niryuu/sni-each-converted huggingface dataset:
Telephone: +61 7 405 974 555 Facsimile: +61 7 3636 5578 Word count Abstract 249 words Main text 2394 words Key words respiratory viruses gastrointestinal infection children real-time polymerase chain reaction cohort studies Page 2 of 33 For peer review only -http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open ARTICLE SUMMARY Article focus Infectious diseases are a common cause of morbidity in early childhood, even in developed economies. A diagnostic gap exists for common respiratory and gastrointestinal syndromes, with the likelihood that as yet undiscovered pathogens are involved. Existing knowledge about these common illnesses relies on research conducted before the rapid developments in molecular diagnostics of recent decades or focusses on disease at the severe end of the spectrum -hospitalisations -affecting a limited number of children and discounting the burden of more common, but less severe, community-managed illness. This protocol outlines a dynamic birth cohort study that will allow for a detailed description of the epidemiology of respiratory and gastrointestinal viruses during the first two years of life. The large biobank of specimens to be collated will act as a rich source of material to answer targeted research questions, including the role of virus acquisition and shedding on clinical illness and the discovery of new infectious agents. As study procedures, including specimen collection and return, are conducted by parents, findings will be free from Hawthorne effects from frequent interactions with study staff. Systematic weekly sampling will provide a control set of specimens for the individual and the cohort, allowing quantification of virus-specific attributable risk to illness. Non-random recruitment and enrolment requires awareness and assessment of potential bias and confounding prior to broad-based generalisation. Similar studies in the past have oversampled from higher socioeconomic households, and we attempt to avoid this by using a recruitment strategy that targets pregnant women in both public and private hospital settings. . van der Zalm MM, Uiterwaal CS, de Jong BM, et al. Viral specimen collection by parents increases response rate in population-based virus studies. J Allergy Clin Immunol 2006;117:955-6; author reply 56-7.
Output: Title page Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study Author affiliations
SARS and travel are intricately interlinked. Travelers belonged to those primarily affected in the early stages of the outbreak, travelers became vectors of the disease, and finally, travel and tourism themselves became the victims. The outbreak of SARS created international anxiety because of its novelty, its ease of transmission in certain settings, and the speed of its spread through jet travel, combined with extensive media coverage. The psychological impacts of SARS, coupled with travel restrictions imposed by various national and international authorities, have diminished international travel in 2003, far beyond the limitations to truly SARS hit areas. Governments and press, especially in non SARS affected areas, have been slow to strike the right balance between timely and frequent risk communication and placing risk in the proper context. Screening at airport entry points is costly, has a low yield and is not sufficient in itself. The low yield in detecting SARS is most likely due to a combination of factors, such as travel advisories which resulted in reduced travel to and from SARS affected areas, implementation of effective pre-departure screening at airports in SARS-hit countries, and a rapid decline in new cases at the time when screening was finally introduced. Rather than investing in airport screening measures to detect rare infectious diseases, investments should be used to strengthen screening and infection control capacities at points of entry into the healthcare system. If SARS reoccurs, the subsequent outbreak will be smaller and more easily contained if the lessons learnt from the recent epidemic are applied. Lessons learnt during the outbreak in relation to international travel will be discussed. Q
Output: The severe acute respiratory syndrome: Impact on travel and tourism
A total of 106 children below 5 years of age admitted to the Kasturba Medical College Hospital Manipal Karnataka (South India) were investigated over a period of 6 months to determine the aetiological role of viruses in acute diarrhoea. Viral aetiological agents isolated were Rotaviruses in 12 (11 per cent) cases, Adenoviruses in 3 (3 per cent) cases, corona virus and astroviruses in two (2 per cent) cases each. Non-viral isolates were Cryptosporidium and Salmonella typhimurium in two cases each, and Entamoeba histolytica and Shigella flexneri in one case each.
Output: Viral Diarrhoea in a Rural Coastal Region of Karnataka India
Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID 50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.
Output: A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection
Background. Bacteria are found in 50%-90% of cases of acute otitis media (AOM) with or without otorrhea, and viruses are found in 20%-49% of cases. However, for at least 15% of patients with AOM, the microbiological etiology is never determined. Our aim was to specify the full etiology of acute middle ear infection by using modern microbiological methods concomitantly for bacterial and viral detection. Methods. The subjects were 79 young children having AOM with new onset (!48 h) of otorrhea through a tympanostomy tube. Middle ear fluid samples were suctioned from the middle ear through the tympanostomy tube. Bacteria were sought by culture and polymerase chain reaction; viruses were analyzed by culture, antigen detection, and polymerase chain reaction. Results. At least 1 respiratory tract pathogen was noted in 76 children (96%). Bacteria were found in 73 cases (92%), and viruses were found in 55 (70%). In 52 patients (66%), both bacteria and viruses were found. Bacteria typical of AOM were detected in 86% of patients. Picornaviruses accounted for 60% of all viral findings. Conclusions. In the great majority of children, AOM is a coinfection with bacteria and viruses. The patent tympanostomy tube does not change the spectrum of causative agents in AOM. A microbiological etiology can be established in practically all cases.
Output: Microbiology of Acute Otitis Media in Children with Tympanostomy Tubes: Prevalences of Bacteria and Viruses
Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold standard assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, respectively. The cELISA and neutralization test results correlated well (Pearson's correlation coefficients = 0.71-0.76, depending on the cELISA serum dilution). This cELISA may be useful for MERS epidemiological investigations on MERS-CoV infection. http://dx.
Output: Characterization of novel monoclonal antibodies against the MERS- coronavirus spike protein and their application in species-independent antibody detection by competitive ELISA
Recent advances in the development and discovery of pharmacological interventions within the ubiquitin-proteasome system (UPS) have uncovered an enormous potential for possible novel treatments of neurodegenerative disease, cancer, immunological disorder and microbial infection. Interference with proteasome activity, although initially considered unlikely to be exploitable clinically, has already proved to be very effective against haematological malignancies, and more specific derivatives that target subsets of proteasomes are emerging. Recent small-molecule screens have revealed inhibitors against ubiquitin-conjugating and -deconjugating enzymes, many of which have been evaluated for their potential use as therapeutics, either as single agents or in synergy with other drugs. Here, we discuss recent advances in the characterisation of novel UPS modulators (in particular, inhibitors of ubiquitin-conjugating and -deconjugating enzymes) and how they pave the way towards new therapeutic approaches for the treatment of proteotoxic disease, cancer and microbial infection.
Output: Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases
The present study aimed to provide information on awareness of the attributable fraction of cancer causes among the Japanese general population. A nationwide representative sample of 2,000 Japanese aged 20 or older was asked about their perception and level of concern about various environmental and genetic risk factors in relation to cancer prevention, as a part of an Omnibus Survey. Interviews were conducted with 1,355 subjects (609 men and 746 women). Results: Among 12 risk factor candidates, the attributable fraction of cancer-causing viral and bacterial infection was considered highest (51%), followed by that of tobacco smoking (43%), stress (39%), and endocrine-disrupting chemicals (37%). On the other hand, the attributable fractions of cancer by charred fish and meat (21%) and alcohol drinking (22%) were considered low compared with other risk factor candidates. For most risk factors, attributable fraction responses were higher in women than in men. As a whole, the subjects tended to respond with higher values than those estimated by epidemiologic evidence in the West. The attributable fraction of cancer speculated to be genetically determined was 32%, while 36% of cancer was considered preventable by improving lifestyle. Our results suggest that awareness of the attributable fraction of cancer causes in the Japanese general population tends to be dominated by cancer-causing infection, occupational exposure, air pollution and food additives rather than major lifestyle factors such as diet.
Output: BMC Public Health Public awareness of risk factors for cancer among the Japanese general population: A population-based survey
Background: Over 90% of the organs transplanted in China before 2010 were procured from prisoners. Although Chinese officials announced in December 2014 that the country would completely cease using organs harvested from prisoners, no regulatory adjustments or changes in China's organ donation laws followed. As a result, the use of prisoner organs remains legal in China if consent is obtained. Discussion: We have collected and analysed available evidence on human rights violations in the organ procurement practice in China. We demonstrate that the practice not only violates international ethics standards, it is also associated with a large scale neglect of fundamental human rights. This includes organ procurement without consent from prisoners or their families as well as procurement of organs from incompletely executed, still-living prisoners. The human rights critique of these practices will also address the specific situatedness of prisoners, often conditioned and traumatized by a cascade of human rights abuses in judicial structures. Conclusion: To end the unethical practice and the abuse associated with it, we suggest to inextricably bind the use of human organs procured in the Chinese transplant system to enacting Chinese legislation prohibiting the use of organs from executed prisoners and making explicit rules for law enforcement. Other than that, the international community must cease to abet the continuation of the present system by demanding an authoritative ban on the use of organs from executed Chinese prisoners.
Output: Human rights violations in organ procurement practice in China
Background-Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infections in young children. AOM and respiratory viruses both display seasonal variation. Our objective was to examine the temporal association between circulating respiratory viruses and the occurrence of pediatric ambulatory care visits for AOM. Methods-This retrospective study included 9 seasons of respiratory viral activity (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) in Utah. We used Intermountain Healthcare's electronic medical records to assess community respiratory viral activity via laboratory-based active surveillance and to identify children <18 years with outpatient visits and ICD-9 codes for AOM. We assessed the strength of the association between AOM and individual respiratory viruses using interrupted time series analyses. Results-During the study period, 96,418 respiratory viral tests were performed; 46,460 (48%) were positive. The most commonly identified viruses were: RSV (22%), rhinovirus (8%), influenza (8%), parainfluenza (4%), human metapneumovirus (3%), and adenovirus (3%). AOM was diagnosed during 271,268 ambulatory visits. There were significant associations between peak activity of RSV, human metapneumovirus, influenza A, and office visits for AOM. Adenovirus, parainfluenza, and rhinovirus were not associated with visits for AOM. Conclusions-Seasonal RSV, human metapneumovirus, and influenza activity were temporally associated with increased diagnoses of AOM among children. These findings support the role of individual respiratory viruses in the development AOM. These data also underscore the potential for respiratory viral vaccines to reduce the burden of AOM.
Output: Seasonality of Acute Otitis Media and the Role of Respiratory Viral Activity in Children
Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.
Output: Genome Organization of the SARS-CoV
The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells. The activation of caspase 3, the up-regulation of both Bim and cleaved poly (ADP-ribose) polymerase (PARP) 1, the down-regulation of Bcl-xL, as well as the release of cytochrome c from mitochondria were significantly induced upon IFN-α treatment, indicating that the intrinsic apoptotic pathway could be activated by IFN-α treatment. In addition, caspase 4-which is involved in the endoplasmic reticulum (ER) stress-induced apoptosis-was activated in response to IFN-α treatment. Knocking down caspase 4 by small interfering RNA (siRNA) markedly reduced the IFN-α-mediated cell apoptosis. However, no significant changes in the expressions of caspases 8 and 10 were observed upon IFN-α treatment, indicating that the apoptosis caused by IFN-α might be independent of the extrinsic apoptotic pathway. These findings suggest that IFN-α may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and caspase-4-related ER stress-induced pathway.
Output: Interferon α Induces the Apoptosis of Cervical Cancer HeLa Cells by Activating both the Intrinsic Mitochondrial Pathway and Endoplasmic Reticulum Stress-Induced Pathway
Translational stalling of ribosome bound to endoplasmic reticulum (ER) membrane requires an accurate clearance of the associated polypeptides, which is not completely understood in mammals. We characterized in mammalian cells the model of ribosomal stalling at the STOP-codon based on proteins tagged at the C-terminus with the picornavirus 2A peptide followed by a termination codon instead of the Proline (2A*). We exploited the 2A* stalling model to characterize the pathway of degradation of ER-targeted polypeptides. We report that the ER chaperone BiP/GRP78 is a new main factor involved. Moreover, degradation of the ER-stalled polypeptides required the activities of the AAA-ATPase VCP/p97, its associated deubiquitinylase YOD1, the ribosome-associated ubiquitin ligase Listerin and the proteasome. In human proteome, we found two human C-terminal amino acid sequences that cause similar stalling at the STOP-codon. Our data suggest that translational stalling at the ER membrane activates protein degradation at the interface of ribosomal-and ERassociated quality control systems.
Output: BiP/GRP78 Mediates ERAD Targeting of Proteins Produced by Membrane-Bound Ribosomes Stalled at the STOP-Codon
We created an immunosensing platform for the detection of proteins in a buffer solution. Our sensing platform relies on graphene oxide (GO) nanosheets conjugated with antibodies to provide quantitative binding sites for analyte proteins. When analyte proteins and standard fluorescein-labelled proteins are competing for the binding sites, the assay exhibits quantitative fluorescence quenching by GO for the fluorescein-labelled proteins as determined by the analyte protein concentration. Because of this mechanism, measured fluorescence intensity from unquenched fluorescein-labelled protein was shown to increase with an increasing analyte protein concentration. As an alternative to the conventional enzyme-linked immunosorbent assay (ELISA), our method does not require an enzyme-linked second antibody for protein recognition and the enzyme for optical signal measurement. Thus, it is beneficial with its low cost and fewer systematic errors caused by the series of antigen-antibody recognition steps in ELISA. Immune globulin G (IgG) was introduced as a model protein to test our method and our results showed that the limit of detection for IgG was 4.67 pmol mL −1 in the buffer solution. This sensing mechanism could be developed into a promising biosensor for the detection of proteins, which would broaden the spectrum of GO applications in both analytical biochemistry and clinical diagnosis.
Output: Quantitative Fluorescence Quenching on Antibody-conjugated Graphene Oxide as a Platform for Protein Sensing OPEN
Many new RNA pseudoknot structures have been detected and proposed in the past year. Although we are still waiting for the first detailed structure of a pseudoknot, their role in processes such as translational autoregulation or ribosomal frameshifting has been extensively studied and is now well established. Pseudoknot structures appear to play a pivotal role in small subunit ribosomal RNA and in the noncoding regions of viral RNAs. There are also strong indications that RNA pseudoknots are highly suitable structural motifs for the recognition and binding of proteins.
Output: RNA pseudoknots
We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ( γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3 + T cells are required for protection.
Output: Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection
The NIAID (National Institute for Allergy and Infectious Diseases) Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org) has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1) The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells) infected by different bacterial (Bacillus anthracis and Salmonella typhimurium) and viral (orthopox) pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2) The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3) Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and prioritization of ten potential diagnostic targets from Bacillus anthracis. The integrative analysis across data sets from multiple centers can reveal potential functional significance and hidden relationships between pathogen and host proteins, thereby providing a systems approach to basic understanding of pathogenicity and target identification.
Output: Systems Integration of Biodefense Omics Data for Analysis of Pathogen-Host Interactions and Identification of Potential Targets
Microsatellites (SSRs) are ubiquitous in coding and non-coding regions of the Ebolavirus genomes. We synthetically analyzed the microsatellites in whole-genome and terminal regions of 219 Ebolavirus genomes from five species. The Ebolavirus sequences were observed with small intraspecies variations and large interspecific variations, especially in the terminal non-coding regions. Only five conserved microsatellites were detected in the complete genomes, and four of them which well base-paired to help forming conserved stem-loop structures mainly appeared in the terminal non-coding regions. These results suggest that the conserved microsatellites may be evolutionary selected to form conserved secondary structures in 5 0 , 3 0 terminals of Ebolavirus genomes. It may help to understand the biological significance of microsatellites in Ebolavirus and also other virus genomes.
Output: Conserved microsatellites may contribute to stem-loop structures in 5 0 , 3 0 terminals of Ebolavirus genomes
Background: Nosocomial, or healthcare-associated infections (HAI), exact a high medical and financial toll on patients, healthcare workers, caretakers, and the health system. Interpersonal contact patterns play a large role in infectious disease spread, but little is known about the relationship between health care workers' (HCW) movements and contact patterns within a heath care facility and HAI. Quantitatively capturing these patterns will aid in understanding the dynamics of HAI and may lead to more targeted and effective control strategies in the hospital setting. Methods: Staff at 3 urban university-based tertiary care hospitals in Canada completed a detailed questionnaire on demographics, interpersonal contacts, in-hospital movement, and infection prevention and control practices. Staff were divided into categories of administrative/support, nurses, physicians, and "Other HCWs" -a fourth distinct category, which excludes physicians and nurses. Using quantitative network modeling tools, we constructed the resulting HCW "co-location network" to illustrate contacts among different occupations and with locations in hospital settings. Results: Among 3048 respondents (response rate 38%) an average of 3.79, 3.69 and 3.88 floors were visited by each HCW each week in the 3 hospitals, with a standard deviation of 2.63, 1.74 and 2.08, respectively. Physicians reported the highest rate of direct patient contacts (> 20 patients/day) but the lowest rate of contacts with other HCWs; nurses had the most extended (> 20 min) periods of direct patient contact. "Other HCWs" had the most direct daily contact with all other HCWs. Physicians also reported significantly more locations visited per week than nurses, other HCW, or administrators; nurses visited the fewest. Public spaces such as the cafeteria had the most staff visits per week, but the least mean hours spent per visit. Inpatient settings had significantly more HCW interactions per week than outpatient settings. Conclusions: HCW contact patterns and spatial movement demonstrate significant heterogeneity by occupation. Control strategies that address this diversity among health care workers may be more effective than "one-strategy-fitsall" HAI prevention and control programs.
Output: Contact among healthcare workers in the hospital setting: developing the evidence base for innovative approaches to infection control
The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV. . CC-BY 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) The copyright holder for this preprint .
Output: Direct Measurement of Rates of Asymptomatic Infection and Clinical Care- Seeking for Seasonal Coronavirus
Necessary screenings must be performed to control the spread of the Corona Virus in daily life and to make a preliminary diagnosis of suspicious cases. The long duration of pathological laboratory tests and the wrong test results led the researchers to focus on different fields. Fast and accurate diagnoses are essential for effective interventions with COVID-19. The information obtained by using X-ray and Computed Tomography (CT) images is vital in making clinical diagnoses. Therefore it was aimed to develop a machine learning method for the detection of viral epidemics by analyzing X-ray images. In this study, images belonging to 6 situations, including coronavirus images, are classified. Since the number of images in the dataset is deficient and unbalanced, it is more convenient to analyze these images with hand-crafted feature extraction methods. For this purpose, firstly, all the images in the dataset are extracted with the help of four feature extraction algorithms. These extracted features are combined in raw form. The unbalanced data problem is eliminated by producing feature vectors with the SMOTE algorithm. Finally, the feature vector is reduced in size by using a stacked auto-encoder and principal component analysis to remove interconnected features in the feature vector. According to the obtained results, it is seen that the proposed method has leveraging performance, especially in order to make the diagnosis of COVID-19 in a short time and effectively.
Output: Classification of Coronavirus Images using Shrunken Features
The purpose of this study was to evaluate the viral frequency, seasonality, and clinical and demographic features of patients hospitalized with acute bronchiolitis. A cross-sectional, descriptive study was performed in 316 infants younger than 2 years of age who were hospitalized for acute viral bronchiolitis. Respiratory tract infection agents were investigated with polymerase chain reaction (PCR). A total of 316 infants were included in this study. Of the 316 infants, at least one respiratory tract pathogen was detected in 75% (237/316). Respiratory syncytial virus (RSV) was the most common virus identified in 127 infants (40.1%) followed by rhinovirus (n = 78, 24.6%). In this study, where viral agents were determined via PCR in patients who were followed-up due to the diagnosis of acute bronchiolitis, RSV was detected as the most common agent, as in other studies. In almost half of the RSV-positive patients, RSV was accompanied by a second or third agent.
Output: Etiology, Seasonality, and Clinical Features of Viral Respiratory Tract Infections in Children Hospitalized With Acute Bronchiolitis: A Single-Center Study
The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.
Output: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody
Background: Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults. Methods: We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I 2 statistics. Results: Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz microconvex transducer and one used a 5-9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99). Conclusions: Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.
Output: Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis
Understanding the causes of infectious disease to facilitate better control requires observational and experimental studies. Often these must be conducted at many scales such as at the molecular, cellular, organism, and population level. Studies need to consider both intrinsic and extrinsic factors affecting the pathogen/host interaction. They also require a combination of study methods covered by disciplines such as pathology, epidemiology, microbiology, and ecology. Therefore, it is important that disciplines work together when designing and conducting studies. Finally, we need to integrate and interpret data across levels and disciplines to better formulate control strategies. This requires another group of specialists with broad crossdisciplinary training in epidemiology and an ability to readily work with others.
Output: Determining Causality and Controlling Disease is Based on Collaborative Research involving Multidisciplinary Approaches
Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specifi c or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identifi ed the large genotypic diversity of rhinoviruses circulating in humans. We identifi ed and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confi rming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identifi ed recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifi es the diversity and explains the reasons for evolution of these viruses.
Output: New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses
Background: Murine norovirus (MNV) is recognized as the most prevalent viral pathogen in captive mouse colonies. The rapid detection assay for MNV would be a useful tool for monitoring and preventing MNV infection. A recombinase polymerase amplification (RPA) assay was established in this study to provide a solution for rapid and sensitive detection of MNV. Results: The detection limit of the RT-RPA assay for the detection of MNV was 1 × 10 2 copies of RNA molecules per reaction. The assay was specific since there was no cross-reaction with other common murine viruses. In addition, the broad reactivity of the RT-RPA assay was validated using the synthesized template carrying seven point mutations among several MNV strains. The MNV RT-RPA assay could detect as few as 1 × 10 2 copies of the mutant per reaction, suggesting the assay could be broadly reactive against a large diversity of MNV strains. Forty eight clinical samples including 16 gastric tissue specimens, 16 cecal tissue specimens and 16 fecal specimens were tested for the validation of the new developed RT-RPA assay. The detection results of RT-RPA and RT-qPCR for clinical samples were very similar, except that a gastric tissue sample which was positive by RT-qPCR, with a RNA titer of 27 copies, was negative by RT-RPA. Conclusions: A broadly reactive RT-RPA assay was successfully established for MNV detection.
Output: Development and evaluation of a broadly reactive reverse transcription recombinase polymerase amplification assay for rapid detection of murine norovirus
Background: Primary ciliary dyskinesia can result from a number of different ciliary defects that adversely affect ciliary function resulting markedly reduced or absent mucociliary clearance. Improvement in diagnostic testing is an area of current research. During diagnostic evaluation of PCD we observed ciliated conical protrusions from part of the apical surface of ciliated cells in those diagnosed with PCD. The aim of this study was to investigate if this abnormality was specific to PCD. Methods: Epithelial edges from 67 consecutively diagnosed PCD patients, 67 patients consecutively referred for PCD diagnostic testing in whom PCD was excluded, 22 with asthma and 18 with Cystic Fibrosis (CF) were studied retrospectively in a blinded manner using light microscopy. Results: Forty six out of 67 patients with PCD had ciliated conical epithelial protrusions, whereas none were seen in patients where PCD was excluded, or in patients with asthma or CF. The sensitivity, specificity, positive predictive value and negative predictive value for the presence of the ciliated conical protrusions to predict a diagnosis of PCD were 76.5, 100, 100 and 77% respectively. Conclusions: Characteristic ciliated conical protrusions from ciliated epithelial cells maybe a useful pointer to the diagnosis of PCD. However, their absence does not exclude the diagnosis of PCD.
Output: Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia
The nucleocapsid (N) gene of the porcine epidemic diarrhea virus (PEDV) strain LJB/03 which was previously isolated in Heilongjiang province, China, was cloned, sequenced and compared with published sequences of other avian and mammalian coronavirus. The nucleotide sequence encoding the entire N gene open reading frame (ORF) of LJB/03 was 1326 bases long and encoded a protein of 441 amino acids with predicted Mr of 49 kDa. It consisted of 405 adenines (30.5%), 294 cytosines (22.1%), 329 guanines (24.8%) and 298 thymines (22.5%) residues. Sequence comparison with other PEDV strains selected from GenBank revealed that the LJB/03 N gene has a high sequence homology to those of other PEDV isolates, 97.4% with JS2004, 95.6% with chinju99, 96.6% with Br1/87, and 96.8% with CV777. The encoded protein shared 96.4% amino acid identities compared with CV777, 96.1% with Brl/87, 98% with JS2004, 96.90% with chinju99, respectively. The amino acid sequence contained seven potential protein kinase C phosphorylation sites, nine Casein kinase II phosphorylation sites, one Tyrosine kinase phosphorylation site, two cAMP-and cGMP-dependent protein kinase phosphorylation sites.
Output: Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03
Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus-bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness.
Output: Therapeutics and Clinical Risk Management Dovepress virus-induced secondary bacterial infection: a concise review
The H7 subtype avian influenza threatens public health with respect to poultry and humans. Thus, a specific and sensitive diagnostic test is essential for the management of H7 subtype influenza infections. In this study, five mouse monoclonal antibodies (mAbs) against hemagglutinin (HA) of influenza A/Anhui/1/2013 (H7N9) were produced and characterized by the Western blot, immunofluorescence, and hemagglutination inhibition assays. All five specific mAbs reacted with the HA protein of H7N9 but not with that of H1N1, H3N2, or H5N1. With the combination arrays of capture and detection antibodies, the matched pair mAbs (1C4-coated and 2D7-labeled) were selected and employed in a double-antibody sandwich ELISA (DAS-ELISA). Detection limits of the sandwich ELISA were 0.45 ng mL -1 for the HA protein derived from A/Anhui/1/2013 (H7N9); or 1 and 2 HA units/50 µL for A/Anhui/1/2013 (H7N9) and A/GD/17SF003/2016 (H7N9), respectively. These anti-HA mAbs against subtype H7 and the novel DAS-ELISA provide a valuable approach for specific detection of the H7 subtype influenza virus and quantification of its HA protein, especially for the novel epidemic H7N9. influenza A, H7 subtype, hemagglutinin, monoclonal antibodies, sandwich ELISA Tan, W. (2020). Development and optimized pairing of mouse monoclonal antibodies for detecting hemagglutinin in novel H7 subtype influenza viruses. Sci China Life Sci 63, 279-289. https://doi.
Output: Development and optimized pairing of mouse monoclonal antibodies for detecting hemagglutinin in novel H7 subtype influenza viruses
Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses. Molecules 2011, 16 8895
Output: molecules Silver Nanoparticles as Potential Antiviral Agents