niryuu/sni-each-converted huggingface dataset:
Paragraph: We compare established docking programs, AutoDock Vina and Schrodinger's Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design. 
 Title: Comparing Neural-Network Scoring Functions and the State of the Art: Applications to Common Library Screening
Output: False
Paragraph: Background. Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. Method. Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. Results. Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. Conclusions. This study suggests that VRTI during the first year after lung transplantation is associated with longterm CLAD development and that coronavirus infections in particular might be a risk factor. 
 Title: Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation
Output: True
Paragraph: The objective of this report is to analyze the value of CMV viral load (VL) in bronchoalveolar lavage (BAL) in recipients of allogeneic hematopoietic stem cell transplantation (AHSCT) and to analyze the concordance between CMV quantification in plasma and BAL samples. Fifty-six patients were included; in 16 (28.6%) patients with symptoms of lung disease a BAL sample was collected, 7 (43.7%) patients had a VL 4150 copies/mL (six had probable CMV pneumonia). Patients with CMV pneumonia were female (100%), of median age 53.5 years, and the median time from transplantion to onset of symptoms was 67.5 days. Pneumonia was early in three cases (incidence 5.4%). Median BAL VL was 53 250 copies/mL and plasma VL was 538 copies/mL (in one patient, the plasma VL was negative). Three (50.0%) patients had an improvement in the first week of treatment, and plasma VL became negative; the other 3 (50.0%) patients died with a CMV pneumonia refractory to treatment. Therefore, any value of CMV VL in BAL, especially if it is greater than plasma, with compatible signs or symptoms, should be considered suggestive of CMV pneumonia in recipients of AHSCT and they should receive specific treatment. 
 Title: CMV viral load in bronchoalveolar lavage for diagnosis of pneumonia in allogeneic hematopoietic stem cell transplantation
Output: True
Paragraph: Background: Adverse events are associated with significant morbidity, mortality and cost in hospitalized patients. Measuring adverse events is necessary for quality improvement, but current detection methods are inaccurate, untimely and expensive. The advent of electronic health records and the development of automated methods for encoding and classifying electronic narrative data, such as natural language processing, offer an opportunity to identify potentially better methods. The objective of this study is to determine the accuracy of using automated methods for detecting three highly prevalent adverse events: a) hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and c) in-hospital falls. Methods/design: This validation study will be conducted at two large Canadian academic health centres: the McGill University Health Centre (MUHC) and The Ottawa Hospital (TOH). The study population consists of all medical, surgical and intensive care unit patients admitted to these centres between 2008 and 2014. An automated detection algorithm will be developed and validated for each of the three adverse events using electronic data extracted from multiple clinical databases. A random sample of MUHC patients will be used to develop the automated detection algorithms (cohort 1, development set). The accuracy of these algorithms will be assessed using chart review as the reference standard. Then, receiver operating characteristic curves will be used to identify optimal cut points for each of the data sources. Multivariate logistic regression and the areas under curve (AUC) will be used to identify the optimal combination of data sources that maximize the accuracy of adverse event detection. The most accurate algorithms will then be validated on a second random sample of MUHC patients (cohort 1, validation set), and accuracy will be measured using chart review as the reference standard. The most accurate algorithms validated at the MUHC will then be applied to TOH data (cohort 2), and their accuracy will be assessed using a reference standard assessment of the medical chart. Discussion: There is a need for more accurate, timely and efficient measures of adverse events in acute care hospitals. This is a critical requirement for evaluating the effectiveness of preventive interventions and for tracking progress in patient safety through time. 
 Title: Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol
Output: True
Paragraph: Canine infectious respiratory disease complex (CIRDC) viruses have been detected in dogs with respiratory illness. Canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), canine adenovirus type 2 (CAdV-2) and canine herpesvirus 1 (CaHV-1), are all associated with the CIRDC. To allow diagnosis, two conventional multiplex polymerase chain reactions (PCR) were developed to simultaneously identify four RNA and two DNA viruses associated with CIRDC. The two multiplex PCR assays were then validated on 102 respiratory samples collected from 51 dogs with respiratory illness by sensitivity and specificity determination in comparison to conventional simplex PCR and a rapid three-antigen test kit. All six viruses were detected in either individual or multiple infections. The developed multiplex PCR assays had a >87% sensitivity and 100% specificity compared to their simplex counterpart. Compared to the three-antigen test kit, the multiplex PCR assays yielded 100% sensitivity and more than 83% specificity for detection of CAdV-2 and CDV, but not for CIV. Therefore, the developed multiplex PCR modalities were able to simultaneously diagnose a panel of CIRDC viruses and facilitated specimen collection through being suitable for use of nasal or oral samples. KEY WORDS: canine infectious respiratory disease complex (CIRDC), diagnosis, multiplex PCRs, Thailand 
 Title: FULL PAPER Virology Development and application of multiplex PCR assays for detection of virus-induced respiratory disease complex in dogs
Output: False
Paragraph: Background: During the 2014 West African Ebola Virus Disease (EVD) outbreak, the U.S. Centers for Disease Control and Prevention recommended that all emergency department (ED) patients undergo travel screening for risk factors of importing EVD. Objectives: We sought to determine the overall adherence rate to the recommended travel screening protocol and to identify factors associated with nonadherence to the protocol. Methods: We conducted a multicenter, retrospective analysis of adherence to the travel screening program in an academic hospital and three affiliated community hospitals. A regression model identified patient and hospital factors associated with nonadherence. Results: Of the 147,062 patients included for analysis, 93.7% (n = 137,834) had travel screenings completed. We identified several characteristics of patients that were most likely to be missed by the screening protocol-patients with low English proficiency, patients who arrive via ambulance or helicopter, and patients with more severe illness or injury based on initial triage acuity. Conclusions: These findings should be used to improve adherence to the travel screening protocol for future emerging infectious disease threats. Ó 
 Title: Original Contributions ADHERENCE TO UNIVERSAL TRAVEL SCREENING IN THE EMERGENCY DEPARTMENT DURING EPIDEMIC EBOLA VIRUS DISEASE
Output: False
Paragraph: Reporter genes inserted into viral genomes enable the easy and rapid quantification of virus replication, which is instrumental to efficient in vitro screening of antiviral compounds or in vivo analysis of viral spread and pathogenesis. Based on a published design, we have generated several replication competent influenza A viruses carrying either fluorescent proteins or Gaussia luciferase. Reporter activity could be readily quantified in infected cultures, but the virus encoding Gaussia luciferase was more stable than viruses bearing fluorescent proteins and was therefore analyzed in detail. Quantification of Gaussia luciferase activity in the supernatants of infected culture allowed the convenient and highly sensitive detection of viral spread, and enzymatic activity correlated with the number of infectious particles released from infected cells. Furthermore, the Gaussia luciferase encoding virus allowed the sensitive quantification of the antiviral activity of the neuraminidase inhibitor (NAI) zanamivir and the host cell interferon-inducible transmembrane (IFITM) proteins 1-3, which are known to inhibit influenza virus entry. Finally, the virus was used to demonstrate that influenza A virus infection is sensitive to a modulator of endosomal cholesterol, in keeping with the concept that IFITMs inhibit viral entry by altering cholesterol levels in the endosomal membrane. In sum, we report the characterization of a novel influenza A reporter virus, which allows fast and sensitive detection of viral spread and its inhibition, and we show that influenza A virus entry is sensitive to alterations of endosomal cholesterol levels. 
 Title: Influenza A Virus Encoding Secreted Gaussia Luciferase as Useful Tool to Analyze Viral Replication and Its Inhibition by Antiviral Compounds and Cellular Proteins
Output: False
Paragraph: Herpes simplex virus (HSV) infection of mice can induce viral encephalitis. Using two-fluorochrome immunofluorescence, our present study shows that though there is extensive myelin loss and necrosis in the brain stem of mice with HSV encephalitis, only some oligodendrocytes, astrocytes and microglial cells are infected. T cells that express CD4 or CD8 and a large number of CD4 +, F4/80 + macrophages are present in perivascular infiltrates close to and in contact with HSV-infected cells in areas of massive myelin loss. These findings suggest that the resultant infiltration of immune cells into the brain during HSV-1 infection may cause as much damage as the virus itself. 0165-5728/89/$03.50  
 Title: Infiltration of immune T cells in the brain of mice with herpes simplex virus-induced encephalitis
Output: True
Paragraph: Despite the significant role of seasonal influenza vaccination in preventing and minimizing the serious complications of influenza infection in type 2 diabetes mellitus (T2DM) patients, unsatisfactory compliance still exists for vaccination. Study objectives were to explore the vaccination status and determinants in T2DM patients in southwestern Saudi Arabia. A cross-sectional study on a representative sample of T2DM patients in Abha city, southwestern Saudi Arabia, was conducted. Data for sociodemographic characteristics, clinical criteria, vaccination status, vaccination motivators and barriers and seasonal influenza knowledge were collected. Out of 353 T2DM patients included in the study, seasonal influenza vaccination coverage was 61% in year 2017. A significant factors associated with non-vaccination were; poor influenza and its vaccine knowledge (OR = 4.31, 95% CI: 2.73-6.80), illiteracy (OR = 1.93, 95% CI: 1.11-3.37), and more than 10 years disease duration (OR = 2.07, 95% CI: 1.11-3.87). Presence of family history of DM and ischemic heart comorbidity minimized the possibility of non-vaccination (OR = 0.54 and 0.28 respectively). Healthcare givers' advice was the most reported vaccination motivator (84.7%) while; fear of vaccine side effects was the most stated barrier (73%). In conclusion, influenza vaccination rate among T2DM in the present study is less than the recommended level. Continuous primary health care center-based educational programs should be implemented to aware and encourage influenza vaccination among T2DM patients. 
 Title: Influenza Vaccination in Type 2 Diabetes Patients: Coverage Status and Its Determinants in Southwestern Saudi Arabia
Output: True
Paragraph: Effective isolation of nucleic acids from samples containing viral materials is an essential step for accurate diagnosis of viral infections. The necessity of this critical step before analytical identification and diagnosis of viral infections is paramount to screening programs and to identifying and monitoring epidemics and pandemics. With molecular assays rapidly evolving into routine practice, clinical laboratories face several challenges, including presence of small amounts of viral nucleic acids in abundant levels of genomic DNA and total RNA, processing of various sample types, and carry-over of polymerase chain reaction inhibitors, which could significantly affect polymerase chain reaction and microarray results. MagaZorb nucleic acid isolation technology overcomes these challenges and offers a simple and reliable method for isolation of highquality and high-yield nucleic acids. Although the MagaZorb technology is readily adaptable to automated platforms, it is also well suited to laboratories in remote areas of resource-poor countries, because a simple magnet is the only device required to perform the procedure manually. Performance characteristics and clinical application of the MagaZorb technology are briefly described here. 
 Title: MagaZorb: A Simple Tool for Rapid Isolation of Viral Nucleic Acids
Output: True
Paragraph: Feline infectious peritonitis (FIP) is a feline coronavirus-induced fatal disease in domestic and wild cats. Several studies have investigated potential treatments for FIP. However, there have been no reports on agents that have exhibited a therapeutic effect. Recently, chloroquine has been reported to antiviral effect. We investigated whether chloroquine can be used to treat FIP in vitro and in vivo. It was demonstrated that chloroquine has inhibitory effect against the replication of FIPV and anti-inflammatory effect in vitro. In vivo study using cats with experimentally induced FIP, the clinical score of chloroquine-treatment groups were better than in chloroquine-untreated group. However, alanine aminotransferase levels increased in the chloroquine-treated groups. It will be necessary to further investigate the possibility of FIP treatment with a combination of chloroquine and other agents. 
 Title: Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo
Output: False
Paragraph: Objectives Erysipelas is an animal disease caused by Grampositive bacteria Erysipelothrix rhusiopathiae. Among the domestic animals, domestic pig (Sus scrofa f. domestica) suffers most frequently from the disease in human environment. This is a typical animal-borne disease observed mainly in occupational groups employed in agriculture, farming (of animals and birds), fishing and manufacturing industry. Methods We are presenting the clinical course of infection (E. rhusiopathiae) and discuss clinical forms. E. rhusiopathiae in humans may have the following clinical course: mild form of skin infection diagnosed as local erythema (erysipeloid), disseminated form of skin infection and the most serious form of infection of systemic course (endocarditis and sepsis). Mild skin infection and local erythema are the most common forms. Very rare case of animal-borne infection course has been presented in which after initial phase the disease was generalised to the abscesses formation in paravertebral space, spondylitis and empyema formation in spinal canal. In the presented clinical case, the patient was suffering from diabetes. It was probably an additional risk factor of the disease generalisation. Patient underwent drainage of empyema in spinal canal, after which his neurological status gradually improved. Antibiotic therapy was implemented and continued for 8 weeks. Such course of erysipelas was not previously described in the literature. After therapy neurological status was improved. In follow MRI control exam empyema and spondylitis was successfully eliminated. Conclusions Various complications of the disease, such as endocarditis and heart valves disturbances, are well known and are the most severe complications of the generalised infection. Proper targeted and long-term antibiotic therapy is crucial. 
 Title: Empyema in spinal canal in thoracic region, abscesses in paravertebral space, spondylitis: in clinical course of zoonosis Erysipelothrix rhusiopathiae
Output: False
Paragraph: DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles. Keywords bacterial vaccine; cellular and humoral immune responses; DNA vaccine; molecular adjuvants Times have changed since Edward Jenner immunized James Phipps against smallpox in 1796 and created what years later became known as a vaccine [1] . From the first live-attenuated or killed vaccines to the era of DNA vaccines in the early 1990s, molecular biology and microbiology have aided medical research in the development of vaccines against infectious diseases, cancer, allergies and autoimmune diseases by inducing rapid and robust immune responses or by creating immune tolerance [2] . From the time of Jenner's first vaccine until the present day, there have been over 60 licensed vaccines in the USA. These vaccines come in many forms: killed microorganisms, live-attenuated microorganisms, subunits, conjugate vaccines or toxoids. Although there are no US FDA-approved DNA vaccines for use in humans, they are the newest vaccine platform currently in development and have already had success in veterinary medicine [3] [4] [5] [6] [7] [8] . 
 Title: DNA vaccines for targeting bacterial infections NIH Public Access
Output: True
Paragraph: To analyze the proteins interacting with the severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein, a SARS-CoV was engineered including two tags associated to the E protein. Using this virus, complexes of SARS-CoV E and other proteins were purified using a tandem affinity purification system. Several viral and cell proteins including spike, membrane, non-structural protein 3 (nsp3), dynein heavy chain, fatty acid synthase and transmembrane protein 43 bound E protein. In the present work, we focused on the binding of E protein to nsp3 in infected cells and cell-free systems. This interaction was mediated by the N-terminal acidic domain of nsp3. Moreover, nsp3 and E protein colocalized during the infection. It was shown that E protein was ubiquitinated in vitro and in cell culture, suggesting that the interaction between nsp3 and E protein may play a role in the E protein ubiquitination status and therefore on its turnover. 
 Title: The envelope protein of severe acute respiratory syndrome coronavirus interacts with the non-structural protein 3 and is ubiquitinated
Output: True
Paragraph: Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005-07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts. 
 Title: Chikungunya: A Potentially Emerging Epidemic?
Output: True
Paragraph: Preterm birth is a major obstetric problem. An exploration of the season of conception in relation to preterm birth may provide direction in the search for risk factors. We conducted a retrospective cohort study of 82 213 singleton livebirths (20-45 weeks' gestation) to 61 630 women at Magee-Womens Hospital, Pittsburgh, PA, from 1995 to 2005. Conception was estimated based on gestational age determined by best obstetric estimate. Fourier series analysis was used to model seasonal trends. Spontaneous preterm birth at <37 weeks was associated with conception season (P < 0.05). The peak prevalence occurred among conceptions in winter and spring (peaking February 23 at 6.9%), with an average trough among late summer/early autumn conceptions (August 25 at 6.2%). The pattern for spontaneous preterm birth <32 weeks was similar (P < 0.05), with the peak on March 13 (1.7%), and nadir on September 12 (1.4%). Results were similar when indicated preterm births were included. These seasonal changes may increase our insight into the role of exposures with seasonal periodicity in the pathophysiology of preterm birth. 
 Title: The prevalence of preterm birth and season of conception
Output: False
Paragraph: Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication. PLOS Pathogens | 
 Title: Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes
Output: False
Paragraph: Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us. 
 Title: Evolution and Variation of the SARS-CoV Genome
Output: False
Paragraph: In the present study, we have generated a murine monoclonal antibody (mAb) named Sal-06 by using the crude outer membrane protein preparation of Salmonella enteric subsp. enterica serovar Typhimurium ATCC 14028 strain as antigen. Sal-06mAb belonging to IgG1 isotype demonstrated broad cross-reactivity to standard and isolated strains of genus Salmonella and others such as Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis. Cross-reactivity across several bacterial genera indicated that the epitopes reactive to Sal-06mAb are conserved among these members. Neutralizing effects of Sal-06mAb on Salmonella growth and survival was evaluated in vitro using bacteriostatic and bactericidal activity with and without complement and bacterial invasion inhibition assay. Sal-06mAb demonstrated a bacteriostatic effect on the growth of S. typhimurium ATCC 14028 strain which is both time and concentration (of mAb) dependent. It was also found that the bacterial growth inhibition was complement independent. When the bacterial cells were preincubated with Sal-06mAb, it reduced the adherence and invasion of bacterial cells into A549 epithelial cell line. This was confirmed by CFU count analysis, phase contrast, and fluorescence microscopy. Scanning electron microscope (SEM) imaging confirmed the antimicrobial effects of Sal-06mAb on S. typhimurium ATCC 14028. The development of broadly reactive and cross protective Sal-06mAb opens new possibilities for immunotherapy of sepsis caused by Gram-negative Enterobacteriaceae members. 
 Title: Functional characterization of a broad and potent neutralizing monoclonal antibody directed against outer membrane protein (OMP) of Salmonella typhimurium
Output: False
Paragraph: Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, a severe, clinically acute, vesicular disease of cloven-hoofed animals. RNA interference (RNAi) is a mechanism for silencing gene expression post-transcriptionally that is being exploited as a rapid antiviral strategy. To identify efficacious small interfering RNAs (siRNAs) to inhibit the replication of FMDV, candidate siRNAs corresponding to FMDV VP1 gene were designed and synthesized in vitro using T7 RNA polymerase. In reporter assays, five siRNAs showed significant sequence-specific silencing effects on the expression of VP1-EGFP fusion protein from plasmid pVP1-EGFP-N1, which was cotransfected with siRNA into 293T cells. Furthermore, using RT-qPCR, viral titration and viability assay, we identified VP1-siRNA517, VP1-siRNA113 and VP1-siRNA519 that transiently acted as potent inhibitors of FMDV replication when BHK-21 cells were infected with FMDV. In addition, variations within multiple regions of the quasispecies of FMDV were retrospectively revealed by sequencing of FMDV genes, and a single nucleotide substitution was identified as the main factor in resistance to RNAi. Our data demonstrated that the three siRNA molecules synthesized with T7 RNA polymerase could have transient inhibitory effects on the replication of FMDV. 
 Title: Transient inhibition of foot-and-mouth disease virus replication by siRNAs silencing VP1 protein coding region
Output: False
Paragraph: Background. Children with acute respiratory tract infection (ARTI) frequently exhibit virus-virus codetection, yet the clinical significance of ARTI remains contentious. Using data from a prospective cohort of children with influenza-like illness, we examined the virology of ARTI and determined the clinical impact of virus-virus codetection. Methods. Children aged 6 to 59 months who presented to a tertiary pediatric hospital between influenza seasons 2008 and 2012 with fever and acute respiratory symptoms were enrolled, and nasal samples were collected. Respiratory viruses were identified by culture and polymerase chain reaction. We compared demographics, presenting symptoms, and clinical outcomes of children with a single-virus infection and those in whom 2 or more viruses were detected (virus-virus codetection). We used logistic regression models and estimated marginal means to calculate the adjusted odds ratios and probabilities of symptom presentation, prescription of antibiotics, and hospitalization. Results. Of 2356 children, a virus was detected in 1630 (69.2%) of them; rhinovirus (40.8%), influenza (29.5%), and respiratory syncytial virus (26.4%) were detected most commonly. Two or more viruses were detected in 25% of these children. After we adjusted for demographic factors, children with virus-virus codetection had greater odds of presenting with cough (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.1) and rhinorrhea (aOR, 1.8; 95% CI, 1.1-2.9) than those with a single-virus infection, although both symptoms were common. Children with influenza and respiratory syncytial virus combined had the highest probability of hospitalization (55%; 95% CI, 35%-73%), which was significantly greater than for those with influenza infection alone (22%; 95% CI, 16%-29%). Conclusions. Overall, virus-virus codetection has limited impact on clinical severity among children with influenza-like illness. However, infection with specific pathogen pairs might be associated with more severe outcomes. Routine diagnostics to identify specific viruses should be restricted to common pathogens. 
 Title: Journal of the Pediatric Infectious Diseases Society Viral Etiology and the Impact of Codetection in Young Children Presenting With Influenza-Like Illness
Output: True
Paragraph: As the lung is a portal between the ambient environment and the internal milieu, it is the most frequent site of serious infections. A number of factors predispose to pulmonary infection, and these include distortions in lung anatomy, decreased mucociliary clearance, as well as abnormal cellular and humoral immune responses. The optimal treatment of infection requires diagnosing its cause. As a large variety of microbes can infect the lung, and as the histopathology of noninfectious conditions frequently mimics infection, the differential diagnosis of pulmonary infection is often broad. While in many cases, the clinical history, radiographic findings, and the noninvasive sampling of secretions can establish the cause of infection, at times, a lung biopsy will be required. 
 Title: Pulmonary Infection
Output: False
Paragraph: With the intention of developing a standardised method for assessment of pathogenicity of Cryptosporidium parvum, the CPB-0 isolate was studied by propagation in 1-day-old calves followed by inoculation into specific pathogen free (SPF) piglets. The experiment was repeated. Diarrhoea and shedding of oocysts were seen in all animals infected with the CPB-0 isolate. Clinical signs included depression, inappetence, vomiting (exclusively in the piglets), and death. Histological examination at 17 and 19 days post-infection revealed parasitic stages and microscopic changes primarily restricted to colon and rectum. The unintended presence of rotavirus in some of the experimental animals revealed an additive or synergistic effect between rotavirus and C. parvum as indicated by prolonged diarrhoea, increased oocyst shedding, decreased weight gain and elevated levels of serum haptoglobin and serum amyloid A (SAA) in piglets infected simultaneously with both pathogens. The difference in daily weight gain between infected and control animals was significant only for piglets co-infected with rotavirus. The acute phase response of haptoglobin and SAA was characterised by a large individual variation. In piglets, co-infected with rotavirus, the levels of serum haptoglobin were 3.5 and 4.6 times higher in the infected versus the controls 6 and 9 dpi, respectively (mean values: 2411 g/ml±S.D. 2023 and 1840 g/ml ± S.D. 1697). In the controls infected with rotavirus, peak haptoglobin concentration was seen 3 dpi (mean: 1022 g/ml ± S.D. 425). Elevated levels of SAA were seen in 1 of 6 piglets infected with C. parvum, and in 5 of 6 piglets co-infected with rotavirus. Tumour necrosis factor alpha (TNF␣) was undetectable in all serum samples from piglets. The obvious advantages of the SPF pig model are the naturally acquired intestinal microflora, the development of distinct clinical signs similar to cryptosporidiosis in humans and calves, the size of the animals, and the accessibility of individuals born within a short time span. This makes the model ideal for dose-response studies, evaluation of therapeutic agents as well as for assessment of differences in the clinical response to isolates of diverse genetic background. In conclusion, it was shown that the CPB-0 isolate was pathogenic to calves and piglets at a dose of 2.5 × 10 5 oocysts, and that the clinical signs could be replicated during separate experiments. Moreover, diarrhoea, oocyst shedding, body weight changes, histological alterations, and the acute phase response of haptoglobin and SAA were identified as useful parameters for discrimination of isolate-specific differences of pathogenicity. 
 Title: Pathogenicity of Cryptosporidium parvum-evaluation of an animal infection model
Output: False
Paragraph: Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 -12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV. 
 Title: Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations
Output: False
Paragraph: The azurophilic granules of human neutrophils contain four a-defensins called human neutrophil peptides (HNPs 1-4). HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils. The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases. ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages (''folded proHNP1'') and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1). Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive. We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases. Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension. NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent. In contrast, misfolded proHNP1 conformers were degraded extensively under the same conditions. Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro. Citation: Tongaonkar P, Golji AE, Tran P, Ouellette AJ, Selsted ME (2012) High Fidelity Processing and Activation of the Human a-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3. PLoS ONE 7(3): e32469. 
 Title: High Fidelity Processing and Activation of the Human a- Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3
Output: True
Paragraph: Virus attachment to host cells is mediated by dedicated virion proteins, which specifically recognize one or, at most, a limited number of cell surface molecules. Receptor binding often involves protein-protein interactions, but carbohydrates may serve as receptor determinants as well. In fact, many different viruses use members of the sialic acid family either as their main receptor or as an initial attachment factor. Sialic acids (Sias) are 9-carbon negativelycharged monosaccharides commonly occurring as terminal residues of glycoconjugates. They come in a large variety and are differentially expressed in cells and tissues. By targeting specific Sia subtypes, viruses achieve host cell selectivity, but only to a certain extent. The Sia of choice might still be abundantly present on non-cell associated molecules, on non-target cells (including cells already infected) and even on virus particles themselves. This poses a hazard, as high-affinity virion binding to any of such "false" receptors would result in loss of infectivity. Some enveloped RNA viruses deal with this problem by encoding virionassociated receptor-destroying enzymes (RDEs). These enzymes make the attachment to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in two types: neuraminidases and sialate-O-acetylesterases. The latter, originally discovered in influenza C virus, are also found in certain nidoviruses, namely in group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution of viral sialate-O-acetylesterases is re-R.J.d. Groot ( ) Virology Section, 
 Title: Structure, function and evolution of the hemagglutinin-esterase proteins of corona-and toroviruses
Output: True
Paragraph: RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. RNAi is an evolutionarily conserved, sequence-specific, posttranscriptional gene silencing phenomenon. It is triggered by 2 Journal of Biomedicine and Biotechnology DNA DNA dsRNA dsRNA processing Dicer ATP siRNA ADP + P i Interferon response Nonspecific gene silencing RISC assembly RISC activation Binding of RISC to target mRNA mRNA degradation Cleavage Target mRNA Expression RISC ATP ADP + P i RISC £ Figure 1 : Mechanism of RNA interference (RNAi) in mammalian systems. Long double-stranded RNA molecules (dsRNA), which are expressed from DNA vectors (left red arrow) or directly enter the cell (center red arrow), are processed by the Dicer complex resulting in the formation of small inhibitory RNAs (siRNAs). Alternatively, to induce RNAi these small 21-23 bp duplexes are directly delivered into the cell (right red arrow). The siRNAs are incorporated into a nuclease-containing multiprotein complex called RISC, which becomes activated upon the ATP-dependent unwinding of the siRNA duplex by an RNA helicase. The now single-stranded siRNA guides the RISC complex to its complementary target mRNA which is then cleaved by the endonucleolytical activity of RISC. While the RISC complex is recovered for further cycles, the cleaved mRNA molecule is rapidly degraded due to its unprotected RNA ends. 
 Title: Review Article Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo
Output: False
Paragraph: Turkey coronavirus (TCoV) infection continues to threaten turkey industry. Because specifi c treatment and effective vaccination program are not available, rapid and cost-effective detection of antibodies to TCoV infection is an important control measure to monitor the disease status in the fi elds. Two antibodycapture enzyme-linked immunosorbent assay (ELISA) procedures for detection of antibodies to TCoV are outlined in this chapter. One ELISA method uses chicken infectious bronchitis coronavirus (IBV) as the coating antigen based on antigenic cross-reactivity between TCoV and IBV. The other method relies on a recombinant TCoV nucleocapsid protein. Both methods are useful for serological diagnosis of TCoV infection in the turkey fl ocks. 
 Title: Antibody-Capture Enzyme-Linked Immunosorbent Assay for Detection of Antibody to Turkey Coronavirus Using Infectious Bronchitis Virus or Recombinant Nucleocapsid Protein as Coating Antigen
Output: False
Paragraph: Acute respiratory infections (ARIs) are extremely common in children, especially those under 5 years old. They can lead to complications, super-infection, respiratory failure, and even compromised respiratory function in adulthood. For some of the responsible pathogens, vaccines are available. This review reports current issues about vaccines against the main respiratory pathogens to highlight the available strategies to reduce the burden of paediatric respiratory disease. The optimal use of influenza, pneumococcal, pertussis and measles vaccines is required in order to reduce ARI burden. Vaccination coverage rates must be improved to achieve the full benefits of these vaccines. Recently, advances in the knowledge of respiratory syncytial virus structural biology and immunology as well as the development of new techniques to generate vaccine candidates have increased the number of promising vaccines even against this harmful pathogen. 
 Title: Vaccination against Paediatric Respiratory Pathogens
Output: False
Paragraph: The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion. D 
 Title: Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion
Output: False
Paragraph: Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine. 
 Title: Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine
Output: False