niryuu/sni-each-converted huggingface dataset:
Background An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. Findings We estimated that the median daily reproduction number (R t ) in Wuhan declined from 2·35 (95% CI 1·15-4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41-2·39) 1 week after. Based on our estimates of R t , assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. Interpretation Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually.
Output: Articles Early dynamics of transmission and control of COVID-19: a mathematical modelling study
Multiplexed and sensitive detection of nucleic acids, proteins, or other molecules from a single solution and a small amount of sample is of great demand in biomarker profiling and disease diagnostics. Here we describe a new concept using combinatorial self-assembly of DNA nanotiles into micrometer-sized two-dimensional arrays that carry nucleic acid probes and barcoded fluorescent dyes to achieve multiplexed detection. We demonstrated the specificity and sensitivity of the arrays by detecting multiple DNA sequences and aptamer binding molecules. This DNA tilearray-based sensor platform can be constructed through DNA self-assembly. The attachment of different molecular probes can be achieved by simple DNA hybridization so bioconjugation is not necessary for the labeling. Accurate control of the interprobe distances and solution-based binding reactions ensures fast target binding kinetics.
Output: Self-Assembled Combinatorial Encoding Nanoarrays for Multiplexed Biosensing
Cells expressing the spike (S) glycoprotein of the neurotropic JHM strain (JHMV) of mouse hepatitis virus (MHV) are susceptible to lysis by B cells derived from naïve mice, including B cells from perforin-deficient mice. Cytolysis requires interaction of the virus receptor and the viral S glycoprotein, is independent of other viral-induced components, and is not a unique property of B cells. Neutralizing anti-S-protein monoclonal antibodies (mAb) and a mAb specific for the viral receptor inhibit lysis. However, cells infected with an MHV strain unable to induce cell-cell fusion are resistant to lysis and lysis of JHMV-infected cells is inhibited by an anti-S-protein nonneutralizing mAb which prevents S-protein-mediated cell fusion. These data suggest that B cells may function as antibody-independent innate immune response during JHMV infection in vivo.
Output: B-Cell-Mediated Lysis of Cells Infected with the Neurotropic JHM Strain of Mouse Hepatitis Virus
The serine proteases of the trypsin-like (S1) family play critical roles in many key biological processes including digestion, blood coagulation, and immunity. Recent studies have identified members of this family which contain amino-or carboxy-terminal domains that serve to tether the serine protease catalytic domain directly at the plasma membrane. These membrane anchored serine proteases are proving to be key components of the cell machinery for activation of precursor molecules in the pericellular microenvironment, playing vital functions in the maintenance of homeostasis. Substrates activated by membrane anchored serine proteases include peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules and viral coat proteins. In addition, new insights into our understanding of the physiological functions of these proteases and their involvement in human pathology have come from animal models and patient studies. This review discusses emerging evidence for the diversity of this fascinating group of membrane serine proteases as potent modifiers of the pericellular microenvironment through proteolytic processing of diverse substrates. We also discuss the functional consequences of the activities of these proteases on mammalian physiology and disease.
Output: The Cutting Edge: Membrane Anchored Serine Protease Activities in the Pericellular Microenvironment
Mathematical models of infectious disease spread are important tools for assessing the threat of a novel pathogen and offer the best information for mitigating an outbreak. Here we present a metapopulation model of disease spread in Great Britain defined at the level of electoral wards. Using data from the United Kingdom 2001 census and the National Travel Survey to define the amount of travel performed by individuals between wards, we examine the effect of assumptions on the regularity of travel. Routine, daily commuter-type movements, characteristic of the working population are shown to lead to a slower epidemic spread compared to movements with random destinations. We demonstrate that routine movements slow down the epidemic spread compared to a standard metapopulation setting by up to 25%. We also show that spurious long distance movements present in the census data do not have a significant impact on the development of a potential epidemic in Great Britain.
Output: The role of routine versus random movements on the spread of disease in Great Britain
Background: Guangzhou reported its first laboratory-confirmed case of influenza A (H7N9) on January 10, 2014. A total of 25 cases were reported from the first wave of the epidemic until April 8, 2014. The fatality rate was much higher than in previous reports. The objective of the current work was to describe the clinical and epidemiological characteristics of A (H7N9) patients in Guangzhou and explore possible reasons for the high fatality rate. Methods: Clinical and epidemiological information regarding A (H7N9) cases in Guangzhou was collected through review of medical records and field research. Data regarding clinical and laboratory features, treatment, and outcomes were extracted. Results: Of the 25 patients, 84 % (21/25) had one or more underlying diseases. Fifteen patients (60.0 %) developed moderate to severe acute respiratory distress syndrome (ARDS), and 14 (56 %) died of the ARDS or multiorgan failure. Patients with longer delay between onset of illness and initiation of oseltamivir treatment were more likely to develop ARDS. Elevated C-creative protein, aspartate aminotransferase, creatine kinase, and lymphocytopenia predicted a higher risk of developing ARDS. Conclusions: The presence of underlying diseases and clinical complications predicted poor clinical outcome. Early oseltamivir treatment was associated with a reduced risk of developing ARDS.
Output: Factors associated with clinical outcome in 25 patients with avian influenza A (H7N9) infection in Guangzhou, China
Ethnopharmacological relevance: Bai-Hu-Tang (BHT) was traditionally used to reduce fever heat and promote generation of body fluids. Aim of the study: To investigate the effect and mechanism of BHT in the prevention of lipopolysaccharide (LPS) fever in manners of immune modulation. Materials and methods: The model of fever syndrome of Chinese medicine pattern was imitated by LPS injection i.v. in rabbits, and BHT was gavaged. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6, 10) and immunoglobulin (IgG, IgA, and IgM) were determined by enzyme-linked immunosorbent assay (ELISA); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested by biochemical methods. Liver tissue damage was detected by hematoxylin-eosin (H&E) stain. Subpopulation of T cells was detected by Fluorescence Activated Cell Sorter (FACS). Genes expression of Toll-like receptor 4 (TLR4) and lipopolysaccharide binding protein (LBP) in liver tissue were assayed by real-time polymerase chain reaction (RT-PCR). Result: The results demonstrated that BHT prevented sudden increase of IL-10, TNF-α, ALT and AST, and liver damage induced by LPS. BHT also prevented significant decrease of the percentage of CD 8+ T cells since LPS injection. At the same time, BHT did not affect the gene expression of TLR4 and serum concentration of three immunoglobulins, which were increased by LPS, but made gene expression of LBP higher. Conclusion: The results of this study indicated that BHT played an important role in immunity protection and anti-injury through preventing immunoinflammatory damage by LPS. The achievement thereby scientifically provided mechanism of BHT in the prevention of febrile disease, and supported its traditional use.
Output: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits
Membrane-spanning α-helices represent major sites of protein-protein interaction in membrane protein oligomerization and folding. As such, these interactions may be of exquisite specifi city. Specifi city oft en rests on a complex interplay of diff erent types of residues forming the helix-helix interfaces via dense packing and diff erent non-covalent forces, including van der Waal's forces, hydrogen bonding, charge-charge interactions, and aromatic interactions. Th ese interfaces oft en contain complex residue motifs where the contribution of constituent amino acids depends on the context of the surrounding sequence. Moreover, transmembrane helix-helix interactions are increasingly recognized as being dynamic and dependent on the functional state of a given protein. Abbreviations: GpA, glycophorin A; H-bond, hydrogen bond; TMD, transmembrane domain.
Output: Helix-helix interaction patterns in membrane proteins
Real-time RT-PCR assay, based on light upon extension (LUX) fluorogenic primer and LightCycle technology, was developed for rapid detection of transmissible gastroenteritis virus (TGEV). Viral RNA from different TGEV isolates and clinical specimens was detected. To evaluate the sensitivity of the assay, a gel-based RT-PCR method targeted at the same 101 bp sequence was also developed. Serial 10-fold dilutions of TGEV RNA were detected by the two methods. Although the real time method used only 2 l RNA for each reaction, a 10-fold increase of sensitivity over that of the gel-based method, which used 10 l RNA was demonstrated. The study indicates that the LUX assay reported below is rapid, reliable and sensitive and it has the potential for use as an alternative molecular method for TGEV diagnosis.
Output: Development of a novel real-time RT-PCR assay with LUX primer for the detection of swine transmissible gastroenteritis virus
The 2015 epidemic of Middle East respiratory syndrome (MERS) in the Republic of Korea has been the largest outbreak outside Middle East. This epidemic had caused 185 laboratory-confirmed cases and 36 deaths in the Republic of Korea until September 2, 2015, which attracted public's attention. Based on the detailed data of patients released by World Health Organization (WHO) and actual propagation of the epidemic, we construct two dynamical models to simulate the propagation processes from May 20 to June 8 and from June 9 to July 10, 2015, respectively and find that the basic reproduction number R 0 reaches up to 4.422. The numerical analysis shows that the reasons of the outbreak spread quickly are lack of self-protection sense and targeted control measures. Through partial correction analysis, the parameters β 1 and γ have strong correlations with R 0 , i.e., the infectivity and proportion of the asymptomatic infected cases have much influence on the spread of disease. By sensitivity analysis, strengthening self-protection ability of susceptible and quickly isolating or monitoring close contacts are effective measures to control the disease.
Output: Modeling the Transmission of Middle East Respirator Syndrome Corona Virus in the Republic of Korea
Cytokine storms are a potentially fatal exaggerated immune response consisting of an uncontrolled positive feedback loop between immune cells and cytokines. The dynamics of cytokines are highly complex and little is known about specific interactions. Researchers at the Ontario Veterinary College have encountered cytokine storms during virotherapy. Multiple mouse trials were conducted where a virus was injected into mice whose leukocytes lacked expression of the type I interferon receptor. In each case a rapid, fatal cytokine storm occurred. A nonlinear differential equation model of the recorded cytokine amounts was produced to obtain some information on their mutual interactions. Results provide insight into the complex mechanism that drives the storm and possible ways to prevent such immune responses.
Output: A Mathematical Model of Cytokine Dynamics During a Cytokine Storm
Background. Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. Method. Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. Results. Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. Conclusions. This study suggests that VRTI during the first year after lung transplantation is associated with longterm CLAD development and that coronavirus infections in particular might be a risk factor.
Output: Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation
Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
Output: Brief Communication
Background: Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. Results: Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback-Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. Conclusion: We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country.
Output: Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt
Background-Patients with the 2019 coronavirus disease have different degrees of psychological pain, such as anxiety and depression, which may related to their prognosis. Psychological intervention can be conducted in different ways to improve psychological pain and improve the treatment effect. Objective-The present study aimed to investigate and analyze the psychological status of patients with COVID-19 during the course of illness, and to evaluate the effect and influencing factors of psychological crisis intervention, so as to explore the effective mode of clinical psychological intervention in acute patients under isolation environment. Methods-A total of 143 persons participated in the study, including 26 patients diagnosed with COVID-19 in the isolation ward (COVID-19 group), 87 patients with general pneumonia in the observation ward (General Pneumonia group) and 30 healthy volunteers (Normal group). All the patients in the ward received comprehensive psychological intervention, including telephone psychological counseling (active and passive), self-adjustment of written materials and one-to-one psychological crisis intervention. Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were used to evaluate the mental health status of all patients on the day of admission and 1 week after treatment. Results-The scores of HAMA and HAMD of all patients (including isolation ward and observation ward) were significantly higher than the healthy volunteers at the time of admission. The total score of HAMA and HAMD in CVOID-19 group were both higher than that General Pneumonia group. After 1 week`s hospitalization with comprehensive psychological intervention, the scores of HAMA and HAMD in CVOID-19 group were significantly decreased. Conclusion-Patients those who diagnosed with COVID-19 in the isolation ward and/or general pneumonia in observation ward have different degrees of anxiety, depression and sleep problems. While receiving antiviral treatment, patients also need psychological intervention. Comprehensive psychological intervention model has been proved to be effective.
Output: Analysis of psychological state and clinical psychological intervention model of patients with COVID-19 Running Title: Psychological state and intervention model in COVID-19 patients
Background: Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to − 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. Methods: In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1-4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1-4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). Results: From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. Conclusion: This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1-3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests.
Output: Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1)
Many economically important cattle diseases spread between herds through livestock movements. Traditionally, most transmission models have assumed that all purchased cattle carry the same risk of generating outbreaks in the destination herd. Using data on bovine viral diarrhoea virus (BVDV) in Scotland as a case example, this study provides empirical and theoretical evidence that the risk of disease transmission varies substantially based on the animal and herd demographic characteristics at the time of purchase. Multivariable logistic regression analysis revealed that purchasing pregnant heifers and open cows sold with a calf at foot were associated with an increased risk of beef herds being seropositive for BVDV. Based on the results from a dynamic within-herd simulation model, these findings may be partly explained by the age-related probability of animals being persistently infected with BVDV as well as the herd demographic structure at the time of animal introductions. There was also evidence that an epidemiologically important network statistic, "betweenness centrality" (a measure frequently associated with the potential for herds to acquire and transmit disease), was significantly higher for herds that supplied these particular types of replacement beef cattle. The trends for dairy herds were not as clear, although there was some evidence that open heifers and open lactating cows were associated with an increased risk of BVDV. Overall, these findings have important implications for developing simulation models that more accurately reflect the industry-level transmission dynamics of infectious cattle diseases.
Output: Not all cows are epidemiologically equal: quantifying the risks of bovine viral diarrhoea virus (BVDV) transmission through cattle movements
Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.
Output: Bat origin of human coronaviruses
Nerve growth factor (NGF) is overexpressed in patients with inflammatory lung diseases, including virus infections. Airway surface liquid (ASL), which is regulated by epithelial cell ion transport, is essential for normal lung function. No information is available regarding the effect of NGF on ion transport of airway epithelium. To investigate whether NGF can affect ion transport, human primary air-interface cultured epithelial cells were placed in Ussing chambers to obtain transepithelial voltage (À7.1 AE 3.4 mV), short-circuit current (I sc , 5.9 AE 1.0 lA), and transepithelial resistance (750 OÁcm 2 ), and to measure responses to ion transport inhibitors. Amiloride (apical, 3.5 9 10 À5 mol/L) decreased I sc by 55.3%. Apically applied NGF (1 ng/mL) reduced I sc by 5.3% in 5 min; basolaterally applied NGF had no effect. The response to amiloride was reduced (41.6%) in the presence of NGF. K-252a (10 nmol/ L, apical) did not itself affect Na + transport, but it attenuated the NGFinduced reduction in Na + transport, indicating the participation of the trkA receptor in the NGF-induced reduction in Na + transport. PD-98059 (30 lmol/L, apical and basolateral) did not itself affect Na + transport, but attenuated the NGF-induced reduction in Na + transport, indicating that trkA activated the Erk 1/2 signaling cascade. NGF stimulated phosphorylation of Erk 1/2 and the b-subunit of ENaC. K-252a and PD-98059 inhibited these responses. NGF had no effect on I sc in the presence of apical nystatin (50 lmol/L). These results indicate that NGF inhibits Na + transport through a trkA-Erk 1/2-activated signaling pathway linked to ENaC phosphorylation.
Output: Nerve growth factor reduces amiloride-sensitive Na + transport in human airway epithelial cells
Retroviruses encode their genetic information with RNA molecules, and have a high genomic recombination rate which allows them to mutate more rapidly, thereby posting a higher risk to humans. One important way to help combat a pandemic of viral infectious diseases is early detection before large-scale outbreaks occur. The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have been used to identify precisely different strains of some very closely related pathogens. However, isolation and detection of viral RNA in the field are difficult due to the unstable nature of viral RNA molecules. Consequently, performing in-the-field nucleic acid analysis to monitor the spread of viruses is financially and technologically challenging in remote and underdeveloped regions that are high-risk areas for outbreaks. A simplified rapid viral RNA extraction method is reported to meet the requirements for in-the-field viral RNA extraction and detection. The ability of this device to perform viral RNA extraction with subsequent RT-PCR detection of retrovirus is demonstrated. This inexpensive device has the potential to be distributed on a large scale to underdeveloped regions for early detection of retrovirus, with the possibility of reducing viral pandemic events.
Output: Viral RNA extraction for in-the-field analysis
Background: Human metapneumovirus (hMPV) infection can cause acute lower respiratory tract illness in infants, the immunocompromised, and the elderly. Currently there are no licensed preventative measures for hMPV infections. Using a variant of hMPV/NL/1/00 that does not require trypsin supplementation for growth in tissue culture, we deleted the M2-2 gene and evaluated the replication of rhMPV/ΔM2-2 virus in vitro and in vivo. In vitro studies showed that the ablation of M2-2 increased the propensity for insertion of U nucleotides in poly-U tracts of the genomic RNA. In addition, viral transcription was up-regulated although the level of genomic RNA remained comparable to rhMPV. Thus, deletion of M2-2 alters the ratio between hMPV genome copies and transcripts. In vivo, rhMPV/ΔM2-2 was attenuated compared to rhMPV in the lungs and nasal turbinates of hamsters. Hamsters immunized with one dose of rhMPV/ΔM2-2 were protected from challenge with 10 6 PFU of wild type (wt) hMPV/NL/1/ 00. Our results suggest that hMPV M2-2 alters regulation of transcription and influences the fidelity of the polymerase complex during viral genome replication. In the hamster model, rhMPVΔM2-2 is attenuated and protective suggesting that deletion of M2-2 may result in a potential live vaccine candidate. A more thorough knowledge of the hMPV polymerase complex and the role of M2-2 during hMPV replication are being studied as we develop a potential live hMPV vaccine candidate that lacks M2-2 expression.
Output: Virology Journal Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters
Positive-strand RNA viruses are known to rearrange cellular membranes to facilitate viral genome replication. The biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virusinduced vesicles. Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. Furthermore, ET reveals vesicle pores that could enable release of newly synthesized viral RNA and reveals budding of DENV particles on ER membranes directly apposed to vesicle pores. Thus, DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus. This architecture of DENV replication and assembly sites could explain the coordination of distinct steps of the flavivirus replication cycle.
Output: Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites
It is possible to interfere with different steps in the dolichol pathway of protein glycosylation and in the processing of asparagine-linked oligosaccharides. Thus some clues about the role of protein-bound carbohydrate can be obtained by comparing the biochemical fates and functions of glycosylated proteins with their non-glycosylated counterparts, or with proteins exhibiting differences in the type of oligosaccharide side chains. Cells infected with enveloped viruses are good systems for studying both aspects of protein glycosylation, since they contain a limited number of different glycoproteins, often with well-defined functions. Tunicamycin, an antibiotic, as well as several sugar analogues have been found to act as inhibitors of protein glycosylation by virtue of their anti-viral properties. They interfere with various steps in the dolichol pathway resulting in a lack of functional lipid-linked oligosaccharide precursors. Compounds that interfere with oligosaccharide trimming represent a second generation o.f inhibitors of glycosylation. They are glycosidase inhibitors that interfere with the processing glucosidases and mannosidases and, as a resulL the conversion of high-mannose into complex-type oligosaccharides is blocked. Depending upon the compound used, glycoproteins contain glucosylated-high-mannose, highmannose or hybrid oligosaccharide structures instead of complex ones. The biglogical consequences of the alterations caused by the inhibitors are manifold: increased susceptibility to proteases, improper protein processing and misfolding of polypeptide chains, loss of biological activity and alteration of the site of virus-budding, to name but a few. protein glycosylation / oligosaccharide trimming / inhibition / viral glycoproteins
Output: Dissecting glycoprotein biosynthesis by the use of specific inhibitors*
A mathematical model to address the efficiency of the isolation and quarantine strategies in the containment of epidemics is constructed based on the SIR model with time delay. The model is investigated with numerical simulation that demonstrates the importance of quick measure in identifying the infected and the subsequent quarantine of his/her neighbors. The model also provides a theoretical framework for the estimation of the cost involved in the containment of the epidemics. Based on a general estimate of the cost, we demonstrate the procedure for the calculation of the optimal set of parameters in our isolation and quarantine strategy through numerical simulation on a model social network. We find an important parameter π which is a combination of several general parameters for the SIR model so that when π > 0, the isolation and quarantine strategy will fail to contain the outbreak. The procedure outlined provides some general guidance in the selection of strategies in the containment of real epidemics, where the balance between social cost and risk must be carefully handled.
Output: Optimal Time Delay in the Control of Epidemic
Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its tumor necrosis factor-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to systemic inflammatory response syndrome (SIRS), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/mL, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis.
Output: Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis ☆
Hepatitis C virus (HCV) infects more than 2 % of the world population with highest prevalence in parts of Africa and Asia. Past standard of care using interferon α and ribavirin had adverse effects and showed modest efficacy for some HCV genotypes spurring the development of direct acting antivirals (DAAs). Such DAAs target viral proteins and are thus better tolerated but they suffer from emergence of vial resistance. Furthermore, DAAs are often HCV genotype specific. Novel drug candidates targeting host factors required for HCV propagation, so called host-targeting antivirals (HTAs), promise to overcome both caveats. The genetic barrier to resistance is usually considered to be high for HTAs and all HCV genotypes presumably use the same host factors. Recent data, however, challenge these assumptions, at least for some HTAs. Here, we highlight the most important hosttargeting strategies against hepatitis C and critically discuss their opportunities and risks.
Output: Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C
There is an ongoing debate regarding the type of respiratory protection that should be recommended for use for healthcare workers. A cross-sectional survey was conducted in three countries: China, Pakistan and Vietnam. In China and Pakistan, the infection control guidelines were developed to be in line with the recommendations from the World Health Organization (WHO) and the Centers for Disease Control and Prevention, while in the Vietnamese guidelines the recommendations correspond with the WHO suggestions only. The guidelines from all three countries document the need for training and fit testing; however there is no system to monitor the training and fit testing programs. Across the three countries, there was some inconsistency with regard to the types of products (i.e. masks vs. respirators) recommended for influenza, severe acute respiratory syndrome (SARS) and tuberculosis. Conclusions: Available evidence should be examined and a comprehensive policy should be developed on the use of masks and respirators. The policy should address critical areas such as regulation, training, fit testing and reuse.
Output: Examining the policies and guidelines around the use of masks and respirators by healthcare workers in China, Pakistan and Vietnam
Ethnopharmacological relevance: Polygonum multiflorum Thunb., which is known as Heshouwu (何首乌 in Chinese) in China. It is traditionally valued and reported for hair-blacking, liver and kidney-tonifying and anti-aging effects as well as low toxicity. The aim of this review is to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of Polygonum multiflorum, based on the scientific literature. Moreover, trends and perspectives for future investigation of this plant are discussed. It will build up a new foundation for further study on Polygonum multiflorum. Materials and methods: A systematic review of the literature on Polygonum multiflorum was performed using several resources, including classic books on Chinese herbal medicine and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, China Knowledge Resource Integrated (CNKI). Results: Polygonum multiflorum is widely distributed throughout the world and has been used as a traditional medicine for centuries in China. The ethnomedical uses of Polygonum multiflorum have been recorded in many provinces of China and Japan for nine species of adulterants in six families. More than 100 chemical compounds have been isolated from this plant, and the major components have been determined to be stilbenes, quinones, flavonoids and others. Crude extracts and pure compounds of this plant are used as effective agents in pre-clinical and clinical practice due to their anti-aging, antihyperlipidaemia, anti-cancer and anti-inflammatory effects and to promote immunomodulation, neuroprotection, and the curing of other diseases. However, these extracts can also lead to hepatotoxicity, nephrotoxicity and embryonic toxicity. Pharmacokinetic studies have demonstrated that the main components of Polygonum multiflorum, such as 2,3,5,4 0 -tetrahydroxystilbene-2-O-β-D-glucopyranoside and emodin are distributed among many organs and tissues. Conclusion: Therapeutic potential of Polygonum multiflorum has been demonstrated in the conditions like Alzheimer's disease, Parkinson's disease, hyperlipidaemia, inflammation and cancer, which is attributed to the presence of various stilbenes, quinones, flavonoids, phospholipids and other compounds in the drug. On the other hand, the adverse effects (hepatotoxicity, nephrotoxicity, and embryonic toxicity) of this plant were caused by the quinones, such as emodin and rhein. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored, especially the combined anthraquinones (Emodin-8-O-β-D-glucopyranoside, Physcion-8-O-β-D-glucopyranoside, etc.) and the variety of stilbenes.
Output: Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review
We have synthesized and characterized a series of compounds containing the 3azatetracyclo[5.2.1.1 5,8 .0 1,5 ]undecane scaffold designed as analogs of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (wt) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two-electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the wt ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC 50 . None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual wt and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays. Amantadine; cage compounds; influenza A virus; M2 proton channel; drug design c MCC: minimum cytotoxic concentration, or concentration producing minimal alterations in cell morphology after 72 hr incubation with compound. d CC 50 : 50% cytotoxic concentration, as determined by the MTS cell viability test. Values shown are the mean of 2-3 determinations. J Med Chem.
Output: 3-Azatetracyclo[5.2.1.1 5,8 .0 1,5 ]undecane derivatives: from wild- type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutant NIH Public Access
The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases.
Output: Monoclonal antibody-based therapies for microbial diseases
Background: Although the COVID-19 has been well controlled in China, it is rapidly spreading outside China that may lead to catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most of these studies have used the early stage data and focused on the China cases. We predicted the COVID-19 epidemic trend in China and across the world using the machine learning approach. We first built the models for predicting the daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on the data from
Output: Predicting the epidemic trend of COVID-19 in China and across the world using the machine learning approach
Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus-and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ "snapshot" of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.
Output: In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection
Background 35 The reasons for the large differences between countries in the sizes of their SARS 36 CoV-2 epidemics is unknown. Individual level studies have found that the use of face 37 masks was protective for the acquisition and transmission of a range of respiratory 38 viruses including SARS CoV-1. We hypothesized that population level usage of face 39 masks may be negatively associated SARS CoV-2 spread. 40 41 At a country level, linear regression was used to assess the association between 43
Output: Widespread use of face masks in public may slow the spread of SARS CoV-2: 1 an ecological study 2 3 4