRMCCV):\n(1)MRMCCV=(∑i=1TMiPi)×100%,\nwhere M\ni is the number of misclassified objects, P\ni is the total number of prediction objects, and T is the times of data splitting; then sensitivity and specificity were calculated to evaluate the performance of classification models:\n(2)Sens.=TPTP+FN′,Spec.=TNTN+TP′,\nwhere TP represents the number of true positives, FN is the number of false negatives, TN represents the number of true negatives, and FP is the number of false positives.</p>\n\n3. Results and Discussions\n<p>Some of the raw NIR spectra of ATT and NATT were demonstrated in Figure 1. The wavenumbers from 9000 to 12000 cm−1 were discarded in further analysis because these wavenumbers had low response signals and carried little information. Seen from Figure 1, although some of the NATT samples have lower absorbance in the range of 4000~5000 cm−1, a part of spectra is highly similar to the spectra of ATT and they can hardly be distinguished just by naked eyes. Therefore, to extract some useful chemical information from these spectra, chemometrics is used to develop classification models.</p><p>Outlier detection was performed by the SDE outlyingness diagnosis. The results were shown in Figure 2. In this paper, a spectrum is recognized as an outlier if its outlyingness is above 3. Seen from Figure 2, 19 ATT objects and 4 NATT objects were removed.</p><p>Then the raw spectral data was preprocessed by SNV, D2, and smoothing. Preprocessed spectra were shown in Figure 3. Compared with the raw spectra, SNV can reduce some spectral variations, D2 can enhance the resolution of some bands and remove most of the baselines, and smoothing can reduce the strength of noise signals.</p><p>For PLSDA, K-S algorithm was used to split the 431 ATT samples and 115 ATT samples into a training set (with 300 ATT samples and 80 NATT samples) and a prediction set (with 131 ATT samples and 35 NATT samples), and then PLSDA models were developed using the raw, D2, and SNV spectra. MCCV was used to estimate the number of PLSDA latent variables; the training set was randomly divided into a secondary training set (50%) and a secondary predicting set (50%) for 20 times. The number of latent variables was selected to calculate the minimal MRMCCV. Therefore, the objects in prediction class were applied to calculate the sensitivity and specificity of PLSDA model. The prediction results and optimized parameters with different preprocessing methods were listed in Table 2. Seen from Table 2, the best model is the SNV-PLSDA with the sensitivity/specificity of 0.931/1.000. The PLSDA model based on smoothing spectra and raw NIR spectra has exactly the same results. It means smoothing had little effect on NIR spectra. However, compared with the raw data, the model based on D2 spectra even gets a lower sensitivity/specificity. It might be caused by the loss of frequency information while taking second derivatives. The training and prediction results of SNV-PLSDA were demonstrated in Figure 4.</p>\n\n4. Conclusion\n<p>The results in this paper demonstrate the feasibility of combining NIR spectroscopy and PLSDA for discriminating the geographical origin of Tieguanyin tea. The sensitivity and specificity of PLSDA model based on SNV preprocessed spectra reached 0.931 and 1.000. Compared with the traditional methods [26, 27], a NIR spectrum of sample can be acquired within a minute and PLSDA model just needs several seconds to make a prediction. Moreover, compared with other NIR-chemometrics methods [16, 17], the samples in this study were scanned by NIR without any pretreatment, like grinding or smashing, so this method is nondestructive for samples as well. For geographical identification of teas, our future work will be trying some other sensitive measuring instruments, for example, inductively coupled plasma mass spectrometry and atomic absorption spectroscopy, and then make a comprehensive comparison with NIR.</p>" }, { "role": "assistant", "content": "This paper focuses on a rapid and nondestructive way to discriminate the geographical origin of Anxi-Tieguanyin tea by near-infrared (NIR) spectroscopy and chemometrics. 450 representative samples were collected from Anxi County, the original producing area of Tieguanyin tea, and another 120 Tieguanyin samples with similar appearance were collected from unprotected producing areas in China. All these samples were measured by NIR. The Stahel-Donoho estimates (SDE) outlyingness diagnosis was used to remove the outliers. Partial least squares discriminant analysis (PLSDA) was performed to develop a classification model and predict the authenticity of unknown objects. To improve the sensitivity and specificity of classification, the raw data was preprocessed to reduce unwanted spectral variations by standard normal variate (SNV) transformation, taking second-order derivatives (D2) spectra, and smoothing. As the best model, the sensitivity and specificity reached 0.931 and 1.000 with SNV spectra. Combination of NIR spectrometry and statistical model selection can provide an effective and rapid method to discriminate the geographical producing area of Anxi-Tieguanyin." } ]
science.drug_combo_extraction_re
science.drug_combo_extraction_re.541
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs. Molecular docking is a reliable method with which to identify the binding conformations of substrates, inducers and inhibitors of cytochrome P450 (CYP) enzymes. We used the docking method to explore possible binding modes of an entry inhibitor (maraviroc) and non-nucleoside reverse transcriptase inhibitors (delavirdine, efavirenz and etravirine) to cytochrome P450 3A4 (CYP3A4). In addition, docking results were compared with the binding conformations of HIV protease drugs to infer the binding site residues and potential drug-drug interaction profiles for combination therapy in the treatment of AIDS. We observed that efavirenz and etravirine induce metabolism of co-administered drugs by binding to a unique position in the active site of CYP3A4 . Dosage adjustment is required for delavirdine and maraviroc when combined with HIV protease drugs. The present results are in good agreement with experimental data from drug interaction profiles. The information provided in this paper will be helpful in furthering our understanding the functions of CYP3A4, and could aid in the design of new drugs that would be metabolized easily without having any drug-drug interaction profile.\n\nsentence: We observed that efavirenz and etravirine induce metabolism of co-administered drugs by binding to a unique position in the active site of CYP3A4 ." }, { "role": "assistant", "content": "[]" } ]
science.bioasq_yesno_qa
science.bioasq_yesno_qa.900
[ { "role": "user", "content": "You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Does Uc.63+ promote sensitivity to treatment in prostate cancer?\n\nContext: Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer.\nThe transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.\nTranscribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer\nThese results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC\nFurthermore , overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation\nThese results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.\nFurthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation.\nThese results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC." }, { "role": "assistant", "content": "no" } ]
science.scireviewgen_multidoc_summarization
science.scireviewgen_multidoc_summarization.72413
[ { "role": "user", "content": "You are presented with multiple paper abstracts, alongside the associated literature review and chapter titles. Given the provided information, you are going to do a literature review. Please generate a coherent literature review that synthesizes the content, draws connections between different works, highlights major findings, and identifies any gaps in the existing research.\n\nLiterature Review Title: A survey on trajectory clustering analysis \nChapter Title: Trajectory Clustering Preparation \n1. Abstract of Cited Paper (BIB001): Activity analysis is a basic task in video surveillance and has become an active research area. However, due to the diversity of moving objects category and their motion patterns, developing robust semantic scene models for activity analysis remains a challenging problem in traffic scenarios. This paper proposes a novel framework to learn semantic scene models. In this framework, the detected moving objects are first classified as pedestrians or vehicles via a co-trained classifier which takes advantage of the multiview information of objects. As a result, the framework can automatically learn motion patterns respectively for pedestrians and vehicles. Then, a graph is proposed to learn and cluster the motion patterns. To this end, trajectory is parameterized and the image is cut into multiple blocks which are taken as the nodes in the graph. Based on the parameters of trajectories, the primary motion patterns in each node (block) are extracted via Gaussian mixture model (GMM), and supplied to this graph. The graph cut algorithm is finally employed to group the motion patterns together, and trajectories are clustered to learn semantic scene models. Experimental results and applications to real world scenes show the validity of our proposed method. \n2. Abstract of Cited Paper (BIB002): Trajectory analysis is the basis for many applications, such as indexing of motion events in videos, activity recognition, and surveillance. In this paper, the Dirichlet process mixture model (DPMM) is applied to trajectory clustering, modeling, and retrieval. We propose an incremental version of a DPMM-based clustering algorithm and apply it to cluster trajectories. An appropriate number of trajectory clusters is determined automatically. When trajectories belonging to new clusters arrive, the new clusters can be identified online and added to the model without any retraining using the previous data. A time-sensitive Dirichlet process mixture model (tDPMM) is applied to each trajectory cluster for learning the trajectory pattern which represents the time-series characteristics of the trajectories in the cluster. Then, a parameterized index is constructed for each cluster. A novel likelihood estimation algorithm for the tDPMM is proposed, and a trajectory-based video retrieval model is developed. The tDPMM-based probabilistic matching method and the DPMM-based model growing method are combined to make the retrieval model scalable and adaptable. Experimental comparisons with state-of-the-art algorithms demonstrate the effectiveness of our algorithm.\n\nLiterature Review:" }, { "role": "assistant", "content": "In some clustering models BIB002 BIB001 [27] BIB003 , trajectory data are required to be set as a unified length so that they could be measured. However, as shown in" } ]
science.multixscience_multidoc_summarization
science.multixscience_multidoc_summarization.6003
[ { "role": "user", "content": "You are provided with the abstract of a scientific paper and the abstracts of the papers it references. Your task is to write a Related Work section for the main paper. This section should concisely summarize and integrate the key points from the cited abstracts, reflecting how they relate to the main paper's contributions and context. In your summary, use numerical citation markers like [1], [2], etc., to refer to the corresponding papers.\n\nMain Abstract:\nTalking face generation aims to synthesize a sequence of face images that correspond to a clip of speech. This is a challenging task because face appearance variation and semantics of speech are coupled together in the subtle movements of the talking face regions. Existing works either construct specific face appearance model on specific subjects or model the transformation between lip motion and speech. In this work, we integrate both aspects and enable arbitrary-subject talking face generation by learning disentangled audio-visual representation. We find that the talking face sequence is actually a composition of both subject-related information and speech-related information. These two spaces are then explicitly disentangled through a novel associative-and-adversarial training process. This disentangled representation has an advantage where both audio and video can serve as inputs for generation. Extensive experiments show that the proposed approach generates realistic talking face sequences on arbitrary subjects with much clearer lip motion patterns than previous work. We also demonstrate the learned audio-visual representation is extremely useful for the tasks of automatic lip reading and audio-video retrieval.\n\nCited Abstract(s):\n[1]: We propose an end-to-end deep learning architecture for word-level visual speech recognition. The system is a combination of spatiotemporal convolutional, residual and bidirectional Long Short-Term Memory networks. We train and evaluate it on the Lipreading In-The-Wild benchmark, a challenging database of 500-size target-words consisting of 1.28sec video excerpts from BBC TV broadcasts. The proposed network attains word accuracy equal to 83.0, yielding 6.8 absolute improvement over the current state-of-the-art, without using information about word boundaries during training or testing.\n\n[2]: Our aim is to recognise the words being spoken by a talking face, given only the video but not the audio. Existing works in this area have focussed on trying to recognise a small number of utterances in controlled environments (e.g. digits and alphabets), partially due to the shortage of suitable datasets.\n\n[3]: Lipreading is the task of decoding text from the movement of a speaker's mouth. Traditional approaches separated the problem into two stages: designing or learning visual features, and prediction. More recent deep lipreading approaches are end-to-end trainable (, 2016; Chung & Zisserman, 2016a). However, existing work on models trained end-to-end perform only word classification, rather than sentence-level sequence prediction. Studies have shown that human lipreading performance increases for longer words (Easton & Basala, 1982), indicating the importance of features capturing temporal context in an ambiguous communication channel. Motivated by this observation, we present LipNet, a model that maps a variable-length sequence of video frames to text, making use of spatiotemporal convolutions, a recurrent network, and the connectionist temporal classification loss, trained entirely end-to-end. To the best of our knowledge, LipNet is the first end-to-end sentence-level lipreading model that simultaneously learns spatiotemporal visual features and a sequence model. On the GRID corpus, LipNet achieves 95.2 accuracy in sentence-level, overlapped speaker split task, outperforming experienced human lipreaders and the previous 86.4 word-level state-of-the-art accuracy (, 2016).\n\n[4]: \n\n[5]: The goal of this work is to recognise phrases and sentences being spoken by a talking face, with or without the audio. Unlike previous works that have focussed on recognising a limited number of words or phrases, we tackle lip reading as an open-world problem - unconstrained natural language sentences, and in the wild videos. Our key contributions are: (1) a 'Watch, Listen, Attend and Spell' (WLAS) network that learns to transcribe videos of mouth motion to characters; (2) a curriculum learning strategy to accelerate training and to reduce overfitting; (3) a 'Lip Reading Sentences' (LRS) dataset for visual speech recognition, consisting of over 100,000 natural sentences from British television. The WLAS model trained on the LRS dataset surpasses the performance of all previous work on standard lip reading benchmark datasets, often by a significant margin. This lip reading performance beats a professional lip reader on videos from BBC television, and we also demonstrate that visual information helps to improve speech recognition performance even when the audio is available.\n\n[6]: Abstract Visual speech information plays an important role in automatic speech recognition (ASR) especially when audio is corrupted or even inaccessible. Despite the success of audio-based ASR, the problem of visual speech decoding remains widely open. This paper provides a detailed review of recent advances in this research area. In comparison with the previous survey [97] which covers the whole ASR system that uses visual speech information, we focus on the important questions asked by researchers and summarize the recent studies that attempt to answer them. In particular, there are three questions related to the extraction of visual features, concerning speaker dependency, pose variation and temporal information, respectively. Another question is about audio-visual speech fusion, considering the dynamic changes of modality reliabilities encountered in practice. In addition, the state-of-the-art on facial landmark localization is briefly introduced in this paper. Those advanced techniques can be used to improve the region-of-interest detection, but have been largely ignored when building a visual-based ASR system. We also provide details of audio-visual speech databases. Finally, we discuss the remaining challenges and offer our insights into the future research on visual speech decoding." }, { "role": "assistant", "content": "The task of audio-visual speech recognition is a recognition problem uses either one or both video and audio as inputs. Using visual information only for recognition is also referred to as . A review of traditional methods for tackling this task has been made in [2]3 thoroughly. In recent years, this field develop quickly with the usage of convolutional neural networks (CNNs) and recurrent neural networks (RNNs) for end-to-end word-level [2] [1] , sentence-level [3] [2]6 , and multi-view [4] lip reading. In the meantime, the exploration of this topic has been greatly pushed forward by the build-up of large-scale word-level lip reading dataset [2] , and the large sentence-level multi-view dataset [4] ." } ]
science.pico_ner
science.pico_ner.4124
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Outcome\", \"Participant\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\" : [\"patients with COPD\", ...], \"Intervention\" : [\"Atenolol\", ...], \"Outcome\" : [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffect of fats high in individual saturated fatty acids on plasma lipoprotein [ a ] levels in young healthy men . Plasma lipoprotein [ a ] ( Lp [ a ] ) is associated with atherogenesis and thrombogenesis . We examined how plasma Lp [ a ] in healthy young men was affected by fats high in stearic ( C18 ) , palmitic ( C16 ) , and lauric+myristic ( C12+ C14 ) acid ( experiment I , 15 subjects ) , and by fats high in myristic ( C14 ) and palmitic ( C16 ) acid ( experiment II , 12 subjects ) . Strictly controlled isocaloric diets with 36 % of energy from test fats were served in random order for 3 weeks separated by wash-out period ( s ) . Diets high in C18 gave significantly higher levels of Lp [ a ] ( 51 ( 12-560 ) mg/L ) than diets high in C16 ( 38 ( 12-533 mg/L ) ( P = 0.020 ) and C12 + C14 ( 34 ( 12-534 ) mg/L ) ( P = 0.002 ) . These differences were observed in several of the subjects in experiment I . In experiment II we saw no difference in plasma Lp [ a ] after diets high in C16 and C14 . Our observations suggest that a fat high in stearic acid might affect Lp [ a ] in a different way than fats high in palmitic and myristic+lauric acid . Lp [ a ] concentrations were not associate with changes in tissue-plasminogen activator ( t-PA ) activity , factor VII coagualant activity , or plasma LDL cholesterol ." }, { "role": "assistant", "content": "{\"Intervention\": [\"isocaloric diets\", \"fats high in stearic ( C18 ) , palmitic ( C16 ) , and lauric+myristic ( C12+ C14 ) acid\", \"fats\", \"and by fats high in myristic ( C14 ) and palmitic ( C16 ) acid ( experiment\", \"high in C16\", \"Diets high in C18\"], \"Outcome\": [\"tissue-plasminogen activator ( t-PA ) activity\", \"Lp [ a ]\", \"plasma lipoprotein [ a ] levels\", \"differences\", \"Plasma lipoprotein [ a ] ( Lp [ a ] )\", \"levels of Lp [ a ]\", \"Lp [ a ] concentrations\", \"factor VII coagualant activity\", \"plasma Lp [ a ]\", \"plasma LDL cholesterol\"], \"Participant\": [\"experiment I , 15 subjects\", \"men\", \"experiment II , 12 subjects\", \"young\", \"healthy\"]}" } ]
science.chia_ner
science.chia_ner.1755
[ { "role": "user", "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Observation\", \"Condition\", \"Procedure\", \"Drug\", \"Temporal\", \"Multiplier\", \"Qualifier\", \"Negation\", \"ReferencePoint\", \"Scope\", \"Value\", \"Mood\", \"Device\", \"Visit\", \"Measurement\", \"Person\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\" : [\"breast cancer\", ...], \"Device\" : [\"ports\", ...], \"Drug\" : [\"Atenolol\", ...], \"Measurement\" : [\"blood pressure\", ...], \"Mood\" : [\"suspected\", ...], \"Multiplier\" : [\"more than two\", ...], \"Negation\" : [\"no\", ...], \"Observation\" : [\"history\", ...], \"Person\" : [\"male\", ...], \"Procedure\" : [\"surgery\", ...], \"Qualifier\" : [\"severe\", ...], \"ReferencePoint\" : [\"enrollment\", ...], \"Scope\" : [\"infection\", ...], \"Temporal\" : [\"one day\", ...], \"Value\" : [\"50%\", ...], \"Visit\" : [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nadults capable of providing consent\nhave a diagnosis of locally advanced or metastatic melanoma" }, { "role": "assistant", "content": "{\"Condition\": [\"melanoma\"], \"Device\": [], \"Drug\": [], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [\"adults\"], \"Procedure\": [], \"Qualifier\": [\"locally advanced\", \"metastatic\"], \"ReferencePoint\": [], \"Scope\": [\"locally advanced or metastatic\"], \"Temporal\": [], \"Value\": [], \"Visit\": []}" } ]
science.medmentions_ner
science.medmentions_ner.97
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"HealthCareActivity\", \"InjuryOrPoisoning\", \"BodySubstance\", \"IntellectualProduct\", \"AnatomicalStructure\", \"SpatialConcept\", \"Chemical\", \"Bacterium\", \"MedicalDevice\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Finding\", \"BiologicFunction\", \"Virus\", \"ResearchActivity\", \"ClinicalAttribute\", \"PopulationGroup\", \"Eukaryote\", \"BodySystem\", \"Food\", \"ProfessionalOrOccupationalGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nNutrient Intakes in Early Life and Risk of Obesity There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI) trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life (\"The first 1000 days \"). Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases." }, { "role": "assistant", "content": "{\"AnatomicalStructure\": [], \"Bacterium\": [], \"BiologicFunction\": [\"obese\", \"nutrition\", \"Obesity\", \"pregnancy\", \"adult diseases\", \"obesity\", \"development\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [\"body fat\", \"body mass index\", \"BMI\"], \"Eukaryote\": [], \"Finding\": [\"present\"], \"Food\": [\"high protein-low fat diet\"], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"subjects\"], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"environmental\"], \"Virus\": []}" } ]
science.mslr2022_ms2_multidoc_summarization
science.mslr2022_ms2_multidoc_summarization.5674
[ { "role": "user", "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nEfficacy of a fabricated customized splint and tendon and nerve gliding exercises for the treatment of carpal tunnel syndrome: a randomized controlled trial.\nAbstract 1:\nOBJECTIVE To compare the effects of a neutral wrist and metacarpophalangeal ( MCP ) splint with a wrist cock-up splint , with and without exercises , for the treatment of carpal tunnel syndrome ( CTS ) . DESIGN A 2x2x3 r and omized factorial design with 3 main factors : splint ( neutral wrist and MCP and wrist cock-up ) , exercise ( exercises , no exercise ) , and time ( baseline , 4wk , 8wk ) . SETTING Subjects were evaluated in an outpatient h and therapy clinic . PARTICIPANTS Sixty-one subjects with mild to moderate CTS ; 51 subjects completed the study . INTERVENTIONS There were 4 groups : the neutral wrist and MCP group and the neutral wrist and MCP-exercise group received fabricated customized splints that supported the wrist and MCP joints ; the wrist cock-up group and the wrist cock-up-exercise group received wrist cock-up splints . The neutral wrist and MCP-exercise and wrist cock-up-exercise groups also received tendon and nerve gliding exercises and were instructed to perform exercises 3 times a day . All subjects were instructed to wear the assigned splint every night for 4 weeks . MAIN OUTCOME MEASURES We used the CTS Symptom Severity Scale ( SSS ) and the Functional Status Scale ( FSS ) to assess CTS symptoms and functional status . RESULTS Analysis of variance showed a significant main effect for splint and time on the SSS ( P<.001 , P=.014 ) and FSS ( P<.001 , P=.029 ) , respectively . There were no interaction effects . CONCLUSIONS Our results vali date the use of wrist splints for the treatment of CTS , and suggest that a splint that supports the wrist and MCP joints in neutral may be more effective than a wrist cock-up splint\n\n\nTitle 2:\nNeutral wrist splinting in carpal tunnel syndrome: a comparison of night-only versus full-time wear instructions.\nAbstract 2:\nOBJECTIVE To compare the effects of night-only to full-time splint wear instructions on symptoms , function , and impairment in carpal tunnel syndrome ( CTS ) . DESIGN R and omized clinical trial with 6-week follow-up . SETTING Veterans Administration Medical Center , outpatient clinic . SUBJECTS Out patients with untreated CTS were consecutively recruited from our electrodiagnostics lab . Twenty-one patients ( 30 h and s ) were enrolled , and 17 patients ( 24 h and s ) completed the study . INTERVENTIONS Thermoplastic , custom-molded , neutral wrist splints with subjects receiving either full-time or night-only wear instructions . OUTCOME MEASURES Symptoms and functional deficits were measured by Levine 's self-administered question naire , and physiologic impairment was measured by median nerve sensory and motor distal latency . COMPLIANCE AND CROSSOVER : Almost all ( 92 % ) of the combined sample reported frequent splint use , but their adherence to specific wearing instructions was limited . A majority ( 73 % ) of the full-time group reported splint wear less than one half of waking hours , and some ( 23 % ) of the night-only group reported occasional daytime wear . Despite this tendency for treatment crossover , the two treatment groups differed in daytime wear as intended ( chi2 analysis , p = .004 ) . RESULTS The combined sample improved in three of four outcome measures : sensory distal latency ( mean = .28msec , st and ard deviation [ SD ] = .37 , p = .004 ) , symptom severity ( mean = .64 , SD = .46 , p = .0001 ) , and functional deficits ( mean = .49 , SD = .51 , p = .0001 ) . Severity of CTS was a factor only in sensory distal latency improvement ( more improvement in severe CTS ) . Subjects receiving full-time wear instructions showed superior distal latency improvement , both motor ( .35 vs -.07msec , p = .04 ) and sensory ( .46 vs . 13msec , p = .05 ) when compared with subjects receiving night-only wear instructions . CONCLUSIONS This study provides added scientific evidence to support the efficacy of neutral wrist splints in CTS and suggests that physiologic improvement is best with full-time splint wear instructions\n\n\nTitle 3:\nAn investigation to compare the effectiveness of carpal bone mobilisation and neurodynamic mobilisation as methods of treatment for carpal tunnel syndrome.\nAbstract 3:\nCarpal tunnel syndrome is the most common peripheral entrapment neuropathy . There is little literature available that addresses the management of this condition , which may partly explain why physiotherapy is often overlooked as a treatment approach in its management . This study investigated the effects of two manual therapy techniques in the treatment of patients experiencing carpal tunnel syndrome . An experimental different subject design compared three groups of subjects in three different conditions ( two treatment interventions and one control group ) . Each group consisted of seven patients . The objectives of the study were : ( 1 ) to investigate differences between treated and untreated groups ; ( 2 ) to investigate differences in the effectiveness of treatment I ( median nerve mobilization ) compared with treatment II ( carpal bone mobilization ) . Measurements were taken applying several measurement tools , including active range of wrist movement ( ROM flexion and extension ) , upper limb tension test with a median nerve bias ( ULTT2a ) , three different scales to evaluate pain perception and function , and lastly numbers of patients continuing to surgery in each group were compared . In visual terms a clear trend was demonstrated between subjects who received treatment compared to those who were not treated , in particular the descriptive analysis of results for ULTT2a and numbers of patients continuing to surgery . When analysed statistically , less could be concluded . Only scores on a Pain Relief Scale ( P<0.01 ) demonstrated highly significant differences between the three groups when analyzed using Kruskal-Wallis Test . In exploring the results of the two intervention groups , no statistically significant difference in effectiveness of treatment was demonstrated between carpal bone mobilization and median nerve mobilization\n\n\nTitle 4:\nNerve and tendon gliding exercises and the conservative management of carpal tunnel syndrome.\nAbstract 4:\nWhile developments continue in the surgical management of carpal tunnel syndrome , little emphasis has been placed on the evaluation of a comprehensive non-surgical treatment . In this study , 197 patients ( 240 h and s ) presenting for treatment of carpal tunnel syndrome were divided into two groups . Patients in both groups were treated by st and ard conservative methods , and those in one group were also treated with a program of nerve and tendon gliding exercises . Of those who did not perform the nerve and tendon gliding exercises , 71.2 % underwent surgery compared with only 43.0 % of patients who did perform them . Patients in the experimental group who did not undergo surgery were interviewed at an average follow-up time of 23 months ( range , 14 - 38 months ) . Of these 53 patients , 47 ( 89 % ) responded to this detailed interview . Of the 47 who responded , 70.2 % reported good or excellent results , 19.2 % remained symptomatic , and 10.6 % were non-compliant . Thus , a significant number of patients who would otherwise have undergone surgery for failure of traditional conservative treatment were spared the surgical morbidity of a carpal tunnel release ( p = 0.0001 )\n\n\nTitle 5:\nAn innovative hand brace for carpal tunnel syndrome: a randomized controlled trial.\nAbstract 5:\nWe developed a h and brace and studied its efficacy and tolerability in patients with carpal tunnel syndrome ( CTS ) . We r and omized 83 subjects into a treated group , which wore the h and brace at night for 4 weeks , and a control group , which received no treatment . The primary efficacy measure was change in the Boston Carpal Tunnel Question naire ( BCTQ ) score . Secondary measures were Subjects ' Global Impression of Change Question naire ( SGICQ ) , median distal motor latency , sensory conduction velocity and amplitude , and neurophysiological class of severity . The treated group showed a reduction in BCTQ symptomatic score ( from 2.75 to 1.54 at 4 weeks ; P < 0.001 ) and functional score ( from 1.89 to 1.48 ; P < 0.001 ) . There were no significant changes in the control subjects . SGICQ documented improvement in all treated subjects ( P = 0.006 ) . No significant difference was found in electrophysiological measurements , but overall neurophysiological classification shifted to less severe classes in the treated group ( P < 0.05 ) . Thus , the study demonstrates that this h and brace is highly efficient in relieving symptoms and functional loss in CTS\n\n\nTitle 6:\nConservative treatment of carpal tunnel syndrome: an outcome study of adjunct exercises.\nAbstract 6:\nWe conducted a prospect i ve study to evaluate the effect of a new non-surgical protocol for treating carpal tunnel syndrome ( CTS ) . It incorporates the Carpal Tunnel Decompression Exercise Program ( Exercise Program ) into conventional non-surgical treatment . Twenty-eight patients ( 33 h and s ) met the inclusion criteria and were followed for 18 months . The outcome measurement tools used were the Symptom Severity Scale ( SSS ) and the Functional Status Scale ( FSS ) . The outcome tools were administered at admission and repeated at 1 , 2 , and 18 months after admission to the treatment program . Using the adjunct treatment , 80 % of the h and s in the mild category and 71 % in the moderate category were successfully treated without surgery . All patients in the severe category required surgery . The average success rate of our adjunct non-surgical treatment protocol was 67 % , a substantial improvement over the 18 % to 34 % success rate reported nationally for conventional treatment methods . Furthermore , improvement in the outcome of carpal tunnel syndrome by the adjunct non-surgical treatment can result in significant savings in human suffering , medical cost , lost work time , and socioeconomic distress\n\n\nTitle 7:\nReliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis.\nAbstract 7:\nThe assessment of a measure of chronic pain , should be reliable , valid and sensitive to change . Our study evaluated the reliability of 3 pain scales , visual analogue scale ( VAS ) , numerical rating scale ( NRS ) and verbal rating scale ( VRS ) in literate and illiterate patients with rheumatoid arthritis ( RA ) . Patients with RA attending an outpatient rheumatology clinic were interviewed and asked to score their pain levels on the 3 pain scales . The scales were presented in r and om order , twice , before and just after a regular medical consultation . Ninety-one patients were studied ( 25 illiterate and 66 literate ) . The Pearson product moment correlation between first and second assessment was 0.937 for VAS , 0.963 for NRS and 0.901 for VRS in the literate patient group and 0.712 for VAS , 0.947 for NRS and 0.820 for VRS in the illiterate patient group . These results indicate that the NRS has the higher reliability in both groups of patients\n\n\nTitle 8:\nThe visual analogue pain intensity scale: what is moderate pain in millimetres?\nAbstract 8:\nAbstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale\n\n\nTitle 9:\nTreatment of Carpal Tunnel Syndrome with Nerve and Tendon Gliding Exercises\nAbstract 9:\nAkalin E , El Ö , Peker Ö , Şenocak Ö , Tamci Ş , Gülbahar S , Çakmur R , Öncel S : Treatment of carpal tunnel syndrome with nerve and tendon gliding exercises . Am J Phys Med Rehabil 2002;81:108–113 . Objective To assess the effect of nerve and tendon gliding exercises in carpal tunnel syndrome . Design The study was a prospect i ve , r and omized , before- and -after treatment trial . A total of 28 patients with the diagnosis of carpal tunnel syndrome in 36 h and s were r and omly assigned to two groups . A custom made neutral volar wrist splint was given to group 1 and group 2 . The patients were instructed to wear the splints all night and during the day as much as possible for 4 wk . The patients in group 2 were also instructed to perform series of nerve and tendon gliding exercises in addition to the splint treatment . Patients were evaluated with clinical parameters , a functional status scale , and a symptom severity scale . Results At the end of treatment , statistically significant improvement was obtained in all parameters in both groups . The improvement in group 2 was slightly greater , but the difference between the groups was not significant , except for the lateral pinch strength value . Patient satisfaction was investigated during the follow-up period , ranging from 5 to 11 mo , with a mean of 8 mo . A total of 72 % of the patients in group 1 and 93 % of the patients in group 2 reported good or excellent results . The difference between the two groups was not statistically significant . Conclusion Although the results in group 2 were better than group 1 , the difference was not statistically significant . Further investigations are required to establish the role of nerve and tendon gliding exercises in the treatment of carpal tunnel syndrome" }, { "role": "assistant", "content": "For all variables , none were consistently favorable toward neural gliding over alternative treatment .\nHowever , comparisons across studies revealed a possible trend toward improved outcomes with the use neural gliding .\nCONCLUSIONS The efficacy of neural gliding is not clear ." } ]
science.scientific_lay_summarisation_elife_single_doc_summ
science.scientific_lay_summarisation_elife_single_doc_summ.3799
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic agonist antibody}\nArticle:\nAbstract:\nIn amyotrophic lateral sclerosis( ALS) and animal models of ALS, including SOD1-G93A mice, disassembly of the neuromuscular synapse precedes motor neuron loss and is sufficient to cause a decline in motor function that culminates in lethal respiratory paralysis. We treated SOD1-G93A mice with an agonist antibody to MuSK, a receptor tyrosine kinase essential for maintaining neuromuscular synapses, to determine whether increasing muscle retrograde signaling would slow nerve terminal detachment from muscle. The agonist antibody, delivered after disease onset, slowed muscle denervation, promoting motor neuron survival, improving motor system output, and extending the lifespan of SOD1-G93A mice. These findings suggest a novel therapeutic strategy for ALS, using an antibody format with clinical precedence, which targets a pathway essential for maintaining attachment of nerve terminals to muscle.\nIntroduction:\nAmyotrophic lateral sclerosis( ALS) is a neurodegenerative disease that progresses relentlessly from a subtle decline in motor function to lethal respiratory paralysis within a few years of diagnosis( Pasinelli and Brown, 2006; Taylor et al., 2016). The disease can be familial and caused by dominant mutations in one of several genes, including SOD1, C9orf72, TDP43, and FUS( Taylor et al., 2016). More commonly, however, the disease is idiopathic. Although motor neuron cell death is a hallmark feature of ALS, the loss of neuromuscular synapses occurs prior to the loss of motor neurons and is the primary cause of motor paralysis in both familial and sporadic forms of ALS( Fischer et al., 2004; Schaefer et al., 2005; Pun et al., 2006). The detachment of motor nerve terminals and withdrawal of motor axons has received less attention than the later loss of motor neurons, but therapeutic approaches designed to preserve neuromuscular synapses have the potential to maintain motor function, especially during the early phases of disease, and provide benefit to the quality of life for patient and family. Transgenic mice bearing dominant mutations in the human SOD1 gene, including SOD1-G93A mice, recapitulate the hallmark features of ALS and provide the most thoroughly studied animal model for ALS( Vinsant et al., 2013a; Vinsant et al., 2013b). Moreover, because detachment of motor nerve terminals is the primary cause for paralysis in SOD1-G93A mice, SOD1-G93A mice represent a clinically relevant model for ALS. The signaling pathways that control attachment of motor axon terminals to muscle are only beginning to be understood, but two genes, Lrp4 and Musk, expressed by muscle, play important roles. Lrp4, a member of the LDL receptor family, is the muscle receptor for the critical neuronal ligand, Agrin( Kim et al., 2008; Zhang et al., 2008). Upon binding Agrin, Lrp4 associates with MuSK, a receptor tyrosine kinase, stimulating MuSK and leading to anchoring and enhanced expression of critical postsynaptic proteins, including Lrp4( Burden et al., 2013). Clustered Lrp4 then signals back to motor axons to stimulate their attachment and differentiation( Yumoto et al., 2012). Recessive mutations in Agrin, Lrp4 or Musk cause congenital myasthenia, a group of neuromuscular disorders, distinct from ALS, which compromise the structure and function of neuromuscular synapses and lead to muscle weakness and fatigue( Engel et al., 2015). Moreover, autoantibodies to Agrin, Lrp4, or MuSK cause myasthenia gravis( MG), which is likewise distinct from ALS( Gilhus and Verschuuren, 2015). In MuSK MG, the pathogenic antibodies are usually directed to the first Ig-like domain in MuSK and reduce MuSK phosphorylation by impairing binding between Lrp4 and MuSK( Huijbers et al., 2013; Koneczny et al., 2013). Although defects in the MuSK signaling pathway are not associated with ALS, increasing MuSK gene expression stabilizes neuromuscular synapses in SOD1-G93A mice, reducing the extent of muscle denervation and improving motor function( Pérez-García and Burden, 2012). However, these experiments used transgenic mice to modestly increase MuSK expression from muscle, beginning during early development, several months prior to disease onset. Therefore, the therapeutic potential of increasing MuSK signaling as a strategy to reduce denervation and improve motor function in patients diagnosed with ALS remained unclear. Here, we sought to determine whether a pharmacological approach to increase MuSK activity in vivo would preserve neuromuscular synapses in SOD1-G93A mice when dosing was initiated after disease onset. This type of approach would have substantially improved potential for translation to ALS patients without the complex requirements for gene therapy( Miyoshi et al., 2017).\nDiscussion:\nALS is a devastating disease that progresses in a relentless manner from detachment of motor nerve terminals to lethal respiratory paralysis within several years of diagnosis. Currently, there is an unmet need for therapies that significantly alter the course of disease. Here, we describe a therapeutic approach designed to slow the loss of motor innervation to muscle by targeting a well-defined molecule and mechanism for forming and maintaining neuromuscular synapses. We show that an agonist antibody to MuSK, introduced after disease onset, decreases muscle denervation, improves motor system output, reduces motor neuron loss and extends survival in an aggressive mouse model of ALS. If this strategy, described here for an aggressive mouse model of ALS, were similarly successful in preserving innervation in sporadic and familial ALS, this therapeutic approach would have the potential to improve the quality of life for ALS patients, and as such warrants further study. Anti-sense RNA directed toward SOD1 is currently being tested as a promising therapeutic for ALS caused by mutations in SOD1( Miller et al., 2013). A similar approach may ultimately be effective for other dominant, familial forms of ALS( Reddy and Miller, 2015; van Zundert and Brown, 2017). However, >80% of ALS patients are diagnosed with sporadic ALS, so strategies to inactivate a single culprit gene are not tenable for most cases of ALS. Instead, multiple, concurrent therapeutic interventions that effectively address the pathology and symptoms of ALS will likely be necessary to alter the course of disease( Brown and Al-Chalabi, 2017). Because synaptic loss and muscle denervation are common to sporadic as well as familial forms of ALS, the approach described here has the potential to be effective for both forms of ALS. Moreover, increasing MuSK activity and retrograde signaling may also slow the deterioration of neuromuscular synapses in other neuromuscular diseases and during aging( Engel et al., 2015; Gilhus and Verschuuren, 2015; Valdez et al., 2012; Poort et al., 2016). Consistent with this idea, adenoviral expression of Dok-7, an inside-outside activator of MuSK, not only extends longevity of SOD1-G93A mice but also provides benefit in other mouse models of neuromuscular disease, including congenital myasthenia and Emery-Dreifuss muscular dystrophy( Miyoshi et al., 2017; Arimura et al., 2014). Further, there is increasing evidence that synaptic loss occurs early during disease progression in other neurodegenerative diseases, such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Frontotemporal dementia and Spinal Muscular Atrophy( Henstridge et al., 2016), so similar strategies, designed to preserve synapses, may slow progression in these diseases as well. Our proof of concept experiments were designed to determine whether boosting retrograde signaling in vivo with the MuSK agonist antibody might slow motor axon withdrawal and muscle denervation in SOD1-G93A mice. As such, we introduced the MuSK agonist antibody after denervation was already evident, during the early phase of denervation in female SOD1-G93A mice and mid-phase in male SOD1-G93A mice, but before SOD1-G93A mice exhibited overt and severe deficits in limb motor function. This timing for delivery of the MuSK agonist antibody may be pertinent and significant for ALS, as denervation is the cause of muscle fibrillations, an early clinical sign in ALS. Because MuSK-dependent retrograde signaling is likely to act focally on nerve terminals and axons that are near the postsynaptic membrane and to be less effective in promoting regeneration of axons that have fully withdrawn, early delivery of a MuSK agonist is likely to be more effective than later delivery in ALS. However, ALS is a diagnosis of exclusion, leading to delays in diagnosis. Nonetheless, even at late stages of disease, a majority of synapses in SOD1-G93A mice are partially innervated, and the MuSK agonist antibody improved nerve terminal coverage at these partially innervated synapses. These findings suggest that the MuSK agonist antibody may also be effective if introduced later during disease. However, because overt motor deficits become evident in SOD1-G93A mice only a month before death, this aggressive mouse model of ALS may not be the optimal and most informative model to infer whether later introduction of the MuSK agonist antibody can stabilize synapses and slow motor dysfunction in ALS. The loss of motor neurons during embryonic development is regulated, at least in part by synapse formation( Hollyday and Hamburger, 1976; Tanaka and Landmesser, 1986; Landmesser, 1992). The increased survival of motor neurons in MuSK agonist antibody-injected SOD1-G93A mice indicates that adult motor neurons can likewise receive trophic support from muscle. Thus, preserving neuromuscular synapses not only maintains the essential attachment of nerve to muscle but also provides the added benefit of promoting motor neuron survival. Although we used an agonist antibody to MuSK to stimulate retrograde signaling from muscle, one can envisage other approaches to stimulate MuSK or enhance retrograde signaling in order to maintain attachment of motor axons to muscle. The MuSK agonist antibody is effective at maintaining neuromuscular synapses in SOD1-G93A mice up to P162, but within the next week, synapses are lost, and the mice die. Because the MuSK agonist antibody is designed to maintain neuromuscular synapses and does not directly target or address the underlying cause of the disease and other pathologies in SOD1-G93A mice and ALS, the benefit of increasing retrograde signaling from muscle to nerve and promoting nerve terminal attachment is limited. Nonetheless, although the antibody cannot override the many pathological pathways that occur in the motor neuron and in non-neuronal cells, this therapeutic approach has a potent effect on the course of disease, reducing synaptic loss, improving motor output and extending the lifespan of SOD1-G93A mice longer than riluzole, the long-standing FDA approved treatment for ALS( Jablonski et al., 2014). Motor neuron cell death is a critical feature in ALS, but elimination of Bax, which prevents apoptotic cell death, fails to preserve neuromuscular synapses and increases survival of SOD1-G93A mice by only 20 days( Gould et al., 2006). Together with our studies, these findings give credence to the idea that combinatorial therapeutic interventions, including those that preserve neuromuscular synapses, will be necessary to fully address the complex pathology and symptoms of ALS and contribute to an improved quality of life for patient and family." }, { "role": "assistant", "content": "Amyotrophic lateral sclerosis – often shortened to ALS – is a disease that starts with difficulties moving and progresses to paralysis of many muscles , including those used for breathing . The disease is usually lethal , with patients rarely surviving more than a few years after diagnosis . There is no cure or effective treatment for the disease . It begins with the breakdown of the connections , or synapses , between the muscles and the nerve cells that connect with them . After this , the nerve cell itself breaks down . Many therapeutic approaches have focused on attempts to prevent the nerve cells from dying , but few target the initial degeneration of the synapse . Cantor et al . asked if intervening when the synapse has already begun to break down could slow the progression of the disease in mice with ALS . Their approach involved using an antibody to bind to a receptor protein called MuSK , which plays an important role in maintaining the synapse between muscle and nerve cell . The antibody boosted the receptor’s activity , helping to preserve synapses , including those that connect nerve cells to the diaphragm muscle . The experiments showed that the antibody treatment led to fewer synapses breaking down , and kept more of the nerve cells alive . Healthier connections between the nervous system and the diaphragm improved the function of this muscle . As a result , the mice given the antibody treatment had a slightly extended lifespan , compared with those given no treatment . The findings suggest a possible new way to develop treatments for ALS , which could be used in combination with other therapies , such as those aimed at improving the health of the nerve cells . Together , this could improve quality of life for the majority of patients with ALS . Similar strategies could be used to develop treatments to preserve synapses in other neurodegenerative diseases , such as Alzheimer’s , Parkinson’s and Huntington’s disease , as well as some kinds of dementia . Preserving synapses early on , before the significant loss of nerve cells , could help to slow the progression of these diseases , improve the patients' quality of life and extend their lifespans too ." } ]
science.scientific_papers_summarization_single_doc_pubmed
science.scientific_papers_summarization_single_doc_pubmed.65031
[ { "role": "user", "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nproteins are the main perpetrators of most biological processes that take place within and between cells .\nhowever , proteins are very social in nature and often perform their function as part of large molecular machines , whose action is coordinated through complex regulatory networks of transient protein interactions .\nit is thus the relationships between molecules , rather than their mere presence , what will ultimately determine the behavior of a biological system .\nconsequently , after the completion of the first genome sequencing projects , much effort has been devoted to unveiling protein interrelationships in a high - throughput manner , and recent years have witnessed the consecution of the first interactome drafts for several model organisms , including human ( 1,2 ) , setting the bases for future systems biology initiatives ( 3 ) .\nhowever , high - throughput interaction discovery experiments indicate only that two proteins interact , but do not provide information about the molecular details or the mechanism of the interaction .\ncurrently , this atomic level of detail can come only from high - resolution 3d structures , where the residue contacts are resolved and the protein interaction interfaces characterized . as a result , several databases have been developed in the last years to capture and store interactions of known 3d structure ( 46 ) .\nthe database of 3d interacting domains ( 3did ) is a collection of protein protein interactions for which a high - resolution 3d structure has been solved . by exploring all interactions of known structure as stored in the protein data bank ( pdb ) ( 7 ) , we could divide them into two main categories on the basis of their contact interfaces : domain domain and domain peptide interactions ( 3 ) .\nwe also used the finding that homologous pairs of interacting proteins tend to interact in the same way ( i.e. all fgfs bind the same fgf receptor pocket ) to further cluster and classify protein interactions in interaction types ( 8) , according to their binding and interface topologies .\ndomain domain interactions involve the binding of two globular domains , which creates a large contact interface of 2000 on average ( 9 ) .\nthese are the type of interactions that usually occur in multimeric enzymes and large multiprotein complexes , and they can be either intra- or inter - molecular ( i.e. between domains in the same or different proteins , respectively ) . to identify all the cases of domain domain interactions of known 3d structure , we first assigned pfam ( 10 ) domains to each individual protein in the pdb .\nwe then computed all the physical interactions between domains requiring at least five contacts ( hydrogen bonds , electrostatic or van der waals interactions ) , and removed those lacking a significant interface as described in refs ( 11,12 ) .\nthis procedure has proven efficient at identifying and purging interaction artifacts from crystal packing ; however , it is likely that 3did still contains some nonbiological associates .\ncurrently , 3did contains 115 559 domain domain interactions of known 3d structure comprising 120 980 proteins .\nwe have classified them in 4887 unique interaction types according to the pfam families mediating them . of these\n, 3535 interaction types always occur between domains placed in different proteins ( intermolecular ) , 738 are only seen between domains in the same polypeptide chain ( intramolecular ) and the remaining 614 occur both inter- and intra - molecular .\nwhen available , 3did also contains functional information about the interacting domains as annotated in the gene ontology ( go ) database ( 13 ) .\ndomain peptide , or peptide - mediated , interactions are those where a globular domain in one protein recognizes and binds a short linear motif in another , creating a relatively small interface .\nsuch interactions are found predominantly in signaling and regulatory networks ( 14 ) and , due to their transient nature , are much more difficult to handle biochemically .\nlinear motifs are short patterns of around 10 residues with a common function ( i.e. binding to a globular domain ) that occur in otherwise unrelated proteins . in isolation , these motifs bind their target proteins with sufficient strength to establish a functional interaction .\nthey are frequently found in disordered or unstructured regions and adopt a well - defined structure only upon binding .\nan example of this type of interactions is the well - studied src - homology-3 ( sh3 ) domain , which binds slightly different variants of proline - rich peptides ( e.g. [ rky]xxpxxp or pxxpx[kr ] ) .\nmost of what is currently known about peptide - mediated interactions is compiled in the eukaryotic linear motif ( elm ) database ( 15 ) , which provides a literature - curated collection of motifs and their interaction partners .\nour procedure to detect all cases of peptide - mediated protein interactions of known 3d structure was recently described in ref .\n( 16 ) . in brief , we first parsed the pdb and identified all those entries containing two or more interacting proteins .\nwe extracted all the information regarding the different 66 ligands involved in peptide - mediated interactions from the elm database and assigned pfam families to all the globular domains involved in the interactions via literature curation .\nwe then assigned pfam families to all interactions of known 3d structure . whenever we identified a protein chain containing an elm - binding domain , we searched all contacting chains for occurrences of the linear consensus motif .\nwhen we found a motif match in close vicinity of the globular domain ( 10 ) we considered it a potential domain \nfinally , we went manually through the 2200 potential hits , comparing the interacting structures to those described in the literature , and removing false positives where the interaction was not mediated by the consensus peptide .\nbecause of the visual inspection , we are confident that the interactions reported here are biologically relevant . at present\n, 3did contains data on 829 hand - curated peptide - mediated interactions of known 3d structure , from 611 protein pairs , involving 32 globular domains and 51 linear motifs .\nthe whole concept of interaction types relies on the observation that homologous pairs of interacting proteins very often interact in the same way , this is , using the same binding interfaces ( 8) .\nhowever , there are exceptions to the norm where homologous protein pairs can interact in a completely different manner . for instance , the interaction between the signaling proteins chey and chea - p2 differs by a rotation of 90 in different bacterial species , despite being close homologs ( 17 ) .\nthis is particularly relevant for those proteins that have evolved to interact with many different partners by only changing a few binding residues , such as antibodies , ankyrin repeats , etc .\nwe have computed and classified all the interaction interfaces for each interaction type using a clustering procedure reminiscent of the one used by kim et al .\nwe then computed a distance matrix for all the interfaces based on the number of shared contacts , and performed a complete linkage hierarchical clustering analysis to discover the different modes of interaction between the two given domains .\nthe result is that , for each interaction type , we are able to identify how many different interfaces are used and how often these occur .\nwe have termed the alternative interaction interfaces within the same interaction type interface topologies , and they are stored in 3did together with the frequency in which they occur .\nalthough the vast majority of known interaction types only display one or a few different topologies , it is also true that some families are able to interact with many partners using a large number of surface patches ( figure 1 ) .\nit is thus important , if one wants to model the structure of one interaction onto another , to make sure that , for this particular interaction type , only one interaction topology is possible or , at least , that there is one whose occurrence clearly stands over the rest . \n\nhalf of the interaction types in 3did always interact using the same topology , and most of the remaining ones show only a few different topologies . for a handful of interaction types , we find over 50 interface topologies ( 66 for ras : ras up to 199 for v - set : v - set ) .\nhalf of the interaction types in 3did always interact using the same topology , and most of the remaining ones show only a few different topologies . for a handful of interaction types , we find over 50 interface topologies ( 66 for ras : ras up to 199 for v - set : v - set ) .\nthe standard way of accessing 3did is through the web - based tool by querying it with a particular domain or motif , although it can also be queried by pasting a protein sequence or directly indicating the pdb codes or go terms of interest . as in previous versions , 3did\nwill then display all domains , or peptides , that do physically interact with our domain of interest and for which the 3d structure of the interaction is known .\nall interaction partners will also be displayed in an interactive network ( figure 2 ) , where the user can choose the depth and a color scheme based on molecular function , biological process or cellular compartment as described by go .\nthe network also gives information on the type of interaction ( domain domain or peptide - mediated ) and whether these interactions are intra- or inter - molecular .\nthe user can then select a particular interaction and retrieve the specific details stored in 3did .\nthe output page for each domain domain interaction displays a table with information concerning all the known 3d structures where this interaction is found ( figure 3 ) .\nthe table shows the exact location of the two domains in the 3d complex and gives empirical potential scores and z - scores , which provide a measure of the number of favorable interacting residue - pairs at the interface ( 11,12 ) .\nthe z - score generally accounts for interaction specificity : the higher it is the more specific the interaction\n. finally , clicking on the rasmol ( 20 ) icon pops up a display of the 3d complex .\nthe two interacting domains are colored and shown in ribbons representation with the residues participating in the interface ( i.e. making hydrogen bonds , salt bridges or van der waals contacts ) shown in ball - and - stick .\nthe newest version of 3did also includes a graphical representation of the different interaction topologies for each interacting domain .\nthis representation indicates which residues of a domain are used in a particular interaction , as well as their frequency ( figure 3 ) . \n\nthe query results for lig_sh2_src show the linear motif pattern and source database ( elm ) , links to the binding domain sh2 and all 3d structures containing this motif , followed by all motifs binding sh2 along with their patterns ( if available ) , sh2 's interface residues and a link to the corresponding domain motif interaction page .\nthe network below visualizes domains and motifs interacting with lig_sh2_src as well as their interactions among each other . \n\ndomain interaction view shows all topologies observed in 3d structures of this interaction type along with their frequencies .\nrainbow color scheme is used to visualize where interface residues lie in the sequence , from n - terminus ( blue ) to c - terminus ( red ) .\neach topology has an identifier ( i d ) of the form x : y , where x is the interface i d in domain 1 ( pdz here ) and y is the interface i d of domain 2 ( trypsin here ) .\nthe interaction details provide pdb i d , domain positions , score and z - score as well as the topology i d , linked to the topology visualization above , for each interaction between these two domains in a known 3d structure .\nthe query results for lig_sh2_src show the linear motif pattern and source database ( elm ) , links to the binding domain sh2 and all 3d structures containing this motif , followed by all motifs binding sh2 along with their patterns ( if available ) , sh2 's interface residues and a link to the corresponding domain motif interaction page .\nthe network below visualizes domains and motifs interacting with lig_sh2_src as well as their interactions among each other .\ndomain interaction view shows all topologies observed in 3d structures of this interaction type along with their frequencies .\nrainbow color scheme is used to visualize where interface residues lie in the sequence , from n - terminus ( blue ) to c - terminus ( red ) .\neach topology has an identifier ( i d ) of the form x : y , where x is the interface i d in domain 1 ( pdz here ) and y is the interface i d of domain 2 ( trypsin here ) .\nthe interaction details provide pdb i d , domain positions , score and z - score as well as the topology i d , linked to the topology visualization above , for each interaction between these two domains in a known 3d structure .\nmysql and flat files containing the entire database are also available through the website for independent studies .\n3did is weekly updated with new 3d structures , and major updates are implemented whenever new versions of pfam or elm are released .\nspanish ministerio de educacin y ciencia ( pse-010000 - 2007 - 1 and bio2007 - 62426 ) partially ; 3d - repertoire from the european commission under fp6 contract lshg - ct-2005 - 512028 ." }, { "role": "assistant", "content": "the database of 3d interacting domains ( 3did ) is a collection of protein interactions for which high - resolution 3d structures are known . \n 3did exploits structural information to provide the crucial molecular details necessary for understanding how protein interactions occur . besides interactions between globular domains , the new release of 3did also contains a hand - curated set of transient peptide - mediated interactions . \n the interactions are grouped in interaction types , based on the mode of binding , and the different binding interfaces used in each type are also identified and catalogued . a web - based tool to query 3did is available at http://3did.irbbarcelona.org ." } ]
science.scientific_papers_summarization_single_doc_arxiv
science.scientific_papers_summarization_single_doc_arxiv.84202
[ { "role": "user", "content": "You will be presented with the full text of a science research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nwe have conducted a spectroscopic analysis of the bulges of a sample of 31 spiral galaxies , spanning the hubble sequence from s0 to scd type , in order to study the radial distribution of their stellar population properties .\nthis is the first sample of this size , allowing at last some statistics .\nwe have in mind the following considerations : * radial spectral information brings insights on the structure of the systems which are considered , as it unveils the light / mass spatial distribution .\nit also gives important clues on time scales at play : either directly from age indicators , or , particularly for old populations , by considering abundance ratios of chemical elements appearing with the explosion of different supernova types , like type ia and type ii .\n* moreover , debates on the formation and evolution of galaxies are , specially for nearby galaxies , more than often based on observations of _ central _ indices , or , more precisely , integrated indices in apertures centered on the galaxy nuclei and of small sizes when compared to the size of the galaxies .\nmeanwhile , models generally follow / predict the global properties of the galaxies , which would find a more natural echo in _ mean _ observational quantities .\nthis is also the case of observations at high redshift .\ntracking the spatial distribution of the stellar population allows one to trace back these galactic _ mean _ spectral indices . *\nnumerical simulations nowadays offer a good deal of various proposals for the origin of the formation of bulges , however data are crucially missing to tackle crucial questions like : how far can we push the parallel between ellipticals and bulges ? by\nhow much do the discs and bulges interplay and when in the galaxy history ?\nwe have selected purely edge - on spirals in order to free our spectra from any disc light .\nwe also centered the slit of the spectrograph and placed it perpendicular to the plane of the discs to avoid any trend due to the rotation of the bulges .\nwe finally could measure our indices up to at least one bulge effective radius ( @xmath0 ) and upx to 5@xmath0 .\nwe chose to measure our spectral features in the lick system ( worthey et al .\n1994 ) , for purposes of comparison with large samples of ellipticals .\nour interest for the present time is not to give absolute values in age or metallicity ( z ) , but to understand whether variations of our indices are due to a radial change in age , in metallicity or in both .\nas there is no one - to - one relation between any individual lick index and age or even the abundance of one single chemical element ( worthey 1994 ) , we use as many indices as possible and consider their different relative sensitivities to age and metallicity .\nthe wavelength coverage of our spectra enable us to measure 25 indices , from h@xmath1 to tio .\nwe present here the example of fe4668 and h@xmath2 .\nfe4668 is around 5 times more sensitive to metallicity than to the logarithm of the age , while h@xmath2 is about as sensitive to log(age ) as to metallicity .\nfigure 1 and figure 2 present the radial gradients of these two indices as a function of the bulge central velocity dispersion .\na different symbol is used for each hubble type .\nthe error bars of our measurements are shown , they are the result of a detailed error propagation from the first steps of data reduction to the final measurements .\nwe show as dotted line the position of a gradient slope of 0 , which would correspond to the absence of any radial variation of the index .\nthe distribution of @xmath3 is flat with a mean value of @xmath4 and a r.m.s .\ndispersion of 1.4 .\nthe distribution of @xmath5 is flat with a mean value of 1.5 and a dispersion of 0.8 .\n[ h ] index as a function of the bulge central velocity dispersion . ]\ntwo remarks can be made : ( note : we discuss the mean observed trends and do not address any individual galaxy that might deviate slightly from those trends ) * while fe4668 decreases , h@xmath2 increases from the center to the outer edges of the bulges . the clear radial change of fe4668 , both by itself and as compared to the variation of h@xmath2 , on one hand , the sign of the slope of the gradients , on the other hand , support the view of a variation in metallicity as primary underlying factor , the bulge inner parts being more metal - rich than the outer regions .\nthis is : a pure age gradient would make fe4668 slope about ten times smaller than that observed , and @xmath6 greater than @xmath7 , therefore this hypothesis is discarded . *\nneither h@xmath2 nor fe4668 radial gradients show any dependence on the hubble type of the galaxies .\nthis is also the case for the other indices . the loose connection between the morphological classification of the spirals and the bulge stellar population had been previously noticed for the central indices of bulges ( jablonka , arimoto & martin 1996 ) . but while the bulge central indices are found to be related to the bulge central velocity dispersion\n, there is no comparable trend for the radial gradients ( except for mg@xmath8 ) . as to the comparison between bulges and ellipticals , interestingly ,\nthe relation between gradients in ellipticals and their central velocity dispersion is a longstanding debate ( gonzalez & gorgas 1996 ; kobayashi & arimoto 1999 ) . a further comparison with the results quoted in gorgas et al .\n( 1997 ) reveals that the mean slope of the mg@xmath8 gradient in ellipticals coincides with the values we find for the bulges of our sample ( @xmath9 @xmath10 0.025 vs @xmath11 @xmath10 0.023 )\nwhile by no means , we have exhausted all the information of our dataset yet , we already see quite clearly that any scenario of formation of bulges requiring long time scales would be in contradiction with the observations .\nwe also stress the apparent continuity between elliptical and bulge properties .\ngonzalez j.j . & gorgas j. 1996 _ fresh views of elliptical galaxies .\naspc series _\nvolume 86 , p. 225 gorgas j. , pedraz s. , guzman , r. , cardiel n. , gonzalez j.j .\n1997 , _ apj _ 481 , l19 jablonka p. , martin p. , arimoto n. 1996 _ aj _ , 112 , 1415 kobayashi c. , arimoto n. 1999 _ aj _ , 257 , 573 worthey g. 1994 _ apjs _ , 95 , 107 worthey g. , faber s.m .\n, gonzalez j.j . ,\nburstein , d. 1994 , _ apjs _ , 94 , 687" }, { "role": "assistant", "content": "we present a few results of a work in progress tackling the radial spectroscopic properties of bulges of spiral galaxies ." } ]
science.scientific_papers_summarization_single_doc_pubmed
science.scientific_papers_summarization_single_doc_pubmed.44174
[ { "role": "user", "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nit is characterized by the presence of histiocytes in the dermis between the collagen bundles arranged separately or in groups .\nthis pattern may be either drug induced or associated with rheumatoid arthritis ( ra ) or autoimmune collagen diseases . here ,\nwe present a case of igd with distinct clinical features in a female patient with ra .\na 70-year - old woman with a 10-year history of ra , who was under treatment with adalimumab at a dose of 40 mg subcutaneously every 2 weeks for the last 2 years , decided to stop her injections .\none month later , she presented to our department with an eruption consisting of symmetrically distributed erythematous papules around the umbilicus ( fig .\n1 ) . biopsy of a papule showed a normal epidermis and a perivascular and diffuse infiltration of the dermis by lymphocytes , histiocytes and a few giant cells , without deposition of mucin ( fig .\nchest x - ray examination , tuberculin skin ( ppd ) test as well as quantiferon - tb test were all negative .\nthe lesions showed no improvement after application of topical steroids and cleared only after re - initiation of adalimumab treatment 2 months later , at the same dose of 40 mg subcutaneously every 2 weeks .\nthis treatment decision was mainly made by the rheumatologists , as the patient had an exacerbation of ra .\nigd most often presents either as an interstitial granulomatous drug reaction ( igdr ) or as igd with arthritis ( igdwa ) .\nigdr clinically presents as asymptomatic , annular , erythematous to violaceous plaques with a predilection for the intertriginous areas , medial thighs and inner aspects of the arms .\ncausative medications include calcium channel blockers , ace inhibitors , lipid - lowering agents , antihistamines , diuretics , anticonvulsants , ganciclovir , antidepressants , interleukin-1 antagonists , trastuzumab , thalidomide and anti - tnf agents [ 2 , 3 , 4 ] .\nanti - tnf agents have been implicated in the pathogenesis of igdrs with histological variations .\napart from the interstitial lymphohistiocytic infiltrate , focal vacuolar degeneration of the basement membrane , necrotic keratinocytes , interstitial eosinophils and mucin may be present .\nigdwa is a rare disorder described mostly in female patients with ra in association with a relapse of the disease or as a drug - related reaction .\nit usually presents with linear , elongated , dermal bands without epidermal changes on the trunk and extremities ( rope sign ) .\nit has been stated to be caused by an antigen - antibody reaction with the formation of auto - antibodies , which may affect several organs ( especially the skin and joints ) .\nthe mechanism of igdwa may also be related to the immune - modulating effects of biologic agents , which may alter the antigenicity of dermal collagen , elicit an immune response , or disturb the normal production of collagen in response to damage . moreover ,\nthe close association between the development of skin lesions after the initiation of anti - tnf therapy and the clearance or improvement of the skin lesions after discontinuation of tnf inhibitors suggests a role of the medication on the development of cutaneous lesions .\nit is possible that anti - tnf agents enhance the likelihood of developing igdwa in ra patients who have granulomatous diathesis , although the true incidence of igdwa in ra patients with or without anti - tnf therapy is not known . on the other hand ,\ntnf is involved in a number of processes which help maintain granuloma induction of adhesion molecules , including endothelial cell activation , as well as growth of new blood vessels and regulation of other inflammatory cytokines .\nanti - tnf antibodies reduce all the above - mentioned interrelated activities and thus may be efficacious in the treatment of igd , while cessation of them may induce granuloma formation again . in a similar case to ours , igdwa developed after sudden discontinuation of anti - tnf therapy , and the restart of this medication led to the resolution of the skin lesions .\nthe fact that this disorder responds to immunomodulatory treatment is consistent with the hypothesis of an altered immunologic reactivity . in our case\n, there was a distinct clinical presentation of igd , composed of symmetrically distributed indurated papules around the umbilicus as well as a mild granulomatous reaction pattern .\nthe whole reaction was probably induced by the cessation of adalimumab and the subsequent gradual exacerbation of ra , although traces of the medication might still have been in the patient 's blood when the initial rash presented . in conclusion , with the increasing use of biologics worldwide , awareness of the clinical spectrum of drug- or ra - associated granulomatous lesions is continuously enriched ." }, { "role": "assistant", "content": "a 70-year - old female patient presented with an eruption consisting of symmetrically distributed erythematous papules around the umbilicus 1 month after the cessation of adalimumab for the treatment of rheumatoid arthritis . \n biopsy of a papule showed an interstitial granulomatous infiltrate in the dermis , without deposition of mucin . \n the lesions cleared only after re - initiation of treatment 2 months later . \n interstitial granulomatous dermatitis is thought to be a distinct histopathological pattern , either drug induced or associated with rheumatoid arthritis or autoimmune collagen diseases . in our case \n , there was a distinct clinical presentation of interstitial granulomatous dermatitis , composed of symmetrically distributed indurated papules around the umbilicus as well as a mild granulomatous reaction pattern ." } ]
science.healthver_entailment
science.healthver_entailment.178
[ { "role": "user", "content": "You will be shown a claim about public health, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: A weaker immune system is one reason people with high blood pressure and other health problems are at higher risk for coronavirus.\n\nAbstract:\nSeveral related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1.\nSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic spread2,3.\nZoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population.\nUsing diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus.\nSARS-CoV-2 S-reactive antibodies, exclusively of the IgG class, were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals with recent HCoV infection and targeted the S2 subunit.\nIn contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, as well as concomitant IgM and IgA antibodies throughout the observation period of 6 weeks since symptoms onset.\nHCoV patient sera also variably reacted with SARS-CoV-2 S and nucleocapsid (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays.\nNotably, HCoV patient sera exhibited specific neutralising activity against SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera.\nDistinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for serology, seroprevalence and vaccine studies, as well as for our understanding of susceptibility to and natural course of SARS-CoV-2 infection." }, { "role": "assistant", "content": "{\"verdict\": \"NEI\", \"evidence\": []}" } ]
science.ddi_ner
science.ddi_ner.668
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Brand\", \"UnapprovedDrug\", \"Drug\", \"DrugGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Brand\" : [\"Aspirin\", ...], \"DrugGroup\": [\"Salicyclate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nNeurochemical and functional consequences following 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and methamphetamine. The neurochemical and functional consequences following MPTP administration to the rat were evaluated and compared to similar effects following methamphetamine administration. It was observed that MPTP induced long lasting depletions of striatal dopamine concentrations and this neurotoxic effect could be prevented by pargyline pretreatment. The MPTP-induced neuronal damage produced a tolerance to the disruptive effects of amphetamine and a supersensitivity to the disruptive effects of apomorphine in rats responding in a schedule controlled paradigm. Methamphetamine, like MPTP, produced depletions of striatal dopamine but these actions were potentiated by pargyline pretreatment. These observations are discussed in reference to possible deleterious effects following the administration of pargyline to patients with Parkinson's Disease." }, { "role": "assistant", "content": "{\"Brand\": [], \"Drug\": [\"pargyline\", \"amphetamine\", \"apomorphine\", \"MPTP\", \"Methamphetamine\", \"methamphetamine\"], \"DrugGroup\": [], \"UnapprovedDrug\": [\"1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine\", \"MPTP\"]}" } ]
science.bioasq_yesno_qa
science.bioasq_yesno_qa.332
[ { "role": "user", "content": "You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is Rheumatoid Arthritis related to myopathy?\n\nContext: Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients\nwe describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ\nOccurrence of chloroquine-induced myopathy after low-dose treatment of rheumatoid arthritis for seven years\na 75 year old female with rheumatoid arthritis treated with daily doses of 250 mg of chloroquine for four years. The patient visited because of several months history of predominantly proximal progressive tetraparesis with areflexia\nMyopathy and neuropathy in rheumatoid arthritis\nwith rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy\nThe study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls" }, { "role": "assistant", "content": "yes" } ]
science.chemprot_ner
science.chemprot_ner.968
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Protein\", \"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nMechanism of action of leflunomide in rheumatoid arthritis.\nLeflunomide, a novel drug with proven efficacy in rheumatoid arthritis, is an isoxazol derivative structurally unrelated to other immunomodulatory drugs. Leflunomide is rapidly metabolized to its active form, A77 1726. Two mechanisms of action have been identified for A77 1726: inhibition of dihydroorotate dehydrogenase (DHODH) and inhibition of tyrosine kinases. DHODH inhibition occurs at lower concentrations of A77 1726 than that of tyrosine kinases and is currently considered the major mode of action. Stimulated lymphocytes must increase ribonucleotide levels from 8 to 16-fold before proceeding from the G1 into the S phase. Increased levels of ribonucleotides can only be met by de novo ribonucleotide synthesis. At low levels of ribonucleotides, p53, a \"sensor\" molecule, gets activated and prevents progression through the cell cycle. Therefore, an inhibitor of de novo uridine monophosphate synthesis would predictably arrest stimulated cells at the G1 phase. In support of this mechanism of action, in vitro mitogen stimulated human peripheral blood lymphocytes treated with A77 1726 undergo arrest at the G1 phase; this inhibition is reversed by uridine." }, { "role": "assistant", "content": "{\"Chemical\": [\"uridine\", \"leflunomide\", \"isoxazol\", \"uridine monophosphate\", \"tyrosine\", \"Leflunomide\", \"dihydroorotate\", \"A77 1726\"], \"Protein\": [\"p53\", \"tyrosine kinases\", \"dihydroorotate dehydrogenase\", \"DHODH\"]}" } ]
science.healthver_entailment
science.healthver_entailment.3787
[ { "role": "user", "content": "You will be shown a claim about public health, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: We don't yet know how frequently cats become infected with SARS-CoV-2 in the real world\n\nAbstract:\nAbstract Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat.\nThis virus is supposed to be spread by human to human transmission.\nCellular angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans.\nMoreover, a recent study predicted that dog might be secondary host during the evolution of SARS-CoV-2 from bat to human.\nTherefore, there is a possibility of spreading SARS-CoV-2 through domestic pets.\nThere are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks.\nExperimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne route.\nBased on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to human; needs to be deeply investigated.\nHumans showing clinical symptoms of respiratory infections have been undergoing for COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic.\nIn this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field.\nThis review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for sero-prevalence studies especially in companion animals." }, { "role": "assistant", "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne route.\"]}" } ]
science.acl_arc_intent_classification
science.acl_arc_intent_classification.1285
[ { "role": "user", "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nrelated work\n\nContext before the citation:\nSome works abstract perception via the usage of symbolic logic representations (Chen et al., 2010; Chen and Mooney, 2011; Matuszek et al., 2012; Artzi and Zettlemoyer, 2013), while others choose to employ concepts elicited from psycholinguistic and cognition studies. Many approaches to multimodal research have succeeded by abstracting away raw perceptual information and using high-level representations instead. The language grounding problem has received significant attention in recent years, owed in part to the wide availability of data sets (e.g. Flickr, Von Ahn (2006)), computing power, improved computer vision models (Oliva and Torralba, 2001; Lowe, 2004; Farhadi et al., 2009; Parikh and Grauman, 2011) and neurological evidence of ties between the language, perceptual and motor systems in the brain (Pulverm¨uller et al., 2005; Tettamanti et al., 2005; Aziz-Zadeh et al., 2006).\n\nCitation Sentence:\nSome works abstract perception via the usage of symbolic logic representations ( Chen et al. , 2010 ; Chen and Mooney , 2011 ; Matuszek et al. , 2012 ; Artzi and Zettlemoyer , 2013 ) , while others choose to employ concepts elicited from psycholinguistic and cognition studies .\n\nContext after the citation:\nWithin the latter category, the two most common representations have been association norms, where subjects are given a \u0000 1http://stephenroller.com/research/ emnlp13 cue word and name the first (or several) associated words that come to mind (e.g., Nelson et al. (2004)), and feature norms, where subjects are given a cue word and asked to describe typical properties of the cue concept (e.g., McRae et al. (2005)). Griffiths et al. (2007) helped pave the path for cognitive-linguistic multimodal research, showing that Latent Dirichlet Allocation outperformed Latent Semantic Analysis (Deerwester et al., 1990) in the prediction of association norms." }, { "role": "assistant", "content": "Background" } ]
science.genia_ner
science.genia_ner.85
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellLine\", \"Protein\", \"DNA\", \"CellType\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nActivation of transcription by binding of NF-E1 (YY1) to a newly identified element in the first exon of the human DR alpha gene. A previously unrecognized element, located downstream of the start site of transcription in the first exon of the DR alpha gene, has been defined that enhances promoter activity up to eightfold in a position-dependent manner. Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level. Significant sequence homology of this element was found in the DNA of the DR beta, DP alpha and-beta, and DQ alpha genes, always located downstream of the transcriptional start site. The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene. It was identified as NF-E1 (YY1). This protein, previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be quite important in the regulation of MHC class II gene expression." }, { "role": "assistant", "content": "{\"CellLine\": [], \"CellType\": [], \"DNA\": [\"Ig heavy chain mu E1 site\", \"DR beta , DP alpha and - beta , and DQ alpha genes\", \"DNA - binding site\", \"start site of transcription\", \"exon\", \"DP alpha and - beta\", \"transcriptional start site\", \"DR alpha promoter\", \"DQ alpha gene\", \"element\", \"human DR alpha gene\", \"DR alpha and DP alpha element\", \"DR alpha gene\", \"Ig kappa 3\\u0027 enhancer\", \"MHC class II gene\"], \"Protein\": [\"nuclear factor\", \"YY1\", \"NF - E1\", \"Ig heavy chain\"], \"RNA\": []}" } ]
science.chemprot_re
science.chemprot_re.703
[ { "role": "user", "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nResearch on the preparation of antioxidant peptides derived from egg white with assisting of high-intensity pulsed electric field. Egg white protein powder, one of the main egg products, was hydrolysed by Alcalase, Trypsin, and Pepsin respectively to prepare antioxidant peptides. All hydrolysates were assayed by determination of reducing power (RP) ability. Three kinds of hydrolysates were prepared under optimal enzymatic parameters that were obtained from the preliminary one-factor-at-a-time (OFAT) and response surface methodology (RSM) experiments. The results showed that the Alcalase hydrolysates exerted the best RP ability. Thereafter, the Alcalase hydrolysates were sequentially fractionated by ultra filtration membranes in cut-off molecular weight (MW) of 30, 10, and 1kDa, and tested their antioxidant activities in terms of RP ability, DPPH radical scavenging ability, ABTS radical scavenging ability, and FRAP assay. Effects of high intensity pulsed electric field treatment were further investigated on antioxidant peptides to improve their activities. The results showed that Alcalase hydrolysates possessed the strongest antioxidant ability compared with the other two hydrolysates, particularly for the Fraction-3 with MW < 1kDa. After PEF treatment, this fraction showed a significant improvement of RP ability within 5h (P<0.05)." }, { "role": "assistant", "content": "[]" } ]
science.chemprot_ner
science.chemprot_ner.669
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Protein\", \"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Dexamethasone\", ...], \"Protein\" : [\"BRCA-1\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPotent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic Acid.\nProtein-protein interfaces provide an important class of drug targets currently receiving increased attention. The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles. One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhibits binding of plasminogen to fibrin. However, the daily dose of TXA is high due to its modest potency and pharmacokinetic properties. In this study, we report a computational approach, where the focus was on finding electrostatic potential similarities to TXA. Coupling this computational technique with a high-quality low-throughput screen identified 5-(4-piperidyl)-3-isoxazolol (4-PIOL) as a potent plasminogen binding inhibitor with the potential for the treatment of various bleeding disorders. Remarkably, 4-PIOL was found to be more than four times as potent as the drug TXA." }, { "role": "assistant", "content": "{\"Chemical\": [\"5-(4-piperidyl)-3-isoxazolol\", \"TXA\", \"lysine\", \"tranexamic acid\", \"4-PIOL\", \"tranexamic Acid\"], \"Protein\": [\"plasminogen\", \"fibrin\"]}" } ]
science.covid_deepset_qa
science.covid_deepset_qa.218
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your repsonse other than the answer.\n\nParagraph: Text: Human metapneumovirus (HMPV) is a single-stranded RNA virus in the family Paramyxoviridae and closely related to human respiratory syncytial virus (RSV) [1] . HMPV causes respiratory disease similar to RSV, ranging from mild upper respiratory infection to bronchiolitis and pneumonia [2] . HMPV infections are seasonal and coinfection with other respiratory pathogens is common [1] . The HMPV genome is approximately 13 kb and comprises eight open reading frames (ORFs) encoding nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion glycoprotein (F), transcription enhancer protein (M2), small hydrophobic protein (SH), attachment glycoprotein (G), and large polymerase protein (L) [3] . The membrane glycoproteins F and G sequences are used to define two major genotypes or groups, A and B, which are further classified into four subgroups (A1, A2, B1, and B2). HMPV A2, the most frequently observed subgroup, is further divided into two proposed sub-lineages (A2a and A2b) [3] . HMPV is reported to have an important contribution to acute respiratory infections (ARI) in Africa. For instance, HMPV-associated hospitalization was estimated at 6.5 per 1000 person years in infants in Soweto, South Africa [4] ; at 4% in hospitalized children with severe ARI during a 2-year period in Cameroon [5] ; and in rural western Kenya, incidence of HMPV associated with ARI cases in outpatient clinic visits was estimated at 0.43 per 100 person-years among outpatients [6] . In Kilifi coastal Kenya, between January 2007 to December 2011, children under 6 months of age accounted for 44% of HMPV positive cases, while 74% were children under 1 year, and 1.3% (2/160) were children > 36 months [7] . In Dadaab and Kakuma refugee camps in Kenya, HMPV was detected in 5.7% hospitalizations, and virus-positive crude hospitalization rate (per 1000 children < 5 years old) was 4 for HMPV [8] . In Mali, contribution of HMPV to pneumonia had a population attributable fraction of 9% (95% CI: 7-11%) [9] ; while in Morocco [10] , 8 .9% of children < 5 years admitted with severe pneumonia were infected with HMPV. HMPV prevalence and incidence elsewhere globally, is indicated in Additional file 4: Table S1 . Of note is that the variations in incidence rates could be attributed to study population, seasonality and even detection methods. Nonetheless, genomic epidemiology of HMPV in Africa is inadequately reported, and comparison of genetic similarity and differences between African and global strains is not documented. Genome sequences provide valuable resources for characterizing viral evolution and disease epidemiology, and for identifying transmission events and outbreaks, which is not always possible with sub-genomic fragments [11] [12] [13] . The increased number of phylogenetically informative variant sites obtained from full genomes may allow better linking of cases and aid public health interventions in real time during epidemics [14, 15] . PCR approaches for targeted whole genome sequencing, in contrast to random amplification, can preferentially amplify the target virus over host or environmental nucleic acids [16, 17] potentially focusing sequencing on the virus of interest. To date, the largest dataset of HMPV whole genomes (n = 61) sequenced from any tropical country is from three Peruvian cities, Lima, Piura and Iquitos [18] . In Africa, apart from one metapneumovirus genome identified from a wild mountain gorilla in Rwanda (GenBank accession number HM197719), there are no HMPV genomes reported according to the NIAID Virus Pathogen Database and Analysis Resource (ViPR, http://www.viprbrc. org/, accessed April 30, 2019). This has led to limited understanding of the genetic and genomic diversity of HMPV in the continent. This work describes a whole genome sequencing (WGS) approach for HMPV from a small number of HMPV positive clinical samples collected at Kilifi County Hospital in Kilifi, Kenya and University Teaching Hospital in Lusaka, Zambia. The genomes were generated by sequencing overlapping PCR amplicons spanning the entire genome. These are the first reported complete genome sequences of locally circulating HMPV strains obtained directly from clinical samples in Africa. We also combined the new genomes with publicly available sequences to examine patterns in global HMPV genetic diversity. Whole genome sequencing was successful for all 5 clinical samples that were attempted. A single genomic sequence was obtained from each sample, and the length of the 5 new HMPV genomes ranged from 13,097 to 13, 134 nt (> 95% length coverage). Sequencing and data assembly parameters, including coverage depth are shown in Table 1 . Sequence annotation of the full-length genomes using Geneious R8.1.5 (https://www.geneious.com) identified the expected eight coding ORFs and non-coding genomic regions. The overall nucleotide identity (i.e., identical sites averaging over all sequence pairs and excluding positions containing gaps) between all 143 genome sequences analyzed (5 new genomes plus 138 from ViPR) was 58.2%. Nucleotide sequence identity was 71.3% within HMPV-A and 80% within HMPV-B. Intrasubgroup, A1, A2, B1 and B2 genomes shared 92.1% (10 sequences), 76.8% (88 sequences), 91% (24 sequences) and 89.6% (21 sequences) amino acid sequence identity. For the 143 HMPV genomes, we checked sequence conservation at transcriptional control regions, at the termini of each gene, as well as the lengths of intergenic sequences between gene boundaries. The length of the F-M2 intergenic region was different between group A and B viruses, that is, 13 nt and 2 nt, respectively. The SH-G and G-L intergenic regions were the longest, up to 125 nt and to 190 nt, respectively. Consensus nucleotides (9 to 19 length) at the putative start and end regions flanking the ORF of the viral genes are shown in Fig. 1 . The gene-start and -end regions of N and P were conserved (> 90% average pairwise identity) in both HMPV groups, and the M2 and M gene-start and -end were also conserved in HMPV group A and B, respectively. The putative ATG start codon was consistently located at positions 14-16 upstream of a gene start motif (consensus: GG/AGAC/TAAA/GTnnnnATG), except for the internal M2-2. An additional ATG start codon upstream of the gene-start motif was observed in the SH gene for the B1 and B2 strains. In five of the eight annotated genes (N, P, F, M2, and G (B1 and B2 strains only)), the intergenic regions were short and the ORFs for these 5 genes terminated within the propositioned gene-end motifs. We combined the five genome sequences from Kenya and Zambia with available global sequences, aligned individual genes and calculated the percent nucleotide (nt) and amino acid (aa) identity ( Table 2) . The coding sequences of N, M, F, M2-1, M2-2, and L genes were conserved at nucleotide and amino acid levels, by sharing > 85% between-subgroup nucleotide identity and 90% protein identity ( Table 3 ). The nucleoprotein gene was the most conserved among all subgroups at the nt and aa levels. SH and G glycoprotein genes were more divergent between the HMPV subgroups at the nucleotide level with 76 and 63% identity, respectively. The SH protein length was variable between group A and B strains due to a nucleotide substitution (CAA ➔ TAA) at gene position 532 in group B, resulting in protein lengths of 178 and 180 aa, respectively. The predicted G protein length also varied among the different HMPV subgroups, between 219 and 241 aa, due to different positions of the Stop codon. Amino acid sequence diversity for G and SH glycoproteins is depicted in Fig. 2 and Additional file 2: Figure S2 , respectively. The diversity of the complete nucleotide sequences of SH and G genes is depicted in phylogenetic trees in Fig. 3 . We evaluated phylogenetic classification and relationship between the 5 new genomes obtained in this study and previously published genomes (Fig. 3) . Full genome Figure S3 . There was phylogenetic congruence with the individual gene sequence sets as with the full genome dataset, except for F and M2 gene (Additional file 3: Figure S3 ). Variant or drifted viral strains may lower the sensitivity of detection resulting in a decreased quantitation of the viral load and underestimation of disease incidence [19] . We checked the new HMPV genomes for nucleotide differences in the genomic regions targeted by our diagnostic rRT-PCR primers and probes (Additional file 7: Table S4 ) used for HMPV detection. Up to eight primer-and probetemplate mismatches were identified (Fig. 4) : one mismatch in the forward primer region in HMPV group A (F gene-based rRT-PCR assay, Fig. 4a ); one mismatch in each of the forward and probe target regions in group B (F gene-based rRT-PCR assay, Fig. 4b) ; and 5 different mismatches with the N-gene based rRT-PCR assay (Fig. 4c) . Note, the F gene-based rRT-PCR assays are different or specific to the two HMPV groups. HMPV causes respiratory illness presenting as mild upper respiratory tract infection or life-threatening severe bronchiolitis and pneumonia primarily in children, sometimes adults as well as immunocompromised individuals [2] . However, HMPV genome sequence data from Africa is sparse and information on genome-wide diversity is limited. In the present study, the whole genome sequences of five HMPV strains from Kenya and Zambia were determined and compared with the genomes published previously from around the world. Comparative sequence analysis indicated fairly conserved positioning of the gene-start and -end regions as well as translational start and -end codons. Variation in genestart and -end sequences can have significant impact on transcription initiation and termination efficiency so that there is more selective pressure preventing changes in these regions [20] , and this likely explains our observation. The additional ATG start codon found upstream of the gene-start motif of the SH gene was consistent with a previous report [21] , though its role in gene expression is yet to be identified. These observed sequence conservation in N, M, F, M2-1, M2-2, and L genes is not unusual and is suggestive of functional and structural constraints on diversity, but less expected of the F gene because of its status as a neutralization and protective antigen, similar to its close 'relative' RSV [22] . It has also been suggested that the low diversity in F gene might make a substantial contribution to cross-neutralization and cross-protection between the HMPV subgroups [21] . The relatively high frequency of amino acid diversity in G (and to a lesser extent SH) could be attributable to selective pressure for amino acid change coming from host immunity; and the ability of the protein to tolerate substitutions, which might be due to its proposed extended, unfolded nature [22] . The phylogenetic incongruence observed between whole genome tree and the F and G gene trees, is as reported previously for HMPV [23] , and could be attributed to differential rates of evolution, selection pressure or past recombination events [24] . The prevalence of HMPV in hospitalized pediatric population in Kilifi county in coastal Kenya has been reported [7, 25] . However, it is notable that in recent years, HMPV has been detected at low prevalence in Kilifi (unpublished observations from hospital-based pneumonia surveillance). Whether this low prevalence is due to reduced virus transmission, or decreased sensitivity of our HMPV molecular diagnostic assay due to progressive primer/probe mismatches, is yet to be established. We present the first full genome sequences of circulating HMPV strains from sub-Saharan Africa. A limitation of our sequencing method, as is common with amplicon sequencing protocols [26, 27] , was absent coverage at the 3′ leader and 5′ trailer regions not captured by these primers. Our results demonstrate the application of amplicon sequencing to generate full length HMPV genomes directly from clinical samples. The observed diversity of the individual genes is comparable to that described previously [20] [21] [22] . This method and data provide a useful reference for design of local molecular diagnostics and for studies aimed at understanding HMPV epidemiology and evolution in Africa. Nasopharyngeal and oropharyngeal (NP-OP) swab samples were collected from children (1-59 months) hospitalized with pneumonia, four of whom were enrolled in the PERCH study [18] in 2012. The fifth sample was collected from a child enrolled in the routine pneumonia surveillance study at Kilifi County Hospital, Kenya, in 2015. The samples were tested for HMPV by multiplex semi-quantitative real-time reverse transcription PCR (rRT-PCR) assays. The rRT-PCR primers and probes used, cycling conditions and assay set up have been described elsewhere [28, 29] . Fusion (F) and glycoprotein (G) encoding genes of the HMPV positive samples were amplified in a one-step RT-PCR assay (OneStep RT-PCR kit, QIAGEN), as described previously [7] . Partial G or F nucleotide sequences were analyzed by maximum likelihood (ML) phylogenetic trees using IQ-TREE [30] , together with reference strains of HMPV subgroups (accession numbers AF371337.2, FJ168779, AY297749, AY530095, JN184401 and AY297748). Five HMPV positive samples from the Kenya and Zambia study sites, belonging to the A2a (n = 1), A2b (n = 2), B1 (n = 1) and B2 (n = 1) genetic subgroups based on their G and F gene sequences, were selected for whole genome sequencing. Data on age, sex and clinical assessment information collected at the time of sample collection, for the five selected samples, are shown in Table 3 . The sequencing protocol consisted of four steps as follows: (i) primer design, (ii) preparation of primer mixes, (iii) cDNA and PCR (iv) Illumina sequencing and data analysis. All human metapneumovirus (HMPV) full genome sequences were retrieved from GenBank (January 2018) using the query (txid162145 (Organism) AND 12000(SLEN): 14000(SLEN) NOT patent).\n\nQuestion: What diseases are caused by HMPV?" }, { "role": "assistant", "content": "mild upper respiratory infection to bronchiolitis and pneumonia" } ]
science.bioasq_factoid_qa
science.bioasq_factoid_qa.644
[ { "role": "user", "content": "You will be shown biomedical passages and your task is to the answer the provided question. Provide a concise and accurate response and do not include any additional text in the response other than the answer.\n\nQuestion: What is the function of the gene MDA5?\n\nContext: Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response.\nThe host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)\nRNA PRRs are comprised of TLR3, TLR7, TLR8, RIG-I, MDA5, NLRP3, NOD2, and some other minorities.\nMelanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases.\nRetinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including melanoma differentiation-associated gene 5 (MDA5) and RIG-I, are crucial for host recognition of non-self RNAs, especially viral RNA." }, { "role": "assistant", "content": "Sensing of non-self RNAs, especially viral RNA" } ]
science.data_reco_mcq_mc
science.data_reco_mcq_mc.1836
[ { "role": "user", "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I want to use a tracking-by-detection algorithm.\n\nKeyphrases: tracking video\n\nDataset description:\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nVOT2018: VOT2018 is a dataset for visual object tracking. It consists of 60 challenging videos collected from real-life datasets.\nInterspeech 2021 Deep Noise Suppression Challenge: The Deep Noise Suppression (DNS) challenge is designed to foster innovation in the area of noise suppression to achieve superior perceptual speech quality. This challenge has two two tracks: Track 1: Real-Time Denoising track for wide band scenario The noise suppressor must take less than the stride time Ts (in ms) to process a frame of size T (in ms) on an Intel Core i5 quad-core machine clocked at 2.4 GHz or equivalent processor.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nCOVERAGE: COVERAGE contains copymove forged (CMFD) images and their originals with similar but genuine objects (SGOs). COVERAGE is designed to highlight and address tamper detection ambiguity of popular methods, caused by self-similarity within natural images.\nDiCOVA: The DiCOVA Challenge dataset is derived from the Coswara dataset, a crowd-sourced dataset of sound recordings from COVID-19 positive and non-COVID-19 individuals. The Coswara data is collected using a web-application2, launched in April-2020, accessible through the internet by anyone around the globe.\nLUNA: The LUNA challenges provide datasets for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified.\n\nOptions:- A: COCO B: VOT2018 C: Interspeech 2021 Deep Noise Suppression Challenge D: SNIPS E: COVERAGE F: DiCOVA G: LUNA" }, { "role": "assistant", "content": "[\"COCO\", \"VOT2018\"]" } ]
science.scicite_classification
science.scicite_classification.3978
[ { "role": "user", "content": "You will be presented with a citation segment from the section of a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nIn conclusion, the present results support an earlier observation (Rowan et al., 1994) that there is a good agreement between pigs and humans for their true ileal digestibility of dietary protein." }, { "role": "assistant", "content": "Result" } ]
science.mslr2022_ms2_multidoc_summarization
science.mslr2022_ms2_multidoc_summarization.8502
[ { "role": "user", "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nLLPi: Liverpool Lung Project Risk Prediction Model for Lung Cancer Incidence\nAbstract 1:\nIdentification of high-risk individuals will facilitate early diagnosis , reduce overall costs , and also improve the current poor survival from lung cancer . The Liverpool Lung Project prospect i ve cohort of 8,760 participants ages 45 to 79 years , recruited between 1998 and 2008 , was followed annually through the hospital episode statistics until January 31 , 2013 . Cox proportional hazards models were used to identify risk predictors of lung cancer incidence . C-statistic was used to assess the discriminatory accuracy of the models . Models were internally vali date d using the bootstrap method . During mean follow-up of 8.7 years , 237 participants developed lung cancer . Age [ hazard ratio ( HR ) , 1.04 ; 95 % confidence interval ( CI ) , 1.02–1.06 ] , male gender ( HR , 1.48 ; 95 % CI , 1.10–1.98 ) , smoking duration ( HR , 1.04 ; 95 % CI , 1.03–1.05 ) , chronic obstructive pulmonary disease ( HR , 2.43 ; 95 % CI , 1.79–3.30 ) , prior diagnosis of malignant tumor ( HR , 2.84 ; 95 % CI , 2.08–3.89 ) , and early onset of family history of lung cancer ( HR , 1.68 ; 95 % CI , 1.04–2.72 ) were associated with the incidence of lung cancer . The LLPi risk model had a good calibration ( goodness-of-fit χ2 7.58 , P = 0.371 ) . The apparent C-statistic was 0.852 ( 95 % CI , 0.831–0.873 ) and the optimism-corrected bootstrap resampling C-statistic was 0.849 ( 95 % CI , 0.829–0.873 ) . The LLPi risk model may assist in identifying individuals at high risk of developing lung cancer in population -based screening programs . Cancer Prev Res ; 8(6 ) ; 570–5 . © 2015 AACR\n\n\nTitle 2:\nVariations in lung cancer risk among smokers.\nAbstract 2:\nBACKGROUND Although there is no proven benefit associated with screening for lung cancer , screening programs are attracting many individuals who perceive themselves to be at high risk due to smoking . We sought to determine whether the risk of lung cancer varies predictably among smokers . METHODS We used data on 18 172 subjects enrolled in the Carotene and Retinol Efficacy Trial (CARET)-a large , r and omized trial of lung cancer prevention-to derive a lung cancer risk prediction model . Model inputs included the subject 's age , sex , asbestos exposure history , and smoking history . We assessed the model 's calibration by comparing predicted and observed rates of lung cancer across risk deciles and vali date d it by assessing the extent to which a model estimated on data from five CARET study sites could predict events in the sixth study site . We then applied the model to evaluate the risk of lung cancer among smokers enrolled in a study of lung cancer screening with computed tomography ( CT ) . RESULTS The model was internally valid and well calibrated . Ten-year lung cancer risk varied greatly among participants in the CT study , from 15 % for a 68-year-old man who has smoked two packs per day for 50 years and continues to smoke , to 0.8 % for a 51-year-old woman who smoked one pack per day for 28 years before quitting 9 years earlier . Even among the subset of CT study participants who would be eligible for a clinical trial of cancer prevention , risk varied greatly . CONCLUSIONS The risk of lung cancer varies widely among smokers . Accurate risk prediction may help individuals who are contemplating voluntary screening to balance the potential benefits and risks . Risk prediction may also be useful for research ers design ing clinical trials of lung cancer prevention\n\n\nTitle 3:\nBenchmarking lung cancer mortality rates in current and former smokers.\nAbstract 3:\nSTUDY OBJECTIVES To develop and vali date a model for estimating the risk of lung cancer death in current and former smokers . The model is intended for use in analyzing a population of subjects who are undergoing lung cancer screening or receiving lung cancer chemoprevention , to determine whether the intervention has altered lung cancer mortality . DESIGN / SETTING / PATIENTS Model derivation was based on analyses of the placebo arm of the Carotene and Retinol Efficacy Trial . Model validation was based on analyses of three other longitudinal cohorts . MEASUREMENTS Observed and predicted number of deaths due to lung cancer . RESULTS In internal validation , the model was highly concordant and well calibrated . In external validation , the model predictions were similar to what was observed in all of the validation analyses . The predicted and observed deaths within 6 years were very similar when assessed in the Johns Hopkins Hospital trial of chest radiography and sputum cytology screening ( 176 predicted , 184 observed , p = 0.53 ) , the Memorial Sloan-Kettering Cancer Center trial of chest radiography and sputum cytology screening ( 108 predicted , 114 observed , p = 0.57 ) , and the National Health and Nutrition Evaluation Survey part I ( 24 predicted , 21 observed , p = 0.52 ) . CONCLUSIONS The number of lung cancer deaths in a population of current or former smokers can be accurately predicted , making model-based evaluations of prevention and early detection interventions a useful adjunct to definitive r and omized trials . We illustrate this potential use with a small example\n\n\nTitle 4:\nSymptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study\nAbstract 4:\nBackground : This prospect i ve cohort study aim ed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis . Methods : Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions ; we also examined primary care and hospital records for diagnostic routes and diagnoses . Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage . Results : Among 963 participants , 15.9 % were diagnosed with primary lung cancer , 5.9 % with other thoracic malignancies and 78.2 % with non-malignant conditions . Only half the cohort had an isolated first symptom ( 475 , 49.3 % ) ; synchronous first symptoms were common . Haemoptysis , reported by 21.6 % of cases , was the only initial symptom associated with cancer . Diagnostic intervals were shorter for cancer than non-cancer diagnoses ( 91 vs 124 days , P=0.037 ) and for late-stage than early-stage cancer ( 106 vs 168 days , P=0.02 ) . Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses ( P=0.003 ) . Conclusions : Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients . Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution\n\n\nTitle 5:\nA prospective study of a total material of lung cancer from a county in Sweden 1997-1999: gender, symptoms, type, stage, and smoking habits.\nAbstract 5:\nThe epidemiology of lung cancer is changing in many parts of the world . In the industrialized countries , there is a trend that the incidence in men is declining , while it is increasing for women . Also , adenocarcinomas are becoming relatively more common , especially among men . The purpose of this study was to investigate whether such trends also occur in Sweden and also to describe other aspects of an unselected lung cancer material today , such as symptoms , stage and smoking habits . In the county of Gaevleborg , Sweden , practically all patients with lung cancer are referred to the lung department , and thus a total material of lung cancer patients with only a minimal selection bias can be studied . All patients with lung cancer in the county from January 1 , 1997 to December 31 , 1999 , were investigated prospect ively regarding stage , type of cancer , and symptoms . In all , there were 364 patients , 237 ( 65.1 % ) men and 127 ( 34.9 % ) women . The mean age for men was 69.8 and for women , 68.1 years . 91.9 % of the men and 78.6 % of the women were smokers or ex-smokers . In general the men were heavier smokers than were the women ( P<0.0001 ) . Adenocarcinoma was the most common subtype found in women and squamous cell carcinoma in men . The excess of adenocarcinoma in women was due to never-smoking women ; for smoking and ex-smoking men and women , the proportion of adenocarcinomas was the same . In all , 240 patients ( 68.0 % ) were diagnosed at Stage IIIb ( 27.2 % ) or IV ( 40.8 % ) , with no significant differences between the sexes . The most common first symptom was cough . Only 7.0 % of patients were asymptomatic . In conclusion , the trend of an increasing proportion of adenocarcinoma in lung cancer is seen also in Sweden . A depressingly high percentage of patients present in late stages and are thus inoperable" }, { "role": "assistant", "content": "The positive predictive value ( PPV ) of diagnostic symptoms depends on an individual 's prior risk of lung cancer , as well as their presenting symptom pattern ." } ]
science.genia_ner
science.genia_ner.1103
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"RNA\", \"CellLine\", \"Protein\", \"DNA\", \"CellType\"].\n\nPlease return the output as a JSON object of the format: {\"DNA\" : [\"TAL1\", ...], \"RNA\": [\"mRNAs\", ...], \"CellLine\": [\"T cells\", ...], \"CellType\": [\"monocytes\", ...], \"Protein\": [\"IL-2\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nThe product of the murine homolog of the Drosophila extra sex combs gene displays transcriptional repressor activity. The heterogeneous nuclear ribonucleoprotein K protein represents a novel class of proteins that may act as docking platforms that orchestrate cross-talk among molecules involved in signal transduction and gene expression. Using a fragment of K protein as bait in the yeast two-hybrid screen, we isolated a cDNA that encodes a protein whose primary structure has extensive similarity to the Drosophila melanogaster extra sex combs (esc) gene product, Esc, a putative silencer of homeotic genes. The cDNA that we isolated is identical to the cDNA of the recently positionally cloned mouse embryonic ectoderm development gene, eed. Like Esc, Eed contains six WD-40 repeats in the C-terminal half of the protein and is thought to repress homeotic gene expression during mouse embryogenesis. Eed binds to K protein through a domain in its N terminus, but interestingly, this domain is not found in the Drosophila Esc. Gal4-Eed fusion protein represses transcription of a reporter gene driven by a promoter that contains Gal4-binding DNA elements. Eed also represses transcription when recruited to a target promoter by Gal4-K protein. Point mutations within the eed gene that are responsible for severe embryonic development abnormalities abolished the transcriptional repressor activity of Eed. Results of this study suggest that Eed-restricted homeotic gene expression during embryogenesis reflects the action of Eed as a transcriptional repressor. The Eed-mediated transcriptional effects are likely to reflect the interaction of Eed with multiple molecular partners, including K protein." }, { "role": "assistant", "content": "{\"CellLine\": [], \"CellType\": [], \"DNA\": [\"Gal4 - binding DNA elements\", \"Drosophila extra sex combs gene\", \"mouse embryonic ectoderm development gene\", \"murine homolog\", \"cDNA\", \"homeotic genes\"], \"Protein\": [\"K protein\", \"the Drosophila Esc\", \"Gal4 - Eed fusion protein\", \"Drosophila melanogaster extra sex combs (esc) gene product\", \"C - terminal half\", \"heterogeneous nuclear ribonucleoprotein K protein\", \"transcriptional repressor\", \"Eed\", \"Esc\", \"WD - 40 repeats\", \"N terminus\", \"Gal4 - K protein\"], \"RNA\": []}" } ]
science.ncbi_ner
science.ncbi_ner.28
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Disease\" : [\"COVID-19\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nCharacterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene. The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys. Mutations in the OCRL1 gene have been associated with the disease. OCRL1 encodes a phosphatidylinositol 4, 5-biphosphate (PtdIns [4, 5] P2) 5-phosphatase. We have examined the OCRL1 gene in eight unrelated patients with OCRL and have found seven new mutations and one recurrent in-frame deletion. Among the new mutations, two nonsense mutations (R317X and E558X) and three other frameshift mutations caused premature termination of the protein. A missense mutation, R483G, was located in the highly conserved PtdIns (4, 5) P2 5-phosphatase domain. Finally, one frameshift mutation, 2799delC, modifies the C-terminal part of OCRL1, with an extension of six amino acids. Altogether, 70% of missense mutations are located in exon 15, and 52% of all mutations cluster in exons 11-15. We also identified two new microsatellite markers for the OCRL1 locus, and we detected a germline mosaicism in one family. This observation has direct implications for genetic counseling of Lowe syndrome families.." }, { "role": "assistant", "content": "{\"Disease\": [\"Lowe syndrome\", \"abnormalities of eyes, nervous system, and kidneys\", \"X-linked disorder\", \"OCRL\", \"oculocerebrorenal syndrome of Lowe\"]}" } ]
science.scientific_papers_summarization_single_doc_pubmed
science.scientific_papers_summarization_single_doc_pubmed.113991
[ { "role": "user", "content": "You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nrestorative proctocolectomy ( rpc ) with ileal pouch - anal anastomosis ( ipaa ) is now considered the procedure of choice for the surgical treatment of patients with ulcerative colitis ( uc).1 - 3 the ipaa can be performed using either a stapling technique or a handsewn technique with mucosectomy .\ncurrently , double stapled ipaa is favoured as it is simpler and provides better functional results than the handsewn ipaa with mucosectomy.1,3 on the other hand , the stapled technique allows the retention of 1 to 2 cm strip of the rectal and anal transition zone mucosa above the dentate line . since uc is a mucosal disease , often originating in the rectum and progressing proximally , retention of the potentially diseased rectal mucosa exposes uc patients not only to chronic inflammation or disease recurrence but also to neoplastic lesions , as already reported.2,4 for this reason , a number of techniques have been proposed in order to eradicate the rectal mucosa,5 - 10 however , these techniques harbor several disadvantages with respect to either technical aspects or histopathologic interpretation of the excised tissue . here , we report on a case in order to introduce an alternative technique , stapled mucosectomy , for the removal of the rectal mucosa retained after previous rpc with stapled ipaa .\na 62-year - old male patient who had had a 7-year history of uc refractory to medical therapy underwent laparoscopic rpc with an ileal j - pouch , ipaa and temporary loop ileostomy in our institution .\nthe j - pouch was created with the stapled technique and the pouch was anastomozed approximately 2 cm above the dentate line using a 31-mm transanal circular stapler .\nthe histopathology of the proctocolectomy specimen showed low grade dysplasia in the proximal rectum with no evidence of malignancy throughout the colon .\nbased on the result of the histolopathology , an elective surgery for a completion mucosectomy at the time of ileostomy closure was scheduled . following re - hospitalization in the eighth postoperative week , a phosphate enema a day before surgery and antibiotic prophylaxis ( cefuroxime 1.5 g , metronidazole 500 mg ) at anesthesia induction\nwere administered to the patient . after the administration of general anesthesia and the placement of an epidural catheter for pain control , the patient was prepared , placed in a lithotomy position and a foley catheter was placed .\nstapled mucosectomy was performed using a 33-mm circular stapler kit ( pph ; ethicon endo - surgery , cincinatti , oh , usa ) .\nfirst , the anal canal was lubricated and the obturator piece of the instrument was used for mild anal dilatation .\nthen , the obturator was removed and an operating anoscope was placed for the exposure of the anal canal .\nthe gap in the anoscope was rotated in the anus for the application of a 2/0 monocryl purse - string suture with a 25-mm curved needle .\nevery bite included mucosal and submucosal layers of the rectum 1 cm above the dentate line .\nthe distance between the purse - string suture and the dentate line was kept the same over the entire circumference .\neach bite of the pursestring suture was taken 2 to 3 mm behind the exit point of the preceding bite in order to prevent sliding of the purse - string .\nthen , the anoscope was removed and the lubricated open circular stapler was inserted with its anvil beyond the purse - string suture .\nthe purse - string was firmly tied on the shaft and its free ends were pulled through the lateral ports of the stapler device with a suture grasper .\nthe tails of the purse - string were pulled as the jaws of the circular stapler were closed .\nthe stapler was fired and it was then gently withdrawn from the anal canal . following the withdrawal of the stapler ,\nthe excised tissue was checked for complete cylindrical doughnut . at the end of this procedure ,\nthere were no bleeding points , and the lumen above the dentate line was seen to be free of the rectal mucosa ( fig .\nafterwards , the ileostomy was closed in the usual fashion with hand - sewn sutures .\nafter surgery , pain control was provided by epidural analgesia and nonsteroidal anti - inflammatory agents as required .\nhistopathologic examination of the excised tissue showed chronic inflammatory reaction within the retained rectal mucosa .\nthe patient had an uneventful post - operative recovery and was discharged home on the sixth postoperative day . on follow - up visits ,\n3 ) and anal manometry performed in the first postoperative month revealed no abnormality of the anal sphincter structure and function , and endoscopic examination of the anal canal and the pouch was normal ( fig .\nno complications have been \n observed during a follow - up period of 5 months .\nit is well documented that chronic inflammation may lead to dysplasia and dysplasia may ultimately lead to neoplasia in patients with long - standing uc.2 in the presented case , the preoperative colonoscopic biopsy did not reveal any evidence of dysplasia until after the histopathologic examination of the proctocolectomy specimen . since the presence of dysplasia in the surgical specimen is a primary risk factor for developing dysplasia in the retained rectal mucosa,2 we preferred a corrective surgical procedure at the time of the ileostomy closure rather than performing an intensive endoscopic surveillance with regular biopsies .\nretained rectal mucosa is considered a disease - bearing tissue and , if left untreated , presents a significant risk for disease persistence , recurrence or malignant degeneration in uc patients.10 thus , the eradication of the rectal mucosa to provide complete surgical care for such patients has been a major concern for surgeons . to date , a number of techniques have been described and these include chemical debridement,5 ultrasonic fragmentation,6 transanal mucosectomy using an ultrasonically activated scalpel7 and endoscopic transanal mucosal ablation with an urologic resectoscope.8 however , these techniques either result in ablation of the rectal mucosa or complete mucosal destruction so that the histolopathologic examination can not always be thoroughly assessed.4,11 another alternative and well - known technique is completion mucosectomy with re - construction of the ipaa .\nit involves a perineal approach to manually excising the retained anorectal mucosa followed by pouch advancement and neoileoanal anastomosis.9,10 however , this complex technique may pose several challenges with respect to mucosal excision and anastomosis reconstruction .\nexcessive anal dilation is often necessary to complete the procedure and there is considerably more tension on the neoileoanal anastomosis because of the relative lack of mobility of the ileal pouch.9 furthermore , there is the risk of sphincter mechanism damage due to the excessive manipulation of the anal canal.10 as it is well known , good continence is primarily dependent on the sphincter function and this is essential for the patient 's return to normal daily life .\nthe idea of the stapled mucosectomy technique was born as a result of the aforementioned disadvantages associated with the previous techniques .\nas clearly seen , stapled mucosectomy has evolved from stapled hemorrhoidopexy , also known as longo 's procedure,12 which is based on the resection of the rectal mucosa and anopexy above the dentate line for the surgical treatment of hemorrhoids . as described , the same principles of longo 's procedure were applied in the presented case for the circumferential removal of the retained rectal mucosa after previous rpc . from a technical perspective , a proper positioning of the stapler within the anal canal is important to avoid damage to the sphincters .\nin addition , the stapler must be kept on an access with the anal canal in order not to result in an asymetrical resection due to the inclination of the stapler .\nour technique , however , differs from longo 's procedure in the level of the purse - string suture since the stapled mucosectomy requires the placement of a lower purse - string suture at a distance of 1 cm above the dentate line in order to resect the retained mucosal strip of the rectal cuff as well as the anal transitional zone mucosa . in cases\nwhere the previous ipaa has been created more than 2 cm above the dentate line , this procedure can be repeated with a new purse - string suture at an appropriate level to ensure complete mucosectomy .\nan important advantage of using the stapled mucosectomy technique is the preservation of the normal architecture of the resected rectal mucosa which therefore enables the pathologist to perform a thorough histopathologic assessment .\nin addition to this , this technique overcomes an incomplete surgical field exposure and the difficult manipulation associated with a complex mucosectomy surgery , as described earlier .\npresumably , the previously reported postoperative complications associated with longo 's procedure such as pain , bleeding , incontinence , septic complications and stenosis13,14 can also be expected to occur with the stapled mucosectomy .\nthese complications are directly related to the operative technique.13 of particular note , postoperative pain can be regarded as a certain limitation since the purse - string suture is performed too close to the dentate line .\nthe administration of epidural analgesia in the presented case enabled a fine control of postoperative pain .\nif epidural analgesia is not considered , infiltration of local anesthetic agents into the dentate line would be helpful in minimizing pain , as previously described for stapled hemorrhoidopexy . based on our limited experience with only one case ,\nstapled mucosectomy seems to be a technically feasible and clinically acceptable alternative procedure for the removal of potentially diseased rectal mucosa retained after rpc ." }, { "role": "assistant", "content": "restorative proctocolectomy ( rpc ) , when performed with a stapled ileal pouch - anal anastomosis ( ipaa ) , allows the retention of the rectal mucosa above the dentate line and can result in disease persistence or recurrence , as well as neoplastic lesions in patients with ulcerative colitis ( uc ) . \n we report the case of a patient with chronic uc who underwent staple mucosectomy , which is an alternative technique that evolved from stapled hemorrhoidopexy , rather than more traditional procedures . \n the patient had undergone laparoscopic rpc with a stapled ipaa 2 cm above the dentate line and a temporary loop ileostomy . because the histopathology showed low - grade dysplasia in the proximal rectum , stapled mucosectomy with a 33-mm circular stapler kit at the time of ileostomy closure was scheduled . \n following the application of a purse - string suture 1 cm above the dentate line , the stapler was inserted with its anvil beyond the purse - string and was fired . \n the excised rectal tissue was checked to ensure that it was a complete cylindrical doughnut . \n histopathology of the excised tissue showed chronic inflammation . \n there were no complications during a follow - up period of 5 months . \n because it preserves the normal rectal mucosal architecture and avoids a complex mucosectomy surgery , stapled mucosectomy seems to be a technically feasible and clinically acceptable alternative to the removal of rectal mucosa retained after rpc ." } ]
science.scireviewgen_multidoc_summarization
science.scireviewgen_multidoc_summarization.62729
[ { "role": "user", "content": "You are presented with multiple paper abstracts, alongside the associated literature review and chapter titles. Given the provided information, you are going to do a literature review. Please generate a coherent literature review that synthesizes the content, draws connections between different works, highlights major findings, and identifies any gaps in the existing research.\n\nLiterature Review Title: Fingerprints, Iris and DNA Features based Multimodal Systems: A Review \nChapter Title: Core, Delta, and Centre Point Distance Based Systems \n1. Abstract of Cited Paper (BIB001): Utilizing more information other than minutiae is much helpful for large-scale fingerprint recognition applications. In this paper, we proposed a polynomial model to approximate the density map of fingerprints and used the model's parameters as a novel kind of feature for fingerprint representation. Thus, the density information can be utilized into the matching stage with a low additional storage cost. A decision-level fusion scheme is further used to combine the density map matching with conventional minutiae-based matching and experimental results showed a much better performance than using single minutiae-based matching. \n2. Abstract of Cited Paper (BIB002): Sweat pores on fingerprints have proven to be useful features for personal identification. Several methods have been proposed for pore matching. The state-of-the-art method first matches minutiae on the fingerprints and then matches the pores based on the minutia matching results. A problem of such minutia-based pore matching method is that the pore matching is dependent on the minutia matching. Such dependency limits the pore matching performance and impairs the effectiveness of the fusion of minutia and pore match scores. In this paper, we propose a novel direct approach for matching fingerprint pores. It first determines the correspondences between pores based on their local features. It then uses the RANSAC (RANdom SAmple Consensus) algorithm to refine the pore correspondences obtained in the first step. A similarity score is finally calculated based on the pore matching results. The proposed pore matching method successfully avoids the dependency of pore matching on minutia matching results. Experiments have shown that the fingerprint recognition accuracy can be greatly improved by using the method proposed in this paper. \n3. Abstract of Cited Paper (BIB003): Latent fingerprint identification is of critical importance to law enforcement agencies in identifying suspects: Latent fingerprints are inadvertent impressions left by fingers on surfaces of objects. While tremendous progress has been made in plain and rolled fingerprint matching, latent fingerprint matching continues to be a difficult problem. Poor quality of ridge impressions, small finger area, and large nonlinear distortion are the main difficulties in latent fingerprint matching compared to plain or rolled fingerprint matching. We propose a system for matching latent fingerprints found at crime scenes to rolled fingerprints enrolled in law enforcement databases. In addition to minutiae, we also use extended features, including singularity, ridge quality map, ridge flow map, ridge wavelength map, and skeleton. We tested our system by matching 258 latents in the NIST SD27 database against a background database of 29,257 rolled fingerprints obtained by combining the NIST SD4, SD14, and SD27 databases. The minutiae-based baseline rank-1 identification rate of 34.9 percent was improved to 74 percent when extended features were used. In order to evaluate the relative importance of each extended feature, these features were incrementally used in the order of their cost in marking by latent experts. The experimental results indicate that singularity, ridge quality map, and ridge flow map are the most effective features in improving the matching accuracy.\n\nLiterature Review:" }, { "role": "assistant", "content": "Wahab proposed a fingerprint recognition system in which ridge direction based image processing technique was used. The matching technique includes following two steps BIB001 : Step 1: Match local features. Step 2: Match global features. Woon Ho Jung established a spiral based fingerprint recognition method. The Woon's algorithm uses following two stages for authentication : Woodard used 3-D finger surface features as a biometric identifier for personal identification. Skin folds and crease patterns were extracted from the finger surface as an identifier and a feature template is generated from the curvature based representation of the registered finger images. In image preprocessing four tasks are required: data re-sampling, hand segmentation, finger extraction, and feature template generation. To locate the finger valleys the hull of the contour of hand's silhouette was used . The pores matching based fingerprint identification methods used RANSAC (RANdom SAmple Consensus) algorithm for finding the corresponding cores features and finally similarity scores are calculated on the basis of pore matching results BIB003 . A ridge pattern flow based data mining approach for fingerprint identification was proposed by [87][9] . This approach calculates the numeric code sequence for each ridge flow pattern of the input fingerprint by dividing it into five categories namely Arch, Tented Arch, Left Loop, Right Loop, and Whorl. The latent-to-rolled/plain matching algorithm utilizes minutiae, reference points (core, delta, center point of reference), overall image characteristics (ridge quality map, ridge flow map, ridge wavelength map), and skeleton image. Feature extraction algorithm consists of preprocessing and post processing [28] BIB002 . In feature extraction; reference points, overall image characteristics, and minutiae points are extracted. Ridge validation and minutiae validation algorithms are used to remove the background noise. Baseline matching algorithm is used for minutiae matching which includes local minutiae matching, global minutiae matching, and matching score computation [68] BIB004 ." } ]
science.bioasq_general_qa
science.bioasq_general_qa.740
[ { "role": "user", "content": "You will be shown a question, followed by excerpts from biomedical research papers. Please answer the question based on the provided context. Do not include any text in your response other than the answer.\n\nQuestion: What is the function of Taraxasterol in rheumatoid arthritis?\n\nContext: Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses\nThese observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice\nThese observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.\nProtective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.\nProtective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice." }, { "role": "assistant", "content": "Taraxasterol suppresses inflammation in rheumatoid arthritis. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses" } ]
science.chia_ner
science.chia_ner.388
[ { "role": "user", "content": "You will be shown inclusion or exclusion criteria for a clinical trial. Given these criteria, your task is to extract all unique entities of the following types: [\"Observation\", \"Condition\", \"Procedure\", \"Drug\", \"Temporal\", \"Multiplier\", \"Qualifier\", \"Negation\", \"ReferencePoint\", \"Scope\", \"Value\", \"Mood\", \"Device\", \"Visit\", \"Measurement\", \"Person\"].\n\nPlease return the output as a JSON object of the format: {\"Condition\" : [\"breast cancer\", ...], \"Device\" : [\"ports\", ...], \"Drug\" : [\"Atenolol\", ...], \"Measurement\" : [\"blood pressure\", ...], \"Mood\" : [\"suspected\", ...], \"Multiplier\" : [\"more than two\", ...], \"Negation\" : [\"no\", ...], \"Observation\" : [\"history\", ...], \"Person\" : [\"male\", ...], \"Procedure\" : [\"surgery\", ...], \"Qualifier\" : [\"severe\", ...], \"ReferencePoint\" : [\"enrollment\", ...], \"Scope\" : [\"infection\", ...], \"Temporal\" : [\"one day\", ...], \"Value\" : [\"50%\", ...], \"Visit\" : [\"ICU\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPregnant or lactating women\nPatients with severe organ dysfunction or failure\nWith severe cardiovascular disease, or mental\nExtraliver metastases" }, { "role": "assistant", "content": "{\"Condition\": [\"Extraliver metastases\", \"metastases\", \"rgan ailure\", \"cardiovascular disease\", \"lactating\", \"organ dysfunction\", \"Pregnant\", \"sease, ntal\\nE\"], \"Device\": [], \"Drug\": [], \"Measurement\": [], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [\"women\"], \"Procedure\": [], \"Qualifier\": [\"severe\", \"Extraliver\"], \"ReferencePoint\": [], \"Scope\": [\"cardiovascular disease, or mental\", \"organ dysfunction or failure\"], \"Temporal\": [], \"Value\": [], \"Visit\": []}" } ]
science.scitldr_aic
science.scitldr_aic.1362
[ { "role": "user", "content": "Below are the abstract, introduction, and conclusion of a computer science research paper. Please summarize the main contribution of the work in a single sentence. Your response should include the summary and no additional text.\n\nPaper text:\n\nWe consider a simple and overarching representation for permutation-invariant functions of sequences (or set functions).\nOur approach, which we call Janossy pooling, expresses a permutation-invariant function as the average of a permutation-sensitive function applied to all reorderings of the input sequence.\nThis allows us to leverage the rich and mature literature on permutation-sensitive functions to construct novel and flexible permutation-invariant functions.\nIf carried out naively, Janossy pooling can be computationally prohibitive.\nTo allow computational tractability, we consider three kinds of approximations: canonical orderings of sequences, functions with k-order interactions, and stochastic optimization algorithms with random permutations.\nOur framework unifies a variety of existing work in the literature, and suggests possible modeling and algorithmic extensions.\nWe explore a few in our experiments, which demonstrate improved performance over current state-of-the-art methods.\nPooling is a fundamental operation in deep learning architectures BID23 .\nThe role of pooling is to merge a collection of related features into a single, possibly vector-valued, summary feature.\nA prototypical example is in convolutional neural networks (CNNs) BID22 , where linear activations of features in neighborhoods of image locations are pooled together to construct more abstract features.\nA more modern example is in neural networks for graphs, where each layer pools together embeddings of neighbors of a vertex to form a new embedding for that vertex, see for instance, BID20 BID0 BID15 Velickovic et al., 2017; BID28 Xu et al., 2018; BID26 BID25 van den Berg et al., 2017; BID12 BID13 Ying et al., 2018; Xu et al., 2019) .A\ncommon requirement of a pooling operator is invariance to the ordering of the input features. In\nCNNs for images, pooling allows invariance to translations and rotations, while for graphs, it allows invariance to graph isomorphisms. Existing\npooling operators are mostly limited to predefined heuristics such as max-pool, min-pool, sum, or average. Another\ndesirable characteristic of pooling layers is the ability to take variable-size inputs. This is\nless important in images, where neighborhoods are usually fixed a priori. However\nin applications involving graphs, the number of neighbors of different vertices can vary widely. Our goal\nis to design flexible and learnable pooling operators satisfying these two desiderata.Abstractly, we will view pooling as a permutation-invariant (or symmetric) function acting on finite but arbitrary length sequences h. All elements\nh i of the sequences are features lying in some space H (which itself could be a high-dimensional Euclidean space R d or some subset thereof). The sequences\nh are themselves elements of the union of products of the H-space: h ∈ ∞ j=0 H j ≡ H ∪ . Throughout the\npaper, we will use Π n to represent the set of all permutations of the integers 1 to n, where n will often be clear from the context. In addition, h\nπ , π ∈ Π |h| , will represent a reordering of the elements of a sequence h according to π, where |h| is the length of the sequence h. We will use the\ndouble bar superscript f to indicate that a function is permutation-invariant, returning the same value no matter the order of its arguments: f (h) = f (h π ), ∀π ∈ Π |h| . We will use the\narrow superscript f to indicate general functions on sequences h which may or may not be permutationinvariant 1 . Functions f without\nany markers are 'simple' functions, acting on elements in H, scalars or any other argument that is not a sequence of elements in H.Our goal in this paper is to model and learn permutation-sensitive functions f that can be used to construct flexible and learnable permutation-invariant neural networks. A recent step in this\ndirection is work on DeepSets by Zaheer et al. (2017) , who argued for learning permutation-invariant functions through the following composition: DISPLAYFORM0 f (|h|, h; θ (f ) ) = |h| j=1 f (h j ; θ (f ) ) and h ≡ h(x; θ (h) ).Here, (a) x ∈ X is one\nobservation\nin the training data (X itself may contain variable-length sequences), h ∈ H is the embedding (output) of the data given by the lower layers h : X × R a → H ∪ , a > 0 with parameters θ (h) ∈ R a ; (b) f : H × R b → F is a middle-layer\nembedding function with parameters θ (f ) ∈ R b , b > 0, and F is the embedding space of f ; and (c) ρ : F × R c → Y is a neural network\nwith parameters θ (ρ) ∈ R c , c > 0, that maps to the final output space Y. Typically H and F are high-dimensional real-valued spaces; Y is often R d in d-dimensional regression problems or the simplex in classification problems. Effectively, the neural network f learns\nan embedding for each element in H, and given a sequence h, its component embeddings are added together before a second neural network transformation ρ is applied. Note that the function h may be the identity\nmapping h(x; ·) = x that makes f act directly on the input data. Zaheer et al. (2017) argue that if ρ is a universal\nfunction approximator, the above architecture is capable of approximating any symmetric function on h-sequences, which justifies the widespread use of average (sum) pooling to make neural networks permutation-invariant in BID12 , BID15 , BID20 , BID0 , among other works. We note that Zaheer et al. (2017) focus on functions\nof sets but the work was extended to functions of multisets by Xu et al. (2019) and that Janossy pooling can be used to represent multiset functions. The embedding h is permuted in all |h|! possible ways\n, and for each permutation h π , f (|h|, h π ; θ (f ) ) is computed. These are summed and passed to a second function ρ(·\n; θ (ρ) ) which gives the final permutation-invariant output y(x; θ (ρ) , θ (f ) , θ (h) ); the gray rectangle represents Janossy pooling. We discuss how this can be made computationally tractable\n.In practice, there is a gap between flexibility and learnability. While the architecture of equations 1 and 2 is a universal\napproximator to permutationinvariant functions, it does not easily encode structural knowledge about y.Consider trying to learn the permutation-invariant function y(x) = max i,j≤|x| |x i − x j |. With higherorder interactions between the elements of h, the\nfunctions f of equation 2 cannot capture any useful intermediate representations towards the final output, with the burden shifted entirely to the function ρ. Learning ρ means learning to undo mixing performed by the summation\nlayer f (|h|, h; θ (f ) ) = |h| j=1 f (h j ; θ (f ) ). As we show in our experiments, in many applications this is too much\nto ask of ρ.Contributions. We investigate a learnable permutation-invariant pooling layer for variable-size\ninputs inspired by the Janossy density framework, widely used in the theory of point processes (Daley & Vere-Jones, 2003, Chapter 7) . This approach, which we call Janossy pooling, directly allows the user to model\nwhat higher-order dependencies in h are relevant in the pooling. FIG0 summarizes a neural network with a single Janossy pooling layer f (detailed\nin Definition 2.1 below): given an input embedding h, we apply a learnable (permutation-sensitive) function f to every permutation h π of the input sequence h. These outputs are added together, and fed to the second function ρ. Examples of\nfunction f include feedforward and recurrent neural networks (RNNs)\n. We call the operation used to construct f from f the Janossy pooling. Definition\n2.1 gives a more detailed description. We will detail three broad strategies\nfor making this computation tractable and discuss\nhow existing methods can be seen as tractability strategies under the Janossy pooling framework.Thus, we propose a framework and tractability strategies that unify and extend existing methods in the literature. We contribute the following analysis: (a) We show DeepSets (Zaheer et al., 2017) is a special\ncase of Janossy pooling where the function\nf depends only on the first element of the sequence h π . In the most general form of Janossy pooling (as described above), f depends on its entire input sequence\nh π . This naturally raises the possibility of intermediate choices of f that allow practitioners to trade between\nflexibility and tractability. We will show that functions f that depend on their first k arguments of h π allow the Janossy pooling layer\nto capture up to k-ary dependencies in h. (b) We show Janossy pooling can be used to learn permutation-invariant neural networks y(x) by sampling a random\npermutation of h during training, and then modeling this permuted sequence using a sequence model such as a recurrent neural network (LSTMs BID17 , GRUs BID6 ) or a vector model such as a feedforward network. We call this permutation-sampling learning algorithm π-SGD (π-Stochastic Gradient Descent). Our analysis explains\nwhy this seemingly unsound procedure is theoretically justified, which sheds light on the recent\npuzzling success of permutation sampling and LSTMs in relational models BID29 BID15 . We show that this property relates to randomized model ensemble techniques. (c) In Zaheer et al. (2017) , the authors\ndescribe a connection between DeepSets and infinite de Finetti exchangeabilty\n. We provide a probabilistic connection between Janossy pooling and finite de Finetti exchangeabilty BID11 .\nOur approach of permutation-invariance through Janossy pooling unifies a number of existing approaches, and opens up avenues to develop both new methodological extensions, as well as better theory.\nOur paper focused on two main approaches: k-ary interactions and random permutations.\nThe former involves exact Janossy pooling for a restricted class of functions f .\nAdding an additional neural network ρ can recover lost model capacity and capture additional higher-order interactions, but hurts tractability and identifiability.\nPlacing restrictions on ρ (convexity, Lipschitz continuity etc.) can allow a more refined control of this trade-off, allowing theoretical and empirical work to shed light on the compromises involved.\nThe second was a random permutation approach which conversely involves no clear trade-offs between model capacity and computation when ρ is made more complex, instead it modifies the relationship between the tractable approximate loss J and the original Janossy loss L. While there is a difference between J and L, we saw the strongest empirical performance coming from this approach in our experiments (shown in the last row of TAB0 ; future work is required to identify which problems π-SGD is best suited for and when its conver-gence criteria are satisfied.\nFurther, a better understanding how the loss-functions L and J relate to each other can shed light on the slightly black-box nature of this procedure.\nIt is also important to understand the relationship between the random permutation optimization to canonical ordering and how one might be used to improve the other.\nFinally, it is important to apply our methodology to a wider range of applications.\nTwo immediate domains are more challenging tasks involving graphs and tasks involving non-Poisson point processes.\nis now a summation over only |h|!/(|h|\n− k)! terms. We can\nconclude that" }, { "role": "assistant", "content": "We propose Janossy pooling, a method for learning deep permutation invariant functions designed to exploit relationships within the input sequence and tractable inference strategies such as a stochastic optimization procedure we call piSGD" } ]
science.qasa_abstractive_qa
science.qasa_abstractive_qa.1543
[ { "role": "user", "content": "You will be shown an excerpt from a computer science scientific research paper, followed by a question about the paper. Please answer the question. Do not include any text in your response other than the answer.\n\nContext: In this work, we are specifically investigating the zero-shot scenario where there exists neither user issued questions nor domain specific data except the passage collection itself. We propose to address the training data scarcity issue by generating synthetic questions Zhou et al. (2017); Duan et al. (2017); Alberti et al. (2019); Nogueira et al. (2019).Leverage the fact that there are large question-answer data sources freely available from the web Shah and Pomerantz (2010); Duan et al. (2017).we first train a question generator using general domain question-answer pairs.The passage collection of a target domain is then fed into this generator to create pairs of noisy question-passage pairs, which are used to train a retrieval model (see Figure 2).In this work, we mine English question-answer pairs from community resources, primarily StackExchange444archive.org/details/stackexchange and Yahoo! Answers555webscope.sandbox.yahoo.com/catalog.php?datatype=l.Note we use stackexchange as it covers a wide range of topics, and we focus on investigating thedomain adaptability of using a question generation approach.We leave comparing question generator trained on different datasets or using different architectures to future work.\n\nQuestion: What are examples of noise for generated questions?" }, { "role": "assistant", "content": "The passage collection of a target domain is fed into this generator to create pairs of noisy question-passage pairs" } ]
science.mslr2022_cochrane_multidoc_summarization
science.mslr2022_cochrane_multidoc_summarization.2862
[ { "role": "user", "content": "You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.\n\n\n\nTitle 1:\nEffect of single-dose ivermectin therapy on human Onchocerca volvulus infection with onchocercal ocular involvement.\nAbstract 1:\nIvermectin has shown promise as a potentially safe and effective microfilaricidal drug for the treatment of onchocerciasis. Several limited studies have shown it to have fewer side effects, especially ocular complications, than the currently available drug, diethylcarbamazine. The detailed ocular findings in 200 moderately to heavily infected Liberians who were enrolled in a safety and dose-finding study are presented. They received either 0, 100, 150, or 200 micrograms/kg of ivermectin and were followed up for 12 months. In clinical studies so far carried out ivermectin in a dose of 100, 150, or 200 micrograms/kg has not been associated with any major adverse reactions nor were there any sight-threatening effects even in the presence of severe ocular disease. Each of these doses significantly reduced the ocular microfilaria load for at least 12 months when compared with either the placebo (p less than 0.05) or pretreatment values (p less than 0.001). However, the 100 and 150 micrograms/kg doses caused fewer minor side effects than the higher dose. These results confirm that ivermectin in a single oral dose may be a safe and effective microfilaricidal drug for the treatment of onchocerciasis and that it appears to be free of major ocular side effects.\n\n\nTitle 2:\nReduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis.\nAbstract 2:\nThe safety and efficacy of ivermectin in the prevention of blindness from onchocerciasis have been established in many studies that have addressed the drug's effects on the front of the eye. We undertook a study with sufficient statistical power to detect an effect on optic nerve disease (OND), probably the main cause of blindness in the disorder. The trial was based in 34 mesoendemic communities in Kaduna State, Nigeria. Villagers aged 5 years and older were randomly assigned annual dosing with ivermectin or placebo for 3 years. Participants underwent medical and ophthalmological examinations before the first, third, and fourth treatments. 3522 villagers aged 15 and older were re-examined at least once. Skin-snip samples were taken at baseline for calculation of microfilarial load. The outcome measure was development of disc pallor accompanied by objective evidence of deterioration in visual function; 116 subjects (45 ivermectin-treated, 71 placebo-treated) showed such changes during the trial. The incidence rate ratio (ivermectin vs placebo) was 0.90 (95% CI 0.54-1.51) for subjects with loads of 0-10 mf (microfilariae) per mg skin and 0.52 (0.29-0.93) for subjects with more than 10 mf/mg. The incidence rate ratio varied little when account was taken of age, sex, presence of pre-existing disc pallor in one eye, previous use of diethylcarbamazine citrate, or doses of ivermectin or placebo received. There was evidence that ivermectin reduced the incidence of OND in subjects with microfilarial loads above 10 mf/mg but had little effect in those with lower loads. Sustained annual delivery of ivermectin could prevent a substantial proportion of onchocercal blindness in mesoendemic communities.\n\n\nTitle 3:\nOphthalmological results from a placebo controlled comparative 3-dose ivermectin study in the treatment of onchocerciasis.\nAbstract 3:\nOne hundred and ninety eight patients with moderate to heavy infection with Onchocerca volvulus and with eye involvement in most, were allocated randomly to treatment with 100, 150 or 200 mcg/kg body weight of ivermectin or placebo given as a single oral dose in a double-blind dose finding study. The patients were drawn from an area under over ten years of vector control in Northern Ghana by the Onchocerciasis Control Programme, OCP. They underwent detailed clinical, laboratory and ophthalmological examination before treatment and in the review period of one year in hospital. Ivermectin given in a dose of 100, 150 or 200 mcg/kg eliminated microfilariae similarly slowly over 3-6 months and was associated with inflammatory reaction in the anterior segment which resolved without treatment. No changes in the fundus of the eye was detected by fluorescein angiography and no no-table other adverse eye reaction was observed. The ceiling of therapeutic activity of ivermectin in the eye is therefore put at 100 mcg/kg which is lower than the level fo 150 mcg/kg found in the skin. The apparent discrepancy may be due to different dose requirements on account of different mechanisms of action of ivermectin at the two sites. In the skin there is active killing while in the eye it is presumed there is a passive elimination of microfilariae." }, { "role": "assistant", "content": "The lack of evidence for prevention of visual impairment and blindness should not be interpreted to mean that ivermectin is not effective, however, clearly this is a key question that remains unanswered. The main evidence for a protective effect of mass treatment with ivermectin on visual field loss and optic nerve disease comes from communities mesoendemic for the savannah strain of O.volvulus. Whether these findings can be applied to communities with different endemicity and affected by the forest strain is unclear. Serious adverse effects were rarely reported. None of the studies, however, were conducted in areas where people are infected with Loa loa (loiasis)." } ]
science.ddi_ner
science.ddi_ner.415
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Brand\", \"UnapprovedDrug\", \"Drug\", \"DrugGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Brand\" : [\"Aspirin\", ...], \"DrugGroup\": [\"Salicyclate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nhttp://www.rxlist.com/cgi/generic3/guanethidine_od.htm" }, { "role": "assistant", "content": "{\"Brand\": [], \"Drug\": [], \"DrugGroup\": [], \"UnapprovedDrug\": []}" } ]
science.chemprot_re
science.chemprot_re.520
[ { "role": "user", "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nA combination of [ + ] and [-]-Huperzine A improves protection against soman toxicity compared to [+]-Huperzine A in guinea pigs. The neuropathologic mechanisms after exposure to lethal doses of nerve agent are complex and involve multiple biochemical pathways. Effective treatment requires drugs that can simultaneously protect by reversible binding to the acetylcholinesterase (AChE) and blocking cascades of seizure related brain damage, inflammation, neuronal degeneration as well as promoting induction of neuroregeneration. [-]-Huperzine A ([-]-Hup A), is a naturally occurring potent reversible AChE inhibitor that penetrates the blood-brain barrier. It also has several neuroprotective effects including modification of beta-amyloid peptide, reduction of oxidative stress, anti-inflammatory, anti-apoptotic and induction and regulation of nerve growth factor. Toxicities at higher doses restrict the neuroporotective ability of [-]-Hup A for treatment. The synthetic stereoisomer, [+]-Hup A, is less toxic due to poor AChE inhibition and is suitable for both pre-/post-exposure treatments of nerve agent toxicity. [+]-Hup A block the N-methyl-d-aspartate (NMDA) -induced seizure in rats, reduce excitatory amino acid induced neurotoxicity and also prevent soman induced toxicity with minimum performance decrement. Unique combinations of two stereo-isomers of Hup A may provide an excellent pre/post-treatment drug for the nerve agent induced seizure/status epilepticus. We investigated a combination of [+]-Hup A with a small dose of [-]-Hup A ([ + ] and [-]-Hup A) against soman toxicity. Our data showed that pretreatment with a combination [ + ] and [-]-Hup A significantly increased the survival rate and reduced behavioral abnormalities after exposure to 1.2 × LD50 soman compared to [+]-Hup A in guinea pigs. In addition, [ + ] and [-]-Hup A pretreatment inhibited the development of high power of EEG better than [+]-Hup A pretreatment alone. These data suggest that a combination of [ + ] and [-]-Hup A offers better protection than [+]-Hup A and serves as a potent medical countermeasure against lethal dose nerve agent toxicity in guinea pigs." }, { "role": "assistant", "content": "[[\"[+]-Hup A\", \"INHIBITOR\", \"AChE\"], [\"[-]-Hup A\", \"INHIBITOR\", \"AChE\"], [\"[-]-Huperzine A\", \"INHIBITOR\", \"AChE\"]]" } ]
science.pico_ner
science.pico_ner.4053
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Outcome\", \"Participant\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\" : [\"patients with COPD\", ...], \"Intervention\" : [\"Atenolol\", ...], \"Outcome\" : [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nEffects of a low-salt diet and of acute salt loading on blood pressure and intralymphocytic sodium concentration in young subjects with borderline hypertension . 1 . Three groups of young patients with borderline hypertension were studied for a 12 months period . The first was on a free sodium diet while the second was on a low-salt diet . The third group of patients underwent acute salt loading . 2 . After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted . Five patients who were re-checked after 24 months also had a significant increase in blood pressure . 3 . Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure . 4 . After acute salt loading , borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal ." }, { "role": "assistant", "content": "{\"Intervention\": [\"low-salt diet\", \"free sodium diet\", \"acute salt loading\", \"acute salt loading .\", \"low-salt diet .\", \"free diet\"], \"Outcome\": [\"intralymphocytic sodium concentration\", \"blood pressure\", \"intralymphocytic sodium\", \"natriuresis\"], \"Participant\": [\"with borderline hypertension .\", \"borderline hypertension\", \"young subjects\", \"young patients\"]}" } ]
science.bc7_litcovid_topic_classification
science.bc7_litcovid_topic_classification.18058
[ { "role": "user", "content": "You are presented with a paragraph from a COVID-19 literature. Classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable topics within the array. Your output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nBACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. OBJECTIVE: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. METHODS: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. RESULTS: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. CONCLUSION: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making." }, { "role": "assistant", "content": "[\"Treatment\", \"Diagnosis\"]" } ]
science.bc7_litcovid_topic_classification
science.bc7_litcovid_topic_classification.3965
[ { "role": "user", "content": "You are presented with a paragraph from a COVID-19 literature. Classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable topics within the array. Your output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nCoronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. In order to explore the effects of comorbid chronic diseases on clinical outcomes of COVID-19, a search was conducted in PubMed, Ovid MEDLINE, EMBASE, CDC, and NIH databases to April 25, 2020. A total of 24 peer-reviewed articles, including 10948 COVID-19 cases were selected. We found diabetes was present in 10.0%, coronary artery disease/cardiovascular disease (CAD/CVD) was in 8.0%, and hypertension was in 20.0%, which were much higher than that of chronic pulmonary disease (3.0%). Specifically, preexisting chronic conditions are strongly correlated with disease severity [Odds ratio (OR) 3.50, 95% CI 1.78 to 6.90], and being admitted to intensive care unit (ICU) (OR 3.36, 95% CI 1.67 to 6.76); in addition, compared to COVID-19 patients with no preexisting chronic diseases, COVID-19 patients who present with either diabetes, hypertension, CAD/CVD, or chronic pulmonary disease have a higher risk of developing severe disease, with an OR of 2.61 (95% CI 1.93 to 3.52), 2.84 (95% CI 2.22 to 3.63), 4.18 (95% CI 2.87 to 6.09) and 3.83 (95% CI 2.15 to 6.80), respectively. Surprisingly, we found no correlation between chronic conditions and increased risk of mortality (OR 2.09, 95% CI 0.26 to16.67). Taken together, cardio-metabolic diseases, such as diabetes, hypertension and CAD/CVD were more common than chronic pulmonary disease in COVID-19 patients, however, each comorbid disease was correlated with increased disease severity. After active treatment, increased risk of mortality in patients with preexisting chronic diseases may reduce." }, { "role": "assistant", "content": "[\"Treatment\", \"Diagnosis\"]" } ]
science.mslr2022_cochrane_multidoc_summarization
science.mslr2022_cochrane_multidoc_summarization.2392
[ { "role": "user", "content": "You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.\n\n\n\nTitle 1:\nBehavior therapy versus clomipramine for the treatment of obsessive-compulsive disorder in children and adolescents.\nAbstract 1:\nTo compare, via a pilot study, the effectiveness of behavior therapy and of drug treatment in children and adolescents with obsessive-compulsive disorder.\n Twenty-two children aged between 8 and 18 years were randomly assigned to behavior therapy (n = 12) or open clomipramine (n = 10) in a parallel design lasting 12 weeks. Behavior therapy included exposure and response prevention administered in weekly sessions. The mean dosage of clomipramine was 2.5 mg/kg (range = 1.4-3.3 mg/kg). The main outcome variables were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Leyton Obsessional Inventory-Child Version (LOI-CV).\n Significant improvement was obtained in both treatment conditions. Behavior therapy produced stronger therapeutic changes than clomipramine on the CY-BOCS (p < .05), whereas on the LOI-CV no significant differences between the results of the two treatments were found. Five of the nine initial nonresponders showed significant changes after extension of treatment for another 12 weeks.\n Behavior therapy is shown to be a good alternative for drug treatment and deserves further study in larger samples of children with obsessive-compulsive disorder.\n\n\nTitle 2:\nEarly childhood OCD: preliminary findings from a family-based cognitive-behavioral approach.\nAbstract 2:\nTo examine the relative efficacy of family-based cognitive-behavioral therapy (CBT) versus family-based relaxation treatment (RT) for young children ages 5 to 8 years with obsessive-compulsive disorder (OCD).\n Forty-two young children with primary OCD were randomized to receive 12 sessions of family-based CBT or family-based RT. Assessments were conducted before and after treatment by independent raters blind to treatment assignment. Primary outcomes included scores on the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Improvement.\n For the intent-to-treat sample, CBT was associated with a moderate treatment effect (d = 0.53), although there was not a significant difference between the groups at conventional levels. For the completer sample, CBT had a large effect (d = 0.85), and there was a significant group difference favoring CBT. In the intent-to-treat sample, 50% of children in the CBT group achieved remission as compared to 20% in the RT group. In the completer sample, 69% of children in the CBT group achieved a clinical remission compared to 20% in the RT group.\n Results indicate that children with early-onset OCD benefit from a treatment approach tailored to their developmental needs and family context. CBT was effective in reducing OCD symptoms and in helping a large number of children achieve a clinical remission.\n\n\nTitle 3:\nCognitive-behavioral family treatment of childhood obsessive-compulsive disorder: a controlled trial.\nAbstract 3:\nTo evaluate the relative efficacy of (1) individual cognitive-behavioral family-based therapy (CBFT); (2) group CBFT; and (3) a waitlist control group in the treatment of childhood obsessive-compulsive disorder (OCD).\n This study, conducted at a university clinic in Brisbane, Australia, involved 77 children and adolescents with OCD who were randomized to individual CBFT, group CBFT, or a 4- to 6-week waitlist control condition. Children were assessed before and after treatment and at 3 months and 6 months following the completion of treatment using diagnostic interviews, symptom severity interviews, and self-report measures. Parental distress, family functioning, sibling distress, and levels of accommodation to OCD demands were also assessed. Active treatment involved a manualized 14-week cognitive-behavioral protocol, with parental and sibling components.\n By an evaluable patient analysis, statistically and clinically significant pretreatment-to-posttreatment change occurred in OCD diagnostic status and severity across both individual and group CBFT, with no significant differences in improvement ratings between these conditions. There were no significant changes across measures for the waitlist condition. Treatment gains were maintained up to 6 months of follow-up.\n Contrary to previous findings and expectations, group CBFT is as effective in reducing OCD symptoms for children and adolescents as individual treatment. Findings support the efficacy and durability of CBFT in treating childhood OCD.\n\n\nTitle 4:\nEvaluation of exposure with response-prevention for obsessive compulsive disorder in childhood and adolescence.\nAbstract 4:\nThe present study was undertaken to estimate the effect of exposure plus response-prevention (E/RP), delivered alone intensively over 5-weeks and without concomitant pharmacotherapy, for children and adolescents with OCD. Twenty children and adolescents with OCD, not receiving medication for this condition, were randomized to E/RP or a wait-list condition. Statistically and clinically significant symptomatic improvement was found in the E/RP group compared with controls, with improvement maintained at follow-up an average of 14 weeks later. Effect size in the main intention-to-treat analysis was 1.23 and in the secondary per protocol analysis was 1.64. This study lends further support to the view that E/RP is an effective treatment for childhood OCD.\n\n\nTitle 5:\nThe effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder.\nAbstract 5:\nThe efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy.\n Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year.\n Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two-year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group.\n Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS.\n\n\nTitle 6:\nGroup cognitive-behavioral therapy versus sertraline for the treatment of children and adolescents with obsessive-compulsive disorder.\nAbstract 6:\nTo compare the effectiveness of group cognitive-behavioral therapy (GCBT) and of sertraline in treatment-naïve children and adolescents with obsessive-compulsive disorder.\n Between 2000 and 2002, 40 subjects between 9 and 17 years old were randomized to receive GCBT (n = 20) or sertraline (n = 20). GCBT consisted of a manual-based 12-week cognitive-behavioral protocol adapted for groups, and treatment with sertraline involved medication intake for 12 weeks. Subjects were assessed before, during, and after treatment (at 1, 3, 6, and 9 months after treatment conclusion). Primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale. Repeated-measures analyses of variance were done.\n Both GCBT and sertraline conditions had significant improvement in obsessive-compulsive disorder symptoms as measured by the Children's Yale-Brown Obsessive-Compulsive Scale after 12 weeks of treatment. After the 9-month follow-up period, subjects in the GCBT condition had a significantly lower rate of symptom relapse than those in the sertraline group.\n The treatment with GCBT may be effective in decreasing obsessive-compulsive symptoms in childhood obsessive-compulsive disorder and should be considered as an alternative to either individual cognitive-behavioral therapy or a medication, such as sertraline. Results support the effectiveness and the maintenance of gains of GCBT in the treatment of youngsters with obsessive-compulsive disorder.\n\n\nTitle 7:\nCognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial.\nAbstract 7:\nThe empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy.\n To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD.\n The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002.\n Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks.\n Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10.\n Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others.\n Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.\n\n\nTitle 8:\nA randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents.\nAbstract 8:\nCognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings." }, { "role": "assistant", "content": "Although only based on a small number of studies which vary in quality, behavioural or cognitive-behaviour therapy alone appears to be an effective treatment for OCD in children and adolescents. It is as effective as medication alone and may lead to better outcomes when combined with medication compared to medication alone. Additional higher quality trials are needed to confirm these findings." } ]
science.ncbi_ner
science.ncbi_ner.584
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\"].\n\nPlease return the output as a JSON object of the format: {\"Disease\" : [\"COVID-19\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIn Swedish families with hereditary prostate cancer, linkage to the HPC1 locus on chromosome 1q24-25 is restricted to families with early-onset prostate cancer. Prostate cancer clusters in some families, and an estimated 5% -10% of all cases are estimated to result from inheritance of prostate cancer-susceptibility genes. We previously reported evidence of linkage to the 1q24-25 region (HPC1) in 91 North American and Swedish families each with multiple cases of prostate cancer (Smith et al. 1996). In the present report we analyze 40 (12 original and 28 newly identified) Swedish families with hereditary prostate cancer (HPC) that, on the basis of 40 markers spanning a 25-cM interval within 1q24-25, have evidence of linkage. In the complete set of families, a maximum two-point LOD score of 1. 10 was observed at D1S413 (at a recombination fraction [theta] of. 1), with a maximum NPL (nonparametric linkage) Z score of 1. 64 at D1S202 (P =. 05). The evidence of linkage to this region originated almost exclusively from the subset of 12 early-onset (age < 65 years) families, which yielded a maximum LOD score of 2. 38 at D1S413 (straight theta = 0) and an NPL Z score of 1. 95 at D1S422 (P =. 03). Estimates from heterogeneity tests suggest that, within Sweden, as many as 50% of early-onset families had evidence of linkage to the HPC1 region. These results are consistent with the hypothesis of linkage to HPC1 in a subset of families with prostate cancer, particularly those with an early age at diagnosis." }, { "role": "assistant", "content": "{\"Disease\": [\"HPC\", \"Prostate cancer\", \"prostate cancer\", \"hereditary prostate cancer\"]}" } ]
science.cdr_ner
science.cdr_ner.489
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Disease\", \"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\" : [\"Naloxone\", ...], \"Disease\" : [\"Hypotensive\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nLamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy. Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT." }, { "role": "assistant", "content": "{\"Chemical\": [\"hepatitis-B surface antigen\", \"nucleoside\", \"lamivudin\", \"alanine\", \"HBSAG\", \"lamivudine\", \"nucleotide\", \"Lamivudine\"], \"Disease\": [\"hematological malignancies\", \"Hepatitis B\", \"cancer\", \"hepatic complication\", \"liver disease\", \"Cancer\", \"hepatitis B\", \"hepatitis\", \"HBV infection\"]}" } ]
science.healthver_entailment
science.healthver_entailment.1907
[ { "role": "user", "content": "You will be shown a claim about public health, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: Inhaling, smoking, or vaping cannabis products in the face of COVID-19 is not recommended\n\nAbstract:\nImportance.\nCovid-19 infection has major international health and economic impacts and risk factors for infection are not completely understood.\nCannabis smoking is linked with poor respiratory health, immunosuppression and multiple contaminants.\nPotential synergism between the two epidemics would represent a major public health convergence.\nCigarettes were implicated with disease severity in Wuhan, China.\nObjective.\nIs cannabis use epidemiologically associated with coronavirus incidence rate (CVIR)?\nDesign.\nCross-sectional state-based multivariable study.\nSetting.\nUSA.\nPrimary and Secondary Outcome Measures.\nCVIR.\nMultivariable-adjusted geospatially-weighted regression models.\nAs the American cannabis epidemic is characterized by a recent doubling of daily cannabis use it was considered important to characterize the contribution of high intensity use.\nResults.\nSignificant associations of daily cannabis use quintile with CVIR were identified with the highest quintile having a prevalence ratio 5.11 (95%C.I. 4.90-5.33), an attributable fraction in the exposed (AFE) 80.45% (79.61-81.25%) and an attributable fraction in the population of 77.80% (76.88-78.68%) with Chi-squared-for-trend (14,782, df=4) significant at P<10-500.\nSimilarly when cannabis legalization was considered decriminalization was associated with an elevated CVIR prevalence ratio 4.51 (95%C.I. 4.45-4.58), AFE 77.84% (77.50-78.17%) and Chi-squared-for-trend (56,679, df=2) significant at P<10-500.\nMonthly and daily use were linked with CVIR in bivariate geospatial regression models (P=0.0027, P=0.0059).\nIn multivariable additive models number of flight origins and population density were significant.\nIn interactive geospatial models adjusted for international travel, ethnicity, income, population, population density and drug use, terms including last month cannabis were significant from P=7.3x10-15, daily cannabis use from P=7.3x10-11 and last month cannabis was independently associated (P=0.0365).\nConclusions and Relevance.\nData indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation.\nRecent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant.\nCannabis thus joins tobacco as a SARS2-CoV-2 risk factor." }, { "role": "assistant", "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Data indicate CVIR demonstrates significant trends across cannabis use intensity quintiles and with relaxed cannabis legislation.\", \"Recent cannabis use is independently predictive of CVIR in bivariate and multivariable adjusted models and intensity of use is interactively significant.\", \"Cannabis thus joins tobacco as a SARS2-CoV-2 risk factor.\"]}" } ]
science.pico_ner
science.pico_ner.1862
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Outcome\", \"Participant\", \"Intervention\"].\n\nPlease return the output as a JSON object of the format: {\"Participant\" : [\"patients with COPD\", ...], \"Intervention\" : [\"Atenolol\", ...], \"Outcome\" : [\"blood pressure\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nTransdermal scopolamine patch in addition to ondansetron for postoperative nausea and vomiting prophylaxis in patients undergoing ambulatory cosmetic surgery . STUDY OBJECTIVE To determine the efficacy of transdermal scopolamine in addition to ondansetron in decreasing the incidence of postoperative nausea and vomiting ( PONV ) . DESIGN Randomized controlled trial . SETTING Academic hospital . PATIENTS 126 ASA physical status I and II patients undergoing outpatient plastic surgery with three or more risk factors for PONV . INTERVENTIONS Patients were randomly assigned to one of two groups to receive ( Group 1 ) a transdermal scopolamine ( TDS ) patch or ( Group 2 ) , a placebo patch two hours before surgery . MEASUREMENTS Occurrence of vomiting , severity of nausea using a visual analog scale ( VAS ) , rescue medication , pain intensity and pain medications , and side effects were recorded every hour until discharge from hospital , then every 4 hours thereafter for a total of 24 hours . MAIN RESULTS A statistically significant reduction in postoperative nausea between 8 and 24 hours in patients receiving TDS was noted . CONCLUSIONS Transdermal scopolamine in addition to ondansetron benefits patients at high risk for PONV undergoing outpatient plastic surgery for up to 20 hours after surgery ." }, { "role": "assistant", "content": "{\"Intervention\": [\"transdermal scopolamine ( TDS ) patch\", \"Transdermal scopolamine patch\", \"transdermal scopolamine\", \"placebo patch\", \"ondansetron\", \"scopolamine\"], \"Outcome\": [\"postoperative nausea\", \"rescue medication\", \"visual analog scale ( VAS )\", \"pain intensity\", \"Occurrence of vomiting\", \"severity of nausea\", \"postoperative nausea and vomiting\", \"side effects\", \"pain medications\"], \"Participant\": [\"ASA physical status I and II patients undergoing outpatient plastic surgery\", \"PONV\", \"undergoing ambulatory cosmetic surgery .\", \"126\", \"postoperative nausea and vomiting\", \"three or more risk factors for PONV\"]}" } ]
science.anat_em_ner
science.anat_em_ner.554
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"AnatomicalEntity\"].\n\nPlease return the output as a JSON object of the format: {\"AnatomicalEntity\": [\"tumor cells\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nIncreased expression of specific protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene. \nProtein tyrosine phosphorylation/dephosphorylation is a fundamental mechanism in the regulation of cell proliferation and neoplastic transformation; this metabolic process is modulated by the opposing activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). While the role of protein tyrosine kinases has been examined extensively in human breast tumorigenesis, the role of PTPases in this process is virtually unknown. To address this issue, an activated neu oncogene was introduced into an immortalized nontumorigenic human breast epithelial cell line (184B5). This resulted in a substantial increase in P185neu expression, which led to the formation of progressively growing carcinomas after such cells were inoculated into athymic nude mice. Importantly, a striking increase in the expression of specific PTPases, LAR and PTP1B, was observed in 3 independently neu transformed cell lines and their derived tumors. This elevation was verified at both the mRNA and protein levels. TC-PTP PTPase expression was only slightly increased in these neu transformed cells, and no expression of CD45 PTPase was observed. The level of neu expression, as well as the differential expression between P185neu and LAR/PTP1B, directly correlated with tumorigenicity. Furthermore, rat mammary carcinomas with elevated neu expression (neu-induced) also had sharply elevated LAR-PTPase expression when compared to rat mammary carcinomas with little or no neu expression (7,12-dimethylbenzanthracene induced); the level of expression of LAR PTPase was directly correlated with the level of neu expression. Thus, our results provide the first evidence that, in human breast carcinoma cells and in rat mammary carcinomas that have an induced increase in neu expression, a consistent and substantial increase in the expression of specific PTPases occurs. The relationship between P185neu-protein tyrosine kinase expression and specific PTPase expression may play a critical role in human breast tumorigenesis." }, { "role": "assistant", "content": "{\"AnatomicalEntity\": [\"breast\", \"tumors\", \"carcinomas\", \"cell\", \"mammary carcinomas\", \"breast epithelial cells\", \"breast epithelial cell line\", \"cells\", \"neoplastic\", \"cell lines\", \"breast carcinoma cells\", \"184B5\"]}" } ]
science.covidfact_entailment
science.covidfact_entailment.178
[ { "role": "user", "content": "You will be shown a claim related to the COVID-19 pandemic, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\".\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract.\n\nFor instance, if the model were given the claim \"the COVID vaccine is safe for healthy adults\", the output might be\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that the risks of severe COVID vaccine side effects are low for healthy adults.\"]\n}\n\nClaim: Mast cells activated by sars-cov-2 release histamine which decreases il-1 levels causing cytokine storm and inflammatory reaction in covid-19\n\nAbstract:\nSARS-CoV-2 virus is an infectious agent commonly found in certain mammalian animal species and today also in humans.\nSARS-CoV-2, can cause a pandemic infection with severe acute lung injury respiratory distress syndrome in patients with COVID-19, that can lead to patient death across all ages.\nThe pathology associated with pandemic infection is linked to an over-response of immune cells, including virus-activated macrophages and mast cells (MCs).\nThe local inflammatory response in the lung that occurs after exposure to SARS-CoV-2 is due to a complex network of activated inflammatory innate immune cells and structural lung cells such as bronchial epithelial cells, endothelial cells and fibroblasts.\nBronchial epithelial cells and fibroblasts activated by SARS-CoV-2 can result in the up-regulation of pro-inflammatory cytokines and induction of MC differentiation.\nIn addition, endothelial cells which control leukocyte traffic through the expression of adhesion molecules are also able to amplify leukocyte activation by generating interleukin (IL)-1, IL-6 and CXC chemokines.\nIn this pathologic environment, the activation of mast cells (MCs) causes the release of histamine, proteases, cytokines, chemokines and arachidonic acid compounds, such as prostaglandin D2 and leukotrienes, all of which are involved in the inflammatory network.\nHistamine is stored endogenously within the secretory granules of MCs and is released into the vessels after cell stimulation.\nHistamine is involved in the expression of chemokine IL-8 and cytokine IL-6, an effect that can be inhibited by histamine receptor antagonists.\nIL-1 is a pleiotropic cytokine that is mainly active in inflammation and immunity.\nAlveolar macrophages activated by SARS-CoV-2 through the TLR produce IL-1 which stimulates MCs to produce IL-6.\nIL-1 in combination with IL-6 leads to excessive inflammation which can be lethal.\nIn an interesting study published several years ago (by E. Vannier et al., 1993), it was found that histamine as well as IL-1 are implicated in the pathogenesis of pulmonary inflammatory reaction, after micorganism immune cell activation.\nIL-1 in combination with histamine can cause a strong increase of IL-1 levels and, consequently, a higher degree of inflammation.\nHowever, it has been reported that histamine alone has no effect on IL-1 production.\nFurthermore, histamine enhances IL-1-induced IL-6 gene expression and protein synthesis via H2 receptors in peripheral monocytes.\nTherefore, since MCs are large producers of histamine in inflammatory reactions, this vasoactive amine, by increasing the production of IL-1, can amplify the inflammatory process in the lung infected with SARS-CoV-2.\nHere, we have proposed for the first time an emerging role for histamine released by MCs which in combination with IL-1 can cause an increase in lung inflammation induced by the viral infection SARS-CoV-2." }, { "role": "assistant", "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"In this pathologic environment, the activation of mast cells (MCs) causes the release of histamine, proteases, cytokines, chemokines and arachidonic acid compounds, such as prostaglandin D2 and leukotrienes, all of which are involved in the inflammatory network.\"]}" } ]
science.bc7_litcovid_topic_classification
science.bc7_litcovid_topic_classification.16014
[ { "role": "user", "content": "You are presented with a paragraph from a COVID-19 literature. Classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable topics within the array. Your output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nOBJECTIVE: To analyze the impact of COVID-19 emergency on elective oncological surgical activity in Italy. SUMMARY OF BACKGROUND DATA: COVID-19 emergency shocked national health systems, subtracting resources from treatment of other diseases. Its impact on surgical oncology is still to elucidate. METHODS: A 56-question survey regarding the oncological surgical activity in Italy during the COVID-19 emergency was sent to referral centers for hepato-bilio-pancreatic, colorectal, esophago-gastric, and sarcoma/soft-tissue tumors. The survey portrays the situation 5 weeks after the first case of secondary transmission in Italy. RESULTS: In total, 54 surgical Units in 36 Hospitals completed the survey (95%). After COVID-19 emergency, 70% of Units had reduction of hospital beds (median -50%) and 76% of surgical activity (median -50%). The number of surgical procedures decreased: 3.8 (interquartile range 2.7-5.4) per week before the emergency versus 2.6 (22-4.4) after (P = 0.036). In Lombardy, the most involved district, the number decreased from 3.9 to 2 procedures per week. The time interval between multidisciplinary discussion and surgery more than doubled: 7 (6-10) versus 3 (3-4) weeks (P < 0.001). Two-third (n = 34) of departments had repeated multidisciplinary discussion of patients. The commonest criteria to prioritize surgery were tumor biology (80%), time interval from neoadjuvant therapy (61%), risk of becoming unresectable (57%), and tumor-related symptoms (52%). Oncological hub-and-spoke program was planned in 29 departments, but was active only in 10 (19%). CONCLUSIONS: This survey showed how surgical oncology suffered remarkable reduction of the activity resulting in doubled waiting-list. The oncological hub-and-spoke program did not work adequately. The reassessment of healthcare systems to better protect the oncological path seems a priority." }, { "role": "assistant", "content": "[\"Prevention\"]" } ]
science.chemdner_ner
science.chemdner_ner.1791
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nControllable adhesive superhydrophobic surfaces based on PDMS microwell arrays. This paper presents a one-step method to fabricate superhydrophobic surfaces with extremely controllable adhesion based on PDMS microwell arrays. The microwell array structures are rapidly produced on PDMS films by a point-by-point femtosecond laser scanning process. The as-prepared superhydrophobic surfaces show water controllable adhesion that ranges from ultrahigh to ultralow by adjusting the extent of overlap of the adjacent microwells, on which the sliding angle can be controlled from 180° (a water droplet can not slide down even when the as-prepared surface is turned upside down) to 3°. A \"micro-airbag effect\" is introduced to explain the adhesion transition phenomenon of the microwell array structures. This work provides a facile and promising strategy to fabricate superhydrophobic surfaces with controllable adhesion." }, { "role": "assistant", "content": "{\"Chemical\": []}" } ]
science.chemprot_re
science.chemprot_re.675
[ { "role": "user", "content": "Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.\n\nThe relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].\n\nPlease format your output as a JSON array. Each entry in the array should express a single relation, formatted as [\"<Entity_A>\", \"<RELATION_A_B>\", \"<Entity_B>\"]. If no relations can be found, please output an empty JSON array [].\n\nAbstract:\n\nBrugada syndrome. A novel clinical entity characterized by ST segment elevation in right precordial leads (V1 to V3), incomplete or complete right bundle branch block, and susceptibility to ventricular tachyarrhythmia and sudden cardiac death has been described by Brugada et al. in 1992. This disease is now frequently called \" Brugada syndrome \" (BrS). The prevalence of BrS in the general population is unknown. The suggested prevalence ranges from 5/1,000 (Caucasians) to 14/1,000 (Japanese). Syncope, typically occurring at rest or during sleep (in individuals in their third or fourth decades of life) is a common presentation of BrS. In some cases, tachycardia does not terminate spontaneously and it may degenerate into ventricular fibrillation and lead to sudden death. Both sporadic and familial cases have been reported and pedigree analysis suggests an autosomal dominant pattern of inheritance. In approximately 20% of the cases BrS is caused by mutations in the SCN5A gene on chromosome 3p21-23, encoding the cardiac sodium channel, a protein involved in the control of myocardial excitability. Since the use of the implantable cardioverter defibrillator (ICD) is the only therapeutic option of proven efficacy for primary and secondary prophylaxis of cardiac arrest, the identification of high-risk subjects is one of the major goals in the clinical decision-making process. Quinidine may be regarded as an adjunctive therapy for patients at higher risk and may reduce the number of cases of ICD shock in patients with multiple recurrences." }, { "role": "assistant", "content": "[]" } ]
science.data_reco_mcq_sc
science.data_reco_mcq_sc.8398
[ { "role": "user", "content": "Given a short query with keyphrases about a research idea in 2019 in the domain of artificial intelligence, recommend the relevant datasets to validate the research idea from options provided. A short description of the datasets is also provided to help you.\n\nQuery: In this paper, we present a comprehensive survey on existing methods for\n\nKeyphrases: quality assessment dibr-synthesized views images videos\n\nDataset description:\nMVTecAD: MVTec AD is a dataset for benchmarking anomaly detection methods with a focus on industrial inspection. It contains over 5000 high-resolution images divided into fifteen different object and texture categories.\nPlaces: The Places dataset is proposed for scene recognition and contains more than 2.5 million images covering more than 205 scene categories with more than 5,000 images per category.\nPolicyQA: A dataset that contains 25,017 reading comprehension style examples curated from an existing corpus of 115 website privacy policies. PolicyQA provides 714 human-annotated questions written for a wide range of privacy practices.\nGSL: Dataset Description The Greek Sign Language (GSL) is a large-scale RGB+D dataset, suitable for Sign Language Recognition (SLR) and Sign Language Translation (SLT). The video captures are conducted using an Intel RealSense D435 RGB+D camera at a rate of 30 fps.\n\nOptions:- A: MVTecAD B: Places C: PolicyQA D: GSL" }, { "role": "assistant", "content": "Places" } ]
science.scientific_papers_summarization_single_doc_arxiv
science.scientific_papers_summarization_single_doc_arxiv.4981
[ { "role": "user", "content": "You will be presented with the full text of a science research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe torsional oscillation was discovered by howard and labonte 1980 as a travelling wave pattern superposed on the differential rotation .\nthe waves propagate from the poles toward the equator and they consist of prograde and retrograde zones with respect to the mean differential rotation profile , the amplitude of the deviations is about 7 m / sec .\ntwo waves ( two prograde and retrograde belts ) coexist in both hemispheres . the feature was absolutely unexpected at the time of discovery and several attempts\nhave been made to check and interpret it .\nthe empirical studies basically confirmed the existence of the phenomenon by using either surface measurements ( ulrich , 2001 ) or subsurface detection by gong and mdi data ( howe et al .\n, 2000 ; komm et al 2001 ; zhao and kosovichev , 2004 ) . as a result of these investigations\nthe torsional oscillation can be regarded to be a persistent feature which extends down to about 0.92 @xmath0 .\nthe theoretical approaches were motivated by the similarity of the equatorward migrations of the shearing belts and the activity belts .\nthis suggested that the activity cycle ( in particular the sprer s law ) must have something to do with the torsional oscillation .\nthe first description was published by yoshimura ( 1981 ) who suggested a mechanism driven by a lorentz force wave as a by - product of the dynamo wave .\nrecent models take into account the presence of the sunspots . in the model of petrovay and forgcs - dajka ( 2002 )\nthe sunspots modify the turbulent viscosity in the convective zone which leads to the modulation of the differential rotation .\nin the model proposed by spruit ( 2003 ) the sunspots exert a cooling effect on the surface and this temperature variation results in geostrophic flows which would drive the torsional oscillation .\nthe present work was motivated by these recent works which suggested a possible connection between the sunspots and the torsional oscillation phenomenon .\nwe would like to find any spatial correlation between the torsional wave and any sunspot feature .\nearlier works also indicated some spatial connections but e.g. labonte and howard ( 1982 ) averaged the latitudinal magnetic activity distribution for a longer time whereas zhao and kosovichev ( 2004 ) only indicated the location of the activity belt with no distribution information .\nthe aim of the present work is to follow the temporal variation of the latitudinal distribution of sunspot parameters in comparison with the migration of the torsional waves . as a first attempt three parameters were chosen to scrutiny .\ntwo of them may be trivial : the number and the total area of sunspots .\nthe third parameter , the mean number of sunspots within the groups characterizes the complexity of the sunspot groups , because it can also be expected that the more complex is a sunspot group the more efficient is its interconnection with the local velocity fields .\nthe sunspot data were taken from the most detailed sunspot database , the debrecen photoheliographic data ( dpd ) .\nthis is the only material which contains the position and area data for each observable spot , even for the smallest ones , for each day .\nthe temporal coverage of the dpd was partial at the time of this work so , as a first attempt , we restricted the study to the years 1986 - 1989 ( gyri et al , 1996 ) .\nthe latitudinal distributions were determined in such a way that 1 degree latitudinal stripes were considered , and all mentioned parameters ( total number and total area of spots , as well as the mean number of spots per goups ) were added up for all stripes and three months .\na total amount xxx spots were taken into account in the given period . to compare the obtained distributions with the torsional pattern one has to determine the latitudinal location of the torsional wave i.e. the latitudes of prograde / retrograde belts and the shearing zones .\nfor this period the most suitable torsional data were provided by ulrich ( 2001 ) . in his figure 1 .\nthe shearing zones were reasonably well recognizable in this period .\nfigure 1 . shows the period 1986 - 89 taken from ulrich ( 2001 ) and the most probable lines of the shear zones ( dark regions indicate the prograde belts ) . in our further figures\nthese lines were adopted to mark the migrating shear zones .\nthe most obvious candidate may be the number of sunspots at a certain latitude .\nthe numbers of all spots have been added up in 1 degree wide stripes and 3-month periods in such a way that each sunspot group was taken into account at that time when it contained the largest number of spots .\nthe resulting distributions were plotted onto the plot of the migrating zones , see figure 2 , where the temporal dimension has been streched in order to minimize the overlap of the distribution curves . in this approach\nthe sizes of the spots were omitted , only the amount of the magnetix flux tubes was considered regardless of their strengths . the next possible candidate is the total area of the spots ( figure 3 ) .\nthe procedure was the same as in the case of the sunspot numbers , all area data were added up by @xmath1 latitude stripes .\nsunspots were taken into account at that time when the total areas of their groups were the largest during their passage through the solar disc . in this approach\nthe total strength was considered regardless of the size distribution .\nthe third candidate was chosen to check the assumption that in case of a certain sunspot - torsion interconnection the more complex sunspot groups could exert more efficient impacts on the ambient flows .\nthe number of spots within the groups has been averaged for the @xmath1 latitude stripes and 3-month periods , the groups were considered at the time of their largest extensions .\nthe resulting distributions are displayed in figure 4 .\nit is remarkable in the figures 2 . and 3 . that the distributions of both the spot number and area are so positioned that the peaks of the curves ( if they have unambiguous peaks at all ) are close to the shear zones but the bulges of the distributions are mostly situated in the faster belts\nthe curves of the number and area are mostly different , as was expected , but the mentioned character seems to be overwhelming on both cases .\nthis behaviour may be the signature of a really functioning interconnection between the torsional pattern and the magnetic flux ropes .\nas for the complexity of the groups , no such trend can be recognized so this feature ( the number of spots per groups ) is apparently unimportant from this point of view .\nthe above features are the first ( preliminary ) results of our project and they seem to be encouraging . in the following works we are intended to extend the temporal domain of the study and to include also some further possible sunspot parameters to reveal the nature of this interaction .\nthe present work was supported by the grants otka t 37725 and esa pecs no.98017 .\none of the authors ( a.l . ) expresses his gratitude for the kind invitation and hospitality of the hvar observatory .\n* gyri , baranyi , t. , csepura , g. , gerlei , o. , ludmny a. 1996 , debrecen photoheliographic data for the year 1986 publ .\ndebrecen obs .\n10 , 1 - 61 .\n* howard , r. , labonte , b. j. : 1980 , _ astrophys . j. _ * 239 * , l33-l36 . * howe , r. _ et al . _\n: 2000,_astrophys . j. _ * 533 * , l163-l166 . * komm r.w . , hill f. , howe r. , 2001 , _ astrophys .\nj. _ * 558 * 428 - 441 . * labonte , b. j.,howard r. : 1982,_solar physics _ * 75 * , 161 - 178 . *\npetrovay , k. , forgcs - dajka e. , : 2002 , _ solar physics _ * 205 * , 39 - 52 . * spruit , h. c. : 2003,_solar physics _ * 213 * , 1 - 21 . * ulrich , r. k. : 2001,_astrophys . j. _ * 560 * , 466 - 475 . * yoshimura , h. _ astrophys . j. _ * 247 * 1102 - 1112 .\n* zhao , j. , kosovichev , a. g. : 2004,_astrophys . j. _ * 603 * , 776 - 784 ." }, { "role": "assistant", "content": "the torsional oscillation is a well established observational fact and there are theoretical attempts for its description but no final solution has yet been accepted . \n one of the possible candidates for its cause is the presence of sunspots modifying the streaming conditions . \n the present work focuses on the temporally varying latitudinal distribution of several sunspot features , such as the spot sizes and spot numbers . \n these features are different faces of the butterfly diagram . \n in fact some weak spatial correlations can be recognized ." } ]
science.bioasq_yesno_qa
science.bioasq_yesno_qa.51
[ { "role": "user", "content": "You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?\n\nContext: Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells.\nWe begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions.\nAlternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state." }, { "role": "assistant", "content": "no" } ]
science.bioasq_yesno_qa
science.bioasq_yesno_qa.141
[ { "role": "user", "content": "You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase?\n\nContext: Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.\nOur findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation.\nKanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.\nAlpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).\nStructural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease).\nWe describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease).\nThree dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes.\nalpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.\nSchindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49).\nThe 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases.\nThese data suggest that a prototype of alpha-NAGA deficiency in Kanzaki disease and factors other than the defect of alpha-NAGA may contribute to severe neurological disorders, and Kanzaki disease is thought to be caused by a single enzyme deficiency.\nAlpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).\nalpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.\nKanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients.\nAlpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).\nKanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49),\nKanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.\nalpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described." }, { "role": "assistant", "content": "yes" } ]
science.multixscience_multidoc_summarization
science.multixscience_multidoc_summarization.15158
[ { "role": "user", "content": "You are provided with the abstract of a scientific paper and the abstracts of the papers it references. Your task is to write a Related Work section for the main paper. This section should concisely summarize and integrate the key points from the cited abstracts, reflecting how they relate to the main paper's contributions and context. In your summary, use numerical citation markers like [1], [2], etc., to refer to the corresponding papers.\n\nMain Abstract:\nQuantum computing (QC) is an emerging computing paradigm with potential to revolutionize the field of computing. QC is a field that is quickly developing globally and has high barriers of entry. In this paper we explore both successful contributors to the field as well as wider QC community with the goal of understanding the backgrounds and training that helped them succeed. We gather data on 148 contributors to open-source quantum computing projects hosted on GitHub and survey 46 members of QC community. Our findings show that QC practitioners and enthusiasts have diverse backgrounds, with most of them having a PhD and trained in physics or computer science. We observe a lack of educational resources on quantum computing. Our goal for these findings is to start a conversation about how best to prepare the next generation of QC researchers and practitioners.\n\nCited Abstract(s):\n[1]: Suppose we have a small quantum computer with only M qubits. Can such a device genuinely speed up certain algorithms, even when the problem size is much larger than M? Here we answer this question to the affirmative. We present a hybrid quantum-classical algorithm to solve 3SAT problems involving n>>M variables that significantly speeds up its fully classical counterpart. This question may be relevant in view of the current quest to build small quantum computers.\n\n[2]: Preface Acknowledgement Nomenclature and notation Part I. Fundamental Concepts: 1. Introduction and overview 2. Introduction to quantum mechanics 3. Introduction to computer science Part II. Quantum Computation: 4. Quantum circuits 5. The quantum Fourier transform and its applications 6. Quantum search algorithms 7. Quantum computers: physical realisation Part III. Quantum Information: 8. Quantum noise, open quantum systems, and quantum operations 9. Distance measurement for quantum information 10. Quantum error-correction 11. Entropy and information 12. Quantum information theory Appendix A. Notes on basic probability theory Appendix B. Group theory Appendix C. Approximating quantum gates: the Solvay-Kitaev theorem Appendix D. Number theory Appendix E. Public-key cryptography and the RSA cryptosystem Appendix F. Proof of Lieb's theorem References Index.\n\n[3]: Noisy Intermediate-Scale Quantum (NISQ) technology will be available in the near future. Quantum computers with 50-100 qubits may be able to perform tasks which surpass the capabilities of today's classical digital computers, but noise in quantum gates will limit the size of quantum circuits that can be executed reliably. NISQ devices will be useful tools for exploring many-body quantum physics, and may have other useful applications, but the 100-qubit quantum computer will not change the world right away --- we should regard it as a significant step toward the more powerful quantum technologies of the future. Quantum technologists should continue to strive for more accurate quantum gates and, eventually, fully fault-tolerant quantum computing.\n\n[4]: We run a selection of algorithms on two state-of-the-art 5-qubit quantum computers that are based on different technology platforms. One is a publicly accessible superconducting transmon device (www.research.ibm.com ibm-q) with limited connectivity, and the other is a fully connected trapped-ion system. Even though the two systems have different native quantum interactions, both can be programed in a way that is blind to the underlying hardware, thus allowing a comparison of identical quantum algorithms between different physical systems. We show that quantum algorithms and circuits that use more connectivity clearly benefit from a better-connected system of qubits. Although the quantum systems here are not yet large enough to eclipse classical computers, this experiment exposes critical factors of scaling quantum computers, such as qubit connectivity and gate expressivity. In addition, the results suggest that codesigning particular quantum applications with the hardware itself will be paramount in successfully using quantum computers in the future." }, { "role": "assistant", "content": "Unlike in classical computation, where the computation happens by manipulating bits, the fundamental computational unit in QC is qubit. A bit can have one of two states: 0 or 1. Similarly, qubit state is a unit vector in a two-dimensional complex vector space [2] . A qubit state can be encoded in a state of a quantum mechanical object, for example as polarization of a single photon [2] . The field of quantum computing is in a state of constant change, and is generally expected to continue changing in the foreseeable future. In the past few years multiple Near-term Intermediate-Scale Quantum (NISQ) hardware implementations have been developed [3] and demonstrated to provide a potential for quantum speedups [1] . Naturally, different implementations come with certain trade-offs. For example, trapped ion qubits are generally less noisy and offer better connectivity, whereas superconducting qubits offer faster gate clock speeds and more clear path to scalability [4] . This diversity of hardware introduces an additional degree of complexity for the development of QC algorithms and software, forcing algorithm developers to stay aware of the trade-offs presented by hardware." } ]
science.craftchem_ner
science.craftchem_ner.8481
[ { "role": "user", "content": "You will be presented a sentence from biomedical research text. Extract all terms that correspond to chemical entities of biological interest (ChEBI).\nReturn your identified terms in a JSON array, formatted like this: [\"Entity1\", \"Entity2\", ...].\nIf no such entities are detected, respond by providing an empty JSON array [].\n\nBiomedical context:\nDiscussion" }, { "role": "assistant", "content": "[]" } ]
science.healthver_entailment
science.healthver_entailment.4954
[ { "role": "user", "content": "You will be shown a claim about public health, and the abstract of a biomedical research paper. Each sentence from the abstract will be on a separate line. Your task is to return a JSON object with two fields:\n\n- \"verdict\": The fact-checking verdict. If the information in the abstract supports the claim, write \"SUPPORT\". If the abstract contradicts the claim, write \"CONTRADICT\". If the abstract does not provide enough information to arrive at a verdict, write \"NEI\" (for \"not enough information\").\n- \"evidence\": An array of sentences providing evidence for the verdict. Please copy all relevant sentences verbatim from the abstract. If the verdict was \"NEI\", then return an empty array.\n\nFor instance, if the model were given the claim \"wearing masks can prevent the spread of COVID\", the output might be\n{\n \"verdict\": \"SUPPORT\",\n \"evidence\": [\"Our findings indicate that mass mask-wearing reduces the transmission rate for COVID-19.\"]\n}\n\nClaim: taking vitamin D supplements could help boost the immune system, an essential piece of the puzzle in terms of how serious Covid-19 can be. \n\nAbstract:\nBACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has affected almost 2.5 million people worldwide with almost 170 000 deaths reported to date.\nSo far, there is scarce evidence for the current treatment options available for COVID-19.\nVitamin C has previously been used for treatment of severe sepsis and septic shock.\nWe reviewed the feasibility of using vitamin C in the setting of COVID-19 in a series of patients.\nMETHODS We sequentially identified a series of patients who were requiring at least 30% of FiO2 or more who received IV vitamin C as part of the COVID-19 treatment and analyzed their demographic and clinical characteristics.\nWe compared inflammatory markers pre and post treatment including D-dimer and ferritin.\nRESULTS We identified a total of 17 patients who received IV vitamin C for COVID-19.\nThe inpatient mortality rate in this series was 12% with 17.6% rates of intubation and mechanical ventilation.\nWe noted a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration.\nCONCLUSION The use of IV vitamin C in patients with moderate to severe COVID-19 disease may be feasible." }, { "role": "assistant", "content": "{\"verdict\": \"NEI\", \"evidence\": []}" } ]
science.bc7_litcovid_topic_classification
science.bc7_litcovid_topic_classification.16902
[ { "role": "user", "content": "You are presented with a paragraph from a COVID-19 literature. Classify the topics of this piece of text by choosing from the following categories:\n\n- Epidemic Forecasting: The content relates to predictions about the spread of COVID-19.\n- Treatment: The paragraph discusses therapeutic methods or medication for COVID-19.\n- Prevention: The content covers measures to prevent the spread of COVID-19.\n- Mechanism: The paragraph explains the biological mechanisms of the virus.\n- Case Report: The content is a report of a COVID-19 case.\n- Transmission: The paragraph discusses how COVID-19 is transmitted.\n- Diagnosis: The content is about diagnosing COVID-19 in individuals.\n\nYour classification should be provided as an element within a JSON array. The array should be formatted with topics enclosed in double quotes and separated by commas, following the JSON format, for example: [\"Topic1\", \"Topic2\", ...]. Include all applicable topics within the array. Your output should be a valid JSON array, and no additional text should be included in your response.\n\nArticle:\n\nBACKGROUND: In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases. METHODS: We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200mg of oral HCQ, three times daily for ten days and 500mg of oral AZ on day 1 followed by 250mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen (\"others\"). Outcomes were death, transfer to the intensive care unit (ICU), >/=10 days of hospitalization and viral shedding. RESULTS: The patients' mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 592 of the 991 (59.7%) patients with minimal clinical symptoms (NEWS score=0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphocytopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase, creatinine phosphokinase, troponin and C-reactive protein) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11-0.27), decreased risk of hospitalization >/=10 days (odds ratios 95% CI 0.38 0.27-0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17-1.42). QTc prolongation (>60ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 12 cases including 3 cases with QTc> 500ms. No cases of torsade de pointe or sudden death were observed. CONCLUSION: Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments." }, { "role": "assistant", "content": "[\"Treatment\"]" } ]
science.medmentions_ner
science.medmentions_ner.711
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"HealthCareActivity\", \"InjuryOrPoisoning\", \"BodySubstance\", \"IntellectualProduct\", \"AnatomicalStructure\", \"SpatialConcept\", \"Chemical\", \"Bacterium\", \"MedicalDevice\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Finding\", \"BiologicFunction\", \"Virus\", \"ResearchActivity\", \"ClinicalAttribute\", \"PopulationGroup\", \"Eukaryote\", \"BodySystem\", \"Food\", \"ProfessionalOrOccupationalGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nExamination of the Involvement of Cholinergic - Associated Genes in Nicotine Behaviors in European and African Americans Cigarette smoking is a physiologically harmful habit. Nicotinic acetylcholine receptors (nAChRs) are bound by nicotine and upregulated in response to chronic exposure to nicotine. It is known that upregulation of these receptors is not due to a change in mRNA of these genes, however, more precise details on the process are still uncertain, with several plausible hypotheses describing how nAChRs are upregulated. We have manually curated a set of genes believed to play a role in nicotine - induced nAChR upregulation. Here, we test the hypothesis that these genes are associated with and contribute risk for nicotine dependence (ND) and the number of cigarettes smoked per day (CPD). Studies with genotypic data on European and African Americans (EAs and AAs, respectively) were collected and a gene-based test was run to test for an association between each gene and ND and CPD. Although several novel genes were associated with CPD and ND at P < 0.05 in EAs and AAs, these associations did not survive correction for multiple testing. Previous associations between CHRNA3, CHRNA5, CHRNB4 and CPD in EAs were replicated. Our hypothesis-driven approach avoided many of the limitations inherent in pathway analyses and provided nominal evidence for association between cholinergic-related genes and nicotine behaviors. We evaluated the evidence for association between a manually curated set of genes and nicotine behaviors in European and African Americans. Although no genes were associated after multiple testing correction, this study has several strengths: by manually curating a set of genes we circumvented the limitations inherent in many pathway analyses and tested several genes that had not yet been examined in a human genetic study; gene-based tests are a useful way to test for association with a set of genes; and these genes were collected based on literature review and conversations with experts, highlighting the importance of scientific collaboration." }, { "role": "assistant", "content": "{\"AnatomicalStructure\": [\"Genes\", \"genes\", \"CHRNA5\", \"CHRNB4\", \"gene\", \"CHRNA3\"], \"Bacterium\": [], \"BiologicFunction\": [\"upregulation\", \"ND\", \"nicotine dependence\", \"upregulated\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"Nicotine\", \"mRNA\", \"nAChRs\", \"receptors\", \"Nicotinic acetylcholine receptors\", \"nAChR\", \"nicotine\"], \"ClinicalAttribute\": [], \"Eukaryote\": [\"human\"], \"Finding\": [\"number of cigarettes smoked per day\", \"CPD\", \"no\"], \"Food\": [], \"HealthCareActivity\": [\"Examination\", \"evaluated\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"literature\", \"pathway analyses\", \"gene-based tests\", \"gene-based test\"], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [\"African Americans\"], \"ProfessionalOrOccupationalGroup\": [\"experts\"], \"ResearchActivity\": [\"study\", \"genetic study\", \"Studies\"], \"SpatialConcept\": [\"bound by\"], \"Virus\": []}" } ]
science.medmentions_ner
science.medmentions_ner.2576
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"HealthCareActivity\", \"InjuryOrPoisoning\", \"BodySubstance\", \"IntellectualProduct\", \"AnatomicalStructure\", \"SpatialConcept\", \"Chemical\", \"Bacterium\", \"MedicalDevice\", \"Organization\", \"BiomedicalOccupationOrDiscipline\", \"Finding\", \"BiologicFunction\", \"Virus\", \"ResearchActivity\", \"ClinicalAttribute\", \"PopulationGroup\", \"Eukaryote\", \"BodySystem\", \"Food\", \"ProfessionalOrOccupationalGroup\"].\n\nPlease return the output as a JSON object of the format: {\"Virus\": [\"HIV\", ...], \"Bacterium\": [\"MRSA\", ...], \"AnatomicalStructure\": [\"Lung\", ...], \"BodySystem\": [\"CNS\", ...], \"BodySubstance\": [\"Serum\", ...], \"Finding\": [\"Headache\", ...], \"InjuryOrPoisoning\": [\"Fracture\", ...], \"BiologicFunction\": [\"Death\", ...], \"HealthCareActivity\": [\"Biopsy\", ...], \"ResearchActivity\": [\"Clinical trial\", ...], \"MedicalDevice\": [\"Lenses\", ...], \"SpatialConcept\": [\"Camps\", ...], \"BiomedicalOccupationOrDiscipline\": [\"Forensic medicine\", ...], \"Organization\": [\"WHO\", ...], \"ProfessionalOrOccupationalGroup\": [\"Provider\", ...], \"PopulationGroup\": [\"Swimmers\", ...], \"Chemical\": [\"Gold\", ...], \"Food\": [\"Rice\", ...], \"IntellectualProduct\": [\"RPAM\", ...], \"ClinicalAttribute\": [\"Biomarker\", ...], \"Eukaryote\": [\"Dogs\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nExpanding biological activities of Ts19 Frag-II toxin: Insights into IL-17 production Tityus serrulatus (Ts) venom is composed of a mixture of toxins presenting diverse biological functions. However, although this venom has been studied over the past three decades, omics analysis revealed that most of its toxins are not identified or their biological activities are unknown. Ts19 Frag-II is included is this group, which function is still uncertain. This study aimed to expand the biological activities of Ts19 Frag-II through in vivo investigation. Our results demonstrates that mice challenged with Ts19 Frag-II presented biochemical alterations, increasing serum levels of urea, ALT and β-globulin, besides decreasing γ-globulins. Moreover, this toxin was also able to induce immunological alterations, increasing NO, IL-6, TNF-α and IL-17, being considered a proinflammatory toxin. The increase of IL-17 was unprecedented regarding Ts toxins and could be a result of the overall produced-effect of cells of innate immunity (neutrophils, monocytes, natural killers and lymphoid tissue inducers - LTis) cells) as well as of adaptive immunity (Th17 cells). This study expanded the biological activities of Ts19 Frag-II, suggesting that this toxin could be contributing to the Ts envenoming through alterations of biochemical parameters as well as triggering the inflammatory response." }, { "role": "assistant", "content": "{\"AnatomicalStructure\": [\"natural killers\", \"monocytes\", \"neutrophils\", \"cells\", \"lymphoid tissue inducers\", \"LTis\", \"Th17 cells\"], \"Bacterium\": [], \"BiologicFunction\": [\"production\", \"biological activities\", \"biochemical\", \"biological functions\", \"inflammatory response\", \"adaptive immunity\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [\"venom\", \"toxins\", \"NO\", \"toxin\", \"ALT\", \"IL-6\", \"IL-17\", \"Ts19 Frag-II\", \"\\u03b3-globulins\", \"proinflammatory toxin\", \"\\u03b2-globulin\", \"TNF-\\u03b1\", \"Ts19 Frag-II toxin\"], \"ClinicalAttribute\": [], \"Eukaryote\": [\"mice\", \"Tityus serrulatus\", \"Ts\"], \"Finding\": [\"serum levels of urea\"], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [\"envenoming\"], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"studied\", \"omics analysis\", \"study\", \"investigation\"], \"SpatialConcept\": [\"in vivo\"], \"Virus\": []}" } ]
science.scientific_lay_summarisation_plos_single_doc_summ
science.scientific_lay_summarisation_plos_single_doc_summ.19372
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Septins restrict inflammation and protect zebrafish larvae from Shigella infection}\nArticle:\nAbstract:\nShigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish( Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor( IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation.\nIntroduction:\nSeptins, a poorly understood component of the cytoskeleton, are highly-conserved guanosine triphosphate( GTP) binding proteins organized into 4 groups based on sequence homology( the SEPT2, SEPT3, SEPT6, and SEPT7 groups). Septins from different groups assemble into hetero-oligomeric complexes which can form non-polar filaments and ring-like structures[1]. By acting as scaffolds for protein recruitment and diffusion barriers for cellular compartmentalization, septins have key roles in numerous biological processes, including cell division and host-pathogen interactions[1, 2]. Studies using human epithelial cells have revealed important roles for septins in cell-autonomous immunity, showing that septins assemble into cage-like structures to prevent the dissemination of cytosolic bacteria polymerizing actin tails[3–5]. Septin cages have also been observed in vivo using bacterial infection of zebrafish( Danio rerio) larvae[6], yet roles for septins in innate immunity in vivo remain largely unexplored. The inflammasome is an intracellular platform that assembles in response to infection to recruit and activate Caspase-1[7]. Caspase-1 activation enables the processing and secretion of the proinflammatory cytokine interleukin 1β( IL-1β) to control infection. How the inflammasome is triggered and assembled is the subject of intense investigation[8, 9], and the mechanisms underlying inflammation regulation are poorly understood[5]. New work has shown that components of the cytoskeleton play important roles in innate immunity and are required for inflammation control[5]. Actin and other proteins involved in actin polymerization regulate the NLRP3( NACHT, LRR and PYD domains-containing protein 3) inflammasome by interacting with Caspase-1 and other inflammasome components[10–12]. A separate study showed that actin depolymerization, as a consequence of mutations in WD repeat-containing protein( WDR1), can trigger disease by activation of the pyrin inflammasome[13, 14]. Other components of the cytoskeleton, including microtubules and the intermediate filament protein vimentin, promote NLRP3 activity by helping to recruit ASC( apoptosis-associated speck-like protein containing a caspase-recruitment domain) and stabilize NLRP3 inflammasomes, respectively[15, 16]. The role of the septin cytoskeleton in inflammation control has not yet been tested. Shigella, a Gram-negative enteroinvasive pathogen, causes nearly 165 million illness episodes and over 1 million deaths annually[17]. Similar to other Gram-negative pathogens in hospital patients, cases of drug-resistant Shigella strains are rising[18]. To explore the innate immune response to Shigella, several infection models have been valuable, helping to discover key roles for NOD-like receptors( NLRs)[19], neutrophil extracellular traps( NETs)[20], bacterial autophagy[21], and inflammasomes[22] in host defence. Remarkably, the major pathogenic events that lead to shigellosis in humans( i. e., macrophage cell death, invasion and multiplication within epithelial cells, cell-to-cell spread, inflammatory destruction of the host epithelium), are faithfully reproduced in a zebrafish model of S. flexneri infection[6]. Exploiting the optical accessibility of zebrafish larvae, we now have the possibility to spatio-temporally examine the biogenesis, architecture, coordination, and resolution of the innate immune response to S. flexneri in vivo. In this study, we use a S. flexneri-zebrafish infection model to discover new roles for septins in host defence. We show that zebrafish septins restrict inflammation and are required for neutrophil-mediated immunity. To rescue septin-deficiency in vivo, we used therapeutic inhibition of Il-1β signaling and prevent neutrophil death and larval mortality. These results demonstrate a previously unknown role for septins in inflammation and infection control, and highlight the cytoskeleton as a target for suppression of inflammation.\nDiscussion:\nThe zebrafish is a powerful non-mammalian vertebrate model to study the innate immune response to bacterial infection[36, 37]. We have previously used Shigella infection of the zebrafish caudal vein to study bacterial autophagy in vivo[6]. Here, using Shigella infection of the zebrafish HBV, we reveal that septins have a crucial role in restricting inflammation in vivo. Strikingly, anakinra is able to counteract septin-deficiency by preventing neutrophil death and reducing zebrafish mortality upon S. flexneri infection. These findings reveal a novel role for septins in inflammation control and host defence. The zebrafish HBV has been used to model infection by other bacterial pathogens including Listeria monocytogenes[38], Salmonella Typhimurium[39], Pseudomonas aeruginosa[40, 41], and M. marinum[42]. In the case of L. monocytogenes, bacteria in the HBV disseminate 2–3 dpi, spreading infection to the trunk and tail muscle. Although S. flexneri is well known for invasion and inflammatory destruction of the human intestinal epithelium, and similarly to L. monocytogenes has the ability to form actin tails and spread from cell-to-cell[43], we did not observe S. flexneri dissemination outside of the zebrafish HBV or forebrain ventricle. This allowed us to analyze S. flexneri-neutrophil interactions in a compartmentalized environment, where we observed that recruited neutrophils efficiently engulf and eliminate a low dose of S. flexneri. This neutrophil behavior is in stark contrast to HBV infections of non-pathogenic E. coli, where neutrophils poorly engulf fluid-borne bacteria[44]. These observations are likely a result of S. flexneri virulence factors which promote bacterial recognition and engulfment by neutrophils. The rabbit ileal loop model is commonly used to study the host response to Shigella infection[28]. Recently, a mouse model of shigellosis by intraperitoneal infection has been described[29]. In both animal models, S. flexneri induces the expression of proinflammatory cytokines, including IL-1β and TNF-α, as observed in humans suffering from shigellosis[45]. However, mammalian models remain poorly suited to spatio-temporally examine the innate immune response to Shigella in vivo. By contrast, the natural translucency of zebrafish larvae enables non-invasive in vivo imaging at high resolution throughout the organism. We show that il-1b:GFP-F larvae can be used to visualize the spatio-temporal dynamics of il-1b during S. flexneri infection. In-depth investigation of infection by Shigella and other bacteria that induce inflammatory signals, including L. monocytogenes and S. Typhimurium, will help to describe more precisely the coordination between septin assembly and inflammation. When applied as a model of vertebrate development, the zebrafish has been key in linking Sept9a and Sept9b to growth defects in vivo[46]. In support of a highly conserved role for septins amongst vertebrates, the depletion of Sept15 induces cell differentiation and division defects in the pancreatic endocrine cells of zebrafish larvae[47]. More recently, the zebrafish has been used to highlight the central role of Sept15 in actin-based myofibril and cardiac function[48]. Septins are known components of the ciliary diffusion barrier in humans, and zebrafish Sept6 and Sept15 morphants present phenotypes resembling human ciliopathies, highlighting translatability of the zebrafish as a model for the study of septin biology in vivo[26, 49]. Here, we report defects in innate immunity that derive from Sept15 depletion, including inflammation and neutropenia, and show that inflammation increases the susceptibility of neutrophils to S. flexneri infection. The mechanisms underlying cell death by Shigella in epithelial cells[50] and macrophages( including apoptosis[51], necrosis[52], pyroptosis[53], and pyronecrosis[54]), have been the subject of intense investigation. The zebrafish can represent a unique experimental system to investigate Shigella-neutrophil interactions and dissect the molecular features underlying Shigella-mediated host cell death in vivo. Moreover, it is envisioned that insights into neutrophil biology arising from our S. flexneri-zebrafish model can enable novel therapeutic approaches towards diseases with an important neutrophil component. The dysregulation of IL-1β is associated with a wide variety of inflammatory diseases[55]. Intervention into this pro-inflammatory pathway, either by blocking IL-1R or by preventing the processing / secretion of IL-1β, is critical for treatment[34]. For example, anakinra has been used to reduce IL-1β levels in a mouse model of chronic granulomatous disease( CGD), an immunodeficiency characterized by defective production of ROS[56]. Anakinra has also been effective in treatment of human patients with Schnitzler syndrome( an autoimmune disorder) or with mutations in cold-induced autoinflammatory syndrome 1 gene( CIAS1)[57]. Results obtained from our S. flexneri-zebrafish HBV infection model show that septins play a key role in the restriction of inflammation and neutrophil clearance of S. flexneri. Other studies performed in zebrafish have identified a role for the inflammasome in leukocyte clearance of L. monocytogenes and S. Typhimurium[58, 59]. What is the precise role of septins in inflammation? Septins are a unique component of the cytoskeleton that associate with cellular membranes, actin filaments, and microtubules[1]. Previous work has described a role for the actin cytoskeleton in inflammation control, by regulating the NLRP3 and pyrin inflammasomes[10–14]. We hypothesize that septins interact with components of the inflammasome and regulate assembly of this multiprotein complex. Although a precise role for septins in the assembly and activity of the inflammasome awaits investigation, these results add weight to previous studies linking inflammation and the cytoskeleton, and suggest that targeting the cytoskeleton can represent an important anti-inflammatory strategy. It is increasingly recognized that interactions between inflammation and the cytoskeleton play important roles in determining disease outcome. It will now be of great interest to further study the link between septins and inflammation, and pursue components of the cytoskeleton as novel molecular targets for inhibition of inflammation." }, { "role": "assistant", "content": "Shigella are human-adapted Escherichia coli and cause bacillary dysentery via inflammatory destruction of the gut epithelium . In this study , we use a zebrafish ( Danio rerio ) model of Shigella infection to discover new roles for the cytoskeleton in inflammation and infection control . Septins , a poorly understood component of the cytoskeleton , are important in numerous biological processes including cell division and host-pathogen interactions . Here , we show that zebrafish septins can restrict inflammation and Shigella infection in vivo . In the absence of septins , larvae infected with Shigella exhibit increased mortality and bacterial burdens associated with increased Caspase-1 activity and neutrophil death . Pharmacological suppression of Il-1β signaling rescues septin-deficiency in vivo by reducing neutrophil death and preventing larval mortality . These findings reveal a new link between septins and inflammation , and highlight the cytoskeleton as a structural determinant of host defence ." } ]
science.scientific_lay_summarisation_elife_single_doc_summ
science.scientific_lay_summarisation_elife_single_doc_summ.2561
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila}\nArticle:\nAbstract:\nMyofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function.\nIntroduction:\nInside cells, proteins are assembled into complex functional units. The correct assembly of these units is crucial for their function( Marsh and Teichmann, 2015). Myofibrils are highly organized assemblies of cytoskeletal proteins forming an array of sarcomeres that are embedded in the cytosol of myotubes and mediate contractility( Huxley and Niedergerke, 1954b; Huxley and Hanson, 1954a; Huxley, 2004; Lemke and Schnorrer, 2017). Sarcomeres are composed of actin-containing thin filaments and myosin-containing thick filaments arranged into antiparallel cables. Thin filaments are anchored to a large multiprotein complex called the Z-disc( Luther, 2009), and thick filaments are anchored to another large multiprotein complex called the M-line( Agarkova and Perriard, 2005). Anchoring of myofibrils to the exoskeleton provides the mechanical tension that aligns sarcomeres into myofibrils and coordinates their development( Weitkunat et al., 2017; Weitkunat et al., 2014). Once aligned, sarcomeres grow to their final size( Lemke and Schnorrer, 2017). Electron and confocal microscopy studies showed that sarcomeres form initially from small structures called Z-bodies that grow eventually into mature Z-discs to which thin filaments are anchored( Loison et al., 2018; Orfanos et al., 2015; Reedy and Beall, 1993; Shafiq, 1963; Sparrow and Schöck, 2009). The size of the Z-disc therefore sets the diameter of the myofibril( Agarkova and Perriard, 2005; Luther, 2009). While mechanisms have been proposed that set the length of sarcomeres( Fernandes and Schöck, 2014; Gokhin and Fowler, 2013; Tskhovrebova and Trinick, 2017), Z-disc growth and growth termination is poorly understood. A hallmark of genetically caused myopathies is the appearance of large aggregates composed mainly of Z-disc proteins( Kley et al., 2016; Maerkens et al., 2016). Interestingly, many myopathy-associated mutations encode Z-disc proteins. Mutations in any of the four α-actinin genes or in Zasp and other Alp/Enigma family genes in humans cause myopathies characterized by the presence of large aggregates( Murphy and Young, 2015; Selcen and Engel, 2005). The aggregation phenotype is conserved among animals: fruit flies with mutations in myopathy-related genes also develop Z-disc aggregates( González-Morales et al., 2017). α-Actinin and Z-disc Alternatively Spliced Protein( Zasp) are conserved proteins that coordinate Z-disc formation( Faulkner et al., 1999; Katzemich et al., 2013; Murphy and Young, 2015). α-Actinin forms a rod-shaped antiparallel homodimer at the Z-disc, where it crosslinks and serves as an attachment point for actin filaments( Djinović-Carugo et al., 1999; Luther, 2009; Murphy and Young, 2015; Ribeiro et al., 2014; Rusu et al., 2017; Takahashi and Hattori, 1989). Zasp and other members of the Alp/Enigma family of proteins are scaffolding proteins with an α-actinin-binding PDZ domain( InterPro: IPR001478), an uncharacterized Zasp Motif( ZM; InterPro: IPR031847 and IPR006643) domain, and one to four protein-protein interaction LIM domains( InterPro: IPR001781)( Finn et al., 2017; Klaavuniemi et al., 2004; Liao et al., 2016). Zasp and α-actinin proteins are present at the earliest stages of Z-disc formation, and are required for Z-disc assembly( Dabiri et al., 1997; Katzemich et al., 2013). Vertebrates have seven Alp/Enigma genes, each encoding several isoforms. The Drosophila genome has three Zasp genes, Zasp52, Zasp66, and Zasp67, which encode 21, 12, and 4 isoforms, respectively( Gramates et al., 2017). Zasp66 and Zasp67 are duplications of Zasp52 and resemble the smallest isoforms of Zasp52( González-Morales et al., 2019). The number of isoform variants and genes adds an additional layer of complexity and regulation to sarcomere formation. We used Drosophila indirect flight muscles and asked if the mechanism that controls Z-disc size relates to the pathological aggregation behavior known for Z-disc-related myopathies. We show that accumulation of multivalent Zasp growing isoforms( with multiple LIM domains) causes Z-disc growth, whereas upregulation of monovalent blocking isoforms at later developmental time points terminates Z-disc growth. An imbalance of growing and blocking Zasp isoforms results either in aggregate formation, enlarged Z-disc size or reduced Z-disc size. We propose that this mechanism has wide implications for diseases caused by aggregate formation.\nDiscussion:\nOur findings indicate that Z-disc formation and growth is driven by multivalent oligomerization of Zasp proteins with multiple LIM domains, and eventually terminated at the proper Z-disc size by the upregulation of blocking isoforms without LIM domains( see model in Figure 5A). The process of Z body and Z-disc formation is reminiscent of membraneless organelles with compositions distinct from the surrounding cytosol, which form through a mechanism of phase separation( e. g. Cajal bodies or P bodies)( Boeynaems et al., 2018; Weber, 2017). Both have sharp boundaries between themselves and the cytoplasm, they form and organize as discrete puncta in the cytosol, and multivalent protein domains are often involved in their formation( Li et al., 2012; Weber, 2017). Sarcomere size is stereotyped in a given muscle type but distinct among different muscles( Schönbauer et al., 2011). How can our model explain differences in sarcomere sizes? The sarcomere grows, while the Zasp growing isoforms dominate the Zasp isoform pool. Different sarcomere sizes can be achieved in two ways. First, the sarcomere growth period – the window of time in which Zasp growing isoforms dominate, might vary among muscle types. Second, the speed at which new Zasp molecules are recruited to the Z-disc, might be different among muscle types, while the growth period remains constant. Given the diversity of muscle types and therefore sarcomere sizes that exist, it is likely that a combination of these two strategies occur simultaneously. Finally, apart from the ZM-LIM mechanism described here, additional redundant mechanisms to control Z-disc growth might exist, as evidenced by the observation that Zasp52-PR overexpression makes big Z-discs and aggregates, while the mutant removing Zasp52 LIM domains reduces Z-disc size to a comparatively small degree. Redundant mechanisms might operate through other LIM domain proteins, or the coordination of Z-disc and M-line growth, all of which may provide important buffering functions to ensure proper myofibril size, which is crucial for fully functional muscles. The ZM domain is a conserved domain without a clearly defined function. On its own, the ZM domain from two mouse Zasp proteins localizes to the Z-disc( Klaavuniemi et al., 2004; Klaavuniemi and Ylänne, 2006). Our data suggest that Z-disc localization is a conserved feature of ZM domains from vertebrates to insects. ZM-containing proteins are tethered to the Z-disc by the physical interaction with the LIM domains of other Zasp proteins. In sum, the LIM domain serves as a recruitment signal for Zasp proteins and potentially other unidentified ZM-containing proteins to join the Z-disc. In addition, given the appearance of the ZM domain in bilateral animals with canonical Z-discs, we postulate that a conserved mechanism involving LIM-ZM binding underlies Z-disc growth and growth termination. In vertebrates, the Zasp proteins are very diverse and are better known as Alp/Enigma family: ZASP/Cypher/Oracle/LDB3/PDLIM6, ENH/PDLIM5, PDLIM7/ENIGMA/LMP-1, CLP36/PDLIM1/Elfin/hCLIM1, PDLIM2/Mystique/SLIM, ALP/PDLIM3, and RIL/PDLIM4. The ZM/DUF4749 motif occurs in ZASP, CLP36, PDLIM2, ALP and RIL( Cheng et al., 2010; D'Cruz et al., 2016; Faulkner et al., 1999; Vallenius et al., 2004; Zheng et al., 2010; Zhou et al., 2001). The LIM domain occurs in all Zasp proteins, either as one domain in Alp family members or as three domains in Enigma family members( Zheng et al., 2010). We identified two Zasp genes that encode only blocking isoforms in fruit flies: Zasp66 and Zasp67, and one gene, Zasp52, that encodes blocking and growing isoforms. Although Zasp66 and Zasp67 genes are insect-specific( González-Morales et al., 2019), vertebrate Alp/Enigma genes also express isoforms without LIM domains that could fulfill a blocking isoform function( Cheng et al., 2011; Zheng et al., 2010). In addition, because Zasp52-PK, which only contains one LIM domain, behaves as a blocking isoform, the Alp members with only one LIM domain might also behave as blocking isoforms. The function of the growing isoforms of Zasp requires multiple functional LIM domains. As the Enigma family members contain three C-terminal LIM domains, they are the ideal candidates to fulfill the growing role in vertebrates. Three Enigma proteins exist in vertebrates: PDLIM7/Enigma/LMP-1, ENH/PDLIM5 and ZASP/Cypher/Oracle/LDB3/PDLIM6. Functional redundancy between them at the Z-disc is likely common and demonstrated in one case( Mu et al., 2015). In Cypher knockout mice sarcomere assembly occurs normally during development, followed by immediate sarcomere failure after postnatal onset of contractility( Zhou et al., 2001). ENH mutants exhibit cardiac dilation and abnormal Z-disc structure in the heart( Cheng et al., 2010). Intriguingly, in both Cypher and ENH single mutants, as well as Cypher ENH double mutants, sarcomeres look considerably smaller in diameter in electron microscopy images( Cheng et al., 2010; Mu et al., 2015; Zhou et al., 2001). Thus, a similar role for Enigma proteins in setting sarcomere diameter in vertebrates appears likely. Is the mechanism that controls Z-disc size related to the protein aggregation defects in human myopathies? Our Z-disc oligomerization hypothesis agrees well with the observation that many myopathies present aggregates, and several human ZASP mutations have been linked to aggregate-forming myopathies( Murphy and Young, 2015; Selcen and Engel, 2005). Many ZASP mutations linked to disease lie within the ZM domain or one of the LIM domains( Selcen and Engel, 2005; Theis et al., 2006; Vatta et al., 2003). Protein aggregation in myopathy patients might be a consequence of an imbalance in the mechanism that controls sarcomere size, favoring the growing over the blocking isoforms. If this were the case, our data points to a potential therapeutic avenue: blocking the growing isoforms with short peptides containing a ZM domain. In conclusion, we propose that a conserved mechanism involving LIM-ZM binding underlies Z-disc growth and therefore myofibril diameter." }, { "role": "assistant", "content": "Muscles are made up of many long muscle fibers , each containing thousands of cylindrical segments called sarcomeres . When animals move , proteins in the sarcomere move past each other , shortening the muscles . Inside each muscle , all sarcomeres have the same length and diameter . The protein titin controls the length of each sarcomere , but it was unknown what controls the diameter . At the end of each sarcomere is a structure called the Z-disc that is composed of many muscle proteins . Mutations in Z-disc proteins are often involved in diseases called myopathies , where muscle structure breaks down . As the size of the Z-disc determines sarcomere diameter , improper regulation of sarcomere diameter could contribute to myopathies . One Z-disc protein called Zasp is a candidate for controlling diameter and can have many different forms in the same cells . Zasp has a similar role in most animals including humans , mice and flies . González-Morales et al . investigated Zasp in the muscles of the fruit fly , Drosophila melanogaster . Gene editing was used to vary the amounts of different forms of Zasp inside the muscles . The results revealed two types of Zasp , those that make sarcomeres wider , and those that limit growth . Reducing the second type of Zasp resulted in bigger Z-discs and in muscle aggregates similar to the ones seen in patients with certain myopathies . This study reveals a mechanism for coordinating the development of muscle . It also reveals the likely cause of certain myopathies and suggests a possible target for future treatment through regulation of Zasp proteins ." } ]
science.scicite_classification
science.scicite_classification.2425
[ { "role": "user", "content": "You will be presented with a citation segment from the section of a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nDTI derived diffusion parameters, such as fractional anisotropy (FA), have been widely used to assess white matter microstructure [16, 17, 25], and has previously been used to detect traumatic brain injury in athletes [6, 10, 18, 49], and military personal following blast-related brain injury [29]." }, { "role": "assistant", "content": "Background" } ]
science.drug_combo_extraction_re
science.drug_combo_extraction_re.658
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Successful treatment of an elderly Langerhans cell sarcoma patient by EPOCH ( etoposide , prednisone , vincristine , cyclophosphamide , and doxorubicin ) chemotherapy . \n\nsentence: Successful treatment of an elderly Langerhans cell sarcoma patient by EPOCH ( etoposide , prednisone , vincristine , cyclophosphamide , and doxorubicin ) chemotherapy ." }, { "role": "assistant", "content": "[[\"etoposide\", \"prednisone\", \"vincristine\", \"cyclophosphamide\", \"doxorubicin\", \"POS\"]]" } ]
science.data_reco_mcq_mc
science.data_reco_mcq_mc.1618
[ { "role": "user", "content": "You are provided with a research question, keyphrases about the question, a description of candidate datasets and dataset options. Read the description of popular datasets provided below and select the ones that can be used to validate the following research question. Use your knowledge of machine learning datasets to make the best judgement.\nYour response should be formatted as a `json` array. For instance, for the query \"Semi supervised image classification\", a sample response might be: [\"CIFAR-10\", \"CIFAR-100\"]. Do not include any extra text in the response other than the answer array.\n\nQuery: I want to train a supervised model for knowledge base completion.\n\nKeyphrases: knowledge base completion\n\nDataset description:\nWN18: The WN18 dataset has 18 relations scraped from WordNet for roughly 41,000 synsets, resulting in 141,442 triplets. It was found out that a large number of the test triplets can be found in the training set with another relation or the inverse relation.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nWord Sense Disambiguation: a Unified Evaluation Framework and Empirical Comparison: The Evaluation framework of Raganato et al. 2017 includes two training sets (SemCor-Miller et al., 1993- and OMSTI-Taghipour and Ng, 2015-) and five test sets from the Senseval/SemEval series (Edmonds and Cotton, 2001; Snyder and Palmer, 2004; Pradhan et al., 2007; Navigli et al., 2013; Moro and Navigli, 2015), standardized to the same format and sense inventory (i.e.\nFB15k: The FB15k dataset contains knowledge base relation triples and textual mentions of Freebase entity pairs. It has a total of 592,213 triplets with 14,951 entities and 1,345 relationships.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nLAMA: LAnguage Model Analysis (LAMA) consists of a set of knowledge sources, each comprised of a set of facts. LAMA is a probe for analyzing the factual and commonsense knowledge contained in pretrained language models.\n\nOptions:- A: WN18 B: SNIPS C: Word Sense Disambiguation: a Unified Evaluation Framework and Empirical Comparison D: FB15k E: ConvAI2 F: LAMA" }, { "role": "assistant", "content": "[\"WN18\", \"FB15k\"]" } ]
science.scientific_papers_summarization_single_doc_arxiv
science.scientific_papers_summarization_single_doc_arxiv.117169
[ { "role": "user", "content": "You will be presented with the full text of a science research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nhere , we shall consider mainly the three well - known groups of chemically peculiar stars on the main - sequence of the hr diagram : fmam , hgmn ( non - magnetic ap or weak magnetic field ) , and magnetic ap stars .\nthey show clearly abundance anomalies of metals with respect to solar abundances .\nthese anomalies extend from factors of about 2 to 10 ( in am stars ) and up to some 10@xmath0 ( in ap stars ) .\nmany abundance determinations have been done for a large number of ap and bp stars , covering a large sample of effective temperatures , for a large number of heavy elements .\none of the most striking aspects of the observational results is the rather wide scatter of abundances determined in these stars for a given element ( see for instance takada - hidai 1990 ) .\nthis scatter is partly due to errors in the abundance determinations and to inaccuracies in the effective temperatures determinations , but not only . despite this scatter ,\na clear correlation with respect to the effective temperature is well established for some elements like mn ( see for instance smith and dworetsky , 1993 ) .\nit is generally accepted that diffusion processes of elements provide the best explanation for cp stars anomalies .\nof course , microscopic diffusion interacts with other processes in stars , such as large scale motions ( convection , turbulence , wind ) and it can not be considered alone : the anomalies are the result of a complex stratification process involving all these motions .\nthe diffusion model was first proposed by g. michaud ( 1970 ) , it is based on two basic findings : on the one hand , the abundance anomalies are related to atmospheric parameters like effective temperature and gravity , on another hand , there is a clear correlation between the superficial abundance anomalies and the radiative accelerations ( one of the main terms involved in the diffusion velocity ) in stellar external layers .\nthe radiative accelerations are different according to the elements and they depend on atmospheric parameters .\nthe anomalies which are found on main - sequence stars are not found among evolved stars , and this suggests that they are confined mostly to external layers .\nmoreover , in the hr diagram , the cp stars are located where the stars outer convection zone is supposed to be the smallest .\nall of these arguments ( with some others which are not discussed here ) give a consistent outline for the diffusion model : when the stars evolve , the external layers are mixed with deeper ones and the abundance stratifications are lost . in the diffusion model , the common property of the cp s is the weakness of the superficial helium abundance ( due to helium gravitational settling ) .\nthis helium underabundance is supposed to lead to the decrease ( am stars ) or the disappearance ( hgmn and magnetic ap stars ) of the superficial convection zone .\nthen , diffusion can occur in layers where stratification time scales are much shorter than in normal stars .\ndiffusion is basically a time - dependent process . to determine what abundances\ncan be observed at the stellar surface one needs to compute the stratification process which requires solving of the following continuity equation ( valid for test particles only , not for helium ) : @xmath1 where @xmath2 is the number density of the considered element ( and @xmath3 for ions ) , @xmath4 is a bulk velocity ( stellar wind for instance ) and @xmath5 is the velocity of ions with respect to protons .\nthe continuity equation must be solved numerically because it is strongly non - linear with respect to @xmath2 ( see the study by alecian and grappin , 1984 , alecian , 1986 ) .\nthe diffusion velocity @xmath6 depends on @xmath3 through the radiative acceleration @xmath7 .\nthis equation is difficult to solve even in the stellar interior ( optically thick , in this case the radiative acceleration is easier to compute ) partly because the diffusion time scale at the bottom ( downward boundary ) is very different from the one at the top . on another hand , for am stars , the characteristic time of the stratification process in deep layers ( below the outer convection zones ) is often of the same order of magnitude than the time needed to the star s structure to evolve significantly and then , a detailed computation should take into account the changes of the internal structure . for am stars , alecian ( 1996 )\nhas solved numerically the continuity equation in the following form ( the non - linearities are kept ) : @xmath8 \\nabla\nc\\;-\\left\\langle d\\right\\rangle \\nabla ^{2}c\\;+\\;\\frac{1}{n_{p}}\\nabla \\left ( n_{p}\\sum\\nolimits_{i}c_{i}v_{ip}\\right ) = 0\\ ] ] c is the element concentration , @xmath9 is the diffusion velocity of ions due to radiative acceleration and gravity .\nhe has used an approximate formula for the radiative acceleration which is mainly valid for test particles . on another hand\n, he has neglected the effects of star s evolution on the main sequence and the feedback of element stratification on the stellar model .\nhe has applied his method on calcium diffusion in am stars ( fig .\nthese computations have shown that , according to some values of the mass - loss rate and thickness of the superficial mixing zone , ca could be overabundant in early phases of stratification ( see the comparison with observations by hui bon hoa , this meeting ) . another kind of method has recently been developed by seaton ( 1997 ) .\nhe has proposed a semi - numerical method based on a linearization of the continuity equation assuming @xmath10 .\nhis method has the advantage to use very accurate radiative acceleration computations but the drawback is that his method can not be generalized to any element and to any star .\nthe group of montreal ( michaud and collaborators , turcotte et al , 1998 ) has undertaken a very impressive task of computing the stratification process in a fully consistent way .\nthe aim is to model the star , its evolution and structure , with detailed opacities ( using opal tables ) .\nthe radiative acceleration is computed in details for many elements and at each time step , taking into account the changes of the detailed opacities due to abundance stratification of all these elements at a time .\nthe continuity equation is solved numerically . presently , as in the previous method , @xmath10 , but this time on numerical grounds .\nthis approach is certainly the most promising one , even if it is very heavy to carry out . in the optically thin case ( for ap stars ) , the situation is much more problematic because radiation transfer , which can no more be solved locally , make the calculations too huge to be carried out ( at the moment ) : the continuity equation is coupled to the equation of the radiation transfer .\nsome attempts have been done in the past to solve these coupled equations , but they were rather inaccurate ( alecian and vauclair 1981 , for silicon in ap stars ) .\nfortunately , interesting results can be obtained without the need to solve the continuity equation .\nthis is the case , for example , for manganese by alecian and michaud ( 1981 ) : the diffusion model allows them to predict the maximum overabundance that can be observed in hgmn stars versus the effective temperature .\nthis prediction is based on a quasi `` zero order '' approximation ( see below ) , and has been confirmed by the observations of smith and dwortesky ( 1993 ) .\ngenerally , the stratification in ap stars atmospheres is studied with some strong approximations .\nfor instance , the `` zero order '' approximation consists in solving @xmath11 which supposes that the final concentration throughout the medium , is such that the diffusion velocity is zero everywhere ( for instance , alecian and artru 1988 , for gallium ) .\na better approximation is to look for a steady state solution @xmath12 ( babel , 1992 ) .\none problem is that one can not be sure that @xmath13 and @xmath14 are solutions of the continuity equation coupled with the transfert equation .\nanother problem is to know what happens at the upper boundary ( babel , 1992 ) , above the photosphere .\nfor instance , are the elements free to leave the atmosphere ( role of magnetic field , turbulence , etc . ) ? despite these difficulties , we may try to have some guesses about the behavior of element stratifications in stellar photosphere ( see also alecian and grappin , 1984 ) . in fig 2 , we present a mental picture of what kind of stratification process could occur in the photosphere of an ap star .\neach window shows the same section of the photosphere at four successive stages ( t1 to t4 ) .\nthe upper part of the atmosphere is denoted by @xmath15=0 ( optical depth ) , the bottom ( @xmath15=1 ) is the point where the medium becomes optically thick .\nlet us consider an element a ( different from hydrogen and helium ) and assume that its atomic properties are well fitted to this mental experiment . at time\nt1 , concentration of a is assumed homogeneous throughout the atmosphere ( the decrease of the gray level represents the decrease of mass density assuming hydrostatic equilibrium ) . at time t2 , diffusion of a leads to form a cloud in the upper atmosphere ( remember that diffusion time - scale is shorter when proton density is smaller , then this cloud should appear first ) .\nthis cloud is mainly supported by the photons coming from @xmath15=1 .\nnow , if another cloud of element a forms ( at time t3 ) below the first one , this second cloud may act as a shield for photons supporting the upper cloud . then , the upper cloud is no more supported and falls .\nthis scenario shows how stratifications built up by diffusion could be unstable in ap stars atmospheres .\nthe time scale of such an instability phenomenon should be of the order of the diffusion time - scales in stellar atmospheres , i.e. around 10 to 10@xmath16 years .\nno hydrodynamics is involved in this scenario .\nif this scenario was confirmed by further theoretical studies ( they are presently in progress ) , it may contribute in explaining the scatter observed in ap stars abundances .\nwe have shown that , at the moment , several works have been done to study the time - dependent diffusion in stellar envelopes .\nsome of them are rather accurate but neglect hydrodynamics and are very heavy to carry out .\nanother one is less accurate , but takes stellar mass - loss into account , and this is more realistic .\nself - consistent modelling , which will determine the evolution on the main - sequence of an am star ( including all known processes ) , is within the scope of the next few years . however , the studies on the stratification processes in ap stars atmospheres are still embryonic . in the long run , the goal would be to perform a fully self - consistent modelling ( including hydrodynamics ) of the envelope together with the atmosphere .\nthis seems to be the only way to answer all the questions raised by observations .\nalecian , g. : 1986 , _ astron .\n_ , 168 , 204 alecian , g. : 1996 , _ astron .\n_ , 310 , 872 alecian , g. , artru , m.c . : 1988 , _ the impact of very high spectroscopy on stellar physics , iau symposium n@xmath17132 _ , ed .\ng.cayrel de strobel and monique spite , 235 alecian , g. , grappin , r. : 1984 , _ astron .\n_ , 140 , 159 alecian , g. , michaud , g. : 1981 , _ astrophys . j. _ , 245 , 226 alecian , g. , vauclair , s. : 1981 , _ astron .\n_ , 101 , 16 babel , j. : 1992 , _ astron .\nastrophys . _ , 258 , 449 michaud , g. : 1970 , _ astrophys . j. _ , 160 , 641 richer , j. , michaud , g. : 1993 , _ astrophys .\n, 416 , 312 seaton , m.j . : 1997 , mon . not .\nr. astron .\nsoc . , 289 , 700 smith k.c . , dworetsky m.m .\n: 1993 , _ astron .\n_ , 274 , 335 takada - hidai , m. : 1990 , _ evolution of stars , the photospheric abundance connection _ , iau symposium n@xmath17145 , golden sands , bulgaria .\nturcotte , s. , richer , j. , michaud g. : 1998 , _ astrophys .\nj. _ , in press" }, { "role": "assistant", "content": "each time diffusion of elements is invoked in explaining abundance anomalies in a star , this supposes implicitly that a stratification process is in progress somewhere in that star . \n this means also , that the element abundances can still be evolving according to the star s age and fundamental parameters . \n moreover , it has been shown that the superficial abundances may have complex temporal behavior . \n this should be detectable through new observations . in some cases \n , it may be already apparent in available data . \n the building up of the elements stratification is a very difficult process to study . \n this is due to the existence of strong non - linearities in the time - dependent equations , which must be solved numerically . \n we will discuss some works that tackle this problem for ap and am stars , and we will present some results concerning mostly am stars . \n future desirable improvements in these studies will be considered ." } ]
science.scicite_classification
science.scicite_classification.6827
[ { "role": "user", "content": "You will be presented with a citation segment from the section of a research paper. Classify the intent behind this citation by choosing from one of the following categories:\n\n- Method: Cites the paper for its methodology or procedure.\n- Background: Cites the paper to provide background information.\n- Result: Cites the paper for its findings or results.\n\nYour answer should be a single word from the following list of options: [\"Method\", \"Background\", \"Result\"]. Do not include any other text in your response.\n\nCitation sentence:\n\nTo determine this canonical set of values, the parameters from the mathematical model of the leech HN neurons were used as a starting point because the silicon neurons were based on this mathematical model [54]." }, { "role": "assistant", "content": "Method" } ]
science.covid_deepset_qa
science.covid_deepset_qa.1369
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your repsonse other than the answer.\n\nParagraph: Patients often present to a hospital with pneumonia, or worse, and secondary bacterial infections have been reported [37, 41] . Disease can progress to acute respiratory distress syndrome and multiorgan system failure [37] . MERS has reportedly killed approximately 35 % of all reported cases, 42 % of cases in the KSA, yet only 19 % of cases in South Korea, where mortality ranged from 7 % among younger age groups to 40 % among those aged 60 years and above [42] ; all may be inflated values with asymptomatic or mild infections sometimes not sought or not reported [34] . General supportive care is key to managing severe cases [43] . Children under the age of 14 years are rarely reported to be positive for MERS-CoV, comprising only 1.1 % (n = 16) of total reported cases. Between 1 st September 2012 and 2 nd December 2013, a study described the then tally of paediatric cases in the KSA, which stood at 11 (two to 16 years of age; median 13 years); nine were asymptomatic (72 %) and one infant died [44] . In Amman, Jordan, 1,005 samples from hospitalized children under the age of two years with fever and/or respiratory signs and symptoms were tested but none were positive for MERS-CoV RNA, despite being collected at a similar time to the first known outbreak of MERS-CoV in the neighbouring town of Al-Zarqa [45] . A second trimester stillbirth occurred in a pregnant woman during an acute respiratory illness and while not RT-rtPCR positive, the mother did subsequently develop antibodies to MERS-CoV, suggestive of recent infection [46] . Her exposure history to a MERS-CoV RT-rtPCR positive relative and an antibody-reactive husband, her incubation period and her symptom history met the WHO criteria for being a probable MERS-CoV case [46] . Diagnostic methods were published within days of the ProMED email announcing the first MERS case [47] , including several now gold standard in-house RT-rtPCR assays (Fig. 2 ) as well as virus culture in Vero and LLC-MK2 cells [18, 47, 48] . A colorectal adenocarcinoma (Caco-2) epithelial cell line has since been recommended for isolation of infections MERS-CoV [49] . We previously [18] . ). Open reading frames are indicated as yellow rectangles bracketed by terminal untranslated regions (UTR; grey rectangles). FS-frame-shift. Predicted regions encompassing recombination break-points are indicated by orange pills. Created using Geneious v8.1 [211] and annotated using Adobe Illustrator. Beneath this is a schematic depicting the location of RT-PCR primers (blue arrows indicate direction) and oligoprobes (green rectangles) used in the earliest RT-rtPCR screening assays and conventional, semi-nested (three primers) RT-PCR confirmatory sequencing assays [47, 48] . Publication order is noted by first [27 th September 2012; red] and second [6 th December 2012; orange] coloured rectangles; both from Corman et al. [47, 48] Those assays recommended by the WHO are highlighted underneath by yellow dots [53] . The NSeq reverse primer has consistently contained one sequence mismatch with some MERS-CoV variants. An altered version of that from Mackay IM, Arden KE. Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd. Virus Res 2015 Vol 202:60-88 with permission from Elsevier [5] reviewed the broad tropism of MERS-CoV [5] . However, as is well described, cell culture is a slow, specialised and insensitive method [50] while PCR-based techniques are the preferred method for MERS-CoV detection. The first open reading frames (ORF 1a and 1b; Fig. 2 ) have become a key diagnostic and taxonomic target for CoV species identification. With less than 80 % identity between the amino acid sequence of MERS ORF 1ab and betacoronavirus relatives, Tylonycteris bat HKU4 and Pipistrellus bat HKU5, it can be concluded that it is a novel and distinct virus. MERS-CoV is predicted to encode ten open reading frames with 5' and 3' untranslated regions [51] . The structural proteins include the spike (S), envelope (E), membrane (M) and nucleocapsid (N) [52] . The products of ORF1a and ORF1b are predicted to encode nonstructural proteins. The majority of specimen testing to date has employed validated RT-rtPCR assays shown to be sensitive and specific [47, 48, 53] . The RealStar® kit uses these WHOrecommended assays [54] . The target sequences of these screening assays have not changed among genomes examined until at least mid-2015 (IMM observation). Other RT-rtPCR assays have been developed and validated for use as laboratory-based diagnostic tools [55] [56] [57] . Additionally, loop-mediated [58, 59] or recombinase polymerase [60] isothermal assays have been designed for field deployment. The detection of MERS-CoV antigen has not been common to date but the combination of short turnaround time from test to result, high throughput and identification of viral proteins makes this an attractive option. Detection of viral proteins rather than viral RNA indicates the likely presence of infectious virus. The first rapid immunochromatographic tool described could detect recombinant MERS-CoV nucleocapsid protein from DC nasal swabs with 94 % sensitivity and 100 % specificity compared to RT-rtPCR [61] . A different approach used a monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein with a sensitivity of 10 3 TCID 50 and specificity [62] . Demonstration of a seroconversion to a MERS-CoV infection meets the current WHO definition of a case so optimized and thoroughly validated sero-assays employed alongside good clinical histories are useful to both identify prior MERS-CoV infection and help support transmission studies. Because serology testing is, by its nature, retrospective, it is usual to detect a viral footprint, in the form of antibodies, in the absence of any signs or symptoms of disease and often in the absence of any viral RNA [63] . Strategic, widespread sero-surveys of humans using samples collected after 2012 are infrequent. Much of the Arabian Peninsula and all of the Horn of Africa lack baseline data describing the proportion of the community who may have been infected by a MERS-CoV. However, sero-surveys have had widespread use in elucidating the role of DCs as a transmission source for MERS-CoV. Because of the identity shared between DC and human MERS-CoV (see Molecular epidemiology: using genomes to understand outbreaks), serological assays for DC sero-surveys should be transferrable to human screening with minimal re-configuration. Also, no diagnostically relevant variation in neutralization activity have been found from among a range of circulating tested MERS-CoV isolates and sera, so whole virus or specific protein-based sero-assays should perform equivalently in detecting serological responses to the single MERS-CoV serotype [49] . The development of robust serological assays requires reliable panels of wellcharacterized animal or human sera, including those positive for antibodies specific to MERS-CoV, as well as to likely sources of cross-reaction [64] . Obtaining these materials was problematic and slowed the development and commercialization of antibody detection assays for human testing [64] . A number of commercial ELISA kits, immunofluorescent assays (IFA) kits, recombinant proteins and monoclonal antibodies have been released [31, [65] [66] [67] [68] . Initially, conventional IFAs were used for human sero-surveys. These relied on MERS-CoV-infected cell culture as an antigen source, detecting the presence of human anti-MERS-CoV IgG, IgM or neutralizing antibodies in human samples [18, 48, 69] . No sign of MERS-CoV antibodies was found among 2,400 sera from patients visiting Hospital in Jeddah, from 2010 through 2012, prior to the description of MERS-CoV [18] . Nor did IFA methods detect any sign of prior MERS-CoV infection among a small sample of 130 healthy blood donors from another Hospital in Jeddah (collected between Jan and Dec 2012) [70] . Of 226 slaughterhouse workers, only eight (3.5 %) were positive by IFA, and those sera could not be confirmed by virus neutralization (NT) test. The study indicated that HCoV-HKU1 was a likely source of crossreactive antigen in the whole virus IFA [70] . Whole virus MERS-CoV IFA also suffered from some cross-reactivity with convalescent SARS patient sera and this could not be resolved by an NT test which was also cross-reactive [71] . IFA using recombinant proteins instead of whole-virus IFA, has been shown to be a more specific tool [31] . Since asymptomatic zoonoses have been posited [72] , an absence of antibodies to MERS-CoV among some humans who have regular and close contact with camels may reflect the rarity of actively infected animals at butcheries, a limited transmission risk associated with slaughtering DCs [70] , a pre-existing cross-protective immune status or some other factor(s) resulting in a low risk of disease and concurrent seroconversion developing after exposure in this group. IFA using recombinant proteins instead. Some sero-assays have bypassed the risks of working with infectious virus by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins [48, 73] , or using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase [74, 75] . A pseudo particle neutralization (ppNT) assay has seen widespread used in animal studies and was at least as sensitive as the traditional microneutralization (MNT) test. [10, 74, [76] [77] [78] ] Studies using small sample numbers and ppNT found no evidence of MERS-CoV neutralizing antibody in sera from 158 children with LRT infections between May 2010 and May 2011, 110 sera from 19 to 52 year old male blood donors and 300 selfidentified animal workers from the Jazan Region of the KSA during 2012 [79, 80] . Similarly, a study of four herdsmen in contact with an infected DC herd in Al-Ahsa, eight people who had intermittent contact with the herd, 30 veterinary surgeons and support staff who were not exposed to the herd, three unprotected abattoir workers in Al-Ahsa and 146 controls who were not exposed to DCs in any professional role, found none with serological evidence of past MERS-CoV infection using the ppNT assay [10] . A delay in the neutralizing antibody response to MERS-CoV infection was associated with increased disease severity in South Korea cases with most responses detectable by week three of illness while others, even though disease was severe, did not respond for four or more weeks [81] . The implications for our ability to detect any response in mild or asymptomatic cases was not explored but may be a signifcant factor in understanding exposure in the wider community. A Jordanian outbreak of acute LRT disease in a hospital in 2012 was retrospectively found to be associated with MERS-CoV infection, initially using RT-rtPCR, but subsequently, and on a larger scale, through positivity by ELISA and IFA or MNT test. [46, 82, 83] This outbreak predated the first case of MERS in the KSA. The ELISA used a recombinant nucleocapsid protein from the group 2 betacoronavirus bat-CoV HKU5 to identify antibodies against the equivalent crossreactive MERS-CoV protein [71] . It was validated using 545 sera collected from people with prior HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63, HRV, HMPV or influenza A(H1N1) infections but was reportedly less specific than the recombinant IFA discussed above. It was still considered an applicable tool for screening large sample numbers [82] . A protein microarray expressing the S1 protein subunit has also been validated and widely used for DC testing [5, 84] . Detection of MERS-CoV infection using ELISA or S1 subunit protein microarray [84] is usually followed by confirmatory IFA and/ or a plaque-reduction neutralization (PRNT) [69, 70, 85] or MNT test. [74, 85, 86] This confirmatory process aims toensure the antibodies detected are able to specifically neutralize the intended virus and are not more broadly reactive to other coronaviruses found in DCs (bovine CoV, BCoV) or humans (HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, SARS-CoV). In the largest study of human sera, a tiered diagnostic process assigned both recombinant IFA and recombinant ELISA positive sera to 'stage 1' seropositivity. A stage 2 seropositive result additionally required a suitably titred PRNT result [87] . The study found 15 sera collected in 2012 to 2013 from 10,009 (0.2 %) people in 13 KSA provinces contained MERS-CoV antibodies, but significantly higher proportions in occurred in camel shepherds (two of 87; 2.3 %) and slaughterhouse workers (five of 140; 3.6 %) [87] . Contemporary surveys are needed. MERS-CoV does not appear to be easily transmitted from DCs to humans, or perhaps it is [72] , but generally does not trigger a detectable immune response if only mild disease or asymptomatic infection results. Serology assays are in need of further validation in this area so care is required when moving newly developed diagnostic serology algorithms from a research setting to one that informs public health decisions. This was reinforced when a false positive US case, purported to have been infected after a handshake and two face-to-face meetings, did not withstand further confirmatory analysis using a more specific, NT assay and was subsequently retracted [88, 89] . The WHO recommends sampling from the LRT for MERS-CoV RT-rtPCR testing, especially when sample collection is delayed by a week or more after onset of symptoms.\n\nQuestion: What is the specificity with which immunochromatographic tool could detect recombinant MERS-CoV nucleocapsid protein?" }, { "role": "assistant", "content": "100 %" } ]
science.scientific_lay_summarisation_plos_single_doc_summ
science.scientific_lay_summarisation_plos_single_doc_summ.17135
[ { "role": "user", "content": "You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.\n\nTitle: Chromulinavorax destructans, a pathogen of microzooplankton that provides a window into the enigmatic candidate phylum Dependentiae}\nArticle:\nAbstract:\nMembers of the major candidate phylum Dependentiae( a. k. a. TM6) are widespread across diverse environments from showerheads to peat bogs; yet, with the exception of two isolates infecting amoebae, they are only known from metagenomic data. The limited knowledge of their biology indicates that they have a long evolutionary history of parasitism. Here, we present Chromulinavorax destructans( Strain SeV1) the first isolate of this phylum to infect a representative from a widespread and ecologically significant group of heterotrophic flagellates, the microzooplankter Spumella elongata( Strain CCAP 955/1). Chromulinavorax destructans has a reduced 1. 2 Mb genome that is so specialized for infection that it shows no evidence of complete metabolic pathways, but encodes an extensive transporter system for importing nutrients and energy in the form of ATP from the host. Its replication causes extensive reorganization and expansion of the mitochondrion, effectively surrounding the pathogen, consistent with its dependency on the host for energy. Nearly half( 44%) of the inferred proteins contain signal sequences for secretion, including many without recognizable similarity to proteins of known function, as well as 98 copies of proteins with an ankyrin-repeat domain; ankyrin-repeats are known effectors of host modulation, suggesting the presence of an extensive host-manipulation apparatus. These observations help to cement members of this phylum as widespread and diverse parasites infecting a broad range of eukaryotic microbes.\nIntroduction:\nThe candidate phylum Dependentiae( also known as TM6) is a phylogenetic group of bacteria that is only known from metagenomic data and from two isolates that infect free-living amoebae. Although relatively little is known about members of the Dependentiae, analysis of environmental 16S-ribosomal RNA sequences and metagenomic data indicate that they are widespread across diverse environments including peat bogs[1], hospital biofilms, soil, and waste water[2, 3]. Moreover, analysis of these data imply that bacteria in this phylum have very limited metabolic capability, but encode an extensive system of transporters, including ATP transporters, as well as genes functions enriched in bacterial endosymbionts such as Chlamydia, Wolbachia, and Rickettsia, suggesting that bacteria in the Dependentiae are symbionts or parasites that rely extensively on eukaryotic hosts for energy and metabolites[2, 3]. The only two previously isolated representatives of the Dependentiae were from amoebae, which are competent hosts to a vast array of bacterial, eukaryotic, and viral symbionts and pathogens[4, 5]. The first isolate, Babela massiliensis, is an obligate pathogen that causes lysis of Acanthamoeba castellanii, while Vermiphilus pyriformis maintains a stable relationship with its host, Vermamoeba vermiformis, indicating that life-history strategies differ among bacteria in the Dependentiae[4, 5]. Both isolates show unusual replication strategies within their hosts that delay cell fission and initially produce large replication bodies before dividing into progeny cells. Since the genome of Babela massiliensis is the only complete genome available for the members of the Dependentiae, a detailed comparison of the genomic complement involved in the different lifestyles is not possible; yet, several almost-complete metagenomically assembled genomes( MAGs) for other members of the phylum suggest that they are distinct from those infecting amoebae[6–8]. Nanoflagellate zooplankton, defined as being between 2 and 20 μm in size are major predators in aquatic systems, preying on bacteria, viruses, and other microbial eukaryotes[9, 10]. They are major engines of microbial mortality that link microbial biomass to higher trophic levels, and fuel biogeochemical cycling[11]. Within this broad functional group are many chrysophytes, a diverse group of nanoflagellates within the stramenopiles that includes phototrophs, mixotrophs and heterotrophs. A particularly widespread and abundant heterotrophic members of this group are members of the genus Spumella[12, 13]. These slightly elongated heterokont flagellates can also form amoeboid cells, occur in fresh and salt waters, and are readily isolated from many environments[14]. Little is known about the agents of mortality affecting members from this ubiquitous and ecologically important genus. Here we present details on a representative isolate from the candidate phylum Dependentiae, Chromulinavorax destructans, which infects and lyses Spumella elongata. Its unusual replication cycle superficially resembles the infection cycle of a virus, and includes the creation of a replication ‘factory’ and the remodelling of the host mitochondrion. The genome is highly reduced and lacks nearly all genes related to energy metabolism, it encodes a large suite of transporters, including ATP transporters that illustrates its dependency on the host. Overall, C. destructans provides a link between molecular survey data and biological observations, and expands the known functional diversity and ecological roles of TM6 bacteria.\nDiscussion:\nChromulinavorax destructans is an intracellular pathogen of S. elongata that appears to be dependent on its host for replication, to the extent that it does not appear to encode any complete metabolic pathways( Fig 5, S4 Fig). Many putative effector molecules, such as proteases, nucleases and ankyrin–repeat domain proteins, that could manipulate and break down host structures contain signal peptides and appear to be secreted from the bacteria( Fig 3). Similarly, putative outer membrane vesicles that could also contain such effector molecules bud during the early stages of infection and might serve a similar function( S1E and S1F Fig). The reorganization and breakdown of host structures provide resources, possibly due to the aforementioned effector molecules, that can be imported into the C. destructans replication bodies( Fig 5). With no evidence of lipid biosynthesis, in combination with the observed host membrane disarray during late infection, suggests that host lipids are used for the bacterial cell membrane. Remodeling of the host mitochondrion is one of the most unusual features of the replication process. The expansion of the mitochondrion while maintaining membrane integrity contrasts with observations from other mitochondrion-invading pathogens and symbionts that actively disrupt the mitochondrial integrity[23, 24]. The proximity of bacterial replication to the expanded mitochondrion would allow for a steady supply of ATP mediated by the encoded ADP/ATP antiporter, but it would also require free radicals to be neutralized, a function likely performed by the bacterial encoded superoxide dismutase, also found in other members of the Dependentiae[2, 3, 5]. This high host-dependence suggests the pathogen is inactive until taken up by a host cell, which may also be the reason that the cells remained infectious after four years at 4°C in the absence of host cells. Complete host dependence and extracellular inactivity are life-cycle characteristics that highlight traits of convergent evolution found in many obligate pathogens. For example, Microsporidia completely lack energy generation pathways, while ATP transporters are widespread[25–27]. The similarity in life style and genome content, such as dedicating more than then percent of their genome to ankyrin-repeat domain proteins, between Dependentiae and giant viruses provides an intriguing example of convergent evolutionary trajectories of obligate pathogens from vastly different evolutionary backgrounds[5, 16]. A rudimentary cell-division machinery and the lack of many hallmark genes( e. g. ftsN, zapB, and zipA) has been highlighted for members of the Dependentiae based on MAGs[2, 3]. Similarly, Babela massiliensis showed delayed cell division after initial growth in amorphous bodies( i. e. replication bodies), and, while not directly described, Vermiphilus pyriformis likely uses a similar replication strategy[4, 5]. Although the replication of C. destructans in replication bodies resembles B. massiliensis, the close association and modulation of the mitochondrion was unique to C. destructans, possibly partially mediated by the mitofilin-like protein encoded exclusively by C. destructans among the Dependentiae. In part, this difference might reflect the availability of cytoplasmic resources, such as metabolites and ATP, that presumably are scarcer in the flagellate cell compared to the much larger amoebae that are hosts to the two previously described isolates; Accordingly, C. destructans causes severe deformation of the cellular architecture of the nanoflagellate that was not seen in amoebae hosts( Figs 1 and 2, S1 Fig). The scarcity of cytoplasmic ATP could lead to the close association of C. destructans with the host mitochondrion and initiate the mitochondrion’s expansion and rearrangement. A limitation of energy could have led to the incomplete replication bodies that were frequently found inside ghost cells, suggesting that ATP availability might restrain C. destructans replication. The differences between amoeba-infecting and nanoflagellate-infecting Dependentiae resemble observations made for giant viruses infecting different hosts. Giant viruses infecting nanoflagellates show highly spatially oriented replication and preserve the mitochondrion; whereas, amoeba-infecting viruses seem to be unrestricted by the host-cell architecture[16, 28]. Additionally, a similarly high percentage of the genome of the lytic Dependentiae representatives is dedicated to ankyrin-repeat domain proteins, suggesting that these are crucial effectors for intra-eukaryotic replication and host cell take-over[5, 16]. Although the specific function of these proteins within these host-pathogen systems remain unknown, their nature as protein-protein interaction domains suggests they might be involved in host modification strategies[17]. Where ankyrin-repeat domain proteins have been explored in other host-pathogen systems, their functions include blocking of the host immune system, the induction of phagocytosis, the facilitation of cytoplasmic invasion, and the self-protection from potentially damaging effector molecules[17, 20, 29–31]. Any one of these functions could benefit C. destructans during its replication and therefore might be deployed. Phylogenetic analysis confidently places C. destructans within the candidate phylum TM6/Dependentiae, making it the first reported isolate of the phylum that does not infect an amoeba, and the first to infect a representative of the stramenopile supergroup of eukaryotes( Fig 4). Other studies have reported metagenomic correlation of Dependentiae with ciliates, suggesting that they infect or are symbionts of other eukaryotic lineages[3]. Life-history strategy seems to be independent of the host taxonomic group, given that C. destructans and B. massiliensis are lytic, but infect distantly related hosts, while V. pyriformis is symbiotic, and like B. massiliensis infects an amoeba. This suggests that life-history strategy, and resulting pathogenicity, is a product of coevolution within a specific host-pathogen pair. The restricted host ranges of C. destructans and V. pyriformis are consistent with members of the Dependentiae being highly adapted to their hosts[4]. The highly restricted host range of members of the Dependentiae suggests that they are extraordinarily diverse, as is reflected by the great diversity of related 16S rRNA sequences from environmental surveys. Given their potentially broad host range and distribution, Dependentiae could play a significant role in controlling the abundance and diversity of aquatic autotrophic and heterotrophic protists. Chromulinavorax destructans is the first described isolate of the candidate phylum Dependentiae that does not infect Acanthamoeba and is the first isolate of the proposed family Chromulinavoraceae that has only been represented by MAGs. Replication causes extensive reorganization of the host cell, most notably the wrapping of the host mitochondrion around the replication bodies of the bacteria. The genomic complement of C. destructans is highly reduced in metabolic capabilities, with no evidence for encoding any complete metabolic pathway and, thus, relies extensively on host resources such as metabolites and even ATP for energy supply. Strikingly, C. destructans is rich in putative effector molecules, putatively breaking down and reorganizing its host, as well as encoding a large number of uncharacterized proteins and proteins not represented in databases. The narrow host range of C. destructans provides hints to a regulatory role of parasitic bacteria in the diversity and abundance of heterotrophic protists." }, { "role": "assistant", "content": "Little is known about the biology of bacteria in the candidate phylum Dependentiae , despite being widespread in nature . Here , we describe a novel isolate of this phylum , Chromulinavorax destructans , which infects an abundant aquatic predatory protist , Spumella elongata . Chromulinavorax destructans is an obligate intracellular parasite , forgoes binary fission and replicates surrounded by the host mitochondrion . The genome of C . destructans encodes no detectable complete metabolic pathways and instead contains extensive transporter systems to import metabolites and even energy in the form of ATP from the host . We also found a surprising number of genes in the C . destructans genome encoding putative host modifying proteins that might be responsible for the extensive host reorganization . Phylogenetic analysis showed that C . destructans is distantly related to intracellular pathogens and symbionts of unrelated amoebae . Hence , Chromulinavorax destructans provides new insights into the biology of a widespread but largely unknown phylum of bacteria . These results imply that members of the Dependentiae are pathogens of diverse aquatic protists and are therefore likely important players in aquatic ecosystems ." } ]
science.covid_deepset_qa
science.covid_deepset_qa.1789
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your repsonse other than the answer.\n\nParagraph: We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1] . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2] . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID -19) . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3] [4] [5] . Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020. The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission. On 27 January 2020, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe asked countries to complete a WHO standard COVID-19 case report form for all confirmed and probable cases according to WHO criteria [6] [7] [8] . The overall aim of surveillance at this time was to support the global strategy of containment of COVID-19 with rapid identification and follow-up of cases linked to affected countries in order to minimise onward transmission. The surveillance objectives were to: describe the key epidemiological and clinical characteristics of COVID-19 cases detected in Europe; inform country preparedness; and improve further case detection and management. Data collected included demographics, history of recent travel to affected areas, close contact with a probable or confirmed COVID-19 case, underlying conditions, signs and symptoms of disease at onset, type of specimens from which the virus was detected, and clinical outcome. The WHO case definition was adopted for surveillance: a confirmed case was a person with laboratory confirmation of SARS-CoV-2 infection (ECDC recommended two separate SARS-CoV-2 RT-PCR tests), irrespective of clinical signs and symptoms, whereas a probable case was a suspect case for whom testing for SARS-CoV-2 was inconclusive or positive using a pan-coronavirus assay [8] . By 31 January 2020, 47 laboratories in 31 countries, including 38 laboratories in 24 European Union and European Economic Area (EU/EEA) countries, had diagnostic capability for SARS-CoV-2 available (close to 60% of countries in the WHO European Region), with cross-border shipment arrangements in place for many of those lacking domestic testing capacity. The remaining six EU/EEA countries were expected to have diagnostic testing available by mid-February [9] . As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died [4] . Data on 38 of these cases (i.e. all except the nine reported in the UK) are included in this analysis. The first three cases detected were reported in France on 24 January 2020 and had onset of symptoms on 17, 19 and 23 January respectively [10] . The first death was reported on 15 February in France. As at 21 February, nine countries had reported cases ( Figure) : Belgium (1), Finland (1), France (12), Germany (16), Italy (3), Russia (2), Spain (2), Sweden (1) and the UK (9 -not included further). The place of infection (assessed at national level based on an incubation period presumed to be up to 14 days [11] , travel history and contact with probable or confirmed cases as per the case definition) was reported for 35 cases (missing for three cases), of whom 14 were infected in China (Hubei province: 10 cases; Shandong province: one case; province not reported for three cases). The remaining 21 cases were infected in Europe. Of these, 14 were linked to a cluster in Bavaria, Germany, and seven to a cluster in Haute-Savoie, France [12, 13] . Cases from the Bavarian cluster were reported from Germany and Spain, whereas cases from the Haute-Savoie cluster were reported from France All but two cases were hospitalised (35 of 37 where information on hospitalisation was reported), although it is likely that most were hospitalised to isolate the person rather than because of severe disease. The time from onset of symptoms to hospitalisation (and isolation) ranged between 0 and 10 days with a mean of 3.7 days (reported for 29 cases). The mean number of days to hospitalisation was 2.5 days for cases imported from China, but 4.6 days for those infected in Europe. This was mostly a result of delays in identifying the index cases of the two clusters in France and Germany. In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six took only a mean of 2 days to be hospitalised. Symptoms at the point of diagnosis were reported for 31 cases. Two cases were asymptomatic and remained so until tested negative. The asymptomatic cases were tested as part of screening following repatriation and during contact tracing respectively. Of the remaining 29, 20 reported fever, 14 reported cough and eight reported weakness. Additional symptoms reported included headaches (6 cases), sore throat (2), rhinorrhoea (2), shortness of breath (2), myalgia (1), diarrhoea (1) and nausea (1). Fever was reported as the sole symptom for nine cases. In 16 of 29 symptomatic cases, the symptoms at diagnosis were consistent with the case definition for acute respiratory infection [16] , although it is possible that cases presented additional symptoms after diagnosis and these were not reported. Data on pre-existing conditions were reported for seven cases; five had no pre-existing conditions while one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases. All hospitalised cases had a benign clinical evolution except four, two reported in Italy and two reported in France, all of whom developed viral pneumonia. All three cases who were aged 65 years or over were admitted to intensive care and required respiratory support and one French case died. The case who died was hospitalised for 21 days and required intensive care and mechanical ventilation for 19 days. The duration of hospitalisation was reported for 16 cases with a median of 13 days (range: 8-23 days). As at 21 February 2020, four cases were still hospitalised. All cases were confirmed according to specific assays targeting at least two separate genes (envelope (E) gene as a screening test and RNA-dependent RNA polymerase (RdRp) gene or nucleoprotein (N) gene for confirmation) [8, 17] . The specimen types tested were reported for 27 cases: 15 had positive nasopharyngeal swabs, nine had positive throat swabs, three cases had positive sputum, two had a positive nasal swab, one case had a positive nasopharyngeal aspirate and one a positive endotracheal aspirate. As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths [18] . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region [19] . In our analysis of early cases, we observed transmission in two broad contexts: sporadic cases among travellers from China (14 cases) and cases who acquired infection due to subsequent local transmission in Europe (21 cases). Our analysis shows that the time from symptom onset to hospitalisation/case isolation was about 3 days longer for locally acquired cases than for imported cases. People returning from affected areas are likely to have a low threshold to seek care and be tested when symptomatic, however delays in identifying the index cases of the two clusters in France and Germany meant that locally acquired cases took longer to be detected and isolated. Once the exposure is determined and contacts identified and quarantined (171 contacts in France and 200 in Germany for the clusters in Haute-Savoie and Bavaria, respectively), further cases are likely to be rapidly detected and isolated when they develop symptoms [15, 20] . In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six were hospitalised after a mean of 2 days. Locally acquired cases require significant resources for contact tracing and quarantine, and countries should be prepared to allocate considerable public health resources during the containment phase, should local clusters emerge in their population. In addition, prompt sharing of information on cases and contacts through international notification systems such as the International Health Regulations (IHR) mechanism and the European Commission's European Early Warning and Response System is essential to contain international spread of infection. All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March [18, 19] . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection of local circulation of COVID-19, including through testing of severe acute respiratory infections in hospitals irrespectively of travel history as recommended in the WHO case definition updated on 27 February 2020 [21] . The clinical presentation observed in the cases in Europe is that of an acute respiratory infection. However, of the 31 cases with information on symptoms, 20 cases presented with fever and nine cases presented only with fever and no other symptoms. These findings, which are consistent with other published case series, have prompted ECDC to include fever among several clinical signs or symptoms indicative for the suspected case definition. Three cases were aged 65 years or over. All required admission to intensive care and were tourists (imported cases). These findings could reflect the average older age of the tourist population compared with the local contacts exposed to infection in Europe and do not allow us to draw any conclusion on the proportion of severe cases that we could expect in the general population of Europe. Despite this, the finding of older individuals being at higher risk of a severe clinical course is consistent with the evidence from Chinese case series published so far although the majority of infections in China have been mild [22, 23] . This preliminary analysis is based on the first reported cases of COVID-19 cases in the WHO European Region. Given the small sample size, and limited completeness for some variables, all the results presented should be interpreted with caution. With increasing numbers of cases in Europe, data from surveillance and investigations in the region can build on the evidence from countries in Asia experiencing more widespread transmission particularly on disease spectrum and the proportion of infections with severe outcome [22] . Understanding the infection-severity is critical to help plan for the impact on the healthcare system and the wider population. Serological studies are vital to understand the proportion of cases who are asymptomatic. Hospital-based surveillance could help estimate the incidence of severe cases and identify risk factors for severity and death. Established hospital surveillance systems that are in place for influenza and other diseases in Europe may be expanded for this purpose. In addition, a number of countries in Europe are adapting and, in some cases, already using existing sentinel primary care based surveillance systems for influenza to detect community transmission of SARS-CoV-2. This approach will be used globally to help identify evidence of widespread community transmission and, should the virus spread and containment no longer be deemed feasible, to monitor intensity of disease transmission, trends and its geographical spread. Additional research is needed to complement surveillance data to build knowledge on the infectious period, modes of transmission, basic and effective reproduction numbers, and effectiveness of prevention and case management options also in settings outside of China. Such special studies are being conducted globally, including a cohort study on citizens repatriated from China to Europe, with the aim to extrapolate disease incidence and risk factors for infection in areas with community transmission. Countries together with ECDC and WHO, should use all opportunities to address these questions in a coordinated fashion at the European and global level. provided input to the outline, multiple versions of the manuscript and gave approval to the final draft.\n\nQuestion: What was the clinical evolution of the hospitalised cases?" }, { "role": "assistant", "content": "All hospitalised cases had a benign clinical evolution except four," } ]
science.chemdner_ner
science.chemdner_ner.38
[ { "role": "user", "content": "You will be shown an abstract from a biomedical research paper. Given this abstract, your task is to extract all unique entities of the following types: [\"Chemical\"].\n\nPlease return the output as a JSON object of the format: {\"Chemical\": [\"Arsenic\", ...]}. The keys should be entity types and values should be lists of extracted entities belonging to the corresponding type. If you cannot find entities belonging to a specific type, the value should be [].\n\nOnly output the JSON object and do not include any additional text.\n\nAbstract:\n\nPlant proteins, minerals and trace elements of Eurycoma longifolia (Tongkat Ali). A water extraction method has been used to extract plant proteins from the roots of Eurycoma longifolia harvested from Perak and Pahang, Malaysia. On the basis of the spectroscopic Bradford assay, Tongkat Ali Perak and Pahang contained 0.3868 and 0.9573 mg mL(-1) of crude protein, respectively. The crude proteins were separated by one dimensional 15% sodium dodecyl sulphate polyacrylamide gel electrophoresis into two (49.8 and 5.5 kD) and four (49.8, 24.7, 21.1 and 5.5 kD) protein spots for Tongkat Ali Perak and Pahang, respectively. Isoleucine was present in the highest concentration significantly. Both plant samples showed differences in the mineral and trace element profiles, but the minerals calcium, magnesium and potassium were present in the highest concentration. The highly concerned toxic metals such as arsenic and lead were not detected." }, { "role": "assistant", "content": "{\"Chemical\": [\"arsenic\", \"calcium\", \"potassium\", \"Isoleucine\", \"magnesium\", \"sodium dodecyl sulphate polyacrylamide\"]}" } ]
science.acl_arc_intent_classification
science.acl_arc_intent_classification.1113
[ { "role": "user", "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nmethod\n\nContext before the citation:\nThis alignment is obtained by following the same set of rules learned from the development dataset as in (Zhang and Chai, 2009). \u0000\u0000\u0000\u0000\u0000\u0000 Note that in this figure the alignment between x5 = suggests from the hypothesis and u4 = opinion from the conversation segment is a pseudo alignment, which directly maps a verb term in the hypothesis to an utterance term represented by its dialogue act. Figure 3 shows an example of alignment between the conversation terms and hypothesis terms in Example 2.\n\nCitation Sentence:\nThis alignment is obtained by following the same set of rules learned from the development dataset as in ( Zhang and Chai , 2009 ) .\n\nContext after the citation:" }, { "role": "assistant", "content": "Uses" } ]
science.mslr2022_ms2_multidoc_summarization
science.mslr2022_ms2_multidoc_summarization.12092
[ { "role": "user", "content": "You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.\n\n\n\nTitle 1:\nValidation of intermediate end points in cancer research.\nAbstract 1:\nInvestigations using intermediate end points as cancer surrogates are quicker , smaller , and less expensive than studies that use malignancy as the end point . We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer . C and i date intermediate end points may be selected from case series , ecologic studies , and animal experiments . Prospect i ve cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association . The most appropriate measure of this association is the attributable proportion . The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0 , but not if it is close to 0 . Usually , the attributable proportion is close to neither 1.0 nor 0 ; in this case , valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation . This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point . We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points . This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer" }, { "role": "assistant", "content": "The use of biomarkers in phase I trials has increased over the period from 1991 to 2002 .\nTo date , biomarker utilization has made a limited and primarily supportive contribution to dose selection , the primary end point of phase I studies ." } ]
science.mslr2022_cochrane_multidoc_summarization
science.mslr2022_cochrane_multidoc_summarization.1952
[ { "role": "user", "content": "You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.\n\n\n\nTitle 1:\nA placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group.\nAbstract 1:\nTo test the safety and efficacy of recombinant human insulin-like growth factor-I (rhIGF-I) in ALS, 183 patients from eight European centers were randomized to receive double-blind placebo (n = 59) or rhIGF-I 0.1 mg/kg/day (n = 124) subcutaneously for 9 months. At study completion, the primary efficacy outcome measure (change in disease progression as assessed by the Appel ALS rating scale) showed no significant difference between treatment groups. RhIGF-I appeared to be safe and well-tolerated.\n\n\nTitle 2:\nEffect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group.\nAbstract 2:\nThe objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects.\n\n\nTitle 3:\nSubcutaneous IGF-1 is not beneficial in 2-year ALS trial.\nAbstract 3:\nPrevious human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS.\n A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used.\n There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period.\n Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis." }, { "role": "assistant", "content": "Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias." } ]
science.drug_combo_extraction_re
science.drug_combo_extraction_re.1004
[ { "role": "user", "content": "You will be shown a paragraph from a biomedical research article. Your task is to extract all drug combinations appearing in a specific sentence within in the paragraph. Each drug combination should be assigned to one of the following three categories:\n\n- POS: Indicates a positive interaction between the drugs in the combination; for instance, drugs that have an additive or synergistic effect.\n- NEG: Indicates a negative interaction between the drugs in the combination; for instance, combining these drugs might result in adverse side effects, or might reduce their efficacy.\n- COMB: Indicates that the drugs are given in combination, but the type of interaction between the drugs cannot be determined based on the provided context.\n\nPlease format your answer as a json array. Each entry in the array should itself be an array formatted as [<drug_1>, <drug_2>, ..., <drug_n>, <category>] where <category> is one of the three categories listed above and <drug_1>, ..., <drug_n> are drug names copied verbatim from the input sentence. Different combinations may involve different numbers of drugs; in other words, the `n` in <drug_n> may vary.\n\nAs an example, the following output describes two extracted drug combinations; one between two drugs, and one between three drugs:\n\n[[\"artesunate\", \"artemether\", \"COMB\"], [\"Nifedipine\", \"Labetalol\", \"Prazosin\", \"POS\"]]\n\nThe paragraph and specific sentence are below. You should only extract relationships expressed in the specific sentence; the paragraph is provided for context.\n\nIn your output, return only the json array and no other text. If no drug combinations appear, return an empty array `[]`.\n\nparagraph: Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone, used as an adjunct to levodopa, in Parkinson's disease (PD) patients. ### Patients And Methods In this parallel group , randomized , double-blind study , 301 PD patients , the majority with motor fluctuations , received entacapone ( 200 mg ) or placebo with each daily dose of standard or controlled-release ( CR ) levodopa . The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off' times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. ### results In the total population, the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off' time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively; P < 0.05), and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). entacapone benefit was lost on withdrawal. entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. ### conclusion entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.\n\nsentence: In this parallel group , randomized , double-blind study , 301 PD patients , the majority with motor fluctuations , received entacapone ( 200 mg ) or placebo with each daily dose of standard or controlled-release ( CR ) levodopa ." }, { "role": "assistant", "content": "[[\"entacapone\", \"levodopa\", \"POS\"]]" } ]
science.bioasq_yesno_qa
science.bioasq_yesno_qa.457
[ { "role": "user", "content": "You have to answer a biomedical question in binary format, i.e. only yes and no are the only acceptable answer formats. A list of paragraphs is provided as context to help you answer the question.\n\nQuestion: Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?\n\nContext: As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes.\nFinally we will address the role of CMR in pre-participation screening." }, { "role": "assistant", "content": "no" } ]
science.chemsum_single_document_summarization
science.chemsum_single_document_summarization.57936
[ { "role": "user", "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\n“Ultra-sensitive” cardiac troponins: Requirements for effective implementation in clinical practice\n\nPaper sections:\nIntroduction\n<p>Despite many efforts made through the adoption of widespread preventive strategies, both morbidity and mortality for acute coronary syndrome (ACS) remain extremely high. Thus, myocardial ischemia has become one of the leading health care challenges worldwide (1). Unlike many other human diseases, the diagnostic approach for patients with suspected ACS has undergone sizable and revolutionary changes since the release of the first diagnostic criteria by the World Health Organization in the early 1970s (2). Irrespective of the presence of typical signs and symptoms of myocardial ischemia and suggestive electrocardiographic (ECG) abnormalities, the measurement of cardiac troponins (cTns), either cardiac troponin I (cTnI) or cardiac troponin T (cTnT), has become the culprit of making a specific clinical decision, particularly for diagnosing non-ST elevation myocardial infarction (NSTEMI) (3, 4). Very recent evidence, combining organization and economic endpoints with diagnostic efficiency, also confirms that the measurement of additional biomarkers, such as the creatine kinase isoenzyme MB (CK-MB), impose a considerable financial burden for the health care system, without providing incremental value to patient care (5).</p>\n\nClinical use of high-sensitivity immunoassays\n<p>The universally agreed analytical mainstays of cTn testing are summarized in Tables 1 and 2, and substantially include limit of detection (LoD), limit of blank (LoB), functional sensitivity (also known as \"Limit of Quantitation\"; LoQ) and the 99th percentile of a healthy reference population (6-8).</p><p>The development and commercialization of cTn immunoassays started nearly 40 years ago, and progressed with the release of methods characterized by gradually enhanced analytical performance, which are now gradually and irreversibly replacing the former generation of \"contemporary-sensitive\" techniques (8). For example, the first-generation cTn immunoassays was characterized by LoD of approximately 500 ng/L and 0% of measurable values (i.e., concentration > LoD) in healthy subjects, while the latest generation of immunoassays is characterized by a LoD over 100-fold lower compared to the original techniques and a percentage of measurable values typically > 50% (9). A substantial revolution has followed the introduction of these so-called \"high-sensitivity\" (HS) immunoassays, driven by the recent evidence that patients with values of both cTnI and cTnT comprised between the LoD and the 99th percentile (i.e., > LoD and < 99th percentile) or between the functional sensitivity of the immunoassay and the 99th percentile (i.e., > LoQ and < 99th percentile) have a higher risk of unfavorable clinical outcomes (both total and cardiovascular) compared to those with lower values (i.e., displaying cTn values < LoD or < LoQ) (10-15). Notably, such an enhanced risk of adverse events apparently lasts for a longer period after evaluation in the emergency rooms, since patients with values comprised between the 99th percentile and LoD (or the functional sensitivity) also have an increased rate of 30-day major adverse cardiovascular events (MACE). According to this paradigm, new diagnostic algorithms no longer use the 99th percentile as the reference diagnostic threshold, but implement lower cTn cut-offs (i.e., conventionally identified with LoD or with the functional sensitivity) and entail shorter-time serial testing (i.e., between 1 and 2 hours after baseline assessment, rather than 3 and 6 hours afterwards) (16-21). The efficiency of this strategy for rapid rule-out of ACS and for identification of patients with enhanced risk of 30-day MACE has already been proven in a consistent number of studies, and it is therefore predictable that this strategy may soon become the standard of care (10-15, 22). Notably, the considerably improved analytical performance of the new generation of cTn HS immunoassays may also allow introducing an additional \"functional\" classification of the methods, based on the ratio between the 99th percentile and LoD (Table 2). In clinical and laboratory practice, the larger the 99th percentile/LoD ratio, the higher the probability to identify subjects with \"measurable\" values will be.</p><p>At the time of publication of this article, four fully-automated HS immunoassays are commercially available and their analytical performance is summarized in Table 3 (three for measuring cTnI and one for measuring cTnT, respectively) (23-27). Although these techniques display different analytical performance and designation according to the conventional criteria of imprecision and analytical sensitivity, they are all characterized by a > 1 ratio between the 99th percentile and LoD (Table 3), thus making them clinically useable even when adopting the new diagnostic algorithms encompassing rule-out and short-time serial testing based on diagnostic thresholds corresponding to either the LoD or the functional sensitivity (7, 8). Whether classifying the assays as clinically useable HS, extremely HS or \"ultra-sensitive\" (US) will determine additional clinical advantages for early rule-in or rule-out of ACS, or for predicting the risk of 30-day MACE, remains to be demonstrated, since no comparison studies have been published so far. Nevertheless, improving further the analytical sensitivity of these methods (i.e., lowering both the LoD and functional sensitivity), may also challenge the new diagnostic paradigm of early rule-out of subjects with cTn values comprised between the 99th percentile and the LoD. Interestingly, the proportion of population with values < 99th percentile and > LoD has increased from 32% with Roche HS-cTnT to 97% with Beckman Coulter HS-cTnI (Figure 1), thus generating new practical dilemmas: is it plausible that all the 97% ostensibly healthy subjects showing Beckman Coulter HS-cTnI values between the 99th percentile and the LoD should be considered at increased risk of ACS or 30-day MACE compared to the remaining 3% of the population displaying unmeasurable values? And, even more challenging, how should these subjects be managed? Quite understandably, the new rule-out strategies based on LoD or functional sensitivity values as diagnostic cut-offs have been clinically validated using the former HS Roche HS-cTnT and Abbott HS-cTnI immunoassays, which display a 99th percentile/LoD ratio of 3 and 10-17, respectively (23, 24). Evidence has been provided showing that the standardization of cTn immunoassays is still an unmet target, even after harmonization with common calibrators, so that diagnostic protocols validated using one cTn immunoassay may be inefficient when another technique is used (28). Notably, the two most recent Siemens and Beckman Coulter HS-cTnI immunoassays are characterized by a 99th percentile/LoD ratio > 20, and are hence more analytically sensitive. This would require developing specific algorithms for these methods.</p>\n\n\n<p>Percentage of measurable values of cardiac troponin in healthy population. HS-cTnT - high sensitive cardiac troponin T. HS-cTnI - high sensitive cardiac troponin I. LoD - limit of detection. 99th percentile - 99th percentile of a reference healthy population.</p>\n\nDiagnostic algorithms with “ultra-sensitive” techniques\n<p>Given that a significant proportion of subjects with cTn values < 99th percentile are at enhanced risk of adverse cardiovascular events, the use of LoD or functional sensitivity as diagnostic thresholds for early rule-out will be no longer feasible due to the obvious increased rate of false positive results using the so-called \"US\" techniques (Figure 1). The decrease of the positive predictive value will likely be magnified as long as the analytical performance of the current immunoassays is improved further, or when newer and even more analytically sensitive techniques are commercialized. For example, a recent study aimed to investigate the analytical performance of the new Sgx cTnI Assay (Singulex Inc., Alameda, USA) reported that the LoB, LoD and functional sensitivity of this assay are 0.02, 0.08 and 0.53 ng/L, whilst measurable cTnI concentrations could be observed in as many as 99.5% of healthy subjects (29). Paradoxically, these considerations pave the way to turn back the clock to nearly 40 years ago, when the strategy used for identifying the most efficient diagnostic thresholds of cTns was based on receiver operating characteristics (ROC) curve analysis (Figure 2). Indeed, the new cTn cut-offs for \"US\" technique will need to combine the best diagnostic performance at patient presentation with the risk of 30-day MACE, yielding a cTn value in the lower end of concentrations comprised between the 99th percentile and the LoD. Although the timing of serial sampling after patient presentation should also be defined with large (and possibly multicenter) clinical studies, it is predictable that 0h/1h or 0h/2h time points may be efficient, reliable and safe using \"US\" techniques, since the reference delta cTn variation selected for optimal ruling-out or ruling-in ACS will now be characterized by excellent performance in terms of analytical imprecision (i.e., much lower than 10%). Therefore, the less specificity of \"US\" techniques, especially when using low diagnostic cut-offs, will be probably overcome by the advantage of enabling a safer and earlier rule out of ACS. More specifically, recent studies showed that the use of a low cTn cut-off, equal or close to the LoD of the immunoassay, may allow adopting 0h/1h rule-in and rule-out algorithms, maintaining virtually the same diagnostic efficiency of the conventional 0h/3h algorithms, but also generating a favourable impact, both organizational and economic, for patient management in short stay units such as the emergency room (13, 30, 31). Notably, 0h/2h serial sampling can be seen as a promising and reliable alternative to the shorter 0h/1h strategy, especially suited for those facilities where the 0h/1h algorithm cannot be straightforwardly implemented due to practical reasons (i.e., the emergency room is far from the core laboratory and/or efficient means of samples transportation such as pneumatic transport system are unavailable) (16).</p>\n\n\n<p>Development of cut-offs for diagnostic algorithms including different cardiac troponin immunoassays. CV10% - coefficient of variation value with ≤ 10% analytical imprecision (functional sensitivity). LoD - limit of detection. 99th percentile - 99th percentile of a reference healthy population.</p>\n\nConclusions\n<p>In conclusion, the gradual introduction in clinical practice of the so-called \"US\" cTn immunoassays will need to be anticipated by large and robust clinical studies aimed to identify the most suitable cut-offs and the most appropriate timing for serial sampling to get the most from these new techniques. For the time being, thoughtful translation of current diagnostic algorithms to these \"US\" and other incoming cTn immunoassays seems unadvisable.</p>\n\n\n<p>Potential conflict of interest: None declared.</p>" }, { "role": "assistant", "content": "The measurement of cardiac troponins, either cardiac troponin I or T, has become the culprit of clinical decision making in patients with suspected acute coronary syndrome (ACS), especially in those with non-ST elevation myocardial infarction (NSTEMI). The leading analytical mainstays of cardiac troponin immunoassays include the limit of blank (LoB), limit of detection (LoD), functional sensitivity, the 99th percentile of a healthy reference population, along with the percentage of “ostensibly healthy” subjects displaying measurable values < 99th percentile. The latest generation of cardiac troponin immunoassays, conventionally defined as “high-sensitive” (HS), is characterized by a LoD over 100-fold lower compared to the first commercialized techniques and a percentage of measurable values consistently > 50% in the general healthy population. The very recent commercialization of methods with further improved analytical sensitivity (i.e., “ultra-sensitive” assays), which allow to measure cardiac troponin values in the vast majority of healthy subjects, is now challenging the diagnostic paradigm based on early rule-out of subjects with cardiac troponin values comprised between the 99th percentile and LoD. New diagnostic strategies, entailing assay-specific cut-offs, must hence be developed and validated in large multicenter studies. The aim of this article is to provide an update on commercially available HS and “ultra”-sensitive techniques for measuring cardiac troponins, along with possible implications of increasingly enhanced analytical sensitivity on diagnostic algorithms for evaluating patients with suspected ACS." } ]
science.acl_arc_intent_classification
science.acl_arc_intent_classification.1092
[ { "role": "user", "content": "You will be presented with a citation segment from the section of an NLP research paper, as well as the context surrounding that citation. Classify the intent behind this citation by choosing from one of the following categories:\n- Background: provides context or foundational information related to the topic.\n- Extends: builds upon the cited work.\n- Uses: applies the methods or findings of the cited work.\n- Motivation: cites the work as inspiration or rationale for the research.\n- CompareOrContrast: compares or contrasts the cited work with others.\n- FutureWork: cites the work as a direction for future research.\n\nYour answer should be a single word from the following list of options: [\"Background\", \"Extends\", \"Uses\", \"Motivation\", \"CompareOrContrast\", \"FutureWork\"]. Do not include any other text in your response.\n\nSection Title:\nintroduction\n\nContext before the citation:\n32 In certain cases an extension of the constraint language with named disjunctions or contexted constraints (Maxwell and Kaplan 1989; Eisele and Dorre 1990; Griffith 1996) can be used to circumvent constraint propagation. The information common to all solutions to the interaction call is lifted up into the lexical entry and becomes available upon lexical lookup. \u0000\u0000\u0000\u0000\u0000\u0000\u0000\u0000\u0000\u0000 Applying constraint propagation to the extended lexical entry of Figure 17 yields the result shown in Figure 23.\n\nCitation Sentence:\n32 In certain cases an extension of the constraint language with named disjunctions or contexted constraints ( Maxwell and Kaplan 1989 ; Eisele and Dorre 1990 ; Griffith 1996 ) can be used to circumvent constraint propagation .\n\nContext after the citation:\nEncoding the disjunctive possibilities for lexical rule application in this way, instead of with definite clause attachments, makes all relevant lexical information available at lexical lookup. For analyses proposing infinite lexica, though, a definite clause encoding of disjunctive possibilities is still necessary and constraint propagation is indispensable for efficient processing. An entry suitable for on-the-fly application (lexical rules 1 and 2 only)." }, { "role": "assistant", "content": "Background" } ]
science.chemsum_single_document_summarization
science.chemsum_single_document_summarization.40150
[ { "role": "user", "content": "You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.\n\nTitle:\nThioether-linked azobenzene-based liquid crystal dimers exhibiting the twist-bend nematic phase over a wide temperature range\n\nPaper sections:\nIntroduction\n<p>In addition to the conventional nematic (N) phase, unknown N (Nx) phases without apparent layer structures are occasionally observed for polymers [1], bent dimers connected with odd numbers of spacers [2][3][4], bent-core molecules [5,6], and a tetrapodtype molecule [7]. The twist-bend nematic (NTB) phase is an example of such an Nx phase with a heliconical helix, in which the local director tilts from the helical axis. This renders the NTB phase distinct from the conventional chiral N phase (or cholesteric phase), in which the local director is perpendicular to the helical axis. The theoretical possibility of the NTB phase was originally predicted by Meyer [8] and later extended by Dozov [9] and simulated by Memmer [10]. In-depth reinvestigation of an LC dimer comprising two 4cyanobiphenyl arms connected by a heptamethylene spacer, 1ʺ,7ʺ-bis(4-cyanobiphenyl-4ʹ-yl)heptane (CB7CB) indicated that the Nx phase is the NTB phase [11] (here, it is to be noted that the Nx phase observed for the tetrapod molecule reported recently by Mandle et al. was distinguished from the NTB phase [7]). Thus, identification of the NTB phase inspired extensive study on a large number of molecules that exhibit the NTB phase, such as bent LC dimers , various oligomers [35,[37][38][39][40][41][42][43][44][45][46], polymers [47], and bent-core molecules [48,49], and on related potential applications [50][51][52][53][54]. Electro-optical analysis [55], transmission electron microscopy [56,57], and soft, tender, and hard resonant X-ray scattering [34,[58][59][60][61] confirmed that the helical pitch of the NTB phase is considerably short, typically the length of several molecules or 10-20 nm. On the other hand, another heliconical model for the Nx phase, identified as the NTB phase, was proposed, and it was named the polar twisted nematic (NPT) phase [62][63][64][65][66]. It has been suggested that the identification of the NTB phase to date is inadequate: the Nx phase identified as the NTB phase is different from the true NTB phase predicted originally by Meyer. The heliconical models and terms involving the NTB or NPT phase are still under debate. As of now, the widely prevalent term 'NTB phase' is used tentatively in this paper.</p><p>With respect to both scientific viewpoints and practical applications, azobenzene is an important building block for LC materials owing to its ability to undergo trans-cis photoisomerisation [67], leading to light-induced phase transitions [68][69][70][71][72] and development of photo-mobile materials [73][74][75], light-induced alignment technologies [76][77][78][79][80], light-induced chiral segregation [81,82], and molecular designs for supramolecular functional materials [82][83][84][85][86]. To date, several azobenzene-containing twist-bend nematogenic dimers have been developed [24][25][26], and the light-induced phase transition has been verified [24,87]. However, azobenzene-based LC dimers that exhibit the NTB phase over a broad temperature range, including room temperature, have yet to be established. refer to the cyano groups, azobenzene arms, thioether linkages, and 4-cyanobiphenyl arms, respectively (Figure 1). Previously, we reported that a symmetric (CN)AzoS7SAzo(CN) with a heptamethylene spacer exhibits the monotropic NTB phase [35]. However, the development of homologues is needed to ascertain the effect of the spacer length on the NTB phase. In addition, the combination of non-symmetric mesogenic arms and thioether linkages has a highly beneficial effect in inducing and broadening the NTB phase [36].</p><p>Aligned with this strategy, the asymmetric series of (CN)AzoSnSCB with a 4-cyanobiphenyl arm was designed. We investigated the phase-transition behaviour of the dimers and conducted phase identification using polarising light optical microscopy (POM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) measurements.</p>\n\nMethods and instruments\n<p>All chemicals were commercially available and used as received. The synthetic pathways are shown in Figure 1. The symmetric (CN)AzoSnSAzo(CN) dimers were synthesised according to the previously reported procedures for (CN)AzoS7SAzo(CN) [35], and the asymmetric (CN)AzoSnSCB dimers were synthesised according to the procedures for (CN)AzoS7SCB, which are described in the following section. The molecular structures were characterised using 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy (see the Supporting Information), recorded on a JNM-ECX500 (500 MHz for 1 H NMR and 126 MHz for 13 C NMR) instrument (JEOL Ltd., Tokyo, Japan), and highperformance liquid chromatography/high resolution mass spectrometry (HPLC/HRMS) with Agilent 1200 HPLC-Chip and 6520 Accurate-Mass Q-TOF. The characterisation details of intermediates and final compounds are described in the Supporting Information.</p><p>The phase-transition behaviour was studied using POM with an Olympus polarised optical microscope (BX50, Tokyo, Japan) and a Linkam (Surrey, UK) temperature controller LK-600PM, and DSC with a Shimadzu DSC 60 (Kyoto, Japan) at a rate of 10 °C min⁻ 1 under a nitrogen gas flow of 50 mL min⁻ 1 . The reproducibility of the DSC measurements was confirmed by repeating the measurements on a few specimens for each compound. The POM images and DSC results of all compounds are either shown in the main text or the Supporting Information. XRD measurements were conducted using a Bruker D8 DISCOVER diffractometer (Cu Kα radiation) equipped with a Vantec-500 detector. The specimens, kept in capillary glass tubes of 1.5 mm diameter (purchased from WJM-Glass Müller GmbH), were aligned under a magnetic field (B = 300 mT).</p>\n\n1′-Bromo-7′-(4-bromophenylthio)heptane\n<p>This compound was synthesised referring to procedures in the literature [36]. 4-Bromobenzenethiol (1.00 g, 5.29 mmol), 1,7-dibromoheptane (2.04 g, 7.91 mmol), K2CO3 (2.18 g, 15.8 mmol), and acetonitrile (60 mL) were added into a flask and the mixture was stirred at ambient temperature for 12 h. The reacted mixture was extracted with dichloromethane (DCM) and washed with water and brine. The organic phase was dried over MgSO4 and the volatiles were removed under reduced pressure. The residue was purified by column chromatography on silica gel with an eluent of DCM/hexane = 1/25 (v/v). The NMR spectral data were similar to those described in Ref. 36.</p>\n\n1′-(4-Aminophenylthio)-7′-(4-bromophenylthio)heptane\n<p>1′-Bromo-7′-(4-bromophenylthio)heptane (0.700 g, 1.91 mmol), 4-aminobenzenethiol (0.251 g, 2.01 mmol), K2CO3 (0.833 g, 6.03 mmol), and acetone (15 mL) were added into a 50 mL flask and the mixture was stirred at ambient temperature for 5 h. The reaction mixture was extracted with DCM and washed with water and brine. The organic phase was dried over MgSO4 and the volatiles were removed under reduced pressure. The residue was purified by column chromatography on silica gel with an eluent of DCM/hexane = 3/1 (v/v). Yield: 92%.</p>\n\n1′′-(4-Bromophenylthio)-7′′-{4′-[(E)-2-(4cyanophenyl)diazenyl]phenylthio}heptane\n<p>This compound was synthesised referring to procedures in the literature [35]. A solution of Oxone ® (0.375 g, 22.0 mmol) in distilled water (8 mL) was added to a solution of 4aminobenzonitrile (0.144 g, 1.22 mmol) dissolved in DCM (2 mL) in a 50 mL two-necked flask, which was stirred at room temperature under an argon atmosphere. After 9 h, the reaction mixture was extracted with DCM, and the organic phase was washed with 1 M HCl aq. and brine, and then the volatiles were removed under reduced pressure. The product (4-nitrosobenzonitrile) was used for the next step without further purification. 1′-</p>\n\nResults and discussion\n<p>Table 1 summarises the thermal phase sequences and phase-transition data, including the temperatures of crystallisation (TCr), glass transition (Tg), N-NTB transition (TNNTB), and isotropic (Iso)-N transition (TIN); as well as the entropy changes (ΔS) scaled by the gas constant (R) at the Iso-N phase transition (ΔSIN/R) upon cooling at a rate of 10 °C min⁻ 1 .</p><p>The phase transitions that occurred during the first heating are presented in the Supporting Information. The phase-transition behaviour of the symmetric homologous series, (CN)AzoSnSAzo(CN), is described first. Using POM and DSC, symmetric homologues with n = 5, 7, 9, and 11 revealed mesophases. (CN)AzoS7SAzo(CN), which exhibits an enantiotropic N phase and a monotropic NTB phase, has been reported previously [35].</p><p>The dimer with the shortest spacer, (CN)AzoS3SAzo(CN), was not mesogenic. was marginally broader than that of (CN)AzoS7SAzo(CN). As presented in the Figure S12, the N-NTB transition at 115.9 °C was captured on the DSC curve, and was similar to the typical second-order N-NTB phase transition characteristic of LC dimers. On the other hand, POM observation of the NTB phase at approximately 114 °C for (CN)AzoS11SAzo(CN) was challenging, since it could only be done in a considerably small supercooled N domain due to crystallisation at 142 °C, as shown in the Figure S4. Next, the phase-transition behaviours of both homologous series were compared in terms of TNNTB, TIN, and ΔSIN/R, which are plotted in Figure 8 as a function of n. Overall, the TNNTB and TIN values for the symmetric (CN)AzoSnSAzo(CN) dimers were higher than those for the non-symmetric (CN)AzoSnSCB dimers, because the former series contains two 4-cyanoazobenzene arms, with larger intermolecular interaction than that of the counter 4-cyanobiphenyl arm of the latter series. It is noteworthy that ΔSIN/R of both series were very similar at the same n. This indicates that the different mesogenic arm structures (4-cyanoazobenzene or 4-cyanobiphenyl) do not significantly change the molecular anisotropy or geometries at the Iso-N phase transition. These results are consistent with previous results, which reported the molecular geometries at the Iso-N phase transition to be largely influenced by the linkage bonds rather than the mesogenic arms [20,36]. temperature. The sulfur-containing materials presented here are useful for investigations related to light-induced photoisomerisation and the resulting helical nano-structural variation of the NTB phase using tender resonant X-ray scattering at the sulfur K edge, which is discussed in another report [90].</p>" }, { "role": "assistant", "content": "Two homologous series of sulfur-containing thioether-linked 4cyanoazobenzene-based liquid crystal (LC) dimers were developed: a symmetric series based on 4-cyanoazobenzene arms [(CN)AzoSnSAzo(CN)] and a non-symmetric series based on 4cyanoazobenzene and 4-cyanobiphenyl arms [(CN)AzoSnSCB]. They contained different flexible oligomethylene spacers (CnH2n) consisting of odd numbers of carbon atoms (n = 3, 5, 7, 9, and 11). The symmetric (CN)AzoSnSAzo(CN) dimers with n = 5, 7, 9, and 11 showed an elusive monotropic twist-bend nematic (NTB) phase, while all the non-symmetric (CN)AzoSnSCB dimers exhibited the NTB phase. Notably, the NTB phase observed for non-symmetric (CN)AzoS7SCB could be supercooled to room temperature, leading to a glassy NTB phase. (CN)AzoS9SCB showed a similar tendency accompanied by partial crystallization. These are the first reported examples of azobenzene-based LC dimers exhibiting a broad temperature range of NTB phases supercooled to room temperature. Such prominent stability of the NTB phase is due to the supercooling effect assisted by the synergy of molecular bend arising from thioether linkages and non-symmetric mesogenic arms. The phase-transition temperatures were overall higher for symmetric (CN)AzoSnSAzo(CN) than for nonsymmetric (CN)AzoSnSCB. It is assumed that the difference in the mesogenic arm structures hardly influenced their molecular geometry or anisotropy in terms of entropy changes." } ]
science.scientific_papers_summarization_single_doc_arxiv
science.scientific_papers_summarization_single_doc_arxiv.57506
[ { "role": "user", "content": "You will be presented with the full text of a science research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.\n\nPaper text:\nthe discovery of an anomalous suppression in the first moment of the polarised proton structure function @xmath3 by the emc collaboration@xcite in 1988 stimulated a period of intense theoretical and experimental activity in the qcd community .\nrecently , the existence of this so - called ` proton spin problem ' has been confirmed by new experiments at cern@xcite and slac@xcite , although the numerical results have been substantially revised . in this contribution , i will review some recent work@xcite with s. narison and g. veneziano which we believe gives a theoretically convincing and quantitative resolution of the problem . in our picture@xcite ,\nthe ` proton spin ' effect is seen as a natural addition to the class of ozi - violating @xmath6 phenomena characteristic of qcd in the flavour singlet pseudoscalar ( or pseudovector ) channel . furthermore , the violation of the ellis - jaffe sum rule , due to the suppression relative to the ozi expectation of the singlet form factor @xmath7 ( usually denoted by @xmath8 ) , is recognised as a generic , target - independent feature of qcd related to the axial @xmath6 anomaly and not as a special property of the proton structure .\nin fact , it reflects an anomalous suppression of the first moment of the qcd topological susceptibility , @xmath2 .\nthe sum rule for the first moment of the polarised proton structure function @xmath3 reads : @xmath9\\end{aligned}\\ ] ] where the @xmath10 are form factors in the proton matrix elements of the axial current : @xmath11 and @xmath12 is an @xmath13 flavour index . here\n, we just display the perturbative corrections to @xmath14 . for further terms , see @xcite .\nsince our results depend smoothly on the quark masses in the chiral limit , we set the light quark masses to zero .\nthe interpretation of these form factors in the naive parton model is , in standard notation : @xmath15 the axial current occurs here since it is the lowest twist , lowest spin , odd - parity operator in the ope of two electromagnetic currents ( see sect.4 ) .\nthe suffix @xmath16 emphasises that the current is the renormalised composite operator . under renormalisation ,\nthe gluon topological density @xmath17 and the divergence of the flavour singlet axial current @xmath18 mix as follows : @xmath19 where @xmath20 and @xmath21 and we have quoted the formulae for @xmath22 flavours .\nthe mixing is such that the combination occurring in the axial anomaly ward identities , e.g. @xmath23 is not renormalised .\nsince @xmath18 is renormalised , its matrix elements satisfy renormalisation group equations with an anomalous dimension @xmath24 , so that in particular @xmath7 depends on the rg scale , set to @xmath25 in eq.(1 ) .\nwe emphasise that @xmath7 does _ not _ , as was initially supposed , measure the spin of the quark constituents of the proton .\nthe rg non - invariance of @xmath26 , which is a consequence of the anomaly , means that it is _ not _ a conserved current . only in the idealised case of a free dirac field\ndo the matrix elements of @xmath27 and spin coincide . to compare the sum rule with experiment , we use the following standard results : @xmath28 where @xmath29 and @xmath30 as fitted from hyperon and beta decays . we also take @xmath31 from tau decay data .\nthe ellis - jaffe sum rule is obtained by assuming that , in parton language , the strange quark polarisation in the proton vanishes , i.e. @xmath32 in eq.(3 ) .\nthis is equivalent to the ozi prediction @xmath33 and corresponds to @xmath34 in contrast , our result @xmath35 leads to @xmath36 we can also compare with the lowest order expectation in the skyrme model@xcite , according to which the proton decouples from the flavour singlet pseudoscalar channel ( @xmath37 in the language of sect.4 ) so that @xmath38 and @xmath39 these theoretical expectations are compared with the experimental data in fig.1 . the original emc result was@xcite @xmath40 which , with the above values for @xmath41 and @xmath42 , allows the following value of @xmath7 to be extracted : @xmath43 clearly , this value is barely consistent with our prediction .\nit is therefore extremely gratifying that the improved analysis by the smc collaboration quoted in @xcite now gives the new ` world average ' @xmath44 from which we deduce @xmath45 notwithstanding the large experimental errors , the agreement between the new data and our prediction is excellent .\nthe essential features of our method are easily described for a general deep inelastic scattering process .\nthe hadronic part of the scattering amplitude is given by the imaginary part of the two - current matrix element @xmath46 .\nthe ope is used to expand the large @xmath25 limit of the product of currents as a sum of wilson coefficients @xmath47 times renormalised composite operators @xmath48 as follows ( suppressing lorentz indices ) , @xmath49 the dominant contributions to the amplitude arise from the operators @xmath48 of lowest twist . within this set of lowest twist operators , those of spin @xmath50 contribute to the @xmath50th moment of the structure functions , i.e. @xmath51 the wilson coefficients are calculable in qcd perturbation theory\n, so the problem reduces to evaluating the target matrix elements of the corresponding operators .\nwe now introduce appropriately defined proper vertices @xmath52 , which are chosen to be 1pi with respect to a physically motivated basis set @xmath53 of renormalised composite operators .\nthe matrix elements are then decomposed into products of these vertices with zero - momentum composite operator propagators as follows , @xmath54 despite being non - perturbative , we can frequently evaluate the composite operator propagators using a combination of exact ward identities and dynamical approximations .\nall this is illustrated in @xcite .\nin essence , what we have done is to split the whole amplitude into the product of a ` hot qcd ' ( high momentum ) part described by qcd perturbation theory , a ` cold qcd ' part described by a ( non - perturbative , zero - momentum ) composite operator propagator and finally a target - dependent proper vertex .\nthe generic expression for a structure function sum rule is then : @xmath55 all the target dependence is contained in the vertex function @xmath52 .\nhowever , these are not unique they depend on the choice of the basis @xmath53 of composite operators .\nthis choice is made on physical grounds based on the relevant degrees of freedom , the aim being to parametrise the amplitude in terms of a minimal , but sufficient , set of vertex functions .\n( these play the rle of the non - perturbative parton distributions in the usual treatment ) .\na good choice can often lead to an almost direct correspondence between the proper vertices and physical couplings such as , e.g. , the pion - nucleon coupling @xmath56 .\nin particular , the proper vertices should be chosen whenever possible to be rg invariant .\nit is important to realise that the decomposition ( 17 ) is an _ exact _\nexpression , independent of the choice of the set of operators @xmath53 . a different choice of basis set merely changes the definition of the proper vertices .\nin particular , it is _ not _ to be understood that the set @xmath53 is in any sense a complete set and that choosing a finite number of operators ( such as the pseudoscalars @xmath57 and @xmath17 in sect.4 ) represents an approximation .\nwe now apply this method to the sum rule for @xmath3 .\nthe relevant ope is : @xmath58 assuming the absence of a massless pseudoscalar ( goldstone ) boson in the @xmath6 channel , we find @xmath59 where we have used the anomalous chiral ward identity to re - express @xmath60 as the forward matrix element of the renormalised gluon topological density @xmath17 .\n@xmath61 is the proton mass .\nwe now choose the composite operator basis @xmath53 to be the set of renormalised flavour singlet pseudoscalar operators @xmath17 and @xmath57 , where , up to a subtle but crucial normalisation factor ( see @xcite and @xcite for an explanation ) , the corresponding bare operator is simply @xmath62 .\nwe may then write ( c.f .\neq.(17 ) ) : @xmath63 where the composite operator propagators are at zero momentum and the proper vertices are 1pi with respect to @xmath17 and @xmath57 only .\nthe composite operator propagator in the first term in eq.(21 ) is the zero - momentum limit of an important quantity in qcd known as the topological susceptibility @xmath64 , viz .\n@xmath65 moreover , it can be shown exactly using chiral ward identities@xcite that the propagator @xmath66 at zero momentum is simply the square root of the first moment of the topological susceptibility .\nwe therefore find : @xmath67 the chiral ward identities also show that for qcd with massless quarks , @xmath68 actually vanishes .\nthis is in contrast to pure yang - mills theory , where @xmath68 is non - zero .\nwe therefore arrive at our basic result@xcite : @xmath69 the quantity @xmath1 is not rg invariant and scales with the anomalous dimension @xmath24 . on the other hand ,\nthe proper vertex has been chosen specifically so as to be rg invariant .\nthe renormalisation group properties of this decomposition are crucial to our resolution of the ` proton spin problem ' .\nour proposal is that we should expect the source of ozi violations to lie in rg non - invariant terms , i.e. in @xmath70 .\nthe reasoning is as follows . in the absence of the @xmath6 anomaly\n, the ozi rule would be an exact property of qcd .\nso the ozi violation is a consequence of the anomaly .\nbut it is the existence of the anomaly that is responsible for the non - conservation and hence non - trivial renormalisation of the axial current @xmath18 .\nwe therefore expect to find ozi violations in quantities sensitive to the anomaly , which we identify through their rg dependence on the anomalous dimension @xmath24 .\nthis seems reasonable since , if the ozi rule were to be good for such quantities , it would mean approximating a rg non - invariant , scale - dependent quantity by a scale - independent one . notice that we are _ not _ saying that the ozi violation is due to a large ( non - perturbative ) scaling effect dependent on @xmath24 .\nwe are simply using the dependence on the anomalous dimension to identify those quantities most likely to display significant differences from their ozi approximations .\nif this proposal is correct , we expect @xmath71 to be significantly suppressed relative to its ozi approximation of @xmath72 .\nthe proper vertex @xmath73 would behave exactly as expected according to the ozi rule .\nthat is , the ellis - jaffe violating suppression of the first moment of @xmath3 observed by emc would _ not _ be a special property of the proton at all , but would simply be due to an anomalously small value of the first moment of the qcd topological susceptibility @xmath70 .\nthis is our conjectured resolution@xcite of the ` proton spin problem ' .\nit is further supported by a number of experimental results in the pseudoscalar @xmath6 channel , notably in @xmath74 decays .\nsee @xcite for further discussion\n. putting all this together , we conjecture the following expression for the singlet form factor : @xmath75\nthe remaining task is to find a non - perturbative estimate of the first moment of the topological susceptibility , @xmath2 .\nthis is a fundamental quantity likely to reappear in many applications of qcd , and an evaluation from first principles represents a strong challenge to lattice gauge theory .\nof course , for a meaningful result it is necessary to work beyond the quenched approximation , close to the chiral limit . instead\n, we estimate @xmath2 using qcd spectral sum rules .\na full description of the calculation is given in @xcite and here we only quote the result . we have evaluated @xmath2 using subtracted dispersion relations with the laplace sum rule method , finding good stability , and have confirmed the result using the finite energy sum rule technique .\nthe spectral function is saturated with the single lightest pseudoscalar state , the @xmath76 .\nwe find @xmath77 a suppression of approx .\n@xmath78 relative to the ozi value @xmath79 .\nsubstituting this into eq.(25 ) finally gives our result ( 9 ) for @xmath7 .\nthe essential input parameter in the spectral sum rules is the @xmath76 mass .\n( a quite different result is found for @xmath2 in pure yang - mills theory , saturating the spectral function with a pseudoscalar glueball . ) in essence , the sum rules allow us to determine the relevant mass scale for ozi breaking in the pseudovector channel using as input the known ozi - violating @xmath76 mass from the pseudoscalar channel .\nthe link is the @xmath6 goldberger - treiman relation@xcite which underlies our approach .\nour conclusions are simply stated .\n@xmath8 does _ not _ measure spin .\nits suppression relative to the ozi ( ellis - jaffe ) value is due to an anomalously small value of @xmath2 in qcd and is _ not _ a special property of the proton .\nthe violation of the ellis - jaffe sum rule is _ not _ a problem in qcd the flavour singlet pseudovector channel is precisely where we should expect to find large ozi violations and , using spectral sum rules , we have given a successful quantitative prediction of @xmath8 and @xmath80 .\nthe @xmath3 sum rule does , however , present some problems for qcd - inspired models of the proton .\nthe skyrme model would have to be significantly extended to incorporate the @xmath81 effects characteristic of the @xmath6 anomaly . in the parton model , the effect can be incorporated ( though not as yet predicted ) by modifying the constituent quark expression ( 3 ) for @xmath8 to include a polarised gluon density @xmath82 with the necessary renormalisation group behaviour . for further details of this approach , see @xcite .\n9 emc : j. ashman et al .\n, phys . lett .\nb206 ( 1988 ) 364 ; nucl .\nb328 ( 1990 ) 1 .\nsmc : d. adams et al .\nb329 ( 1994 ) 399 .\ne143 : v. breton , these proceedings .\ns. narison , g.m .\nshore and g. veneziano , cern - th.7223/94 g.m .\nshore and g. veneziano , nucl .\nb381 ( 1992 ) 23 j. ellis , s.j . brodsky and m. karliner ,\nb206 ( 1988 ) 309 .\ng. altarelli and g. ross , phys .\nb212 ( 1988 ) 391 ; g. altarelli , these proceedings ." }, { "role": "assistant", "content": "recent work by the author in collaboration with s. narison and g. veneziano on the emc - smc - slac ` proton spin ' effect is reviewed . \n this uses a novel approach to deep inelastic scattering in which the matrix elements arising from the ope are factorised into composite operator propagators and proper vertices . for polarised @xmath0 scattering \n , the composite operator propagator is equated to the square root of the first moment of the qcd topological susceptibility , @xmath1 . \n we evaluate @xmath2 using qcd spectral sum rules and find a significant suppression relative to its ozi expectation . \n this is identified as the source of the violation of the ellis - jaffe sum rule for the first moment of the polarised proton structure function @xmath3 . \n our predictions , @xmath4 and @xmath5 , are in excellent agreement with the new smc data . \n this supports our earlier conjecture that the suppression in the flavour singlet component of the first moment of @xmath3 is a target - independent feature of qcd related to the @xmath6 anomaly and is not a special property of the proton structure ." } ]