niryuu/sni-each-converted huggingface dataset:
Paragraph: H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses. 
 Title: Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia
Output: True
Paragraph: Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses. 
 Title: Virus interactions with human signal transduction pathways NIH Public Access
Output: False
Paragraph: C ell-to-cell spread of retroviruses via virological synapse (VS) contributes to overall progression of disease. VS are specialized pathogen-induced cellular structures that facilitate cell-to-cell transfer of HIV-1 and HTLV-1. VS provide a mechanistic explanation for cell-associated retroviral replication. While VS share some common features with neurological or immunological synapses, they also exhibit important differences. The role of VS might not be limited to human retroviruses and the emerging role of a plant synapse suggests that VS might well be conserved structures for cell-cell spreading of both animal and plant viruses. Dissection of the VS is just at its beginning, but already offers ample information and fascinating insights into mechanisms of viral replication and cell-to-cell communication. The complex functioning of biological systems requires the capacity of cells to interact in a synchronized manner. The capacity of cells to come in close contact with one another enables rapid exchange of information through directed secretion. In complex systems such as the nervous and immune systems, characteristic rearrangements of plasma membrane proteins appear at the cell-cell junction, called synapse. A synapse is defined as "a stable adhesive junction across which information is relayed by directed secretion".^ The concept of the neural synapse (NS) was first introduced over a century ago and was depicted as a stable structure organized and specialized in intercellular signaling between neurons. Plasma membranes of the pre and post-synaptic neurons are contiguous and information is conveyed to the downstream cell via secretion of neurotransmitters. In order to generate a favorable microenvironment, stabilization of synapse by scaffolding proteins, mainly cadherins and other adhesion molecules, is required (reviewed in re£ 1). In the immune system, interactions between T cells and antigen presenting cells (APC) are essential for an effective adaptive immune response. By analogy with the nervous system, these specialized interactions occur via an immunological synapse (IS). The concept of the IS has been extended to several types of cell-cell interactions within the context of the immune system (signaling via receptor engagement, lytic granules, directed secretion of cytokines) since its first description 20 years ago (reviewed in refs. 2,3) . Although the IS shares many similarities with the NS, it also differs in two aspects. First, the panel of receptors and adhesion proteins recruited to the IS diverges from those in the neural synapse: integrins play the central role in stabilizing IS. Second, the establishment of an IS is a dynamic process between moving cells, whereas the neural synapse is long-lived. Therefore, in 
 Title: Virological Synapse for Cell-Cell Spread of Viruses
Output: False
Paragraph: We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day ؊5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P ‫؍‬ .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI. 
 Title: CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1-Gy Total Body Irradiation
Output: False
Paragraph: ACE2 is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1-7). We hypothesized that ACE2 is part of the brain renin-angiotensin system (RAS) and its expression regulated by the other elements of this system. ACE2 immuno-staining was performed in transgenic mouse brain sections from NSE-AT 1A (overexpressing AT 1A receptors), R + A + (overexpressing angiotensinogen, and renin) and control (non transgenic littermates) mice. Results show that ACE2 staining is widely distributed throughout the brain. Using cell type-specific antibodies, we observed that ACE2 staining is present in the cytoplasm of neuronal cell bodies but not in glial cells. In the subfornical organ, an area lacking the blood brain barrier and sensitive to blood borne angiotensin-II, ACE2 was significantly increased in transgenic mice. Interestingly, ACE2 mRNA and protein expression were inversely correlated in the nucleus of tractus solitarius/dorsal motor nucleus of the vagus and the ventrolateral medulla, when comparing transgenic to non-transgenic mice. These results suggest that ACE2 is localized to the cytoplasm of neuronal cells in the brain, and that ACE2 levels appear highly regulated by other components of the RAS, confirming its involvement in this system. Moreover, ACE2 expression in brain structures involved in the control of cardiovascular function suggests that the carboxypeptidase may have a role in the central regulation of blood pressure and diseases involving the autonomic nervous system such as hypertension. 
 Title: Differential Expression of Neuronal ACE2 in Transgenic Mice with Overexpression of the Brain Renin-angiotensin System
Output: False
Paragraph: Purpose of the review-We describe the history of passive immunization to provide context for the series of articles to follow. The history of passive immunization with antibodies to prevent or treat infectious diseases is a story of different eras. There was an extraordinary era of discovery and clinical implementation before the chemical nature of antibodies was even known. This empirical process provided the resources and reagents used to describe and characterize humoral immunity, better define the chemical properties and structure of antibodies, and extend the clinical use of immunoglobulin products to treat or prevent multiple viral and bacterial diseases over the ensuing several decades. The next distinct era came with the discovery of processes to produce monoclonal antibodies (mAb), and development of more specific therapies. Interestingly, mAb technology resulted in many products to treat autoimmune and allergic diseases, but only one common infectious disease, respiratory syncytial virus, and only in a restricted population of highrisk infants. Recent findings-The current era began with a series of publications in 2008 demonstrating processes for rapidly producing human mAbs. Summary-This technology combined with new sequencing technology, advances in structural biology, atomic-level molecular design, and increased capacity for synthetic biology, promises new opportunities to apply passive immunization to the prevention and treatment of infectious diseases. 
 Title: History of Passive Antibody Administration for Prevention and Treatment of Infectious Diseases
Output: True
Paragraph: The paramyxovirus family includes important human pathogens such as measles, mumps, respiratory syncytial virus and the recently emerged, highly pathogenic Hendra and Nipah viruses. The viral fusion (F) protein plays critical roles in infection, promoting both the viral-cell membrane fusion events needed for viral entry as well as cell-cell fusion events leading to syncytia formation. We describe the surprising finding that addition of the short epitope HA tag to the cytoplasmic tail (CT) of the Hendra virus F protein leads to a significant increase in cell-cell membrane fusion. This increase was not due to alterations in surface expression, cleavage state, or association with lipid microdomains. Addition of a Myc tag of similar length did not alter Hendra F fusion activity, indicating that the observed stimulation was not solely a result of lengthening the CT. Three tyrosine residues within the HA tag were critical for the increase in fusion, suggesting C-terminal tyrosines may modulate Hendra fusion activity. The effects of HA tag addition varied with other fusion proteins, as parainfluenza virus 5 F-HA showed decreased surface expression and no stimulation in fusion. These results indicate that additions to the C-terminal end of the F protein CT can modulate protein function in a sequence specific manner, reinforcing the need for careful analysis of epitope tagged glycoproteins. In addition, our results implicate C-terminal tyrosine residues in modulation of the membrane fusion reaction promoted by these viral glycoproteins. 
 Title: C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein
Output: False
Paragraph: The study evaluated the effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain (ADG) and mortality and described the clinical manifestations in four herds suffering from the syndrome. NNPDS is a diarrhoeic syndrome affecting piglets within the first week of life, which is not caused by enterotoxigenic Escherichia coli (ETEC), Clostridium perfringens (C. perfringens) type A/C, Clostridium difficile (C. difficile), rotavirus A, coronavirus, Cystoisospora suis, Strongyloides ransomi, Giardia spp or Cryptosporidium spp. Results: Piglets were estimated to have a negative ADG of 9 and 14 g when diarrhoeic for 1 day and >1 day respectively. However, if only diarrhoeic on the day of birth, no negative effect on ADG was seen. Piglets originating from severely affected litters were estimated to have a reduced ADG of 38 g. The study did not show an overall effect of diarrhoea on mortality, but herd of origin, sow parity, birth weight, and gender were significantly associated with mortality. In one of the herds, approximately 25% of the diarrhoeic piglets vs. 6% of the non-diarrhoeic piglets died, and 74% of necropsied piglets were diagnosed with enteritis. These findings indicate that the high mortality seen in this herd was due to diarrhoea. Conclusions: NNPDS negatively affected ADG in piglets, and even piglets that were diarrhoeic for one day only experienced a reduction in ADG. However, the study showed that diarrhoea restricted to the day of birth did not affect ADG and suggested this phenomenon to be unrelated to the syndrome. Since the diarrhoeal status of the litter had important effects on ADG, future research on NNPDS probably ought to focus on piglets from severely affected litters. The study showed important dissimilarities in the course of diarrhoea between the herds, and one herd was considerably more affected than the others. Within this herd, NNPDS seemed to be associated with a higher mortality, whereas in general the study did not show lethal effects of NNPDS. 
 Title: The effect of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) on average daily gain and mortality in 4 Danish pig herds
Output: False
Paragraph: Background: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR), transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website 
 Title: Coronavirus 3CL pro proteinase cleavage sites: Possible relevance to SARS virus pathology
Output: True
Paragraph: The ability to comprehensively characterize exposures and immune responses to viral infections will be critical to better understanding human health and disease. We previously described the VirScan system, a phage-display based technology for profiling antibody binding to a comprehensive library of peptides designed to represent the human virome. The previous VirScan analytical approach did not fully account for disproportionate representation of viruses in the library or for antibody cross-reactivity among sequences shared by related viruses. Here we present the 'AntiViral Antibody Response Deconvolution Algorithm' ('AVARDA'), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection at species-level resolution by considering alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. By comparing acute and convalescent sera, AVARDA successfully confirmed or detected antibody responses to human herpesviruses 1, 3, 4, 5, and 6, thereby improving the rate of diagnosing viral encephalitis in this cohort by 62.5%. We further assessed AVARDA's utility in the setting of an epidemiological study, demonstrating its ability to determine infections acquired in a child followed prospectively from infancy. We consider ways in which AVARDA's conceptual framework may be further developed in the future and describe how its analyses may be extended beyond investigations of viral infection. AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases. All rights reserved. No reuse allowed without permission. 
 Title: Deconvoluting Virome-Wide Antiviral Antibody Profiling Data
Output: True
Paragraph: Background-The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M-, L-and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesised in the liver. Methods-Serum samples from 75 patients enrolled by the U.S. ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich-type immunoassays (ELISA, TRIFMA). Results-At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls ((median(interquartile range) 0.72 μg/ml(0.91) vs. 1.15(1.92)(p=0.02)), and increased significantly by day 3 (0.83 μg/ml(0.94)(p=0.01)). The M-ficolin level was 60% lower (0.54 μg/ ml(0.50) vs. 1.48(1.01)(p<0.0001)). The CL-L1 level at day 1 was slightly higher compared with healthy controls (3.20 μg/ml(2.37) vs. 2.64(0.72)(p=0.11)); this was significant at day 3 (3.35(1.84)(p=0.006)). H-and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 (0.96 μg/ml(1.15) vs. 0.60(0.60)(p=0.02)) and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted (1.61 μg/ ml(1.19) vs. 2.17(2.19)(p=0.02)). 
 Title: Circulating mannan-binding lectin, M-, L-, H-ficolin, and collectin-liver-1 levels in patients with acute liver failure
Output: False
Paragraph: An explosion of knowledge and technology is revolutionizing medicine and patient care. Novel testing must be brought to the clinic with safety and accuracy, but also in a timely and cost-effective manner, so that patients can benefit and laboratories can offer testing consistent with current guidelines. Under the oversight provided by the Clinical Laboratory Improvement Amendments, laboratories have been able to develop and optimize laboratory procedures for use in-house. Quality improvement programs, interlaboratory comparisons, and the ability of laboratories to adjust assays as needed to improve results, utilize new sample types, or incorporate new mutations, information, or technologies are positive aspects of Clinical Laboratory Improvement Amendments oversight of laboratory-developed procedures. Laboratories have a long history of successful service to patients operating under Clinical Laboratory Improvement Amendments. A series of detailed clinical examples illustrating the quality and positive impact of laboratory-developed procedures on patient care is provided. These examples also demonstrate how Clinical Laboratory Improvement Amendments oversight ensures accurate, reliable, and reproducible testing in clinical laboratories. 
 Title: The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care
Output: True
Paragraph: HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4 + T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection. 
 Title: Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy
Output: False
Paragraph: Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple infected lions and anecdotal reports of lion morbidity associated with FIV sero-prevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple infected lions displayed a significant elevation in the prevalence of AIDS defining conditions: lymphandenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters and elevated liver enzymes and serum proteins. Spleen and lymph node laparoscopic biopsies from free-ranging FIVple infected lions (N=8) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodefieciency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude 
 Title: PATHOLOGICAL MANIFESTATIONS OF FELINE IMMUNODEFICIENCY VIRUS (FIV) INFECTION IN WILD AFRICAN LIONS NIH Public Access
Output: False
Paragraph: The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro-and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding (''lectin'') and receptor-destroying sialate O-acetylesterase (''esterase'') domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O-to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis. 
 Title: The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture
Output: True
Paragraph: Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens-Ebola virus, influenza virus, SARS CoV, and rabies virus-self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development. Citation Webb SR, Smith SE, Fried MG, Dutch RE. 2018. Transmembrane domains of highly pathogenic viral fusion proteins exhibit trimeric association in vitro. mSphere 3:e00047-18. 
 Title: Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro
Output: False
Paragraph: The ultimate goal of proteomics is to identify biologically active proteins and to produce them using biotechnology tools such as bacterial hosts. However, proteins produced by Escherichia coli must be refolded to their native state. Protein folding liquid chromatography (PFLC) is a new method developed in recent years, and it is widely used in molecular biology and biotechnology. In this paper, the new method, PFLC is introduced and its recent development is reviewed. In addition the paper includes definitions, advantages, principles, applications for both laboratory and large scales, apparatus, and effecting factors of PFLC. In addition, the role of this method in the future is examined. 
 Title: Protein folding liquid chromatography and its recent developments ଝ
Output: True
Paragraph: Programmed frameshifting is a recoding event in which a ribosome shifts reading frame by one or more nucleotides at a specific mRNA signal between overlapping genes. Programmed frameshifting is involved in the expression of many genes in a wide range of organisms, especially in viruses and bacteria. The mechanism of programmed frameshifting is not fully understood despite many studies, and there are few databases available for detailed information on programmed frameshifting. We have developed a database called FSDB (Frameshift Signal Database), which is a comprehensive compilation of experimentally known or computationally predicted data about programmed ribosomal frameshifting. FSDB provides a graphical view of frameshift signals and the genes using programmed frameshifting for their expression. It also allows the user himself/herself to find programmed frameshift sites in genomic sequences using a program called FSFinder (http://wilab.inha.ac.kr/fsfinder2). We believe FSDB will be a valuable resource for scientists studying programmed ribosomal frameshifting. FSDB is freely accessible at http://wilab.inha.ac.kr/fsdb/. 
 Title: FSDB: A frameshift signal database
Output: False
Paragraph: The apical and basolateral surfaces of airway epithelial cells demonstrate directional responses to pathogen exposure in vivo. Thus, ideal in vitro models for examining cellular responses to respiratory pathogens polarize, forming apical and basolateral surfaces. One such model is differentiated normal human bronchial epithelial cells (NHBE). However, this system requires lung tissue samples, expertise isolating and culturing epithelial cells from tissue, and time to generate an air-liquid interface culture. Calu-3 cells, derived from a human bronchial adenocarcinoma, are an alternative model for examining the response of proximal airway epithelial cells to respiratory insult Safety Measures: Perform all procedures in a biosafety cabinet using sterile culture technique. 
 Title: Establishing a Liquid-covered Culture of Polarized Human Airway Epithelial Calu-3 Cells to Study Host Cell Response to Respiratory Pathogens In vitro
Output: False
Paragraph: Circoviruses are highly prevalent porcine and avian pathogens. In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches. In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported. Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples. Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirusand the recently proposed Cyclovirus genera of the Circoviridae. Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop. 
 Title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil
Output: False
Paragraph: Despite the formidable progress in Nuclear Magnetic Resonance (NMR) spectroscopy, quality assessment of NMR-derived structures remains as an important problem. Thus, validation of protein structures is essential for the spectroscopists, since it could enable them to detect structural flaws and potentially guide their efforts in further refinement. Moreover, availability of accurate and efficient validation tools would help molecular biologists and computational chemists to evaluate quality of available experimental structures and to select a protein model which is the most suitable for a given scientific problem. The 13 C α nuclei are ubiquitous in proteins, moreover, their shieldings are easily obtainable from NMR experiments and represent a rich source of encoded structural information that makes 13 C α chemical shifts an attractive candidate for use in computational methods aimed at determination and validation of protein structures. In this chapter, the basis of a novel methodology of computing, at the quantum chemical level of theory, the 13 C α shielding for the amino acid residues in proteins is described. We also identify and examine the main factors affecting the 13 C α -shielding computation. Finally, we illustrate how the information encoded in the 13 C chemical shifts can be used for a number of applications, viz., from protein structure prediction of both α-helical and β-sheet conformations, to determination of the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH or to accurate detection of structural flaws, at a residuelevel, in NMR-determined protein models. 
 Title: 3 C Chemical Shifts in Proteins: A Rich Source of Encoded Structural Information
Output: False
Paragraph: Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including antiviral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell cultureproduced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release. 
 Title: Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro
Output: False
Paragraph: , the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1Smediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription. Oncotarget 272 
 Title: Oncotarget, Vol. 6, No. 1 GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action
Output: True
Paragraph: Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host-pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment-disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management. 
 Title: Applying evolutionary concepts to wildlife disease ecology and management
Output: False
Paragraph: RNA interference (RNAi) as a mechanism to selectively degrade messenger RNA (mRNA) expression has emerged as a potential novel approach for drug target validation and the study of functional genomics. Small interfering RNAs (siRNA) therapeutics has developed rapidly and already there are clinical trials ongoing or planned. Although other challenges remain, delivery strategies for siRNA become the main hurdle that must be resolved prior to the full-scale clinical development of siRNA therapeutics. This article provides an overview of the current delivery strategies for synthetic siRNA, focusing on the targeted, self-assembled nanoparticles which show potential to become a useful and efficient tool in cancer therapy. 
 Title: Non-viral Methods for siRNA Delivery
Output: True
Paragraph: Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and antiinflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON. 
 Title: Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model
Output: False
Paragraph: We studied the course of demyelination and subsequent remyelination of nerve fibers after heat injury in the dorsal funiculus of the rat spinal cord. Four weeks after heat treatment, we observed, in addition to normally remyelinated axons, a few aberrantly remyelinated axons which had both CNS-and PNS-type myelin sheaths: the CNS-type myelin sheaths were always situated inside the PNS-type sheaths. This finding indicates that in some conditions Schwann cells can form myelin sheaths around those formed by oligodendrocytes. 
 Title: Ileurol tholog a Aberrant remyelination of axons after heat injury in the dorsal funiculus of rat spinal cord
Output: True
Paragraph: Virus infection often results in diverse outcomes. This variability of virus pathogenesis is not well understood. Here we revise theoretical arguments to further our understanding of factors controlling infection and its severity. We propose that variability in these factors results in different clinical outcomes, which ultimately ensure virus reproduction. A link between parasite virulence and its transmission efficiency is a paramount concept in modern epidemiology. The trade-off between these two pathogen's features has been studied and discussed for decades. 
 Title: Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections Virulence versus transmission: a trade-off
Output: False
Paragraph: Background: COVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing. We conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples. Findings: On the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, using a maximum pool size of 64, with only 7.3 tests on average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%. Interpretation: The pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available. 
 Title: Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments
Output: True
Paragraph: Background: Middle East Respiratory Syndrome (MERS) is a viral respiratory illness that was recently recognized in humans. Recently, the Ministry of Health in Saudi Arabia reported a substantial increase in MERS cases, primarily from the Riyadh region. The objective of the present study was to evaluate knowledge, attitude and practices towards MERS among physicians, nurses, pharmacist and technicians individually. Methods: A cross sectional study conducted at King Khalid University Hospital, Riyadh, Saudi Arabia among individual healthcare workers. The survey questionnaire was self-administrated and consisted of five sections: Demographic; Source of MERS information; Knowledge; Attitude; and Practice of healthcare workers towards MERS. Results: A total of 391 participants of which physicians (162; 41.4%), pharmacists (18; 4.6%), nurses (130; 33.3%) and technicians (81; 20.7%) were included with a response rate of 95.71%. The majority of the participants were female (53.70%) and mostly in the nurse's category (40.5%). The participants reported the highest main source of information was seminars and workshops (n = 191; 48%) followed by social media (n = 179; 45%). The overall score indicates good knowledge among physicians (95.7%), pharmacists (88.9%), nurses (86.2%) and technicians (91.4%) and showed statistically significant (p = 0.039). The study showed a positive attitude among physicians (96.3%), pharmacist (94.4%), nurses (94.6%) and technicians (90.1%) with no statistically significant (p = 0.273). However, the majority of the participants showed average practices towards MERS. However, the least practice among participants was the use of facemask in the crowds (24.2%). The demographic characteristic's age, gender and professions showed significantly associated with mean knowledge score. Similarly, statistical significance observed in gender and experience demographic variables with a mean attitude score. Conclusions: The study concludes that different health workers showed good knowledge and positive attitudes, but low to average practices towards MERS with low adherence to facemask practice. When comparing workers, physicians have a high degree of knowledge and attitude when compared to nurses, pharmacist and technicians. 
 Title: JIPH-1134; No. of Pages 8
Output: True
Paragraph: Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. 
 Title: Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone
Output: True