niryuu/sni-each-converted huggingface dataset:
Rapid diagnosis of adenoviral respiratory infections is required in order to decide optimal treatment strategies. The adenovirus antigen immunochromatography Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain), was evaluated versus the shell-vial culture and multiplex PCR (Clart Pneumovir Version 3.0, Genomica, Madrid, Spain), in nasopharyngeal washes and oropharyngeal swabs specimens from subjects with respiratory tract infections. Between April 2011 and November 2012, 224 patients were included. The IC Adeno Respiratory Card Letitest was positive for 77.9% (74 of 95) of patients diagnosed at bedside. Using multiplex-PCR as the reference standard, the overall sensitivity was 77.9% and the specificity was 73.6%. Taking shell-viral culture as the reference method, the Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain) sensitivity and specificity values were 80.0% and 60.9%, respectively. Using RT-PCR (Clart Pneumovir Version 3.0, Genomica, Madrid, Spain) as the reference standard, the viral culture sensitivity was 53.2% and the specificity was 100%. The Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain) assay could be a simple and rapid method for antigenic detection of adenovirus in pediatric respiratory samples although it would be necessary to improve the specificity and sensitivity of the test.
Output: Immunochromatographic test for detection of adenovirus from respiratory samples: Is it a real solution for pediatric emergency department?
Background: The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum. Here, the depletion of 12 of the most abundant serum proteins, followed by two-dimensional gel electrophoresis coupled with identification of these proteins using matrix-assisted laser desorption/ionization time-offlight (MALDI-TOF) mass spectrometry, has allowed for the identification of differentially expressed, low abundant serum proteins. We have analyzed and compared serum samples from HIV-1 infected subjects who are being treated using highly active antiretroviral therapy (HAART) to those who are latently infected but have not progressed to AIDS despite the absence of treatment, i.e. long term non-progressors (LTNPs). Here we have identified unique serum proteins that are differentially expressed in LTNP HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. We focused on the cdk4/6 cell cycle inhibitor p16 INK4A and found that the treatment of HIV-1 latently infected cell lines with p16 INK4A decreases viral production despite it not being expressed endogenously in these cells. Identification of these unique proteins may serve as an indication of altered viral states in response to infection as well as a natural phenotypic variability in response to HIV-1 infection in a given population.
Output: Open Access RESEARCH The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients
Background: Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. Purpose: To summarize the clinical and radiologic characteristics of NCIP cases and analyze the association of radiologic findings with mortality cases. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. Results: 27 patients included 12 men and 15 women, with median age of 60 years . 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. Conclusions: 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.
Output: Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China
This research examines whether maternal optimism/pessimism is associated with unplanned Cesarean section deliveries in China. If so, does the association remain after controlling for clinical factors associated with C-sections? A sample of 227 mostly primiparous women in the third trimester of pregnancy was surveyed in a large tertiary care hospital in Beijing, China. Postdelivery data were collected from medical records. In bivariate analysis, both optimism and pessimism were related to unplanned c-section. However, when optimism and pessimism were entered into a regression model together, optimism was no longer statistically significant. Pessimism remained significant, even when adjusting for clinical factors such as previous abortion, previous miscarriage, pregnancy complications, infant gestational age, infant birthweight, labor duration, birth complications, and selfrated difficulty of the pregnancy. This research suggests that maternal mindset during pregnancy has a role in mode of delivery. However, more research is needed to elucidate potential causal pathways and test potential interventions.
Output: Is Generalized Maternal Optimism or Pessimism During Pregnancy Associated with Unplanned Cesarean Section Deliveries in China?
Severe acute respiratory syndrome (SARS) is a highly infectious, rapidly progressive, emerging disease. Early diagnosis and preventive measures are key for treatment and minimization of secondary spread. In the context of the armed forces, aggressive containment measures are essential to prevent an outbreak. In this study, we present the first reported case, to our knowledge, of SARS in a naval diver. The special physical requirements for divers and the potential complications associated with deep sea diving necessitate extensive investigation before certification of fitness for diving after SARS. In the early recovery period, potential problems during diving are caused by inadequate lung ventilation in relation to exercise level and increased breathing resistance attributable to weak respiratory muscles, with corresponding risk of hypoxia and hypercapnia, as well as decreased ability to respond to nonrespiratory problems during diving. Problems in the late recovery period include increased risk of diving complications (such as pulmonary barotrauma) resulting from fibrosis and scarring within the lung parenchyma, which are known complications of SARS. From our experience, we suggest that computed tomographic scans of the thorax, lung function tests, and careful follow-up monitoring should play a vital role in the assessment of patients during the convalescent period, before certification of fitness to dive.
Output: Severe Acute Respiratory Syndrome in a Naval Diver
The major pigment in eggshells of brownegg laying hens is protoporphyrin IX, but traces of biliverdin and its zinc chelates are also present. The pigment appears to be synthesized in the shell gland. The protoporphyrin IX synthetic pathway is well defined, but precisely where and how it is synthesized in the shell gland of the brown-egg laying hen is still ambiguous. The pigment is deposited onto all shell layers including the shell membranes, but most of it is concentrated in the outermost layer of the calcareous shell and in the cuticle. Recently, the genes that are involved in pigment synthesis have been identified, but the genetic control of synthesis and deposition of brown pigment in the commercial laying hen is not fully understood. The brown coloration of the shell is an important shell quality parameter and has a positive influence on consumer preference. The extent of pigment deposition is influenced by the housing system, hen age, hen strain, diet, stressors, and certain diseases such as infectious bronchitis. In this article, the physiological and biochemical characteristics of the brown pigment in commercial brown-egg layers are reviewed in relation to its various functions in the poultry industry.
Output: Review Eggshell color in brown-egg laying hens -a review
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-, and MCP-1 were elevated in VP and coinfection subjects ( < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls ( > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.
Output: The Expression of IL-6, TNF-, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV-activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-L-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis.
Output: Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling
The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34 + stem cells, (2) fetal derived liver, thymus and CD34 + stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus. PLOS Neglected Tropical Diseases | https://doi.Onchocerciasis, caused by the filarial parasitic nematode Onchocerca volvulus, remains a significant source of morbidity throughout sub-Saharan Africa and is a primary cause of infectious blindness. Research on this disease has been hindered by an absence of suitable small animal hosts. Here we describe the development of humanized mouse models that are susceptible to O. volvulus infection supporting both growth and maturation of the parasite. These novel mouse models have enabled the identification of a number of new O. volvulus biomarkers with potential to play a role in the development of specific and sensitive diagnostic tests for presence of viable parasites. Development of Onchocerca volvulus in NSG mice PLOS Neglected Tropical Diseases | https://doi.
Output: Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum
New variants of infectious bronchitis virus (IBV) have emerged in Australia despite its geographical isolation and intensive vaccination programs. In the present study, the 3 0 terminal 7.2 kb of the genome of a recently isolated variant of IBV (N1/03) was sequenced and compared with the sequences of classical and novel strains of IBV, the two main groups of these viruses in Australia. The comparison revealed that recombination between classical and novel IBVs was responsible for the emergence of the new variant. It was concluded that novel IBVs, which have not been detected since 1993, and which are phylogenically more distant from classical IBVs than turkey coronaviruses, might still be circulating and contributing to the evolution of IBV in Australia.
Output: Naturally occurring recombination between distant strains of infectious bronchitis virus
Bats have been widely known as natural reservoir hosts of zoonotic diseases, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) caused by coronaviruses (CoVs). In the present study, we investigated the whole genomic sequence of a SARS-like bat CoV (16BO133) and found it to be 29,075 nt in length with a 40.9% G+C content. Phylogenetic analysis using amino acid sequences of the ORF 1ab and the spike gene showed that the bat coronavirus strain 16BO133 was grouped with the Beta-CoV lineage B and was closely related to the JTMC15 strain isolated from Rhinolophus ferrumequinum in China. However, 16BO133 was distinctly located in the phylogenetic topology of the human SARS CoV strain (Tor2). Interestingly, 16BO133 showed complete elimination of ORF8 regions induced by a frame shift of the stop codon in ORF7b. The lowest amino acid identity of 16BO133 was identified at the spike region among various ORFs. The spike region of 16BO133 showed 84.7% and 75.2% amino acid identity with Rf1 (SARS-like bat CoV) and Tor2 (human SARS CoV), respectively. In addition, the S gene of 16BO133 was found to contain the amino acid substitution of two critical residues (N479S and T487 V) associated with human infection. In conclusion, we firstly carried out whole genome characterization of the SARS-like bat coronavirus discovered in the Republic of Korea; however, it presumably has no human infectivity. However, continuous surveillance and genomic characterization of coronaviruses from bats are necessary due to potential risks of human infection induced by genetic mutation.
Output: Complete genome analysis of a SARS-like bat coronavirus identified in the Republic of Korea
The yeast two-hybrid (Y2H) system is a powerful method to identify and analyze binary protein interactions. In the fi eld of virology, the Y2H system has signifi cantly increased our knowledge of structure and function of viral proteins by systematically assessing intraviral protein interactions. Several comprehensive approaches to determine virus-host interactions have provided insight into viral strategies to manipulate the host for effi cient replication and to escape host-derived countermeasures. To expand our knowledge of intraviral and virus-host protein interactions, we here present a Y2H protocol that is well suited for high-throughput screening. Yeast mating followed by liquid handling in a 96-well format as well as fl uorescent readout of the reporter system provides a highly standardized and fully automated screening situation. The protocol can either be applied to screen complex host cDNA libraries or protein pairs arrayed for cross-testing. The ease of use, the cost-effectiveness as well as the robotic handling allows for extensive and multiple rounds of screening providing high coverage of protein-protein interactions. Thus, this protocol represents an improved "deep" screening method for high-throughput Y2H assays.
Output: Chapter 1 A High-Throughput Yeast Two-Hybrid Protocol to Determine Virus-Host Protein Interactions
Avian coronaviruses, including infectious bronchitis virus (IBV), are important respiratory pathogens of poultry. The heavily glycosylated IBV spike protein is responsible for binding to host tissues. Glycosylation sites in the spike protein are highly conserved across viral genotypes, suggesting an important role for this modification in the virus life cycle. Here, we analyzed the N-glycosylation of the receptor-binding domain (RBD) of IBV strain M41 spike protein and assessed the role of this modification in host receptor binding. Ten single Asn-to-Ala substitutions at the predicted N-glycosylation sites of the M41-RBD were evaluated along with two control Val-to-Ala substitutions. CD analysis revealed that the secondary structure of all variants was retained compared with the unmodified M41-RBD construct. Six of the 10 glycosylation variants lost binding to chicken trachea tissue and an ELISA-presented ␣2,3-linked sialic acid oligosaccharide ligand. LC/MS E glycomics analysis revealed that glycosylation sites have specific proportions of N-glycan subtypes. Overall, the glycosylation patterns of most variant RBDs were highly similar to those of the unmodified M41-RBD construct. In silico docking experiments with the recently published cryo-EM structure of the M41 IBV spike protein and our glycosylation results revealed a potential ligand receptor site that is ringed by four glycosylation sites that dramatically impact ligand binding. Combined with the results of previous array studies, the glycosylation and mutational analyses presented here suggest a unique glycosylation-dependent binding modality for the M41 spike protein.
Output: Glycosylation of the viral attachment protein of avian coronavirus is essential for host cell and receptor binding
Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin bor transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.
Output: Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1- Dependent Disruption of HIV Rev Trafficking
The One Health concept recognizes that the health of human beings, animals, plants and the environment is interconnected and interdependent. This idea has been shaped over the centuries and has gained momentum and traction as anatomy, physiology, microbiology and other disciplines have substantiated earlier theories. Here we recall major historical milestones which have contributed to shaping the One Health concept as it is today, and discuss the past and future drivers in view of future challenges in an evolving scenario.
Output: One Health (r)Evolution: Learning from the Past to Build a New Future
Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M-and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)b promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-b mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.
Output: Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus
Bm-BacPAK6 DNA, and the recombinant silkworm baculovirus Bm-ORF containing the full ORF of FMDV was obtained. The results of indirect immunofluorescence assay (IFA) showed that Bm-ORF could be expressed efficiently in Bm-N cell. After inoculating the early 5th instar larvae of silkworm, the polyprotein of FMDV could be detected by sandwich ELISA and empty capsid-like particles could be observed under the electron microscope. Expression products from silkworm were used as the antigen to immunize the cattle. The specific antibody was induced in all vaccinated animals. The immunized cattle were challenged with the virulent FMDV Asia I/XJ strain, two of the four cattle were completely protected and clinical symptoms were alleviated and delayed in the others. The results suggest that this strategy might be used to develop the new subunit FMDV vaccine. foot-and-mouth disease virus, open reading frame, silkworm-baculovirus expression system, immunogenicity, subunit vaccine
Output: Chinese Science Bulletin Immune response in cattle inoculated with the recombinant complete polyprotein of foot-and-mouth disease virus from Bombyx mori larvae
Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet-and plate-based single cell RNA sequencing applied to ~75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution. All rights reserved. No reuse allowed without permission.
Output: A molecular cell atlas of the human lung from single cell RNA sequencing
Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and antiinflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 lg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8 ? T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
Output: Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages
Fangcang shelter hospitals are a novel public health concept. They were implemented for the first time in China in February, 2020, to tackle the coronavirus disease 2019 (COVID-19) outbreak. The Fangcang shelter hospitals in China were large-scale, temporary hospitals, rapidly built by converting existing public venues, such as stadiums and exhibition centres, into health-care facilities. They served to isolate patients with mild to moderate COVID-19 from their families and communities, while providing medical care, disease monitoring, food, shelter, and social activities. We document the development of Fangcang shelter hospitals during the COVID-19 outbreak in China and explain their three key characteristics (rapid construction, massive scale, and low cost) and five essential functions (isolation, triage, basic medical care, frequent monitoring and rapid referral, and essential living and social engagement). Fangcang shelter hospitals could be powerful components of national responses to the COVID-19 pandemic, as well as future epidemics and public health emergencies.
Output: Health Policy Fangcang shelter hospitals: a novel concept for responding to public health emergencies
Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy.
Output: Immunological Barriers in Cancer Immunotherapy
Introduction: Determining the cause of community-acquired pneumonia (CAP) remains problematic. In this observational study, we systematically applied currently approved diagnostic techniques in patients hospitalized for CAP in order to determine the proportion in which an etiological agent could be identified. Methods: All patients admitted with findings consistent with CAP were included. Sputum and blood cultures, urine tests for pneumococcal and Legionella antigens, nasopharyngeal swab for viral PCR, and serum procalcitonin were obtained in nearly every case. Admissionrelated electronic medical records were reviewed in entirety. Results: By final clinical diagnosis, 44 patients (17.0%) were uninfected. A causative bacterium was identified in only 60 (23.2%) cases. PCR identified a respiratory virus in 42 (16.2%), 12 with documented bacterial coinfection. In 119 (45.9%), no cause for CAP was found; 69 (26.6%) of these had a syndrome indistinguishable from bacterial pneumonia. Procalcitonin was elevated in patients with bacterial infection and low in uninfected patients or those with viral infection, but with substantial overlap. Conclusions: Only 23.2% of 259 patients admitted with a CAP syndrome had documented bacterial infection; another 26.6% had no identified bacterial etiology, but findings closely resembled those of bacterial infection. Nevertheless, all 259 received antibacterial therapy. Journal of Infection (2013) 67, 11e18 Careful attention to the clinical picture may identify uninfected patients or those with viral infection, perhaps with reassurance by a non-elevated procalcitonin. Determining an etiologic diagnosis remains elusive. Better discriminators of bacterial infection are sorely needed. Published by Elsevier Ltd on behalf of The British Infection Association.
Output: Can an etiologic agent be identified in adults who are hospitalized for community-acquired pneumonia: Results of a one-year study
Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. The TCI device was a hydrogel patch (antigen-free) applied to the left brachial medial skin of 22 healthy volunteers for 48 h. Next, the hydrogel patch, containing 2 mg tetanus toxoid (TT) and 2 mg diphtheria toxoid (DT) as the TCI formulation, was applied to 27 healthy volunteers for 24 h and some volunteers were vaccinated again by TCI formulation. For safety assessment, the patch application site was observed to assess local adverse events, and systemic adverse events were determined by a blood test. The antigen-free hydrogel patch and TCI formulation containing TT and DT did not induce local or systemic severe adverse events. For vaccine efficacy estimation, toxoid-specific serum antibody titers were determined by ELISA and the toxin-neutralizing activity of the induced antibody was evaluated in a passive-challenge experiment. The anti-TT IgG titer and the anti-DT IgG titer increased, and a significant effect was detected by paired t-test. The antibody titers were maintained at higher level than that before vaccination for at least 1 year. Moreover, toxoid-specific antibodies were produced by the second vaccination in some subjects. Antibodies induced by application of the TCI formulation neutralized the toxin and prevented toxic death in mice. In addition, changes in the skin condition due to application of the TCI formulation were observed under in vivo confocal Raman spectroscopy. The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases.
Output: Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria
Respiratory infections that complicate pregnancy are encountered frequently, and they encompass a broad range of disorders. Although respiratory infections usually are not seen more commonly in pregnancy, they often result in greater morbidity and mortality secondary to the physiologic adaptations that occur during pregnancy. Pregnant patients who have one of these disorders require a higher level of surveillance and intervention. Pulmonary physiologic changes during pregnancy are discussed in detail elsewhere in this issue. As with many of the other organ systems, the respiratory system undergoes several adaptations during pregnancy. Tidal volume increases although the respiratory rate remains unchanged which results in an increase in minute ventilation that up to 50% higher than in nonpregnant women [1] [2] [3] [4] [5] . Minute oxygen uptake also increases, and allows for the increasing oxygen requirements as the pregnancy advances. There is no change in forced vital capacity, lung compliance, or diffusing capacity; however, functional residual capacity decreases by 15% to 20% at term. Total pulmonary resistance also decreases during pregnancy, possibly because of an increase in progesterone levels. Although overall hemoglobin amount increases and allows for an increase in total oxygencarrying capacity, the increase in blood volume-which is disproportionate to the increase in hemoglobin concentration-results in a physiologic anemia that 0889-8561/06/$ -see front matter D
Output: Sheff ield)
Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-a, IFN-b) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-b and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-b for the treatment of SARS.
Output: Ribavirin and interferon-b synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines
Over the past 3 decades, and similar to the horse industry, fresh embryo transfer has been widely practiced on large commercial scales in different camelid species, especially the dromedary camel and alpaca. However, the inability to cryopreserve embryos significantly reduces its broader application, and as such limits the capacity to utilize elite genetic resources internationally. In addition, cryopreservation of the semen of camelids is also difficult, suggesting an extreme sensitivity of the germplasm to cooling and freezing. As a result, genetic resources of camelids must continue to be maintained as living collections of animals. Due to concerns over disease outbreaks such as that of the highly pathogenic Middle East Respiratory Syndrome in the Middle East and Asia, there is an urgent need to establish an effective gene banking system for camelid species, especially the camel. The current review compares and summarizes recent progress in the field of camelid embryo cryopreservation, identifying four possible reasons for the slow development of an effective protocol and describing eight future directions to improve the current protocols. At the same time, the results of a recent dromedary camel embryo transfer study which produced a high morphologic integrity and survival rate of Open Pulled Straw-vitrified embryos are also discussed.
Output: Current status and future direction of cryopreservation of camelid embryos
Arboviruses are often maintained in complex cycles involving vertebrates such as mammals or birds and blood-feeding mosquitoes. However, the role of wildlife hosts in their emergence or re-emergence in human populations has received little attention. The recent emergence of Zika virus in America, and previous occurrences of chikungunya and dengue, forces us to confront a potential new disease-emergence phenomenon. Using a spatial data mining framework to identify potential biotic interactions, based on the degree of co-occurrence between different species, we identified those mammal species with the highest potential for establishing mammal-vector interactions, considering as principal vector Aedes aegypti. Seven of the top ten identified mammal species with highest potential were bats, with two of them having previously been confirmed as positive hosts for dengue in Mexico. We hope that this will raise interest of Mexican public health authorities and academic institutions to assess the role of wild hosts in the maintenance and spread of arboviruses.
Output: Predicting the Potential Role of Non-human Hosts in Zika Virus Maintenance
Objectives: To improve our understanding of the global epidemiology of common respiratory viruses by analysing their contemporaneous incidence at multiple sites. Methods: 2010-2015 incidence data for influenza A (IAV), influenza B (IBV), respiratory syncytial (RSV) and parainfluenza (PIV) virus infections were collected from 18 sites (14 countries), consisting of local ( n = 6), regional ( n = 9) and national ( n = 3) laboratories using molecular diagnostic methods. Each site submitted monthly virus incidence data, together with details of their patient populations tested and diagnostic assays used. Results: For the Northern Hemisphere temperate countries, the IAV, IBV and RSV incidence peaks were 2-6 months out of phase with those in the Southern Hemisphere, with IAV having a sharp out-of-phase difference at 6 months, whereas IBV and RSV showed more variable out-of-phase differences of 2-6 months. The tropical sites Singapore and Kuala Lumpur showed fluctuating incidence of these viruses throughout the year, whereas subtropical sites such as Hong Kong, Brisbane and Sydney showed distinctive biannual peaks for IAV but not for RSV and PIV. Conclusions: There was a notable pattern of synchrony of IAV, IBV and RSV incidence peaks globally, and within countries with multiple sampling sites (Canada, UK, Australia), despite significant distances between these sites.
Output: Comparative global epidemiology of influenza, respiratory syncytial and parainfluenza viruses Marion Koopmans o , on behalf of the INSPIRE (International Network for the Sequencing of Respiratory Viruses)
SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.
Output: Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase
The current re-emergence of human monkeypox (HMPX) is a global concern for endemic and non-endemic countries, but healthcare workers in some regions, like Asia, have less experience with identifying and treating HMPX cases. This study aimed to assess the confidence and its predictors in HMPX case management among general practitioners (GPs), the frontline doctors in Indonesia, and to explore their perspectives on HMPX. Between May and July 2019, GPs in Indonesia completed an online-based survey. The questionnaire collected information on GPs' confidence, perspective, sociodemographic, workplace and professional characteristics, exposure to HMPX information and knowledge on HMPX. A logistic regression analysis was employed to explore the explanatory variables influencing the confidence and the perspective. We included 395 GPs in our analysis (77.4% out of 510 responses received) of which 10.1% and 34.9% were classified having good confidence using an 80% and 70% cut-off for confidence score, respectively. In the adjusted analysis, receiving information about HMPX during medical training was the only variable significantly associated with good confidence (adjusted odds ratio 2.74, 95% confidence interval 1.57 to 4.78 and p < 0.001). Approximately 73.6% and 77.
Output: Confidence in managing human monkeypox cases in Asia: A cross-sectional survey among general practitioners in Indonesia
The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to colocalize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.
Output: Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts