niryuu/sni-each-converted huggingface dataset:
Paragraph: Bcl-XL is a pro-survival member of the Bcl-2 family that can be found in the outer mitochondrial membrane and in soluble cytosolic homodimers. Bcl-XL can bind pro-apoptotic members of this family preventing them from activating the execution phase of apoptosis. Bcl-XL has been shown to homodimerize in different ways, although most binding and structural assays have been carried out in the absence of its carboxyl terminal transmembrane domain. We show here that this domain can by itself direct protein oligomerization, which could be related to its previously reported role in mitochondrial morphology alterations and apoptosis inhibition. Vamp2 physically interacts with Vamp2 by blue native page (View interaction) Vamp2 physically interacts with Vamp2 by cross-linking study (View interaction) Bcl-Xl physically interacts with Bcl-Xl by blue native page (View interaction) Bcl-Xl physically interacts with Bcl-Xl by cross-linking study (View interaction) Ó 
 Title: Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL
Output: True
Paragraph: Background: Despite the seriousness of dengue-related disease, with an estimated 50-100 million cases of dengue fever and 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virusinfected cell lines and in patients developing dengue fever. Methodology/Principal Findings: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-kB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication. Conclusion/Significance: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy. 
 Title: Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients
Output: True
Paragraph: In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49Hmediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able PLOS Pathogens | 
 Title: Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus
Output: True
Paragraph: To extend the frontier of genome editing and enable the radical redesign of mammalian genomes, we developed a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks (DSBs) and single-strand breaks (SSBs). We used a set of gRNAs targeting repetitive elementsranging in target copy number from about 31 to 124,000 per cell. dBEs enabled survival after 5 large-scale base editing, allowing targeted mutations at up to ~13,200 and ~2610 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering. One Sentence Summary: Base editing with reduced DNA nicking allows for the simultaneous 10 
 Title: Enabling large-scale genome editing by reducing DNA nicking
Output: True
Paragraph: SARS-CoV-2 can be shed in the stool of patients in the recovery phase. Children show a longer shedding time than adults. We analyzed the possible causes of this finding and recommend that a negative stool sample be included in a patient's discharge criteria. Please cite this article as: Ma X et al., Do children need a longer time to shed SARS-CoV-2 in stool than adults?, Journal of Microbiology, Immunology and Infection, https://doi. 
 Title: Do children need a longer time to shed SARS- CoV-2 in stool than adults?
Output: True
Paragraph: Background: Anterior gradient homolog 2 (AGR2) is a functional protein with critical roles in a diverse range of biological systems, including vertebrate tissue development, inflammatory tissue injury responses, and cancer progression. Clinical studies have shown that the AGR2 protein is overexpressed in a wide range of human cancers, including carcinomas of the esophagus, pancreas, breast, prostate, and lung, making the protein as a potential cancer biomarker. However, the general biochemical functions of AGR2 in human cells remain undefined, and the signaling mechanisms that drive AGR2 to inhibit p53 are still not clearly illustrated. Therefore, it is of great interest to develop molecular probes specifically recognizing AGR2 for its detection and for the elucidation of AGR2-associated molecular mechanism. Methodology/Principal Findings: Through a bead-based and flow cytometry monitored SELEX technology, we have identified a group of DNA aptamers that can specifically bind to AGR2 with K d values in the nanomolar range after 14 rounds of selections. Aptamer C14B was chosen to further study, due to its high binding affinity and specificity. The optimized and shortened C14B1 has special G-rich characteristics, and the G-rich region of this binding motif was further characterized to reveal an intramolecular parallel G-quadruplex by CD spectroscopy and UV spectroscopy. Our experiments confirmed that the stability of the G-quadruplex structure was strongly dependent on the nature of the monovalent ions and the formation of G-quadruplex structure was also important for the binding capacity of C14B1 to the target. Furthermore, we have designed a kind of allosteric molecule beacon (aMB) probe for selective and sensitive detection of AGR2. Conclusion/Significance: In this work, we have developed new aptamer probes for specific recognition of the AGR2. Structural study have identified that the binding motif of aptamer is an intramolecular parallel G-quadruplex structure and its structure and binding affinity are strongly dependent on the nature of the monovalent ion. Furthermore, with our design of AGR2-aMB, AGR2 could be sensitively and selectively detected. This aptamer probe has great potential to serve as a useful tool for early diagnosis and prognosis of cancer and for fundamental research to elucidate the biochemical functions of AGR2. 
 Title: Identification, Characterization and Application of a G- Quadruplex Structured DNA Aptamer against Cancer Biomarker Protein Anterior Gradient Homolog 2
Output: False
Paragraph: The complete nonstructural NS5 gene of Japanese encephalitis virus (JEV) was amplified and cloned into an expression vector. The NS5 protein was expressed in Escherichia coli and purified by His-tag based affinity chromatography. This recombinant NS5 protein exhibited RNA-dependent RNA polymerase (RdRp) activity in vitro in the absence of other viral or cellular factors. The RNA polymerase activity was dependent on divalent cations, and Mn 2þ was found to be 20 times more effective than Mg 2þ in coordinating the catalytic reaction of RdRp, while Ca 2þ inhibited enzyme activity. The optimal reaction conditions for the in vitro RdRp reaction were established. Characterization of the RdRp reaction products demonstrated that the JEV NS5 protein can initiate RNA synthesis through a de novo initiation mechanism in our in vitro reaction system. Comparing the efficiency of different RNA templates, we found that JEV NS5 protein was more efficient in using negative-strand RNA templates, indicating that the JEV NS5 protein is in-volved in regulating the ratio of positive-to negativestrand RNA. Four amino acid sequence motifs crucial for RdRp activity were also identified using site-directed mutagenesis analysis. All substitutions of the conserved residues within these motifs led to a complete inactivation or severe loss of enzyme activity. 
 Title: Identification and characterization of RNA-dependent RNA polymerase activity in recombinant Japanese encephalitis virus NS5 protein
Output: False
Paragraph: The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods. The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results. Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions. Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations. 
 Title: Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience
Output: True
Paragraph: The field of viral molecular biology has reached a precipice for which pioneering studies on the structure of viral RNAs are beginning to bridge the gap. It has become clear that viral genomic RNAs are not simply carriers of hereditary information, but rather are active players in many critical stages during replication. Indeed, functions such as cap-independent translation initiation mechanisms are, in some cases, primarily driven by RNA structural determinants. Other stages including reverse transcription initiation in retroviruses, nuclear export and viral packaging are specifically dependent on the proper 3-dimensional folding of multiple RNA domains to recruit necessary viral and host factors required for activity. Furthermore, a large-scale conformational change within the 5′-untranslated region of HIV-1 has been proposed to regulate the temporal switch between viral protein synthesis and packaging. These RNA-dependent functions are necessary for replication of many human disease-causing viruses such as severe acute respiratory syndrome (SARS)-associated coronavirus, West Nile virus, and HIV-1. The potential for antiviral development is currently hindered by a poor understanding of RNA-driven molecular mechanisms, resulting from a lack of structural information on large RNAs and ribonucleoprotein complexes. Herein, we describe the recent progress that has been made on characterizing these large RNAs and provide brief descriptions of the techniques that will be at the forefront of future advances. Ongoing and future work will contribute to a more complete understanding of the lifecycles of retroviruses and RNA viruses and potentially lead to novel antiviral strategies. 
 Title: Progress and outlook in structural biology of large viral RNAs NIH Public Access
Output: True
Paragraph: Supplementary Text 1: Details of specimen collection, processing, polymerase chain reaction 34 assays, quality control measures, and assay parameters used to identify respiratory viruses. Specimen collection 36 All swabs were collected using a plastic-shaft, rayon-budded swab in a transport tube with a foam 37 pad reservoir soaked with viral transport medium (Virocult MW950, Medical Wire & Equipment, 38 Wiltshire, England). A single swab was used to sample both nostrils. 39 Quality Control measures 40 A known amount of whole equine herpesvirus (EHV) spiked into each sample assessed nucleic 41 acid extraction quality and presence of polymerase chain reaction (PCR) inhibitors. 1 Any extract 42 having a >3 cycle-threshold (Ct) difference to that of the expected value by EHV real-time PCR 43 assays was considered to have failed quality control and the sample was re-extracted. Specimen quality was assessed by testing for a marker of human genomic DNA, endogenous 46 retrovirus-3 (ERV-3). 2 We have demonstrated previously that among specimens with an ERV-3 Ct a adjusted for clustering using sandwich estimators to account for within-infant correlation between observations; b Individual rhinovirus species do not add up to 'All rhinovirus' detections because of a combination of more than one rhinovirus species detected within the same ARI episode, or single new virus detection episodes where HRV positive specimens could not be sequenced. 
 Title: Viruses causing lower respiratory symptoms in children younger than 2-years of age: 1 findings from the ORChID birth cohort. 2
Output: True
Paragraph: Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus-host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses. 
 Title: Virus-Host Coevolution with a Focus on Animal and Human DNA Viruses
Output: False
Paragraph: An association between many psychiatric and gluten-related disorders has been known for some time. In the case of schizophrenia and mood disorders, the major psychiatric disorders, there is much evidence, not without contradictions, of a possible association between schizophrenia and celiac disease. The association between mood disorders and gluten-related disorders, especially celiac disease, has only been studied for depression, often coupled with anxiety, and very recently for bipolar disorder. Since non-celiac gluten sensitivity is now known to be different from celiac disease, many studies have shown that gluten sensitivity is also associated with major psychiatric disorders. Here we review the literature on the association between schizophrenia/mood disorders and celiac disease/ gluten sensitivity, pointing out the differences between these associations. 
 Title: Celiac and non-celiac gluten sensitivity: a review on the association with schizophrenia and mood disorders
Output: False
Paragraph: Lentiviral vectors are increasingly used in clinical trials to treat genetic diseases. Our research has focused on strategies to improve lentiviral gene transfer efficiency in the airways. Previously we demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the baculovirus envelope glycoprotein GP64 (GP64-FIV) efficiently transduced mouse nasal epithelia in vivo but transduced mouse intrapulmonary airways with 10-fold less efficiency. Here, we demonstrate that members of a family of proteins with antiviral activity, interferon-induced transmembrane proteins (IFITMs), are more highly expressed in mouse intrapulmonary airways as compared with mouse nasal airways. Using GP64-and VSV-G (vesicular stomatitis virus G glycoprotein)-pseudotyped FIV, we show that expression of mouse IFITM1, IFITM2, and IFITM3 restricts gene transfer. Further, we show that both the nasal and intrapulmonary airways of IFITM locus knockout mice are more efficiently transduced with GP64-FIV than their heterozygous littermates. In anticipation of transitioning our studies into pig models of airway disease and clinical trials in humans, we investigated the ability of pig and human IFITMs to restrict lentiviral gene transfer. We observed that both human and pig IFITMs partially restricted both VSV-G-FIV and GP64-FIV transduction in vitro. Previous studies have focused on IFITM-mediated restriction of replication-competent wild-type viruses; however, these results implicate the IFITM proteins as restriction factors that can limit lentivirus-based vector gene transfer to airway epithelia. The findings are relevant to future preclinical and clinical airway gene therapy trials using lentivirus-based vectors. 
 Title: Human, Pig, and Mouse Interferon-Induced Transmembrane Proteins Partially Restrict Pseudotyped Lentiviral Vectors
Output: True
Paragraph: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted. 
 Title: BMC Immunology Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells
Output: True
Paragraph: The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC ¼ 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC ¼ 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homology-reduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at: 
 Title: Predicting linear B-cell epitopes using string kernels
Output: True
Paragraph: An updated literature survey identified 1,407 recognized species of human pathogen, 58% of which are zoonotic. Of the total, 177 are regarded as emerging or reemerging. Zoonotic pathogens are twice as likely to be in this category as are nonzoonotic pathogens. Emerging and reemerging pathogens are not strongly associated with particular types of nonhuman hosts, but they are most likely to have the broadest host ranges. Emerging and reemerging zoonoses are associated with a wide range of drivers, but changes in land use and agriculture and demographic and societal changes are most commonly cited. However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population. 
 Title: Host Range and Emerging and Reemerging Pathogens Host Range and Emerging and Reemerging Pathogens Emerging Infectious Diseases • www
Output: False
Paragraph: Aims: The chronic consumption of alcohol is known to result in neurodegeneration and impairment of cognitive function. Pathological and neuroimaging studies have confirmed that brain atrophy in alcoholics is mainly due to widespread white matter (WM) loss with neuronal loss restricted to specific regions, such as the prefrontal cortex. Neuroimaging studies of cigarette smokers also suggest that chronic inhalation of tobacco smoke leads to brain atrophy, although the neurotoxic component is unknown. As a high proportion of chronic alcoholics also smoke cigarettes it has been hypothesized that at least some alcohol-related brain damage is due to tobacco smoke exposure. Methods: 39 Long Evans rats were subjected to 8 weeks exposure to alcohol and/or 5 weeks coexposure to nicotine-specific nitrosamine ketone (NNK), a proxy for tobacco smoke. Their frontal WM was then assayed with transmission electron microscopy. Results: NNK and ethanol co-exposure had a synergistic effect in decreasing myelinated fibre density. Furthermore, NNK treatment led to a greater reduction in myelin sheath thickness than ethanol whereas only the ethanol-treated animals showed a decrease in unmyelinated fibre density. Conclusion: These data suggest that NNK causes WM degeneration, an effect that is exacerbated by alcohol, but unlike alcohol, it has little impact on the neuronal components of the brain. 
 Title: The Differential Effects of Alcohol and Nicotine- Specific Nitrosamine Ketone on White Matter Ultrastructure
Output: False
Paragraph: The bovine enteric calici-like virus, Newbury agent 1 (NA1) was characterised to determine if it is a member of the Caliciviridae and to establish its antigenic relationship to the established bovine enteric calicivirus Newbury agent 2 (NA2). Solid phase immune electron microscopy (SPIEM) allowed quantification of NA1 virions and identification of faecal samples with optimal virus levels. NA1 particles were 36.6 nm in diameter, had an indefinite surface structure resembling that of human small round structured viruses (SRSVs), and a buoyant density of 1.34 g ml 31 . A single capsid protein of 49.4 kDa was detected by Western blotting in purified NA1 preparations prepared from post-infection but not pre-infection faecal samples and with post-but not pre-infection sera. NA1 was antigenically unrelated to the bovine enteric calicivirus NA2 by SPIEM. These properties were consistent with classification of NA1 within the Caliciviridae but demonstrated heterogeneity in the capsid composition of bovine enteric caliciviruses. ß 
 Title: Characterisation of the bovine enteric calici-like virus, Newbury agent 1
Output: False
Paragraph: Background: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals. Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop. Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines. Methodology and Principal Findings: A recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed. Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette. Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle. Specific antibody was induced in all vaccinated animals. After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one. Furthermore, a PD 50 (50% bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine. The result showed the subunit vaccine could achieve 6.34 PD 50 per dose. The results suggest that this strategy might be used to develop the new subunit FMDV vaccine. 
 Title: Expression of Foot-and-Mouth Disease Virus Capsid Proteins in Silkworm-Baculovirus Expression System and Its Utilization as a Subunit Vaccine
Output: False
Paragraph: Background: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). Results: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. Conclusions: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application. 
 Title: The discovery and identification of a candidate proteomic biomarker of active tuberculosis
Output: False
Paragraph: For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. Ultimately, these kinases, and the cellular signaling pathways that they exploit, may serve as therapeutic targets for treating patients. Currently, small molecule inhibitors of kinases are under investigation as therapy for herpes viral infections. Additionally, a number of cellular or host-directed tyrosine kinase inhibitors that have been previously FDA-approved for cancer treatment are under study in animal models and clinical trials, as they have shown promise for the treatment of various viral infections as well. This review will highlight the wide range of viral proteins phosphorylated by viral and cellular kinases, and the potential for variability of kinase recognition sites within viral substrates to impact phosphorylation and kinase prediction. Research studying kinase-targeting prophylactic and therapeutic treatments for a number of viral infections will also be discussed. 
 Title: Phosphorylation events during viral infections provide potential therapeutic targets
Output: True
Paragraph: After infecting the Vero E6 cells by nasal/throat swabs collected from SARS patients, we studied the SARS-associated virus by electron microscopy and molecular biological technique. The results show that the diameter of newly isolated virus is about 50nm without envelope or 100 nm with envelope. The virus was proved to be a new coronavirus by RT-PCR and it responded positively to convalescent-phase serum specimen from SARS patients, which is the evidence that this new virus is etiologically linked to the outbreak of SARS. The morphogenesis and distribution of the virus are also discussed in this article. 
 Title: Morphology and Morphogenesis of Severe Acute Respiratory Syndrome (SARS)-associated Virus
Output: True
Paragraph: The objective of this study was to develop a symptom scoring system for use in clinical studies that differentiates children with cold symptoms who have an identifiable viral etiology for their upper respiratory tract infection (URI) from those in whom no virus is detected. Nasal swabs for PCR testing for identification of respiratory viruses were obtained on children aged 2-11 y at baseline and when parents thought their child was developing a cold. Parentalrecorded severity of specific symptoms in children with and without a documented viral URI were compared. Nasal swabs were obtained on 108 children whose parents reported their child was developing a cold. A viral etiology was identified in 62 of 108 (57.4%) samples. Symptom measures that best differentiated children with a viral etiology from those without were significant runny nose and significant cough on days 1-4 of the illness. A URI symptom score was developed based on these symptoms, with a sensitivity of 81.4%, specificity of 61.9%, and accuracy of 73.3%. Parental impression is only a moderately accurate predictor of viral URI in children. Our URI symptom score provided a more accurate method for identifying children with viral URIs for clinical studies. (Pediatr Res 68: 252-257, 2010) 
 Title: Development of a Symptom Score for Clinical Studies to Identify Children With a Documented Viral Upper Respiratory Tract Infection
Output: True
Paragraph: Background Acute respiratory tract infections (ARTIs) are one of the major causes of morbidity and mortality among young children in developing countries. Information on the incidence of human metapneumovirus (hMPV) and human bocavirus (HBoV) infections in developing countries, especially among rural children, is very limited. Objectives This study was conducted to identify whether these viruses were associated with ARTI among children B5 years of age in rural and peri-urban populations in South India. Methods The study was cross-sectional with prospective sample collection. Oropharyngeal swabs were collected from children B5 years of age presenting with ARTI. None of the children in this study were known to have any immunosuppressive conditions. The two viruses, hMPV and HBoV, were identified using semi-nested polymerase chain reaction (PCR) assays and one-step PCR assays, respectively. The lower limits of detection of hMPV and HBoV were 6.69 9 10 5 plasmid copies and 5.77 9 10 3 plasmid copies, respectively, per 5 lL PCR reaction input. Results The frequency of hMPV infection in children was higher than that of HBoV infection. The different frequencies of hMPV in patients in various age groups with upper and lower respiratory tract infections were compared, and the variance was found to be insignificant. In the 38 children who were hMPV positive, the majority (73.7 %) were from rural communities. The overall hMPVpositive rate was higher in the rural population than in the peri-urban population, but the difference was statistically insignificant. The youngest age at which hMPV-positive status was recorded was 5 months. Conclusion This study demonstrated that hMPV was associated with a significant number (i.e.[10 %) of ARTIs in children in South India, whereas a relatively smaller number of HBoV infections was observed. 
 Title: Molecular Detection of Human Metapneumovirus and Human Bocavirus on Oropharyngeal Swabs Collected from Young Children with Acute Respiratory Tract Infections from Rural and Peri-Urban Communities in South India
Output: True
Paragraph: Background: Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US. We developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US. The model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years. Since not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development. 
 Title: BMC Infectious Diseases The United States and Canada as a coupled epidemiological system: An example from hepatitis A
Output: False
Paragraph: In this study, the results of an airflow investigation conducted on 7 June 2015 as part of a series of epidemiologic investigations at Pyeongtaek St. Mary's Hospital, South Korea, were investigated. The study involved 38 individuals who were infected directly and indirectly with Middle East Respiratory Syndrome (MERS), by a super-spreader patient. Tracer gas experiments conducted on the eighth floor, where the initial patient was hospitalized, confirmed that the tracer gas spread to adjacent patient rooms and rooms across corridors. In particular, the experiment with an external wind direction and speed similar to those during the hospitalization of the initial patient revealed that the air change rate was 17-20 air changes per hour (ACH), with air introduced through the window in the room of the infected patient (room 8104). The tracer gas concentration of room 8110, which was the farthest room, was 7.56% of room 8104, indicating that a high concentration of gas has spread from room 8104 to rooms across the corridor. In contrast, the tracer gas was barely detected in a maternity ward to the south of room 8104, where there was no secondary infected patient. Moreover, MERS is known to spread mainly by droplets through close contact, but long-distance dispersion is probable in certain environments, such as that of a super-spreader patient hospitalized in a room without ventilation, hospitals with a central corridor type, and indoor airflow dispersion due to external wind. 
 Title: Airflow as a Possible Transmission Route of Middle East Respiratory Syndrome at an Initial Outbreak Hospital in Korea
Output: False
Paragraph: G-Cubed is a multi-country, multi-sector, intertemporal general equilibrium model that has been used to study a variety of policies in the areas of environmental regulation, tax reform, monetary and fiscal policy, and international trade. It is designed to bridge the gaps between three areas of research e econometric general equilibrium modeling, international trade theory, and modern macroeconomics e by incorporating the best features of each. This chapter describes the theoretical and empirical structure of the model, summarizes its applications and contributions to the literature, and discusses two example applications in detail. 
 Title: A Global Approach to Energy and the Environment: The G-Cubed Model
Output: False
Paragraph: The COVID-19 pandemic has shown a markedly low proportion of cases among children. Age disparities in observed cases could be explained by assortative mixing patterns and reactive school closures which decrease mixing between children, or by children exhibiting lower susceptibility to infection, or by children having a lower propensity to show clinical symptoms. We formally test these hypotheses by fitting an age-structured mathematical model to epidemic data from six countries, finding 1 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint . https://doi.org/10.1101/2020.03.24.20043018 doi: medRxiv preprint / strong age dependence in the probability of developing clinical symptoms, rising from around 20% in under 10s to over 70% in older adults. We find that interventions aimed at halting transmission in children may have minimal effects on preventing cases depending on the relative transmissibility of subclinical infections. Our estimated age-specific clinical fraction has implications for the expected global burden of clinical cases because of demographic differences across settings. In younger populations, the expected clinical attack rate would be lower, although it is likely that comorbidities in low-income countries will affect disease severity. Without effective control measures, regions with older populations may see disproportionally more clinical cases, particularly in the later stages of the pandemic. 
 Title: Age-dependent effects in the transmission and control of COVID-19 epidemics
Output: False
Paragraph: Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. 
 Title: Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives
Output: False
Paragraph: a b s t r a c t N-7 and 2 0 -O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m 7 GpppN; cap 1, m 7 GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2 0 -O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2 0 -O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5 0 -end of viral RNA modulate host pathogen recognition responses to promote infection and disease. 
 Title: Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation
Output: True
Paragraph: The metabolism of Epimedium-derived flavonoid glycosides (EF, with icariin as the main component) in rabbit intestinal flora and its inhibition by gluconolactone were investigated in this paper to help reveal the metabolic pathway of EF in rabbits and to identify the in vivo bioactive components of EF in the prevention of steroid-associated osteonecrosis. METHODS: EF were incubated at 37 °C anaerobically with rabbit intestinal flora, and then water-saturated ethyl acetate was used for sample extraction at different time points. Furthermore, gluconolactone was added at different concentrations (8, 12 and 16 mg·mL −1 ) to study its inhibition of the metabolism of EF in rabbit intestinal flora. The separation was performed on a ODS column by gradient elution with acetonitrile-water (including 0.1% formic acid respectively) as mobile phase at detection wavelength of 335 nm. RESULTS: EF were metabolized to icariside II in 2 h, and then to icaritin when incubated for 8 h; gluconolactone showed the inhibition of EF metabolism in rabbit intestinal flora in a concentration-dependent manner. CONCLUSION: EF were found to be metabolized rapidly by hydrolysis of rabbit intestinal flora to produce icariside II and icaritin; and the total inhibition was achieved by gluconolactone at a concentration of 16 mg·mL −1 . [KEY WORDS] Epimedium-derived flavonoid glycosides; Prevention of steroid-associated osteonecrosis; Metabolism in rabbit intestinal flora; Gluconolactone; Inhibition [CLC Number] R965 [Document code] A [Article ID] 1672-3651(2011)06-0461-05 [*Corresponding author] YAO Zhi-Hong: Associate Prof., 
 Title: Chinese Journal of Natural Medicines Metabolism of Epimedium-derived Flavonoid Glycosides in Intestinal Flora of Rabbits and Its Inhibition by Gluconolactone
Output: False
Paragraph: Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea (PED). PED, characterized by acute diarrhea, vomiting, dehydration, has caused serious economic losses in pig industry worldwide. Here, we demonstrate that activation of a disintergrin and metalloprotease 17 (ADAM17) induced the decrease of PEDV infection in HEK293 and IPEC-J2 cells and the downregulation of cell surface aminopeptidase N (APN) expression, an important entry factor for PEDV infection. Furthermore, overexpression of ADAM17 suppressed PEDV infection in HEK293 and IPEC-J2 cells, whereas ablation of ADAM17 expression using ADAM17 specific siRNA resulted in a corresponding increase of PEDV infection and an upregulation of cell surface APN expression. Taken together, these data demonstrate that modulation of APN expression by metalloprotease ADAM17 regulates PEDV infection. Hence, the reduction in APN expression represents another component of the anti-PEDV infection response initiated by ADAM17. 
 Title: Metalloprotease ADAM17 regulates porcine epidemic diarrhea virus infection by modifying aminopeptidase N
Output: False