niryuu/sni-each-converted huggingface dataset:
Combinations of porcine respiratory coronavirus (PRCV) and either of two swine influenza viruses (H1N1 or H3N2) were administered intranasally and by aerosol to six-to eight-week-old specific pathogen:free pigs. The clinical responses, gross respiratory lesions and growth performances of these pigs were studied and compared with those of single (PRCV, H1N1 or H3N2) and mock-infected animals. PRCV infection caused fever, growth retardation and lung lesions, but no respiratory symptoms. Infection with swine influenza viruses caused rather similar, mild symptoms of disease, with H1N1 infection being the least severe. Combined infections with influenza viruses and PRCV did not appear to enhance the pathogenicity of these viruses. Furthermore, viruses were isolated more frequently from tissues and nasal swabs taken from 'single' than 'dual' infected animals, suggesting a possible in vivo interference between replication of PRCV and swine influenza virus.
Output: Pathogenicity of concurrent infection of pigs with porcine respiratory coronavirus and swine influenza virus
Background: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained. We postulated that a quantitative analysis of beat pattern would improve PCD diagnosis. We compared quantitative parameters with the qualitative evaluation of ciliary beat pattern in patients in whom the diagnosis of PCD was confirmed or excluded. Methods: Nasal nitric oxide measurement, nasal brushings and biopsies were performed prospectively in 34 patients with suspected PCD. In combination with qualitative analysis, 12 quantitative parameters of ciliary beat pattern were determined on high-speed videomicroscopy recordings of beating ciliated edges. The combination of ciliary ultrastructural abnormalities on transmission electron microscopy analysis with low nasal nitric oxide levels was the "gold standard" used to establish the diagnosis of PCD. Results: This "gold standard" excluded PCD in 15 patients (non-PCD patients), confirmed PCD in 10 patients (PCD patients) and was inconclusive in 9 patients. Among the 12 parameters, the distance traveled by the cilium tip weighted by the percentage of beating ciliated edges presented 96% sensitivity and 95% specificity. Qualitative evaluation and quantitative analysis were concordant in non-PCD patients. In 9/10 PCD patients, quantitative analysis was concordant with the "gold standard", while the qualitative evaluation was discordant with the "gold standard" in 3/10 cases. Among the patients with an inconclusive "gold standard", the use of quantitative parameters supported PCD diagnosis in 4/9 patients (confirmed by the identification of disease-causing mutations in one patient) and PCD exclusion in 2/9 patients. Conclusions: When the beat pattern is normal or virtually immotile, the qualitative evaluation is adequate to study ciliary beating in patients suspected for PCD. However, when cilia are still beating but with moderate alterations (more than 40% of patients suspected for PCD), quantitative analysis is required to precise the diagnosis and can be proposed to select patients eligible for TEM.
Output: Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study
We present an optimized probe design for copy number variation (CNV) and SNP genotyping in the Plasmodium falciparum genome. We demonstrate that variable length and isothermal probes are superior to static length probes. We show that sample preparation and hybridization conditions mitigate the effects of host DNA contamination in field samples. The microarray and workflow presented can be used to identify CNVs and SNPs with 95% accuracy in a single hybridization, in field samples containing up to 92% human DNA contamination.
Output: An optimized microarray platform for assaying genomic variation in Plasmodium falciparum field populations
A dataset of 103 SARS-CoV isolates (101 human patients and 2 palm civets) was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations (SNVs) and insertions and deletions, with respect to a "profile", were determined and discussed ("profile" being a sequence containing the most represented letter per position). Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid (a.a.) property changes. Similar analysis was performed for the spike (S) protein in all the isolates (55 of them being predicted for the first time). The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes: TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.
Output: SARS-CoV Genome Polymorphism: A Bioinformatics Study
Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We demonstrate that the ligand binds with fast kinetics to a surface-exposed groove and interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide did not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase-fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Output: Structural basis for human coronavirus attachment to sialic acid receptors HHS Public Access Author manuscript
A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the ability of Echinacea purpurea to prevent infection with rhinovirus type 39 (RV-39). Forty-eight previously healthy adults received echinacea or placebo, 2.5 mL 3 times per day, for 7 days before and 7 days after intranasal inoculation with RV-39. Symptoms were assessed to evaluate clinical illness. Viral culture and serologic studies were performed to evaluate the presence of rhinovirus infection. A total of 92% of echinacea recipients and 95% of placebo recipients were infected. Colds developed in 58% of echinacea recipients and 82% of placebo recipients ( , by Fisher's exact test). Administration of echinacea before and after exposure to rhinovirus did not P p .114 decrease the rate of infection; however, because of the small sample size, statistical hypothesis testing had relatively poor power to detect statistically significant differences in the frequency and severity of illness. Colds are the most common acute infectious illnesses in humans. Prevention of the common cold with immunization is not practical because of the antigenic diversity of the many viruses causing colds. For example, rhinoviruses, which account for ∼40% of adult colds, have 1100 antigenic serotypes. Viruses of different and distinct families, such as coronavirus, parainfluenza virus, respiratory syncytial virus, influenza virus, adenovirus, and metapneumovirus, also cause colds. Products derived from Echinacea purpurea, the purple coneflower, are among the most popular herbal remedies in the United States. It is estimated that Americans spend more than $300 million/year on these products [1], which are commonly self-administered for the prevention and treatment of the common cold. The 3
Output: Echinacea purpurea for Prevention of Experimental Rhinovirus Colds
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. The Microbiology of Respiratory System Infections. http://dx. The variant 1 of the human bocavirus (HBoV-1) that causes respiratory infections in primates and humans belongs to the family of Parvoviridae, subfamily Parvovirinae, genus Bocaparvovirus, was discovered originally in 2005 by Tobias Allander 1 and his team and represents together with the strains HBoV-3 and the gorilla bocavirus the species Primate bocaparvovirus 1. 2 The discovery of HBoV-1 was one among a series of virus discoveries in the first decade of our millennium that was based on novel virus discovery systems developed in order to reduce the considerable number of cases in which a clinical diagnosis of a respiratory infection could not be confirmed by detection of a pathogen. Following the initial description of the virus, a huge number of clinical studies and case reports have been published which were supplemented by some basic research reports. Unfortunately, HBoV research still relies on clinical studies and case reports with accompanying cell culture studies as the major source of information on HBoV biology, as so far no animal model has been identified.
Output: RESPIRATORY INFECTIONS OF THE HUMAN BOCAVIRUS
Manipulation of the coronavirus genome to accommodate and express foreign genes is an attractive approach for gene delivery and vaccine development. By using an infectious cloning system developed recently for the avian coronavirus infectious bronchitis virus (IBV), the enhanced green fluorescent protein (EGFP) gene, the firefly luciferase gene and several host and viral genes (eIF3f, SARS ORF6, Dengue virus 1 core protein gene) were inserted into various positions of the IBV genome, and the effects on gene expression, virus recovery, and stability in cell culture were studied. Selected viruses were also inoculated into chicken embryos for studies of foreign gene expression at different tissue level. The results demonstrated the stability of recombinant viruses depends on the intrinsic properties of the foreign gene itself as well as the position at which the foreign genes were inserted. For unstable viruses, the loss of expression of the inserted genes was found to result from a large deletion of the inserted gene and even IBV backbone sequences. This represents a promising system for development of coronavirus-based gene delivery vectors and vaccines against coronavirus and other viral infections in chicken.
Output: Towards construction of viral vectors based on avian coronavirus infectious bronchitis virus for gene delivery and vaccine development
The behavior and myelinogenic properties of glial cells have been well documented following transplantation into regions of focal experimental demyelination in animal models. However, the ability of glial cell preparations to remyelinate in such models does not necessarily indicate that their transplantation into demyelinated lesions in clinical disease will be successful. One of the precluding factors in this regard is a greater understanding of the environmental conditions that will support transplant-mediated remyelination. In this study, we determined whether the complex and reactive CNS environment of the mouse hepatitis virus (MHV) model of multiple sclerosis (MS) could support transplant-mediated remyelination. Striatal neural precursors derived from postnatal day 1 mice were committed to a glial cell lineage and labeled. Immunohistochemical staining indicated that this population generated >93% glial cells following differentiation in vitro. Transplantation of glial-committed progenitor cells into the T8 spinal cord of MHV-infected mice demonstrating complete hindlimb paralysis resulted in migration of cells up to 12 mm from the implantation site and remyelination of up to 67% of axons. Transplanted-remyelinated animals contained approximately 2Â the number of axons within sampled regions of the ventral and lateral columns as compared to nontransplanted animals, suggesting that remyelination is associated with axonal sparing. Furthermore, transplantation resulted in behavioral improvement. This study demonstrates for the first time that transplant-mediated remyelination is possible in the pathogenic environment of the MHV demyelination model and that it is associated with locomotor improvement.
Output: Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis
Shiga toxins (Stx1 and Stx2) are the main virulence factors of enterohemorrhagic Escherichia coli (EHEC), a foodborne pathogen associated with diarrhea, hemorrhagic colitis and hemolytic uremic syndrome. The aim of this study was to evaluate the antibodies against Stx2 obtained from egg yolks of laying hens immunized with a recombinant Stx2B subunit. A high specific response in serum was observed 25 days after the first immunization and IgY antibodies were extracted from day 47th and purified from egg yolk. A concentration of 0.84 mg of total IgY/ml of egg yolk was obtained, of which 8% were antigen specific. The ability of anti-Stx2B IgY to recognize Stx2B and Stx2 either in solid-phase or in solution were evaluated and compared with anti-Stx2B rabbit antibodies by Western blotting and ELISA. The protective efficacy of IgY against Stx2 was determined by in vitro and in vivo experiments. The results show that IgY was able to recognize Stx2B and Stx2 in denatured conditions, attached to a solid-phase and free in solution. The anti-Stx2B IgY could effectively block the biological activity of Stx2 on Vero cells and protect mice from Stx2 challenge. The data suggest that immunization of hens with Stx2B could be a strategy to obtain at low cost a relatively high concentration of anti-Stx2 egg yolk IgY, able to neutralize Stx2 lethal activity. IgY technology could be an useful tool for research, diagnosis and therapy of EHEC infection.
Output: Antibodies anti-Shiga toxin 2 B subunit from chicken egg yolk: Isolation, purification and neutralization efficacy
In this paper, we propose and analyze a nonautonomous predator-prey model with disease in prey, and a discrete time delay for the incubation period in disease transmission. Employing the theory of differential inequalities, we find sufficient conditions for the permanence of the system. Further, we use Lyapunov's functional method to obtain sufficient conditions for global asymptotic stability of the system. We observe that the permanence of the system is unaffected due to presence of incubation delay. However, incubation delay affects the global stability of the positive periodic solution of the system. To reinforce the analytical results and to get more insight into the system's behavior, we perform some numerical simulations of the autonomous and nonautonomous systems with and without time delay. We observe that for the gradual increase in the magnitude of incubation delay, the autonomous system develops limit cycle oscillation through a Hopf-bifurcation while the corresponding nonautonomous system shows chaotic dynamics through quasiperiodic oscillations. We apply basic tools of non-linear dynamics such as Poincaré section and maximum Lyapunov exponent to confirm the chaotic behavior of the system.
Output: Chaos in a nonautonomous eco-epidemiological model with delay
2 cases of precursor T cell lymphoma and 37 cases of peripheral T cell lymphoma were investigated for their reactivity with the monoclonal antibody (mAb) HML-1, which recognises human intestinal T lymphocytes but not lymph-node T cells. In all but one of the lymphomas studied, the tumour cells were unreactive with the mAb HML-1. The HML-1+ lymphoma was the only tumour that was primarily localised in the epithelium and lamina propria of the small intestine, and was associated with ulcerative jejunitis and coeliac disease. This result suggests that the HML-1+ lymphoma was derived from intestinal mucosa T lymphocytes and differs from precursor T cell lymphoblastic lymphomas and nodal and cutaneous peripheral T cell lymphomas.
Output: Preliminary Communication IDENTIFICATION OF A T CELL LYMPHOMA CATEGORY DERIVED FROM INTESTINAL-MUCOSA-ASSOCIATED T CELLS
We describe the isolation, biological and genetic characterization of a host-range variant of bovine coronavirus (BCoV) detected in water buffalo (Bubalus bubalis). By conventional and real-time RT-PCR assays, the virus was demonstrated in the intestinal contents of two 20-day-old buffalo calves dead of a severe form of enteritis and in the feces of additional 17 buffalo calves with diarrhea. Virus isolation, hemagglutination and receptor-destroying enzyme activity showed that the buffalo coronavirus (BuCoV) is closely related to BCoV but possesses some different biological properties. Sequence and phylogenetic analyses of the 3′ end (9.6 kb) of the BuCoV RNA revealed a genomic organization typical of group 2 coronaviruses. Moreover, the genetic distance between BuCoV and BCoV was proven to be the same or even higher than the distance between other ruminant coronaviruses and BCoV. In conclusion, our data support the existence of a host-range variant of BCoV associated with enteritis in buffaloes.
Output: Biological and genetic analysis of a bovine-like coronavirus isolated from water buffalo (Bubalus bubalis) calves
Host resistance to viral infection requires type I (a/b) and II (g) interferon (IFN) production. Another important defense mechanism is the degradative activity of macroautophagy (herein autophagy), mediated by the coordinated action of evolutionarily conserved autophagy proteins (Atg). We show that the Atg5-Atg12/Atg16L1 protein complex, whose prior known function is in autophagosome formation, is required for IFNg-mediated host defense against murine norovirus (MNV) infection. Importantly, the direct antiviral activity of IFNg against MNV in macrophages required Atg5-Atg12, Atg7, and Atg16L1, but not induction of autophagy, the degradative activity of lysosomal proteases, fusion of autophagosomes and lysosomes, or the Atg8-processing protein Atg4B. IFNg, via Atg5-Atg12/Atg16L1, inhibited formation of the membranous cytoplasmic MNV replication complex, where Atg16L1 localized. Thus, the Atg5-Atg12/Atg16L1 complex performs a pivotal, nondegradative role in IFNg-mediated antiviral defense, establishing that multicellular organisms have evolved to use portions of the autophagy pathway machinery in a cassette-like fashion for host defense.
Output: Article Nondegradative Role of Atg5-Atg12/ Atg16L1 Autophagy Protein Complex in Antiviral Activity of Interferon Gamma
Literature review shows that little research has done so far to estimate how tourism indicators are affected by new High Speed Rail (HSR) lines. In 2012, a multivariate panel analysis developed by Chen and Haynes was applied to the Chinese regions to quantify the HSR impact on tourism output. The Chinese experience confirmed that, during the period 1999-2010, emerging high speed rail services did have significant positive impacts on boosting tourism in China. Since them, no similar empirical tool has ever been tested in Europe. The aim of this paper is to analyze and validate the suitability of this tool to assess empirically the effects of HSR on Spanish tourism during the period 1999-2014, and to enhance the abovementioned model with a tourism database. With more than 20 years' HSR experience, and operating the longest HSR network in Europe (2,900 km), Spain offers a good scenario for this model application because Spanish tourism sector represents 10.2% of its gross domestic product (GDP). Results clearly show that there is a direct linkage between the evolution of certain Spanish tourism outputs and the construction of the HSR network. However, authors´ recommendations include future new research on some variables limitations like the type of tourism output considered or the consideration of alternative explanatory indicators.
Output: ScienceDirect The assessment of the HSR impacts on Spanish tourism: an approach based on multivariate panel data analysis-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-review under responsibility of the organizing committee of CIT 2016
Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization-defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia. Keywords. pneumonia; viral load; viral density; RSV; PERCH. For diagnosing viral pneumonia, upper respiratory tract (URT) specimens have become the most common specimen type due to their logistical ease of collection [1, 2]. However, detection of viruses in URT specimens has low specificity as this finding might simply reflect an URT infection without lower respiratory tract involvement or coincidental asymptomatic or past infection [2] [3] [4] . A possible solution to the lack of specificity of simply detecting the presence or absence of a virus in the URT of pneumonia patients is to determine whether the density of a virus in the URT can better distinguish its causative role in pneumonia. There are reports that a higher pathogen load in the URT is associated with pneumonia, for both Streptococcus pneumoniae S U P P L E M E N T A R T I C L E
Output: Clinical Infectious Diseases Clinical Infectious Diseases ® 2017;64(S3):S337-46 Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study
Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit an immune response, there has been much progress in understanding the basic biology of this platform. A large amount of data has been generated in preclinical model systems, and more sustained cellular responses and more consistent antibody responses are being observed in the clinic. Four DNA vaccine products have recently been approved, all in the area of veterinary medicine. These results suggest a productive future for this technology as more optimized constructs, better trial designs and improved platforms are being brought into the clinic. DNA vaccines burst into the scientific limelight in the early 1990s. Tang and Johnston described the delivery of DNA into the skin of mice using a 'gene gun', in an attempt to deliver human growth hormone as a gene therapy 1 . The authors felt that this could be a useful technique to generate antibody responses against specific transgene products. At the same time, three presentations at the annual vaccine meeting at the Cold Spring Harbor Laboratory in 1992 reported the use of DNA vectors to drive both humoral and cellular immune responses against pathogens or tumour antigens in vivo. Margaret Liu and her colleagues at the pharmaceutical company Merck reported injecting 'naked' plasmids intramuscularly to deliver immunogens that would generate immune responses against influenza virus antigens in mice 2 . Similarly, Robinson described the ability of DNA plasmids to drive immune responses against influenza virus antigens 3 . A presentation by Weiner described the ability of plasmids carrying HIV antigens or tumour antigens to produce immune responses and protection from tumour challenge in mice 4 . Although none of these studies used the same delivery method, formulation or plasmid, together they provided evidence to the scientific community that this simple technique could be developed as an immunization platform.
Output: DNA vaccines: ready for prime time? NIH-PA Author Manuscript
Newcastle disease virus (NDV) and Goose parvovirus (GPV) are considered to be two of the most important and widespread viruses infecting geese. In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. Expression of the VP3 protein in rmNA-VP3 infected cells was detected by immunofluorescence and Western blot assay. The genetic stability was examined by serially passaging 10 times in 10-day-old embryonated SPF chicken eggs. Goslings were inoculated with rmNA-VP3 showed no apparent signs of disease and developed a strong GPV and NDV neutralizing antibodies response. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds.
Output: Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings
Background: Pairing up primers to amplify desired targets and avoid undesired cross reactions can be a combinatorial challenge. Effective prediction of specificity and inclusivity from multiplexed primers and TaqMan®/ Luminex® probes is a critical step in PCR design. Results: Code is described to identify all primer and probe combinations from a list of unpaired, unordered candidates that should produce a product. It predicts and extracts all amplicon sequences in a large sequence database from a list of primers and probes, allowing degenerate bases and user-specified levels of primer-target mismatch tolerance. Amplicons hit by TaqMan®/Luminex® probes are indicated, and products may be annotated with gene information from NCBI. Fragment length distributions are calculated to predict electrophoretic gel banding patterns. Simulate_PCR is the only freely available software that can be run from the command line for high throughput applications which can calculate all products from large lists of primers and probes compared to a large sequence database such as nt. It requires no prior knowledge of how primers should be paired. Degenerate bases are allowed and entire amplicon sequences are extracted and annotated with gene information. Examples are provided for sets of TaqMan®/Luminex® PCR signatures predicted to amplify all HIV-1 genomes, all Coronaviridae genomes, and a group of antibiotic resistance genes. The software is a command line perl script freely available as open source.
Output: Simulate_PCR for amplicon prediction and annotation from multiplex, degenerate primers and probes
Objective: The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods: High-resolution CT (HRCT) findings of 106 patients with presumed/laboratoryconfirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results: The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n = 29, 27.4%), with unilateral or bilateral consolidation (n = 50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p < 0.01, 2 test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions: The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S-OIV (H1N1).
Output: Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings
The reliable and rapid detection of viral pathogens that cause respiratory infections provide physicians several advantages in treating patients and managing outbreaks. The Luminex respiratory virus panel (RVP) assay has been shown to be comparable to or superior to culture/direct fluorescent-antibody assays (DFAs) and nucleic acid tests that are used to diagnose respiratory viral infections. We developed a multiplex asymmetric reverse transcription (RT)-PCR assay that can simultaneously differentiate all influenza A virus epidemic subtypes. The amplified products were hybridized with an electrochemical DNA sensor, and the results were automatically acquired. The limits of detection (LoDs) of both the Luminex RVP assay and the multiplex RT-PCRelectrochemical DNA sensor were 10 1 TCID 50 for H1N1 virus and 10 2 TCID 50 for H3N2 virus. The specificity assessment of the multiplex RT-PCR-electrochemical DNA sensor showed no cross-reactivity among different influenza A subtypes or with other noninfluenza respiratory viruses. In total, 3098 respiratory tract specimens collected from padiatric patients diagnosed with pneumonia were tested. More than half (43, 53.75%) of the specimens positive for influenza A viruses could not be further subtyped using the Luminex RVP assay. Among the remaining 15 specimens that were not subtyped, not degraded, and in sufficient amounts for the multiplex RT-PCR-electrochemical DNA sensor test, all (100%) were H3N2 positive. Therefore, the sensitivity of the Luminex RVP assay for influenza A virus was 46.25%, whereas the sensitivity of the multiplex RT-PCR-electrochemical DNA sensor for the clinical H1N1 and H3N2 specimens was 100%. The sensitivities of the multiplex RT-PCR-electrochemical DNA sensor for the avian H5N1, H5N6, H9N2, and H10N8 viruses were 100%, whereas that for H7N9 virus was 85.19%. We conclude that the multiplex RT-PCR-electrochemical DNA sensor is a reliable method for the rapid and accurate detection of highly variable influenza A viruses in respiratory infections with greater detection sensitivity than that of the Frontiers in Microbiology | www.frontiersin.org 1 June 2018 | Volume 9 | Article 1405 Xu et al. Influenza A Viruses Detection Luminex xTAG assay. The high mutation rate of influenza A viruses, particularly H3N2 during the 2014 to 2016 epidemic seasons, has a strong impact on diagnosis. A study involving more positive specimens from all influenza A virus epidemic subtypes is required to fully assess the performance of the assay.
Output: ) A Multiplex Asymmetric Reverse Transcription-PCR Assay Combined With an Electrochemical DNA Sensor for Simultaneously Detecting and Subtyping Influenza A Multiplex Asymmetric Reverse Transcription-PCR Assay Combined With an Electrochemical DNA Sensor for Simultaneously Detecting and Subtyping Influenza A Viruses
Background The aim of this study was to assess multiplex PCR analysis in detecting causative viruses in children with febrile seizures. Methods The study was a retrospective analysis comparing data from a pre-multiplex era (2009) with a period after the introduction of routine respiratory multiplex analysis (2010-2013) in children with febrile seizures. Results We included 200 children with febrile seizures (mean age: 29.5 ± 1.4.months; 104 male) in the study. In 2009, in 10 out of 49 (20 %) children, microbiology testing (bacterial/fungal) was positive compared with a rate of 74 out of 151 (49 %) children during 2010-2013 (p < 0.01). The rate of positive virological studies increased from 10 (20 %) in 2009 to 73 (48.3 %) in the period 2010-2013 (p < 0.01). Multiplex PCR analysis confirmed viral infections in 52 of 73 cases (71.2 %). Conclusion Routine multiplex PCR analysis fosters the detection of respiratory viruses in children with febrile seizure. The precise role of multiplex analysis in the J.
Output: Role of multiplex PCR analysis in children with febrile seizures management of these children awaits further clarifi- cation
Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL pro ) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL pro of severe-acute-respiratory-syndrome-coronavirus. The IC 50 values of the inhibitors were in the range of 4.6e49 mM, demonstrating that the nitrile warhead can effectively inactivate the 3CL pro autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was w10x more potent than the other inhibitors tested. Crystal structures of the enzymeeinhibitor complexes showed that the nitrile warhead inhibits 3CL pro by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1eS4 substratebinding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broadspectrum inhibition against 3CL pro from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC 50 values ranging from 1.3 to 3.7 mM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL pro , and they inhibit 3CL pro from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.
Output: Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases
The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed. Cimicifuga simplex; Ranunculaceae; Cycloartenol triterpenoid saponins; Biological effects [CLC Number] R284, R965 [Document code] A [Article ID] These authors have no any conflict of interest to declare. Published by Elsevier B.V. All rights reserved and biological perspectives. C. simplex, also known as Ku lou ya gen and Long yan gen, is an important species in the original Chinese drug Shengma. In Chinese traditional medicine, as along with other Cimicifuga species, it has been used to clear heat, relieve toxicity, disperse exterior pathogen, promote eruption, and lift spirit [3] . Plant-based formulations for various medicinal applications use different preparation methods, including powders, alcohol extracts, water extracts, and honey processed pills. The roots of C. simplex have been used to treat headache, toothache, aphtha, sore throat, measles, rectocele, and uterine prolapse [11] . The most important biologically active components of C. simplex are the cycloartenol triterpenoid saponins which have good immunosuppressive activities [12] . C. simplex Wormsk. ex DC. (Shengma in Chinese) is a deciduous perennial herb, and is widely distributed in China [13] . Currently, more than 120 cycloartane-type triterpenoids from Cimicifuga simplex have been isolated by several groups [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] , including compounds of cycloartanol type, 16,23-dione type, shengmanol type, hydroshengmanol type, cimifugenin type, cimiacerogenin type, and the cimigenol type. The chemical structures of these cycloartenol triterpenoid saponins are shown in Fig.s 1−7 and are listed in Table 1 . The isolation scheme WU Lun, et al. / Chin J Nat Med, 2015, 13(2): 8189 -82 -for the 9,19-cyclolanostane triterpenoid glycosides from C. simplex is shown in Fig. 8 .
Output: Cycloartenol triterpenoid saponins from Cimicifuga simplex (Ranunculaceae) and their biological effects
The recent Zika outbreak in the Americas, Ebola epidemic in West Africa and the increased frequency and impact of emerging and re-emerging infections of animal origin have increased the calls for greater preparedness in early detection and responses to public health events. One-Health approaches that emphasize collaborations between human health, animal health and environmental health sectors for the prevention, early detection and response to disease outbreaks have been hailed as a key strategy. Here we highlight three main efforts that have progressed the implementation of One Health in Kenya.
Output: Disease Surveillance, Vector and Zoological Services, Ministry of Agriculture, Livestock and Fisheries
Animals that hunt and scavenge are often exposed to a broad array of pathogens. Theory predicts the immune systems of animals specialized for scavenging should have been molded by selective pressures associated with surviving microbial assaults from their food. Spotted hyenas (Crocuta crocuta) are capable hunters that have recently descended from carrion feeding ancestors. Hyenas have been documented to survive anthrax and rabies infections, and outbreaks of several other viral diseases that decimated populations of sympatric carnivores. In light of the extreme disease resistance manifested by spotted hyenas, our objective was to identify tools available for studying immune function in spotted hyenas and use these tools to document the hyena antibody response to immunization. Domestic cats (Felis catus) are the closest phylogenetic relatives of hyenas that have been studied in detail immunologically, and we hypothesized that anti-cat isotype-specific antibodies would cross react with hyena immunoglobulin epitopes. We used ELISA and Western blots to test isotype-specific anti-feline antibodies for specific cross-reaction to hyena Ig epitopes. Molecular weights of heavy (IgA, IgG, IgM) and light chains of hyena immunoglobulins were determined by protein electrophoresis, and as expected, they were found to be similar to feline immunoglobulins. In order to further validate the cross-reactivity of the anti-feline antibodies and document the hyena humoral response, eight spotted hyenas were immunized with dinitrophenol conjugated keyhole limpet hemocyanin (DNP-KLH) and serum anti-DNP responses were monitored by enzyme-linked immunosorbent assay (ELISA) for one year. The full array of isotype-specific antibodies identified here will allow veterinarians and other researchers to
Output: Development of a hyena immunology toolbox
Background: Chronic Obstructive Pulmonary Disease (COPD) exacerbations are associated with viral infections. We wished to determine if respiratory viral infection of children in the community was associated with hospital admissions of patients with exacerbations of COPD. Methods: We collected data over a 45-month period from the Northern Ireland Regional Virus Laboratory and from a general hospital in the same locality. We studied the relationship between upper respiratory infections in children and COPD admissions. We also examined the role of school holidays. Results: Correlations were seen between the frequency of all viral infections in children and the number of adult COPD hospitalizations ðPo0:005Þ. Subgroup analysis showed distinct relationships with epidemics of; influenza A ðPo0:001Þ, influenza B ðPo0:05Þ, adenovirus ðP ¼ 0:05Þ, respiratory syncytial virus ðPo0:005Þ and hospital admissions of patients with COPD. There were significantly fewer COPD admissions in the week after the start of a school holiday period ðPo0:05Þ. Conclusions: When children are hospitalized with viral respiratory infection there is an associated rise in adult COPD admissions. This suggests exacerbations of COPD are associated with epidemics of respiratory viruses. When children are on school holidays there is a reduction in COPD admissions in the community. This provides further support for respiratory viruses in the pathogenesis of COPD exacerbations.
Output: Childhood respiratory infections and hospital admissions for COPD ARTICLE IN PRESS
The rapid improvements in DNA synthesis technology hold the potential to revolutionize biosciences in the near future. Traditional genetic engineering methods are template dependent and make extensive but laborious use of site-directed mutagenesis to explore the impact of small variations on an existing sequence ''theme.'' De novo gene and genome synthesis frees the investigator from the restrictions of the pre-existing template and allows for the rational design of any conceivable new sequence theme. Viruses, being among the simplest replicating entities, have been at the forefront of the advancing biosciences since the dawn of molecular biology. Viral genomes, especially those of RNA viruses, are relatively short, often less than 10,000 bases long, making them amenable to whole genome synthesis with the currently available technology. For this reason viruses are once again poised to lead the way in the budding field of synthetic biology-for better or worse.
Output: Putting Synthesis into Biology: A Viral View of Genetic Engineering through De Novo Gene and Genome Synthesis
Background: Human rhinoviruses (HRVs) are associated with more acute respiratory tract infections than any other viral group yet we know little about viral diversity, epidemiology or clinical outcome resulting from infection by strains, in particular the recently identified HRVs. Objectives: To determine whether HRVC-QCE was a distinct HRV-C strain, by determining its genome and prevalence, by cataloguing genomic features for strain discrimination and by observing clinical features in positive patients. Study design: Novel real-time RT-PCRs and retrospective chart reviews were used to investigate a welldefined population of 1247 specimen extracts to observe the prevalence and the clinical features of each HRV-QCE positive case from an in-and out-patient pediatric, hospital-based population during 2003. An objective illness severity score was determined for each HRVC-QCE positive patient. Results: Differences in overall polyprotein and VP1 binding pocket residues and the predicted presence of a cis-acting replication element in 1B defined HRVC-QCE as a novel HRV-C strain. Twelve additional HRVC-QCE detections (1.0% prevalence) occurred among infants and toddlers (1-24 months) suffering mild to moderate illness, including fever and cough, who were often hospitalized. HRVC-QCE was frequently detected in the absence of another virus and was the only virus detected in three (23% of HRVC-QCE positives) children with asthma exacerbation and in two (15%) toddlers with febrile convulsion. Conclusions: HRVC-QCE is a newly identified, genetically distinct HRV strain detected in hospitalized children with a range of clinical features. HRV strains should be independently considered to ensure we do not overestimate the HRVs in asymptomatic illness.
Output: Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC-QCE, detected in children with fever, cough and wheeze during 2003
a b s t r a c t Most respiratory tract infections are self-limiting and caused by viruses, and do not warrant antibiotic treatment. Despite this, patients with respiratory tract infections often receive antibiotics, fuelling the rise of antibiotic resistance. Therefore, there is a need to encourage patients to try alternative non-antibiotic therapies, which ideally treat the symptoms and the cause. Lozenges containing amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA lozenges) as well as lozenges containing hexylresorcinol have been shown to provide effective symptomatic relief for sore throat. In this study, we investigated whether these lozenges also have virucidal effects in vitro against two viruses associated with respiratory tract infections, parainfluenza virus type 3 and cytomegalovirus. Both viruses were incubated with AMC/DCBA lozenge, placebo lozenge or the active ingredients (AMC/DCBA) as free substances, and parainfluenza virus type 3 was incubated with hexylresorcinol lozenge, placebo lozenge or hexylresorcinol as a free substance. Virucidal effects were observed with the active lozenges and the active ingredients as free substances against both parainfluenza virus type 3 and cytomegalovirus. Mean reductions in viral titre were significantly greater compared with placebo lozenge and peak effects were observed for the shortest incubation time, 1 min. These findings suggest that AMC/DCBA lozenge and hexylresorcinol lozenge have the potential to have local antiviral effects in patients with sore throat due to viral respiratory tract infections. Use of such over-the-counter treatments for self-limiting respiratory tract infections may satisfy patients' desire for an anti-infective medication and reduce the demand for antibiotics.
Output: Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus