niryuu/sni-each-converted huggingface dataset:
Purpose: The aim of this study was to evaluate whether infants with rhinovirus (RV) infection-induced wheezing and those with respiratory syncytial virus (RSV) infection-induced wheezing have different cytokine profiles in the acute stage. Methods: Of the infants with lower respiratory tract infection (LRTI) between September 2011 and May 2012, 88 were confirmed using reverse transcription polymerase chain reaction and hospitalized. Systemic interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, IL-4, IL-5, IL-13, and Treg-type cytokine (IL-10) responses were examined with multiplex assay using acute phase serum samples. Results: Of the 88 patients, 38 had an RV infection (RV group) and 50 had an RSV infection (RSV group). In the RV group, the IFN-γ and IL-10 concentrations were higher in the patients with than in the patients without wheezing (P=0.022 and P=0.007, respectively). In the RSV group, the differences in IFN-γ and IL-10 concentrations did not reach statistical significance between the patients with and the patients without wheezing (P=0.105 and P=0.965, respectively). The IFN-γ and IL-10 concentrations were not significantly different between the RV group with wheezing and the RSV group with wheezing (P=0.155 and P=0.801, respectively), in contrast to the significant difference between the RV group without wheezing and the RSV group without wheezing (P=0.019 and P=0.035, respectively). Conclusion: In comparison with RSV-induced LRTI, RV-induced LRTI combined with wheezing showed similar IFN-γ and IL-10 levels, which may have an important regulatory function.
Output: Comparison of cytokine expression profiles in infants with a rhinovirus induced lower respira tory tract infection with or without wheez ing: a comparison with respiratory syn cytial virus
Estimating temporal changes in a target population from phylogenetic or count data is an important problem in ecology and epidemiology. Reliable estimates can provide key insights into the climatic and biological drivers influencing the diversity or structure of that population and evidence hypotheses concerning its future growth or decline. In infectious disease applications, the individuals infected across an epidemic form the target population. The renewal model estimates the effective reproduction number, R, of the epidemic from counts of its observed cases. The skyline model infers the effective population size, N, underlying a phylogeny of sequences sampled from that epidemic. Practically, R measures ongoing epidemic growth while N informs on historical caseload. While both models solve distinct problems, the reliability of their estimates depends on p-dimensional piecewise-constant functions. If p is misspecified, the model might underfit significant changes or overfit noise and promote a spurious understanding of the epidemic, which might misguide intervention policies or misinform forecasts. Surprisingly, no transparent yet principled approach for optimising p exists. Usually, p is heuristically set, or obscurely controlled via complex algorithms. We present a computable and interpretable p-selection method based on the minimum description length (MDL) formalism of information theory. Unlike many standard model selection techniques, MDL accounts for the additional statistical complexity induced by how parameters interact. As a result, our method optimises p so that R and N estimates properly adapt to the available data. It also outperforms comparable Akaike and Bayesian information criteria on several classification problems. Our approach requires some knowledge of the parameter space and exposes the similarities between renewal and skyline models.
Output: Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models
Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly transmissible vaccine poses substantial evolutionary risks, including reversion to high virulence as has been documented for the oral polio vaccine. An alternative, and far safer approach, is to rely on genetically engineered and weakly transmissible vaccines that have reduced scope for evolutionary reversion. Here, we use mathematical models to evaluate the potential efficacy of such weakly transmissible vaccines. Our results demonstrate that vaccines with even a modest ability to transmit can significantly lower the incidence of infectious disease and facilitate eradication efforts. Consequently, weakly transmissible vaccines could provide an important tool for controlling infectious disease in wild and domestic animal populations and for reducing the risks of emerging infectious disease in humans.
Output: Eradicating infectious disease using weakly transmissible vaccines
Porcine parvovirus (PPV) can cause reproductive failure in swine, resulting in economic losses to the industry. Antiviral effects of diammonium glycyrrhizinate (DG) have been reported on several animal viruses; however, to date it has yet to be tested on PPV. In this study, the antiviral activity of DG on swine testis (ST) cell infection by PPV was investigated using an empirically determined, non-toxic concentration of DG and three different experimental designs: (1) pre-treatment of virus prior to infection; (2) pre-treatment of cells prior to infection; and (3) direct treatment of virus-infected cells. The results showed that DG possesses potent inhibitory effects on PPV when the virus was treated before incubation with ST cells and that virus infectivity decreased in a dose-dependent manner. Results were confirmed by indirect immunofluorescence assays and real-time quantitative PCR. In addition, deoxycholate was used as a control to exclude the possibility that DG acted as a detergent to inhibit PPV infectivity. The study clearly indicates that DG has a direct anti-PPV effect in vitro. Pengchong Li and Hao Zou are co-first authors.
Output: Antiviral Effect of Diammonium Glycyrrhizinate on Cell Infection by Porcine Parvovirus
Several new viral respiratory tract infectious diseases with epidemic potential that threaten global health security have emerged in the past 15 years. In 2003, WHO issued a worldwide alert for an unknown emerging illness, later named severe acute respiratory syndrome (SARS). The disease caused by a novel coronavirus (SARS-CoV) rapidly spread worldwide, causing more than 8000 cases and 800 deaths in more than 30 countries with a substantial economic impact. Since then, we have witnessed the emergence of several other viral respiratory pathogens including infl uenza viruses (avian infl uenza H5N1, H7N9, and H10N8; variant infl uenza A H3N2 virus), human adenovirus-14, and Middle East respiratory syndrome coronavirus (MERS-CoV). In response, various surveillance systems have been developed to monitor the emergence of respiratory-tract infections. These include systems based on identifi cation of syndromes, web-based systems, systems that gather health data from health facilities (such as emergency departments and family doctors), and systems that rely on self-reporting by patients. More eff ective national, regional, and international surveillance systems are required to enable rapid identifi cation of emerging respiratory epidemics, diseases with epidemic potential, their specifi c microbial cause, origin, mode of acquisition, and transmission dynamics.
Output: Series Emerging respiratory tract infections 1 Surveillance for emerging respiratory viruses
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. braz j infect dis 2 0 2 0;2 4(1):73-80 Outpatient Children Vaccine Lineages Phylogeny Cohort a b s t r a c t Introduction: Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives: Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. : 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.
Output: Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons
The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002-2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis. Published by Elsevier Ltd.
Output: Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for Severe Acute Respiratory Syndrome coronavirus (SARS-CoV)
Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.
Output: Markers and Biomarkers of Endothelium: When Something Is Rotten in the State
Cultures of an isolate of Penicillium verrucosum var. cyclopium, obtained from stored maize in an area of Balkan (endemic) nephro-pathy&mdash;Vratza, Bulgaria&mdash;has consistently induced renal tubular lesions when force-fed to rats for 20 days. The lesions, confined to the lower reaches of the proximal convoluted tubules (pars recta and junctional zone), closely resemble the tubular changes in patients with Balkan nephropathy. Preliminary evidence suggests that this nephrotoxin-producing strain of P. verrucosum var. cyclopium may be implicated in the &aelig;tiology of Balkan nephropathy.
Output: Archs Neurol. 1974, 30, 113. 14 Hebb
The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2 À/À ) in order to determine if signaling by this chemokine is relevant in host defense. Intracerebral infection of CCL2 À/À mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR2 À/À mice and CCL2 À/À mice cleared replicating virus from the brain. In contrast, CCR2 À/À mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen-specific T cells as compared to both CCL2 À/À and wild-type mice. The paucity in T cell accumulation within the central nervous system (CNS) of MHV-infected CCR2 À/À mice was not the result of either a deficiency in antigen-presenting cell (APC) accumulation within draining cervical lymph nodes (CLN) or the generation of virus-specific T cells within this compartment. A similar reduction in macrophage infiltration into the CNS was observed in both CCL2 À/À and CCR2 À/À mice when compared to wild-type mice, indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to macrophage migration and accumulation within the CNS following MHV infection. Together, these data demonstrate that CCR2, but not CCL2, is important in host defense following viral infection of the CNS, and CCR2 ligand(s), other than CCL2, participates in generating a protective response.
Output: Differential roles of CCL2 and CCR2 in host defense to coronavirus infection
Background: Acute-phase proteins (APPs) are sensitive markers of inflammation, and serum C-reactive protein (CRP) recently has been shown to be a useful diagnostic marker in dogs with bacterial pneumonia (BP). In humans with community-acquired pneumonia, APPs also have great utility as follow-up markers aiding in the assessment of treatment response. Objectives: The aim of our study was to investigate the applicability of APPs as markers of treatment response in dogs with BP. Animals: Nineteen dogs diagnosed with BP and 64 healthy dogs. Methods: The study was conducted as a prospective longitudinal observational study. Serum CRP, serum amyloid A (SAA), and haptoglobin concentrations were followed during a natural course of BP. Normalization of serum CRP was used to guide the duration of antibiotic treatment (treatment was stopped 5-7 days after CRP normalized) in 8 of 17 dogs surviving to discharge; 9 of 17 dogs were treated according to conventional recommendations. Results: All measured APPs initially were significantly increased, but the magnitude of increase was not correlated to disease severity. C-reactive protein and SAA concentrations decreased rapidly after initiation of antimicrobial treatment. When normalization of serum CRP was used to guide the duration of antibiotic treatment, treatment duration was significantly (P = .015) decreased without increasing the number of relapses. Conclusions and Clinical Importance: Serum CRP and SAA reflected the recovery process well and therefore may be used as markers of treatment response. According to the results, the normalization of serum CRP may be used to guide the duration of antibiotic treatment in dogs with BP.
Output: The Utility of Acute-Phase Proteins in the Assessment of Treatment Response in Dogs With Bacterial Pneumonia
The research aims was to determine the cytotoxic effects and the highest safe concentration of curcumin and PGV-0 on vero cells. This research also compare the effect of curcumin and PGV-0 against vero cells infected by Dengue virus (in vitro) in one and three days incubation period. The highest safe concentrations against vero cells from curcumin was 6.25 ppm and 1.5625 ppm for PGV-0. Immunocytochemistry test of curcumin and PGV-0 in both incubation period (one and three days) shows no significant difference (significant value 0.925), but RT-PCR result indicates that PGV -0 have potential antiviral better than curcumin.
Output: -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-review under responsibility of scientific committee of the ICTCRED 2014 ScienceDirect Effects of Curcumin and Pentagamavunon-0 Against Dengue-2 Virus Infection In Vero Cells; an In Vitro Study
Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines. Viruses 2019, 11, 74 2 of 17 Preclinical vaccine development for both SARS-CoV and MERS-CoV has largely aimed to stimulate a robust immune response against the viral envelope-protruding spike (S) glycoprotein [28, 29] , a class I fusion protein, and/or the nucleocapsid (N) protein [30, 31] . MERS-CoV S is proteolytically cleaved by host furin [32] during maturation into an S1 domain responsible for binding to DPP4 as well as an S2 domain containing two heptad-repeat regions that facilitate membrane fusion (Figure 1 ). The S1 domain can be further divided into the N-terminal domain (NTD), or S1 A , associated with binding sialic acid [33] , and the receptor binding domain (RBD), comprising the majority of the C-terminal domain of S1. Cryo-electron microscopy studies have shown that the RBD is flexible and opens upward or away from the viral envelope in order to establish contact with DPP4, which may expose S2' [34], a second protease cleavage site within S2. Cleavage at S2' is necessary for membrane fusion upon viral entry [32] . The centrality of S to viral entry helps explain why antibodies that target it are potently neutralizing [35] . On the other hand, while CoV N proteins are abundantly expressed during infection [36] , immunization with SARS-CoV N did not induce strongly neutralizing antibodies [37], likely because N is not displayed on the viral surface. However, N is more conserved than S within CoV lineage [38] , and vaccination with SARS-CoV N was shown to induce cytotoxic T cell responses in mice [39] . Therefore, N may help induce cell-mediated immunity to CoV infection [40] , as may S [41]. CD4+ and CD8+ T cell responses from recovered MERS-CoV patients were particularly strong towards N peptides [42] . However, vaccination with N-based immunogens may carry risks associated with T h 2-related eosinophilic immune enhancement [43] , as may S-based vaccines [44] . Notwithstanding, because of the protection afforded by the robust immune response it generates, S has been the target of most vaccine candidates for MERS-CoV. In this review, we summarize the current state of MERS-CoV vaccine candidates and also describe potential barriers to MERS-CoV vaccine efficacy that first surfaced during research on developing a SARS-CoV vaccine.
Output: viruses Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism
The development and characterization of a quartz crystal microbalance (QCM) sensor for the direct detection of aerosolized influenza A virions is reported. Self-assembled monolayers (SAMs) of mercaptoundecanoic acid (MUA) are formed on QCM gold electrodes to provide a surface amenable for the immobilization of anti-influenza A antibodies using NHS/EDC coupling chemistry. The surface-bound antibody provides a selective and specific sensing interface for the capture of influenza virions. A nebulizer is used to create aerosolized samples and is directly connected to a chamber housing the antibody-modified crystal ("immunochip"). Upon exposure to the aerosolized virus, the interaction between the antibody and virus leads to a dampening of the oscillation frequency of the quartz crystal. The magnitude of frequency change is directly related to virus concentration. Control experiments using aerosols from chicken egg allantoic fluid and an anti-murine antibody based immunosensor confirm that the observed signal originates from specific viral binding on the chip surface. Step-by-step surface modification of MUA assembly, antibody attachment, and antibody-virus interaction are characterized by atomic force microscopy (AFM) imaging analysis. Using the S/N = 3 principle, the limit of detection is estimated to be 4 virus particles/mL. The high sensitivity and real-time sensing scheme presented here can play an important role in the public health arena by offering a new analytical tool for identifying bio-contaminated areas and assisting in timely patient diagnosis.
Output: Microgravimetric immunosensor for direct detection of aerosolized influenza A virus particles
Background: Lycoris aurea, also called Golden Magic Lily, is an ornamentally and medicinally important species of the Amaryllidaceae family. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for L. aurea using high-throughput sequencing technology. Methodology and Principal Findings: Total RNA was isolated from leaves with sodium nitroprusside (SNP), salicylic acid (SA), or methyl jasmonate (MeJA) treatment, stems, and flowers at the bud, blooming, and wilting stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, a total of 937,990 high quality reads (308.63 Mb) with an average read length of 329 bp were generated. Clustering and assembly of these reads produced a non-redundant set of 141,111 unique sequences, comprising 24,604 contigs and 116,507 singletons. All of the unique sequences were involved in the biological process, cellular component and molecular function categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literatures, many putative genes involved in Amaryllidaceae alkaloids synthesis, including PAL, TYDC OMT, NMT, P450, and other potentially important candidate genes, were identified for the first time in this Lycoris. Furthermore, 6,386 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in L. aurea. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will provide useful information for functional genomic research in future.
Output: De novo Sequence Assembly and Characterization of Lycoris aurea Transcriptome Using GS FLX Titanium Platform of 454 Pyrosequencing
To study the host-dependent genetic variations in murine hepatitis virus type 3 (MHV 3) induced diseases, we localized the sites of MHV 3 (Mill Hill strain) expression within liver and brain by immunohistochemistry or hybridization in situ. Two strains of mice were studied: BALB/c mice, which develop an acute and lethal hepatitis and C3H mice which develop a chronic brain infection. In BALB/c mice, viral RNA and antigens appeared during the first 24 h post infection (p.i.) in liver, whereas viral RNA was barely detectable in brain, up until death at day 3 p.i. In C3H mice, viral RNA and antigens were detected simultaneously in liver and brain only at day 2 p.i. In brain, the virus was detected in meningeal and ependymal cells and in perivascular cortical areas (days 5 and 7 p.i.). After day 49, the virus was no longer detected in brain parenchyma, but persisted in meningeal cells. Two host-dependent genetic differences in viral processing were observed in the liver: (1) the virus was first detected in Kupffer cells in BALB/c mice and mostly in hepatocytes in C3H mice; (2) in BALB/c mice, the 180kDa S viral glycoprotein appeared more frequently cleaved in 90 kDa form than in C3H mice.
Output: Genetic restriction of murine hepatitis virus type 3 expression in liver and brain: comparative study in BALB]c and C3H mice by immunochemistry and hybridization in situ
Bats are found to be the natural reservoirs for many emerging viruses. In most cases, severe clinical signs caused by such virus infections are normally not seen in bats. This indicates differences in the virus-host interactions and underlines the necessity to develop natural host related models to study these phenomena. Due to the strict protection of European bat species, immortalized cell lines are the only alternative to investigate the innate anti-virus immune mechanisms. Here, we report about the establishment and functional characterization of Myotis myotis derived cell lines from different tissues: brain (MmBr), tonsil (MmTo), peritoneal cavity (MmPca), nasal epithelium (MmNep) and nervus olfactorius (MmNol) after immortalization by SV 40 large T antigen. The usefulness of these cell lines to study antiviral responses has been confirmed by analysis of their susceptibility to lyssavirus infection and the mRNA patterns of immune-relevant genes after poly I:C stimulation. Performed experiments indicated varying susceptibility to lyssavirus infection with MmBr being considerably less susceptible than the other cell lines. Further investigation demonstrated a strong activation of interferon mediated antiviral response in MmBr contributing to its resistance. The pattern recognition receptors: RIG-I and MDA5 were highly upregulated during rabies virus infection in MmBr, suggesting their involvement in promotion of antiviral responses. The presence of CD14 and CD68 in MmBr suggested MmBr cells are microglia-like cells which play a key role in host defense against infections in the central nervous system (CNS). Thus the expression pattern of MmBr combined with the observed limitation of lyssavirus replication underpin a protective mechanism of the CNS controlling the lyssavirus infection. Overall, the established cell lines are important tools to analyze antiviral innate immunity in M. myotis against neurotropic virus infections and present a valuable tool for a broad spectrum of future investigations in cellular biology of M. myotis.
Output: Establishment of Myotis myotis Cell Lines -Model for Investigation of Host-Pathogen Interaction in a Natural Host for Emerging Viruses
Poly-g-glutamic acid (g-PGA) is an anionic polypeptide secreted by Bacillus sp. that has been shown to activate immune cells through interactions with toll-like receptor 4 (TLR4). However, its ability to induce the type I interferon (IFN) response has not yet been characterized. Here, we demonstrate that g-PGA induces type I IFN signaling pathway via the TLR4 signaling pathway. The induction required both myeloid differentiation factor 2 (MD2) and the pattern-recognition receptor CD14, which are two TLR4associated accessory proteins. The g-PGA with high molecular weights (2000 and 5000 kDa) was able to activate the subsequent signals through TLR4/MD2 to result in dimerization of IRF-3, a transcription factor required for IFN gene expression, leading to increases in mRNA levels of the type I IFN-response genes, 2 0 e5 0 OAS and ISG56. Moreover, g-PGA (2000 kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight g-PGA as a TLR4 ligand and demonstrate that g-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer g-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.
Output: The antiviral activity of poly-g-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses
N-glycans were released from the SARS coronavirus (SARS-CoV) spike glycoprotein produced in Vero E6 cells and their structures were determined by a combination of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, negative ion electrospray collision-induced dissociation time-of-flight mass spectrometry and normal-phase high-performance liquid chromatography with exoglycosidase digestion. Major glycans were high-mannose (Man 5-9 GlcNAc 2 ), hybrid and bi-, tri-and tetra-antennary complex with and without bisecting GlcNAc and core fucose. Complex glycans with fewer than the full complement of galactose residues were present and sialylation was negligible. Treatment with the glucosidase inhibitor Nbutyl-deoxynojirimycin (NB-DNJ) inhibited N-glycan processing as evidenced by the appearance of glycans of composition Glc 3 Man 7-9 GlcNAc 2 . However, some complex glycans remained suggesting the presence of an α-endomannosidase. Our data in tissue culture indicate that inhibition of N-glycan processing may be considered as a therapeutic strategy against SARS CoV infections.
Output: Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein
We developed an alternative steroid-associated osteonecrosis (ON) rabbit model using a combination of a single injection of low-dose lipopolysaccharide (LPS) and three subsequent injections of pulsed high-dose methylprednisolone (MPS). The usefulness of this experimental ON model was evaluated using both conventional and advanced bio-imaging techniques, including contrast-enhanced dynamic MRI and a high-resolution micro-CT. Details on establishment of methodology are described, which were adopted into an efficacy study on a herbal Epimedium-derived phytoestrogenic extract (HEPE) developed for prevention of steroid-associated ON using an established rabbit model. The underlying mechanisms of HEPE for prevention of steroid-associated ON were found to be associated with inhibition of both intravascular thrombosis and extravascular bone marrow lipid deposition, the two known mechanistic pathways in pathogenesis of ON. Our experimental results provide for potential clinical trials or applications of HEPE in the prevention of ON among highrisk patients undergoing steroid treatment.
Output: Contrast-Enhanced MRI and Micro-CT Adopted for Evaluation of a Lipid-Lowering and Anticoagulant Herbal Epimedium-Derived Phytoestrogenic Extract for Prevention of Steroid-Associated Osteonecrosis
The 2014-2016 Ebola virus disease epidemic in West Africa highlighted challenges faced by the global response to a large public health emergency. Consequently, the US Centers for Disease Control and Prevention established the Global Rapid Response Team (GRRT) to strengthen emergency response capacity to global health threats, thereby ensuring global health security. Dedicated GRRT staff can be rapidly mobilized for extended missions, improving partner coordination and the continuity of response operations. A large, agencywide roster of surge staff enables rapid mobilization of qualified responders with wide-ranging experience and expertise. Team members are offered emergency response training, technical training, foreign language training, and responder readiness support. Recent response missions illustrate the breadth of support the team provides. GRRT serves as a model for other countries and is committed to strengthening emergency response capacity to respond to outbreaks and emergencies worldwide, thereby enhancing global health security.
Output: Establishment of CDC Global Rapid Response Team to Ensure Global Health Security
Background: Although feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) have similar risk factors and control measures, infection rates have been speculated to vary in geographic distribution over North America. Since both infections are endemic in North America, it was assumed as a working hypothesis that their geographic distributions were similar. Hence, the purpose of this exploratory analysis was to investigate the comparative geographical distribution of both viral infections. Counts of FIV (n=17,108) and FeLV (n=30,017) positive serology results (FIV antibody and FeLV ELISA) were obtained for 48 contiguous states and District of Columbia of the United States of America (US) from the IDEXX Laboratories website. The proportional morbidity ratio of FIV to FeLV infection was estimated for each administrative region and its geographic distribution pattern was visualized by a choropleth map. Statistical evidence of an excess in the proportional morbidity ratio from unity was assessed using the spatial scan test under the normal probability model. Results: This study revealed distinct spatial distribution patterns in the proportional morbidity ratio suggesting the presence of one or more relevant and geographically varying risk factors. The disease map indicates that there is a higher prevalence of FIV infections in the southern and eastern US compared to FeLV. In contrast, FeLV infections were observed to be more frequent in the western US compared to FIV. The respective excess in proportional morbidity ratio was significant with respect to the spatial scan test (p < 0.05). The observed variability in the geographical distribution of the proportional morbidity ratio of FIV to FeLV may be related to the presence of an additional or unique, but yet unknown, spatial risk factor. Putative factors may be geographic variations in specific virus strains and rate of vaccination. Knowledge of these factors and the geographical distributions of these infections can inform recommendations for testing, management and prevention. However, further studies are required to investigate the potential association of these factors with FIV and FeLV.
Output: Comparison of the geographical distribution of feline immunodeficiency virus and feline leukemia virus infections in the United States of America (2000-2011)
Advances in nanoparticle-based systems constitute a promising research area with important implications for the treatment of bacterial infections, especially against multidrug resistant strains and bacterial biofilms. Nanosystems may be useful for the diagnosis and treatment of viral and fungal infections. Commercial diagnostic tests based on nanosystems are currently available. Different methodologies based on nanoparticles (NPs) have been developed to detect specific agents or to distinguish between Gram-positive and Gram-negative microorganisms. Also, biosensors based on nanoparticles have been applied in viral detection to improve available analytical techniques. Several point-of-care (POC) assays have been proposed that can offer results faster, easier and at lower cost than conventional techniques and can even be used in remote regions for viral diagnosis. Nanoparticles functionalized with specific molecules may modulate pharmacokinetic targeting recognition and increase anti-infective efficacy. Quorum sensing is a stimuli-response chemical communication process correlated with population density that bacteria use to regulate biofilm formation. Disabling it is an emerging approach for combating its pathogenicity. Natural or synthetic inhibitors may act as antibiofilm agents and be useful for treating multi-drug resistant bacteria. Nanostructured materials that interfere with signal molecules involved in biofilm growth have been developed for the control of infections associated with biofilm-associated infections.
Output: Molecular Sciences Nanoparticles for Signaling in Biodiagnosis and Treatment of Infectious Diseases
Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by
Output: molecules The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis
A series of novel 5-pyrazoline substituted 4-thiazolidinones have been synthesized. Target compounds were evaluated for their anticancer activity in vitro within DTP NCI protocol. Among the tested compounds, the derivatives 4d and 4f were found to be the most active, which demonstrated certain sensitivity profile toward the leukemia subpanel cell lines with GI 50 value ranges of 2.12e4.58 mM (4d) and 1.64e3.20 mM (4f). The screening of antitrypanosomal and antiviral activities of 5-(3-naphthalen-2yl-5-aryl-4,5-dihydropyrazol-1-yl)-thiazolidine-2,4-diones was carried out with the promising influence of the mentioned compounds on Trypanosoma brucei, but minimal effect on SARS coronavirus and influenza types A and B viruses.
Output: Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones
Background: Under conditions of no strand bias the number of Gs is equal to that of Cs for each DNA strand; similarly, the total number of Ts is equal to that of As. However, within each strand there are considerable local deviations from the A = T and G = C equality. These asymmetries in nucleotide composition have been extensively analyzed in prokaryotic and eukaryotic genomes and related to chromosome organization, transcription orientation and other processes in certain organisms. To carry out analysis of intra-strand nucleotide distribution several graphical methods have been developed. Results: GraphDNA is a new Java application that provides a simple, user-friendly interface for the visualization of DNA nucleotide composition. The program accepts GenBank, EMBL and FASTA files as an input, and it displays multiple DNA nucleotide composition graphs (skews and walks) in a single window to allow direct comparisons between the sequences. We illustrate the use of DNA skews for characterization of poxvirus and coronavirus genomes. GraphDNA is a platform-independent, Open Source, tool for the analysis of nucleotide trends in DNA sequences. Multiple sequence formats can be read and multiple sequences may be plotted in a single results window.
Output: GraphDNA: a Java program for graphical display of DNA composition analyses
Although the frequency of respiratory viral infection in patients with pulmonary acute respiratory distress syndrome (ARDS) is not uncommon, clinical significance of the condition remains to be further elucidated. The purpose of this study was to compare characteristics and outcomes of patients with pulmonary ARDS infected with influenza and other respiratory viruses. Methods: Clinical data of patients with pulmonary ARDS infected with respiratory viruses January 2014-June 2018 were reviewed. Respiratory viral infection was identified by multiplex reverse transcription-polymerase chain reaction (RT-PCR). Results: Among 126 patients who underwent multiplex RT-PCR, respiratory viral infection was identified in 46% (58/126): 28 patients with influenza and 30 patients with other respiratory viruses. There was no significant difference in baseline and clinical characteristics between patients with influenza and those with other respiratory viruses. The use of extracorporeal membrane oxygenation (ECMO) was more frequent in patients with influenza than in those with other respiratory viruses (32.1% vs 3.3%, p=0.006). Co-bacterial pathogens were more frequently isolated from respiratory samples of patients with pulmonary ARDS infected with influenza virus than those with other respiratory viruses. (53.6% vs 26.7%, p=0.036). There were no significant differences regarding clinical outcomes. In multivariate analysis, acute physiology and chronic health evaluation II was associated with 30-mortality (odds ratio, 1.158; 95% confidence interval, 1.022-1.312; p=0.022). Conclusion: Respiratory viral infection was not uncommon in patients with pulmonary ARDS. Influenza virus was most commonly identified and was associated with more co-bacterial infection and ECMO therapy.
Output: Characteristics and Outcomes of Patients with Pulmonary Acute Respiratory Distress Syndrome Infected with Influenza versus Other Respiratory Viruses
Objectives To identify the factors that influence hand hygiene compliance of final year medical students, using a theoretical behavioural framework. Design Cross-sectional survey assessing self-reported compliance and its behavioural correlates. Internships of medical students in the Netherlands. 322 Medical students of the Erasmus Medical Center were recruited over a period of 12 months during the internship Public health, which is the final compulsory internship after an 18 month rotation schedule in all major specialties. Behavioural factors influencing compliance to hand-hygiene were measured by means of a questionnaire based on the Theory of Planned Behaviour and Social Ecological Models . Multiple linear regression analysis was used to identify the effect of including attitudes, social norms, selfefficacy, knowledge, risk perception and habit on hand hygiene compliance. We included 313 students in the analysis (response of 97%). The behavioural model explained 40% of the variance in self-reported compliance (adjusted R 2 = 0.40). Hand hygiene compliance was strongly influenced by attitudes (perceived outcomes of preventive actions), self-efficacy (perception of the ability to perform hand hygiene at the clinical ward) and habit, but was not associated with knowledge and risk perception. Targeting medical students' behaviour should focus on the empowerment of these juniors and provide them with evidence on the health benefits of prevention, rather than increasing their factual knowledge of procedures. Clinical teaching environments could help them form good patient safety habits during this vital phase of their career. 1. This study uses a hand hygiene questionnaire, based on insights from both the Theory of Planned Behaviour and Social Ecological Models. 2. The hand hygiene behaviour of medical students is investigated from a behavioural perspective in a large sample of students at the same stage of their internships. 3. The main limitations of this study are its cross-sectional design and the self-reported compliance with hand hygiene guidelines.
Output: Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study Assessment of correlates of hand hygiene compliance among final year medical students: a cross-sectional study Article Summary
Early and rapid detection of dengue virus (DENV) infection during the acute phase of illness is crucial for proper patient management and prevention of the spread of the infection. In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. The performance of the RT-LAMP was compared to RT-PCR, CDC 1-4 Real time PCR and the NS1 antigen ELISA, IgM and IgG anti DENV antibodies. Acute DENV infection was confirmed in 250/300 patients suspected clinically of DENV infection. RT-LAMP and CDC 1-4 Real time PCR assay was positive in 148/250 patients, while 92/250 patients were positive for anti-Dengue IgM and IgG antibodies. The RT-LAMP assay and the CDC real-time RT-PCR assay showed high concordance (k = 1.0). The detection rate of acute DENV infection improved to 96% (240/250) when the results of RT-LAMP were combined with NS1 Ag, IgM and IgG ELISA. The RT-LAMP had a detection limit of 100 copies for DEN-1 and DEN-2, 10 copies for DEN-3 and DEN-4 compared to 1000 copies for DEN-1 and DEN-2, 100 copies for DEN-3 and DEN-4 by the conventional RT-PCR. The assay showed 100% specificity. The RT-LAMP assay developed in this study has potential use for early clinical diagnosis, serotyping and surveillance of DENV infection in endemic countries such as India.
Output: Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India
We investigated the sensitivity of human rotavirus rapid antigen detection (RAD) kits, RT-PCR and next-generation DNA sequencing (NGS) for detection of bovine group A rotavirus (RVA). The Dipstick 'Eiken' Rota (Dipstick) showed the highest sensitivity out of the seven RAD kits against all selected strains in limited dilution analyses, which was consistent with the results for equine rotavirus previously reported. RT-PCR had 10 0 -10 3 -fold higher sensitivity than the Dipstick. NGS using thirteen RT-PCR-negative fecal samples revealed that all samples yielded RVA reads and especially that two of them covered all 11 genome segments. Moreover, mapping reads to reference sequences allowed genotyping. The NGS would be sensitive and useful for analysis of less dependent on specific primers and screening of genotypes.
Output: Yukie KATAYAMA 2) , Mami OBA 2) , Naomi NISHIURA 2) , Yukiko SASSA 2) , Tsutomu OMATSU 2) , Tetsuya FURUYA 2,4) , Satoshi KOYAMA 5)
Acute undifferentiated fever (AUF) is frequently observed in tropical settings, but diagnosing the cause of AUF is often a challenge for local physicians and the physicians treating returning travellers. We conducted a case-control study in central Vietnam in 2016. A total of 378 febrile adult patients (AUFs) with a fever for ≤21 days, no evidence of localized infection and negative screening tests for dengue and malaria, and 384 afebrile adult patients (Controls) were prospectively enrolled. Whole blood, plasma, eschar swab, throat swab and urine specimens were collected and analysed. Quantitative PCR and RT-PCR were used to test for 55 bacteria, viruses and their subtypes. Serological tests were also used to test for rickettsial agents. The most common aetiology was influenza virus (20.9% in AUFs vs. 0% in Controls), followed by rickettsial agents (mainly Orientia tsutsugamushi and Rickettsia typhi) (10.8% vs. 0.3%), dengue virus (7.7% vs. 0.5%), Leptospira (4.8% vs. 0.8%), adenovirus (4.8% vs. 1.0%), and enterovirus (2.1% vs. 0%) (p < .05). The real proportion of dengue in AUF cases was underestimated because patients with denguepositive rapid diagnosis tests were excluded from the study. The emerging agent Rickettsia felis, which had not been previously observed in Vietnam, was detected in this study. In total, 216 patients (57.1%) were given causative diagnoses, comprising 143 (66.2%) monoinfections and 73 (33.8%) coinfections. The infections caused by these agents should be considered in clinical practice and further studies. Additionally, agents susceptible to doxycycline were detected in 15.6% of AUFs; thus, this drug should be included in the panel used to treat AUF patients.
Output: Prospective case-control analysis of the aetiologies of acute undifferentiated fever in Vietnam