title: Virome heterogeneity and connectivity in waterfowl and shorebird communities

text: Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity (host sharing) and heterogeneity (host specificity). Virome connectivity was apparent in two well described multi-host virus species -avian coronavirus and influenza A virus- and a novel Rotavirus species that were shared among some Anseriform species, while virome heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes, as well as differences in viral abundance and alpha diversity among species. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.


title: Clinical Features and Factors Associated with Severity and Fatality among Patients with Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection in Northeast China

text: BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV) was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6%) of 115 patients presented with multiple organ dysfunction, and 22 (19.1%) of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2%) were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin ≤30 g/l (OR, 8.09; 95% CI, 2.58-25.32), APTT ≥ 66 seconds (OR, 14.28; 95% CI, 3.28-62.24), sodium ≤130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40), and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12). Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48–14.19) and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38–13.03) were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians.


title: Effect of chicken egg yolk immunoglobulins on serum biochemical profiles and intestinal bacterial populations in early‐weaned piglets

text: This study was conducted to test the hypothesis that dietary supplementation with anti‐E. coli, chicken egg yolk immunoglobulins (IgY), may affect early weaned piglet (EWP) intestinal functions and enteric micro‐organisms. One hundred and forty‐eight ([Landrace × Yorkshire] × Duroc) piglets, weaned at age day 21, were randomly assigned to receive one of three diets for 14 days. Treatment group one (control group) was fed the base diet. Treatment group two (antibiotics group) was fed the base diet which was supplemented with 100 ppm colistin sulphate and 15 ppm enramycin; treatment group three (IgY group) was fed the base diet which was supplemented with 500 mg/kg anti‐E. coli IgY. The study evaluated the effects on EWPs of IgY on growth, serum biochemical, inflammatory profiles and also digestion content intestinal bacterial populations. Results showed no significant difference in diarrhoea rates between IgY‐fed EWPs and antibiotic‐treated EWPs. Serum biochemical analysis showed that EWPs fed an IgY‐containing diet had both lower (p < 0.05) cholesterol and low‐density lipoprotein compared to antibiotic‐treated EWPs. Escherichia coli populations measured in IgY‐fed EWP ileal contents, compared to the control group, were significantly reduced (p < 0.05). Enterococcus, Lactobacillus, Clostridium and Bifidobacterium populations were unaffected by the IgY treatment. Larger (p < 0.05) Enterococcus populations and lower (p < 0.05) expression levels of heat‐stable enterotoxin b (STb) were observed in IgY‐fed EWP caecal digesta compared to the control group. Enteric Lactobacillus significantly decreased (p < 0.05) in EWPs fed antibiotics while it was unaffected by IgY treatment. Dietary supplementation with anti‐E. coli IgY has the potential to suppress enteric E. coli growth, but not Lactobacillus, Clostridium and Bifidobacterium. This promotes and maintains a healthy EWP intestinal environment. These findings suggest that IgY may be used as an alternative to antibiotics in EWP diets.


title: D-Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID-19 and Poor Prognosis

text: OBJECTIVE: To investigate the value of coagulation indicators D-dimer (DD), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (Fg) in predicting the severity and prognosis of COVID-19. METHODS: A total of 115 patients with confirmed COVID-19, who were admitted to Tianyou Hospital of Wuhan University of Science and Technology between January 18, 2020, and March 5, 2020, were included. The dynamic changes of DD, PT, APTT, and Fg were tested, and the correlation with CT imaging, clinical classifications, and prognosis was studied. RESULTS: Coagulation disorder occurred at the early stage of COVID-19 infection, with 50 (43.5%) patients having DD increased and 74 (64.3%) patients having Fg increased. The levels of DD and Fg were correlated with clinical classification. Among 23 patients who deceased, 18 had DD increased at the first lab test, 22 had DD increased at the second and third lab tests, and 18 had prolonged PT at the third test. The results from ROC analyses for mortality risk showed that the AUCs of DD were 0.742, 0.818, and 0.851 in three times of test, respectively; PT was 0.643, 0.824, and 0.937. In addition, with the progression of the disease, the change of CT imaging was closely related to the increase of the DD value (P < 0.01). CONCLUSIONS: Coagulation dysfunction is more likely to occur in severe and critically ill patients. DD and PT could be used as the significant indicators in predicting the mortality of COVID-19.


title: Mixed community-acquired lower respiratory tract infections

text: Although mixed infections are known to be clinically relevant in conditions such as nosocomial pneumonia and ventilator-related pneumonia, it is increasingly recognized that a substantial number of community-acquired lower respiratory tract infections may also be attributed to more than one pathogenic organism. A better definition of the true incidence of mixed infections in community-acquired lower respiratory tract infections is partly derived from recent advances in available diagnostic methods (eg, molecular biology). Two points still must be determined: whether the presence of a mixed infection is associated with altered outcomes and whether empirical antibiotic selection should be modified to account for potential polymicrobial infections.


title: A review of cutaneous hypersensitivity reactions in infants: From common to concerning

text: Cutaneous hypersensitivity reactions in infants present in a variety of patterns. These skin eruptions can be dramatic, causing alarm in parents and medical personnel. Many of these syndromes have overlapping features, which adds to the confusion and uncertainty regarding diagnosis and management. This review discusses the spectrum of hypersensitivity responses with a focus on their presentation in infants. The clinical findings, pathophysiology, histopathology, management, and complications of these conditions will be reviewed.


title: Reopening Colleges and Universities During the COVID-19 Pandemic

text: In their article, Cheng and colleagues present the plan for reopening colleges and universities in Taiwan. There are important differences between Taiwan and other countries, but residential colleges and universities present similar challenges to pandemic control for all. Considering how well Taiwan has managed COVID-19 overall, the editorialists believe that the plan for safely reopening colleges and universities in Taiwan offers important principles.


title: Research in counselling and psychotherapy Post‐COVID‐19

text: The COVID‐19 pandemic brings to light many areas the field of counselling and psychotherapy may need to address in future research. We outline several issues stemming from or exacerbated by the pandemic and offer suggestions for future research to address the mental health needs of those impacted. Our suggestions focus on five domains: (a) the health and well‐being of helping professionals, (b) the infodemic, (c) discrimination and minority stress, (d) spiritual and existential dynamics in mental health and (e) couple and family stress and resilience. We aim to provide a multi‐systemic perspective of mental health and well‐being in the time of COVID‐19, as well as encourage current and future studies to incorporate these suggestions to advance the health and well‐being of our communities through evidence‐based treatment approaches.


title: Agriculture, transportation, and the COVID‐19 crisis

text: In this short paper, I assess how COVID‐19‐related disruptions in transportation services, as well as new demands for transportation services, could impact Canadian agricultural supply chains. The brief analysis reveals that agricultural access to bulk ocean freight, rail movement, and trucking has generally improved in the pandemic, bolstered by the reduced demand for these transportation services by other sectors of the economy. The intermodal containerized movement of grains and food products has seen some disruption from the lack of empty containers in North America. The widespread consumer adoption of physical distancing measures has vastly increased the demand for retail food pickup and delivery services to the point where these services are being rationed by long wait times. From a policy perspective, there is an apparent need for (a) continued supply chain monitoring and industry engagement, (b) the proactive development of strategies to deal with absenteeism and other potential threats to the supply chain, and (c) an assessment of the economic and health merits of providing additional public resources to provide greater access to grocery pickup and delivery services.


title: Comparison of fit factors among healthcare providers working in the Emergency Department Center before and after training with three types of N95 and higher filter respirators

text: INTRODUCTION: N95 or higher filtering respirators have been recommended in healthcare settings, although there is still a risk of infection due to the improper selection and wearing of respirators. We aimed to assess the effects of training with N95 or higher filter respirators on the protection performance of respirators among healthcare providers in the emergency medical center (EMC). METHODS: This randomized crossover study evaluated 23 healthcare providers. Quantitative fit tests (QNFTs) were performed before and after training using three types of N95 or higher filter respirators (cup-type, fold-type, valve-type). Training was performed by lecture, real-time feedback, and fit check. The primary outcome was the fit factor, and the secondary outcomes were overall fit factor, adequate protection rate, and respiratory preference. RESULTS: Fit factors, overall fit factor, and adequate protection rate were higher after training than before training for the 3 types of respirators (all P < .05). For normal breathing, fit factors before and after training were 121 (10–185) vs 192 (161–200) for cup-type, 200 (39–200) vs 200 (200–200) for fold-type, and 85 (18–157) vs 173 (117–200) for valve-type. For normal breathing, the adequate protection rates before and after training were 62 (0–100) vs 100 (90–100) for cup-type, 100 (0–100) vs 100 (100–100) for fold-type, and 19 (0–100) vs 100 (44–100) for valve-type (all P < .05). The most preferred respirator type was the valve-type (10 persons, 45.5%). CONCLUSIONS: Training on wearing an N95 or higher respirator improved the protection performance of respirators among healthcare providers working in the EMC. The selection of proper respirators and training would be beneficial to the safety of healthcare providers.


title: Proteomic analysis of purified coronavirus infectious bronchitis virus particles

text: BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.


title: Low-grade fever during COVID-19 convalescence: A report of 3 cases

text: BACKGROUND: Low-grade fever during convalescence is an atypical symptom of coronavirus disease 2019 (COVID-19). Reports of such cases are rare, and the mechanism and outcome of low-grade fever during COVID-19 convalescence are not completely clear. We report 3 cases with low-grade fever during COVID-19 convalescence and highlight the main clinical, radiographic, and laboratory characteristics, thereby increasing the level of expertise in the clinical management of COVID-19 during convalescence and facilitating individualized decision-making. CASE SUMMARY: We describe 3 patients with COVID-19, two females aged 62 and 66 years and a male 55 years, who had low-grade fever during COVID-19 convalescence. All 3 patients had no other discomfort or comorbidities during low-grade process. Lesions on computed tomography in all 3 patients had resolved during this period. Two patients tested negative on two consecutive severe acute respiratory syndrome coronavirus 2 tests with an interval of at least 24 h between tests. Body temperature in all 3 patients returned to normal after several days without treatment, and fever recurrence was not observed. CONCLUSION: Enhancing the knowledge of low-grade fever during COVID-19 convalescence may increase the expertise in the delivery of optimal healthcare services.


title: Current status of COVID-19 therapies and drug repositioning applications

text: Summary The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2.


title: Bear bile: dilemma of traditional medicinal use and animal protection

text: Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future.


title: Impact of an Education Intervention on Missouri K‐12 School Disaster and Biological Event Preparedness

text: BACKGROUND: A 2011 nationwide school pandemic preparedness study found schools to be deficient. We examined the impact of a school nurse educational intervention aimed at improving K‐12 school biological event preparedness. METHODS: Missouri Association of School Nurses (MASN) members were e‐mailed a survey link in fall 2013 (ie, preintervention), links to online education modules (ie, intervention) in late fall, and a postintervention survey link in spring, 2014. School biological event readiness was measured using 35 indicators, for a possible score range of 0‐35. A paired t‐test compared pre‐ to postintervention preparedness scores. RESULTS: A total of 133 school nurses (33.6% response rate) completed a survey; 35.3% of those (N = 47) completed both pre‐ and postintervention survey that could be matched. Pre‐ and postintervention preparedness scores ranged from 5 to 28.5 ([Formula: see text] = 13.3) and 6.5 to 25 ([Formula: see text] = 14.8), respectively. Postintervention scores were significantly higher than preintervention scores for those who watched at least 1 module (t = −2.3, p < .05). CONCLUSION: The education intervention was effective at improving school preparedness, though the impact was small. The education intervention needs to be reassessed, especially in regard to providing a longer intervention period.


title: Dans le syndrome respiratoire aigu sévère (SRAS), la tomodensitométrie (TDM) montre le plus souvent des opacités en verre dépoli et des épaississements inter et intra-lobulaires K.T. Wong

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title: Surfactant-based prophylaxis and therapy against COVID-19: a possibility

text: Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19. That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.


title: Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases

text: Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity.


title: Discriminating self from non-self in nucleic acid sensing

text: Innate immunity against pathogens relies on an array of immune receptors to detect molecular patterns that are characteristic of the pathogens, including receptors that are specialized in the detection of foreign nucleic acids. In vertebrates, nucleic acid sensing is the dominant antiviral defence pathway. Stimulation of nucleic acid receptors results in antiviral immune responses with the production of type I interferon (IFN), as well as the expression of IFN-stimulated genes, which encode molecules such as cell-autonomous antiviral effector proteins. This Review summarizes the tremendous progress that has been made in understanding how this sophisticated immune sensory system discriminates self from non-self nucleic acids in order to reliably detect pathogenic viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2016.78) contains supplementary material, which is available to authorized users.


title: A strategy to prevent future epidemics similar to the 2019-nCoV outbreak

text: Abstract A novel bat-origin coronavirus emerged in Wuhan, China in December 2019 and continues to spread across China and the world. At the time of writing, a massive global response has been implemented to control the disease as it spreads from person to person. Yet the high-risk human-wildlife interactions and interfaces that led to the emergence of SARS-CoV and of 2019-nCoV continue to exist in emerging disease hotspots globally. To prevent the next epidemic and pandemic related to these interfaces, we call for research and investment in three areas: 1) surveillance among wildlife to identify the high-risk pathogens they carry; 2) surveillance among people who have contact with wildlife to identify early spillover events; and 3) improvement of market biosecurity regarding the wildlife trade. As the emergence of a novel virus anywhere can impact the furthest reaches of our connected world, international collaboration among scientists is essential to address these risks and prevent the next pandemic.


title: Strengthening Public Health Partnerships in India: Envisioning the Role of Law Enforcement During Public Health Emergencies

text: Unique challenges posed by complex public health emergencies have often called for institutions, responsible for restoring health, well-being, and order among affected populations, to realign their operating procedures and work in concordance with each other. To ensure optimal health, the growth of the individuals and societies, and development in a greater sense, it is essential to understand the scope of collaboration between law enforcement agencies and public health institutions during emergencies and their aftermath. To foster such partnerships, policy-level advocacy to overcome challenges posed by existing policies and legislation that limit the autonomy of the law enforcement and public health institutions for making informed decisions would be necessary. Human resources working at different levels should be sensitized about the nature and significance of the kind of collaboration, and they should be allowed to express and clarify their doubts about the same. Evidence-based standard operating procedures should be developed for different cadres of professionals, keeping harmony with the operational diversities. Critical issues such as financing the ventures, coordinating and implementing the protocols and projects, following up the cases and suspects, and examining every scenario using evidence-based scientific and legal methodologies would be crucial for the success of such collaborations.


title: C-reactive protein serum levels as an early predictor of outcome in patients with pandemic H1N1 influenza A virus infection

text: BACKGROUND: Data for predicting which patients with pandemic influenza A (H1N1) infection are likely to run a complicated course are sparse. We retrospectively studied whether the admission serum C-reactive protein (CRP) levels can serve as a predictor of illness severity. METHODS: Included were all consecutive adult patients who presented to the emergency department (ED) between May-December, 2009 with a flu-like illness, a confirmed diagnosis of pandemic influenza A (H1N1) infection and a serum CRP level measured within 24 hours of presentation. Patients with a proven additional concurrent acute illness (e.g., bacteremia) were excluded. We used the ROC curve analysis, Kaplan-Meier curves and the Cox proportional hazard model to evaluate the predictive ability of CRP as a prognostic factor. RESULTS: Seventeen (9%) of the 191 enrolled patients were admitted to the intensive care unit (ICU), of whom eight (4%) required mechanical ventilation and three (2%) died. The median admission serum CRP levels were significantly higher among patients who required subsequent ICU care and mechanical ventilation than among patients who did not (123 mg/L and 112 mg/L vs. 40 mg/L, p < .001 and 43 mg/L, p = .017, respectively). A Cox proportional hazard model identified admission serum CRP levels and auscultatory findings over the lungs as independent prognostic factors for ICU admission. Admission serum CRP levels were the only independent prognostic factor for mechanical ventilation. Thirty days after presenting to the ED, none of the patients with admission serum CRP level <28 mg/L (lower tertile) required either ICU admission or mechanical ventilation. At the same time point, 19% of the patients with admission serum CRP level ≥70 mg/L (upper tertile) needed to be admitted to the ICU and 8% of the same upper tertile group required mechanical ventilation. The differences in the rates between the lower vs. upper tertile groups were significant (Log-Rank p < .001 for ICU and p < .024 for mechanical ventilation). CONCLUSIONS: In our study group, serum CRP levels obtained in the early ED admission stage from patients presenting with pandemic H1N1 influenza A infection were found to serve as a useful gauge for predicting disease course and assisting in patient management.


title: Movement control as an effective measure against Covid-19 spread in Malaysia: an overview

text: AIM: The first Covid-19 cases were reported in Malaysia on 25 January 2019 followed by a quiescent period before an upward swing of the cases at the end of February 2020, partly attributed to mass gathering during a religious event. This short communication aims to provide an overview of the measures taken by the Malaysian Government in response to Covid-19, and of the effectiveness of the Movement Control Order. SUBJECTS AND METHODS: This short communication reviews articles and government announcements related to containment measures and the Movement Control Order of Malaysia, and graphically presents data pertinent to Covid-19 in Malaysia in order to show the relationship between fluctuations in Covid-19 cases and movement control. RESULTS: At the onset of the Covid-19 outbreak, Malaysia had initiated travel restrictions and quarantine; but with a persistent increase in new Covid-19 cases, the Movement Control Order was finally rolled out on 18 March 2020, requiring closure of all businesses except those providing essential services and items. Enforcement of the order was tightened progressively, resulting in significant improvement of compliance, while other interventions such as tracking of potential contacts and medical screening were underway, and the media continued to provide updates and general advices. The numbers of new and active Covid-19 cases started showing evident downtrends from mid-April, thus indicating the effectiveness of movement control and its compliance. CONCLUSION: The article provides insight into crucial factors contributing to the success of movement control to effectively contain Covid-19, and highlights the need to prevent future upsurge through continuous monitoring and enforcement.


title: Overexpression of Tripartite Motif Conaining 55 (TRIM55) Inhibits Migration and Invasion of Hepatocellular Carcinoma (HCC) Cells via Epithelial-Mesenchymal Transition and Matrix Metalloproteinase-2 (MMP2)

text: BACKGROUND: Tripartite motif containing 55 (TRIM55) plays a regulatory role in assembly of sarcomeres, but few studies have assessed its function in hepatocellular carcinoma (HCC). MATREIAL/METHODS: Immunohistochemistry (IHC) was used to detect expression of TRIM55 in tissues samples of HCC patients. Transwell assay was used to study migration and invasion ability of HCC cells. Western blot and immunofluorescence (IF) were used to analyze mechanism of TRIM55 in cell migration and invasion. RESULTS: We found TRIM55 was downregulated in HCC tissues and was associated with prognosis of HCC patients. Cox regression analysis showed that TRIM55 was an independent risk factor of prognosis of HCC patients. Overexpression of TRIM55 was associated with lower cell migration and invasion ability, and it led to high expression of E-cadherin and low expression of Vimentin and MMP2. CONCLUSIONS: Our study found TRIM55 is an independent factor affecting the prognosis of HCC patients, and overexpression of TRIM55 inhibits migration and invasion of HCC cells through epithelial-mesenchymal transition and MMP2.


title: Endoplasmic reticulum stress-induced apoptosis in the development of reproduction

text: Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress (ERS) response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction (IUGR). The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy.


title: CD40 Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population

text: Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression of CD40 ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role of CD40L in the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate the CD40 polymorphism in KD and CAL formation. Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) of CD40 (rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay. Results. A significant association was noted with regards to CD40 tSNPs (rs1535045) between controls and KD patients (P = 0.0405, dominant model). In KD patients, polymorphisms of CD40 (rs4810485) showed significant association with CAL formation (P = 0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms of CD40 and susceptibility/disease activity of KD. Conclusions. This study showed for the first time that polymorphisms of CD40 are associated with susceptibility to KD and CAL formation, in the Taiwanese population.


title: Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily

text: In December 2019, severe cases of pneumonia of unknown aetiology were reported in Wuhan city, in China. Lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the diseases was termed coronavirus disease-2019 (COVID-19). At the end of January 2020, the infection spread all over Italy, but with high infection rates and mortality in the northern part, especially in Lombardy, the most industrialized and polluted region of the country. It is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. Air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). Volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. Pulmunary diseases spread by means of small droplets in the breath, also called aerosols, and air pollution may facilitate the outside survival of viruses. We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. In fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. Clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns.


title: Immunosuppressive Mechanisms During Viral Infectious Diseases

text: For a virus to establish persistence in the host, it has to exploit the host immune system such that the active T-cell responses against the virus are curbed. On the other hand, the goal of the immune system is to clear the virus, following which the immune responses need to be downregulated, by a process known as immunoregulation. There are multiple known immunoregulatory mechanisms that appear to play a role in persistent viral infections. In the recent past, IL-10 and PD-1 have been identified to be playing a significant role in the regulation of antiviral immune responses. The evidence that viruses can escape immunologic attack by taking advantage of the host’s immune system is found in LCMV infection of mice and in humans persistently infected with HIV and HCV. The recent observation that the functionally inactive T-cells during chronic viral infections can be made to regain their cytokine secretion and cytolytic abilities is very encouraging. Thus, it would be likely that neutralization negative immune regulation during persistent viral infection would result in the preservation of effector T-cell responses against the virus, thereby resulting in the elimination of the persistent infection.


title: Radiological and nuclear terrorism: are you prepared?

text: Abstract Another terrorist attack on our nation is virtually inevitable. Most believe that it is not a question of if but when. The form of the terrorism, the time, and the place will not be of our choosing. Radiology professionals (radiologists, technologists, radiologists’ assistants, and nurses) will be involved in caring for the victims of the attack, whether the method employed is chemical, biological, radiological, or nuclear. If chemical or biological weapons are used, we must be ready to help with the diagnoses and follow-up care of these patients. Probably the greatest challenges to the radiology community will arise if the terrorist act involves a radiological or a nuclear explosive device. Understanding terrorists’ goals of creating pandemonium and causing economic disruption is important. Radiology professionals need to be prepared to be resources for the medical community in providing patient care and for the community at large, especially if the terrorist attack involves detonation of a nuclear device, an attack on a nuclear power plant, or the use of a simple radiation dispersal device in a highly populated area.


title: Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants

text: Programmed frameshifting is one of the translational recoding mechanisms that read the genetic code in alternative ways. This process is generally programmed by signals at defined locations in a specific mRNA. In this study, we report the identification of hepta- and octo-uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of severe acute respiratory syndrome coronavirus (SARS-CoV) ORF 3a variants. SARS-CoV ORF 3a encodes a minor structural protein of 274 amino acids. Over the course of cloning and expression of the gene, a mixed population of clones with six, seven, eight and nine T stretches located 14 nt downstream of the initiation codon was found. In vitro and in vivo expression of clones with six, seven and eight Ts, respectively, showed the detection of the full-length 3a protein. Mutagenesis studies led to the identification of the hepta- and octo-uridine stretches as slippery sequences for efficient frameshifting. Interestingly, no stimulatory elements were found in the sequences upstream or downstream of the slippage site. When the hepta- and octo-uridine stretches were used to replace the original slippery sequence of the SARS-CoV ORF 1a and 1b, efficient frameshift events were observed. Furthermore, the efficiencies of frameshifting mediated by the hepta- and octo-uridine stretches were not affected by mutations introduced into a downstream stem–loop structure that totally abolish the frameshift event mediated by the original slippery sequence of ORF 1a and 1b. Taken together, this study identifies the hepta- and octo-uridine stretches that function as sole elements for efficient +1 and −1 ribosomal frameshift events.


title: The management of coronavirus disease 2019 (COVID‐19)

text: In December 2019, a novel coronavirus causing severe acute respiratory disease occurred in Wuhan, China. It is an emerging infectious disease with widespread and rapid infectiousness. The World Health Organization declared the coronavirus outbreak to be a public health emergency of international concern on 31 January 2020. Severe COVID‐19 patients should be managed and treated in a critical care unit. Performing a chest X‐ray/CT can judge the severity of the disease. The management of COVID‐19 patients includes epidemiological risk and patient isolation; treatment entails general supportive care, respiratory support, symptomatic treatment, nutritional support, psychological intervention, etc. The prognosis of the patients depends upon the severity of the disease, the patient's age, the underlying diseases of the patients, and the patient's overall medical condition. The management of COVID‐19 should focus on early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control.


title: A novel benzo-heterocyclic amine derivative N30 inhibits influenza virus replication by depression of Inosine-5’-Monophospate Dehydrogenase activity

text: BACKGROUD: Influenza virus is still a huge threat to the world-wide public health. Host inosine-5’- monophosphate dehydrogenase (IMPDH) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. Herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative N30, which was designed to inhibit IMPDH. RESULTS: The results demonstrated that N30 inhibited the replication of H1N1, H3N2, influenza B viruses, including oseltamivir and amantadine resistant strains in vitro. Mechanistically, neuraminidase inhibition assay and hemagglutination inhibition assay suggested that N30 did not directly target the two envelope glycoproteins required for viral adsorption or release. Instead, the compound could depress the activity of IMPDH type II. Based on these findings, we further confirmed that N30 provided a strong inhibition on the replication of respiratory syncytial virus, coronavirus, enterovirus 71 and a diverse strains of coxsackie B virus. CONCLUSIONS: We identified the small molecule N30, as an inhibitor of IMPDH, might be a potential candidate to inhibit the replication of various viruses.


title: Economic impacts of Wuhan 2019‐nCoV on China and the world

text: Uncertainties over the Wuhan 2019 Novel Coronavirus (2019-nCoV), which has killed 1,017 people and sickened more than 43,100 as of Feb 11,1 has interrupted global trade and supply chains, depressed asset prices, and forced multinational businesses to make hard decisions with limited information. This article is protected by copyright. All rights reserved.


title: CT findings of patients infected with SARS-CoV-2

text: BACKGROUND: We aimed to describe the chest CT findings in sixty-seven patients infected by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We retrospectively reviewed 67 patients hospitalized in Ruian People’s Hospital. All the patients received the positive diagnosis of SARS-CoV-2 infection. The CT and clinical data were collected between January 23rd, 2020 and February 10th, 2020. The CT images were analyzed by the senior radiologists. RESULTS: There are 54 patients with positive CT findings and 13 patients with negative CT findings. The typical CT findings in hospitalized patients with SARS-CoV-2 infection were ground glass opacities (42/54), lesions located in the peripheral area (50/54), multiple lesions (46/54), and lesions located in the lower lobes (42/54). There were less typical CT findings, including air bronchogram (18/54), pleural thickening or pleural effusion (14/54), consolidation (12/54), lesions in the upper lobes (12/54), interlobular septal thickening (11/54), reversed halo sign (9/54), single lesion (8/54), air cavities (4/54), bronchial wall thickening (3/54), and intrathoracic lymph node enlargement (2/54). CONCLUSIONS: CT features can play an important role in the early diagnosis and follow-up of COVID-19 patients.


title: Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury

text: The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00253-y) contains supplementary material, which is available to authorized users.


title: Identification of Capsid/Coat Related Protein Folds and Their Utility for Virus Classification

text: The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures. Viruses encoding similar capsid/coat related folds were pooled into lineages, after benchmarking against published literature. Remarkably, the in silico exercise reproduced all previously described members of known structure-based viral lineages, along with several proposals for new additions, suggesting it could be a useful supplement to experimental approaches and to aid qualitative assessment of viral diversity in metagenome samples.


title: Acute viral infections in immunocompetent patients

text: Abstract Viruses play a significant role in serious infections in adults and sometimes lead to the need for hospitalization and admission to intensive care units, especially in cases of severe respiratory distress or encephalopathy. Influenza and parainfluenza viruses, syncytial respiratory virus, herpes viruses and adenovirures are the most frequent causes of these severe infections. A review of the literature has been performed in order to update the epidemiology, pathogenesis and therapeutic approach of viral infections affecting immunocompetent patients. Furthermore, ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units and has a high morbidity and mortality rate. It is mainly a bacterial disease, although the potential role of viruses as pathogens or copathogens in VAP is under discussion. Therefore, a brief review of the potential pathogenic role of viruses in VAP has also been performed.


title: Does my personal protective equipment really work? A simulation‐based approach

text: Healthcare workers have substantial concerns about the effectiveness of the personal protective equipment. Staff desired a refresher training with individual feedback of their abilities to don and doff effectively and assurance that if they donned and doffed correctly their equipment was effective. A nontoxic fluorescent solution, only visible under ultraviolet light, was utilized during the training. This solution was sprayed on and given as a nebulized treatment to a high-fidelity simulator during the scenario. It allowed educators and learners to easily visualize any contamination. This innovative training method demonstrated that following the PPE training improves workplace safety and decreases the risk of transmission.


title: The role of microbes in the pathogenesis of acute rhinosinusitis in young adults

text: OBJECTIVES/HYPOTHESIS: To provide information on the course of acute rhinosinusitis (ARS) with sequential nasal and paranasal microbiological data and their correlation with clinical outcomes. STUDY DESIGN: We conducted a prospective cohort study among 50 Finnish military recruits with clinically diagnosed ARS in spring 2012. METHODS: We collected symptom, nasal endoscopy, and cone‐beam CT (CBCT) scores during the early (2–3 days from onset) and later phases (9–10 days). We took viral samples from the nasopharynx (multiplex respiratory virus polymerase chain reaction [PCR]), bacterial culture from the middle meatus during both phases, and both viral and bacterial samples from the maxillary sinus aspirate (respiratory virus PCR, bacterial culture, broad‐range bacterial PCR) during the later phase. Cilia destruction and microbial biofilms were sought from a nasal mucosal biopsy sample. RESULTS: We found that 42 (84%) of the subjects had viral nucleic acid in the nasopharynx during ARS. During the early phase, 28 (56%) of the subjects had nontypeable H. influenzae (NTHi) in the middle meatus, which was associated with wider paranasal mucosal changes in CBCT scans and increased symptoms during the study period. After 9 to 10 days from the onset, NTHi was found in the maxillary sinus in eight subjects (40%, 8/20) and led to prolonged symptoms. Bacterial biofilm was ruled out in 39 (78%) cases, and cilia destruction did not correlate with microbiological or clinical outcomes. CONCLUSION: Nasal and paranasal H. influenzae coinfection during viral infection may modify the symptoms and the extent of sinonasal mucosal disease observed in CBCT scans already from the beginning of the ARS episode. LEVEL OF EVIDENCE: N/A. Laryngoscope, 125:E1–E7, 2015


Perceived worsening of tics in adult patients with Tourette syndrome after the COVID‐19 outbreak


title: Common Cold and Acute Rhinosinusitis: Up-to-Date Management in 2020

text: PURPOSE OF REVIEW: The purposes of the review are as follows: (1) to define acute rhinosinusitis (ARS) and their phenotypes, (2) to highlight the ARS management according to international guidelines, (3) to compare the physicians’ management with the ARS guideline recommendations, and (4) to report ARS socioeconomic burden. RECENT FINDINGS: Bacterial and non-bacterial ARS have similar symptoms, although they can be discriminated by using a combination of specific signs and symptoms. The prescription of antibiotics should be limited to clearly suspected bacterial ARS. There is an overuse of diagnosis tools and treatment prescriptions. The total cost per ARS episode in Europe is over €1000. SUMMARY: ARS is mainly an inflammatory disease triggered by viral infection, and few cases end up developing bacterial infection. In most of the cases, it is a self-resolving disease which diagnosis is mainly clinical and the treatment symptomatic. The incidence of complications is low and independent of antibiotic use. There is a high socioeconomic burden associated to ARS.


Trust is a key factor in the willingness of health professionals to work during the COVID‐19 outbreak: Experience from the H1N1 pandemic in Japan 2009


title: The association of viral proteins with host cell dynein components during virus infection

text: After fusion with the cellular plasma membrane or endosomal membranes, viral particles are generally too large to diffuse freely within the crowded cytoplasm environment. Thus, they will never reach the cell nucleus or the perinuclear areas where replication or reverse transcription usually takes place. It has been proposed that many unrelated viruses are transported along microtubules in a retrograde manner using the cellular dynein machinery or, at least, some dynein components. A putative employment of the dynein motor in a dynein‐mediated transport has been suggested from experiments in which viral capsid proteins were used as bait in yeast two‐hybrid screens using libraries composed of cellular proteins and dynein‐associated chains were retrieved as virus‐interacting proteins. In most cases DYNLL1, DYNLT1 or DYNLRB1 were identified as the dynein chains that interact with viral proteins. The importance of these dynein–virus interactions has been supported, in principle, by the observation that in some cases the dynein‐interacting motifs of viral proteins altered by site‐directed mutagenesis result in non‐infective virions. Furthermore, overexpression of p50 dynamitin, which blocks the dynein–dynactin interaction, or incubation of infected cells with peptides that compete with viral polypeptides for dynein binding have been shown to alter the viral retrograde transport. Still, it remains to be proved that dynein light chains can bind simultaneously to incoming virions and to the dynein motor for retrograde transport to take place. In this review, we will analyse the association of viral proteins with dynein polypeptides and its implications for viral infection.


Insights into pediatric multi-system inflammatory syndrome and COVID-19


title: Molecular characterization of a panel of murine monoclonal antibodies specific for the SARS-coronavirus

text: Abstract The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is important for the development of both diagnostic tools and treatment of infection. A molecular characterization of nine monoclonal antibodies raised in immune mice, using highly purified, inactivated SARS-CoV as the inoculating antigen, is presented in this report. These antibodies are specific for numerous viral protein targets, and six of them are able to effectively neutralize SARS-CoV in vitro, including one with a neutralizing titre of 0.075nM. A phylogenetic analysis of the heavy and light chain sequences reveals that the mAbs share considerable homology. The majority of the heavy chains belong to a single Ig germline V-gene family, while considerably more sequence variation is evident in the light chain sequences. These analyses demonstrate that neutralization ability can be correlated with specific murine VH-gene alleles. For instance, one evident trend is high sequence conservation in the VH chains of the neutralizing mAbs, particularly in CDR-1 and CDR-2. The results suggest that optimization of murine mAbs for neutralization of SARS-CoV infection will likely be possible, and will aid in the development of diagnostic tools and passive treatments for SARS-CoV infection.


title: Human metapnuemovirus infections in hospitalized children and comparison with other respiratory viruses. 2005-2014 prospective study

text: BACKGROUND: Human metapneumovirus (HMPV) has an important etiological role in acute lower respiratory infections in children under five years. Our objectives were to estimate the relative contribution of HMPV to hospitalization in children with acute respiratory infection, to define the clinical and epidemiological features of HMPV single and multiple infections, and to compare HMPV infections with respiratory syncytial virus (HRSV), rhinovirus (HRV), adenovirus and human bocavirus infections in the same population. METHODS AND FINDINGS: A prospective study performed on all children less than 14 years of age with a respiratory tract disease admitted to a secondary hospital between September 2005- June 2014. Clinical characteristics of patients were analyzed. Nasopharyngeal aspirate was taken at admission for viral study with polymerase chain reaction for 16 respiratory viruses. A total of 3,906 children were included. At least one respiratory virus was detected in 75.2% of them. The most common identified virus was HRSV, followed by HRV. HMPV was detected in 214 cases (5.5%); 133 (62%) were single infections and the remaining were detected in coinfection with other viruses. 90.7% cases were detected between February and May. Children’s mean age was 13.83 ± 18 months. Fever was frequent (69%), and bronchiolitis (27%), and recurrent wheezing (63%) were the main clinical diagnosis. Hypoxia was present in 65% of the patients and 47% of them had an infiltrate in X-ray. Only 6 (2.8%) children were admitted to the intensive care unit. Only the duration of the hospitalization was different, being longer in the coinfections group (p <0.05). There were many differences in seasonality and clinical characteristics between HMPV and other respiratory viruses being more similar to HRSV. CONCLUSIONS: HMPV infections accounted for 5.5% of total viral infections in hospitalized children. The clinical characteristics were similar to HRSV infections, but seasonality and clinical data were different from other viral infections.


title: Frontiers in Molecular Evolutionary Medicine

text: This paper surveys some of the important insights that molecular evolution has contributed to evolutionary medicine; they include phage therapy, cancer biology, helminth manipulation of the host immune system, quality control of gametes, and pathogen outbreaks. Molecular evolution has helped to revolutionize our understanding of cancer, of autoimmune disease, and of the origin, spread, and pathogenesis of emerging diseases, where it has suggested new therapies, illuminated mechanisms, and revealed historical processes: all have practical therapeutic implications. While much has been accomplished, much remains to be done.


title: COVID-19: an update on diagnostic and therapeutic approaches

text: The unexpected pandemic set off by the novel coronavirus 2019 (COVID-19) has caused severe panic among people worldwide. COVID-19 has created havoc, and scientists and physicians are urged to test the efficiency and safety of drugs used to treat this disease. In such a pandemic situation, various steps have been taken by the government to control and prevent the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This pandemic situation has forced scientists to rework strategies to combat infectious diseases through drugs, treatment, and control measures. COVID-19 treatment requires both limiting viral multiplication and neutralizing tissue damage induced by an inappropriate immune reaction. Currently, various diagnostic kits to test for COVID-19 are available, and repurposing therapeutics for COVID-19 has shown to be clinically effective. As the global demand for diagnostics and therapeutics continues to rise, it is essential to rapidly develop various algorithms to successfully identify and contain the virus. This review discusses the updates on specimens/samples, recent efficient diagnostics, and therapeutic approaches to control the disease and repurposed drugs mainly focusing on chloroquine/hydroxychloroquine and convalescent plasma (CP). More research is required for further understanding of the influence of diagnostics and therapeutic approaches to develop vaccines and drugs for COVID-19.


title: Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States

text: BACKGROUND: The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r (2) = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r (2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. CONCLUSIONS: We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.


title: The potential of targeted antibody prophylaxis in SARS outbreak control: A mathematic analysis

text: Summary Background Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak. Method We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios. Results Assuming a basic reproduction number R 0=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration. Conclusions Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R 0 values and restricts both the size and duration of an outbreak.


Cardiac injury and ARDS meta-analysis validity – Correspondence in response to Santoso et al.


title: Emerging and re-emerging infectious diseases: challenges and opportunities for militaries

text: The communal nature of living and training environments, alongside suboptimal hygiene and stressors in the field, place military personnel at higher risk of contracting emerging infectious diseases. Some of these diseases spread quickly within ranks resulting in large outbreaks, and personnel deployed are also often immunologically naïve to otherwise uncommonly-encountered pathogens. Furthermore, the chance of weaponised biological agents being used in conventional warfare or otherwise remains a very real, albeit often veiled, threat. However, such challenges also provide opportunities for the advancement of preventive and therapeutic military medicine, some of which have been later adopted in civilian settings. Some of these include improved surveillance, new vaccines and drugs, better public health interventions and inter-agency co-operations. The legacy of successes in dealing with infectious diseases is a reminder of the importance in sustaining efforts aimed at ensuring a safer environment for both military and the community at large.


Immune checkpoint inhibitors in SARS-COV-2 infected cancer patients: the spark that ignites the fire?


title: The potential insights of Traditional Chinese Medicine on treatment of COVID-19

text: Corona Virus Disease 2019 (COVID-19) broke out in 2019 and spread rapidly around the world. There is still no specific antiviral therapy to the current pandemic. In China, historical records show that Traditional Chinese Medicine (TCM) is effective in prevention and enhancing the resistance to pandemic with unique insights. To fight with COVID-19, National Health and Commission of PRC has recommended some TCM in the guideline, such as HuoxiangZhengqi, LianhuaQingwen ShufengJiedu and XueBijing, and actually displayed a remarkable effect in clinical treatment strategic for COVID-19. We review studies to provide an in-depth understanding into the effect of TCM, and also introduce the possible mechanism involved in COVID-19 treatment.


title: Estimation of airborne viral emission: quanta emission rate of SARS-CoV-2 for infection risk assessment

text: Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking, whispering), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The results showed that high quanta emission rates (>100 quanta h(-1)) can be reached by an asymptomatic infectious SARS-CoV-2 subject performing vocalization during light activities (i.e. walking slowly) whereas a symptomatic SARS-CoV-2 subject in resting conditions mostly has a low quanta emission rate (<1 quantum h(-1)). The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.


title: Relapsing symmetric livedo reticularis in a patient with COVID‐19 infection

text: During the Coronavirus 2019 (COVID‐19) pandemic, several associated skin conditions were reported in infected patients, including; urticaria [1], exanthema [1], erythema multiforme [2], chickenpox‐like vesicles [1], pityriasis rosea [3], herpes simplex reactivation [4], erythema nodosum like Sweet’s syndrome [5], Symmetrical Drug‐Related Intertriginous and Flexural Exanthema [6], petechial rash [7], vasculitic purpura [7], acro‐ischemia/necrosis [8], Kawasaki disease [2] and chilblain lesions [9].


Parenteral Fish‐Oil Emulsions in Critically Ill COVID‐19 Emulsions


title: Seroepidemiologic Survey of Potential Pathogens in Obligate and Facultative Scavenging Avian Species in California

text: Throughout the world, populations of scavenger birds are declining rapidly with some populations already on the brink of extinction. Much of the current research into the factors contributing to these declines has focused on exposure to drug residues, lead, and other toxins. Despite increased monitoring of these declining populations, little is known about infectious diseases affecting scavenger bird species. To assess potential infectious disease risks to both obligate and facultative scavenger bird species, we performed a serosurvey for eleven potential pathogens in three species of scavenging birds in California: the California condor (Gymnogyps californianus), turkey vulture (Cathartes aura) and golden eagle (Aquila chrysaetos). California condors were seropositive for avian adenovirus, infectious bronchitis virus, Mycoplasma gallisepticum, avian paramyxovirus-2, West Nile virus (WNV) and Toxoplasma gondii. Golden eagles were seropositive for avian adenovirus, Chlamydophila psittaci and Toxoplasma gondii, and turkey vultures were seropositive for avian adenovirus, Chlamydophila psittaci, avian paramyxovirus-1, Toxoplasma gondii and WNV. Risk factor analyses indicated that rearing site and original release location were significantly associated with a positive serologic titer to WNV among free-flying condors. This study provides preliminary baseline data on infectious disease exposure in these populations for aiding in early disease detection and provides potentially critical information for conservation of the endangered California condor as it continues to expand its range and encounter new infectious disease threats.


title: A large-scale location-based social network to understanding the impact of human geo-social interaction patterns on vaccination strategies in an urbanized area

text: Cities play an important role in fostering and amplifying the transmission of airborne diseases (e.g., influenza) because of dense human contacts. Before an outbreak of airborne diseases within a city, how to determine an appropriate containment area for effective vaccination strategies is unknown. This research treats airborne disease spreads as geo-social interaction patterns, because viruses transmit among different groups of people over geographical locations through human interactions and population movement. Previous research argued that an appropriate scale identified through human geo-social interaction patterns can provide great potential for effective vaccination. However, little work has been done to examine the effectiveness of such vaccination at large scales (e.g., city) that are characterized by spatially heterogeneous population distribution and movement. This article therefore aims to understand the impact of geo-social interaction patterns on effective vaccination in the urbanized area of Portland, Oregon. To achieve this goal, we simulate influenza transmission on a large-scale location-based social network to 1) identify human geo-social interaction patterns for designing effective vaccination strategies, and 2) and evaluate the efficacy of different vaccination strategies according to the identified geo-social patterns. The simulation results illustrate the effectiveness of vaccination strategies based on geosocial interaction patterns in containing the epidemic outbreak at the source. This research can provide evidence to inform public health approaches to determine effective scales in the design of disease control strategies.


title: Improvement of SARS‐CoV2 symptoms following Guselkumab injection in a psoriatic patient

text: We read with great interest the publication of Messina et al (1) reporting the first case of SARS‐CoV2 infection in a young patient of 32‐year‐old suffering from psoriasis and psoriatic arthritis treated by Guselkumab, a monoclonal antibody that targets specifically the p19 subunit of Interleukin (IL)‐23(2).The patient contracted the SARS‐CoV2 infection after a dinner with some friends but fortunately she developed very discrete symptoms including only mild fever and rhinorrhea. These findings support the potential role of IL‐23p19 inhibitors to counteract the « cytokine storm » triggered by the SARS‐CoV2 and which is potentially implicated in the severity of the symptoms (3).


title: Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19

text: BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C(0)) and at 1 (C(1)) and 24 h (C(24)) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C(0) (6- to 7-fold higher than EC(50) from in vitro studies) and a notable decay at C(1). GS-441524 plasma concentrations reached a peak at C(1) and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.


title: Microarray-based identification of antigenic variants of foot-and-mouth disease virus: a bioinformatics quality assessment

text: BACKGROUND: The evolution of viral quasispecies can influence viral pathogenesis and the response to antiviral treatments. Mutant clouds in infected organisms represent the first stage in the genetic and antigenic diversification of RNA viruses, such as foot and mouth disease virus (FMDV), an important animal pathogen. Antigenic variants of FMDV have been classically diagnosed by immunological or RT-PCR-based methods. DNA microarrays are becoming increasingly useful for the analysis of gene expression and single nucleotide polymorphisms (SNPs). Recently, a FMDV microarray was described to detect simultaneously the seven FMDV serotypes. These results encourage the development of new oligonucleotide microarrays to probe the fine genetic and antigenic composition of FMDV for diagnosis, vaccine design, and to gain insight into the molecular epidemiology of this pathogen. RESULTS: A FMDV microarray was designed and optimized to detect SNPs at a major antigenic site of the virus. A screening of point mutants of the genomic region encoding antigenic site A of FMDV C-S8c1 was achieved. The hybridization pattern of a mutant includes specific positive and negative signals as well as crosshybridization signals, which are of different intensity depending on the thermodynamic stability of each probe-target pair. Moreover, an array bioinformatic classification method was developed to evaluate the hybridization signals. This statistical analysis shows that the procedure allows a very accurate classification per variant genome. CONCLUSION: A specific approach based on a microarray platform aimed at distinguishing point mutants within an important determinant of antigenicity and host cell tropism, namely the G-H loop of capsid protein VP1, was developed. The procedure is of general applicability as a test for specificity and discriminatory power of microarray-based diagnostic procedures using multiple oligonucleotide probes.


title: Medical Waste Management Practice during the 2019-2020 Novel Coronavirus Pandemic: Experience in a General Hospital

text: It is currently a critical period for the prevention and control of the COVID-19 pandemic. Since the medical waste disposal could be an important way to control the source of infection, standardization and strict implementation of the management of COVID-19 related medical waste should be with careful consideration to reduce the risk of epidemic within hospitals. This study illustrates the practice of medical waste disposal responding to the 2019-2020 novel coronavirus pandemic.


Rheumatologists rapidly adjust patient care during COVID-19 pandemic


title: Hybrid deep learning for detecting lung diseases from X-ray images

text: Lung disease is common throughout the world. These include chronic obstructive pulmonary disease, pneumonia, asthma, tuberculosis, fibrosis, etc. Timely diagnosis of lung disease is essential. Many image processing and machine learning models have been developed for this purpose. Different forms of existing deep learning techniques including convolutional neural network (CNN), vanilla neural network, visual geometry group based neural network (VGG), and capsule network are applied for lung disease prediction. The basic CNN has poor performance for rotated, tilted, or other abnormal image orientation. Therefore, we propose a new hybrid deep learning framework by combining VGG, data augmentation and spatial transformer network (STN) with CNN. This new hybrid method is termed here as VGG Data STN with CNN (VDSNet). As implementation tools, Jupyter Notebook, Tensorflow, and Keras are used. The new model is applied to NIH chest X-ray image dataset collected from Kaggle repository. Full and sample versions of the dataset are considered. For both full and sample datasets, VDSNet outperforms existing methods in terms of a number of metrics including precision, recall, F0.5 score and validation accuracy. For the case of full dataset, VDSNet exhibits a validation accuracy of 73%, while vanilla gray, vanilla RGB, hybrid CNN and VGG, and modified capsule network have accuracy values of 67.8%, 69%, 69.5%, 60.5% and 63.8%, respectively. When sample dataset rather than full dataset is used, VDSNet requires much lower training time at the expense of a slightly lower validation accuracy. Hence, the proposed VDSNet framework will simplify the detection of lung disease for experts as well as for doctors.


title: 80 RETINAL AUTOANTIBODIES

text: ABSTRACT Retinal autoantibodies, commonly referred to as antiretinal antibodies (ARA), have been implicated in the pathogenicity of a variety of immune-mediated visual disorders. In the paraneoplastic syndrome, cancer-associated retinopathy (CAR), ARA with their targeted retinal antigens have been identified. There are many other infectious, inflammatory as well as degenerative retinopathies associated with the presence of ARA. More than 15 ARA have been identified in CAR. For these autoantibodies, the autoantigens still remain unknown. Recoverin, a calcium-binding retinal protein involved in the reversal of the phototransduction cascade, is well established as the most common CAR autoantigen. The proposed mechanism of antibody-mediated degeneration involves molecular mimicry and loss of peripheral tolerance to residing retinal antigens. In vitro, ARA have been shown to cause apoptotic death of photoreceptors. Questions remain though, regarding the access and penetration of these antibodies into the retina. Furthermore, the titer of ARA does not always correlate with clinical disease status. There exists lack of standardization of antibody and antigen detection. Thus, results from different laboratories cannot exactly be compared. Sensitivity and specificity for the detection of pathogenic ARA is also lacking. Though there are many caveats, presence of ARA still serves as an adjunctive study for the clinician to confirm a diagnosis, which often is difficult to make. The study of ARA serves as an excellent model for the elucidation of pathological mechanisms underlying autoimmune retinopathy and its allied disorders.


title: Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020): Statement of the Austrian Society of Pneumology (ASP)

text: The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV‑2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.


title: “It's about how much we can do, and not how little we can get away with”: Coronavirus-related legislative changes for social care in the United Kingdom

text: The coronavirus pandemic, referred to here as Covid-19, has brought into sharp focus the increasing divergence of devolved legislation and its implementation in the United Kingdom. One such instance is the emergency health and social care legislation and guidance introduced by the United Kingdom Central Government and the devolved Governments of Wales, Scotland and Northern Ireland in response to this pandemic. We provide a summary, comparison and discussion of these proposed and actual changes with a particular focus on the impact on adult social care and safeguarding of the rights of citizens. To begin, a summary and comparison of the relevant changes, or potential changes, to mental health, mental capacity and adult social care law across the four jurisdictions is provided. Next, we critique the suggested and actual changes and in so doing consider the immediate and longer term implications for adult social care, including mental health and mental capacity, at the time of publication.several core themes emerged: concerns around process and scrutiny; concerns about possible changes to the workforce and last, the possible threat on the ability to safeguard human rights. It has been shown that, ordinarily, legislative provisions across the jurisdictions of the UK are different, save for Wales (which shares most of its mental health law provisions with England). Such divergence is also mirrored in the way in which the suggested emergency changes could be implemented. Aside from this, there is also a wider concern about a lack of parity of esteem between social care and health care, a concern which is common to all. What is interesting is that the introduction of CVA 2020 forced a comparison to be made between the four UK nations which also shines a spotlight on how citizens can anticipate receipt of services.


title: Cutaneous manifestations in COVID‐19: the experiences of Barcelona and Rome

text: In December 2019, a new virus called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causing Coronavirus disease 2019 (COVID‐19) emerged in Wuhan, Hubei Province, China. SARS‐CoV‐2 is transmitted through respiratory droplets and object infected with droplets containing the virus. The diagnosis is made employing quantitative reverse transcriptase polymerase chain reaction to identify the viral nucleic acid in respiratory specimens or blood samples.


title: Molecular characterization of an infectious bronchitis virus strain isolated from northern China in 2012

text: This study reports the complete genome sequence of an infectious bronchitis virus (CK/CH/SD/121220, KJ128295) isolated in 2012 from Shandong Province in northern China. The genome is 27,666 nt long, comprising six genes and 5′ and 3′ untranslated regions. The full-length genome of the CK/CH/SD/121220 isolate had the highest nucleotide sequence identity (96.7 %) to the YX10 strain. Sites of recombination were identified in the genes 1ab, S, 5a, 5b and N, with their putative parental strains belonging to the QX- and YN-type subgroups, which are already circulating in China. Our findings suggest an important role played by recombination in IBV evolution.


REHABILITACIÓN RESPIRATORIA EN PACIENTES CON COVID-19


title: Prisoners in a pandemic: We should think about detainees during Covid-19 outbreak

text: In Italy, where the Covid-19 emergency developed immediately after China, the spread of the pandemic has highlighted some unsolved problems inherent to the prison system. This theme is already, unfortunately, of distressing topicality. Among these, the complex balance between the security needs and the protection of the prisoner’s right to health deserves particular attention. The detainees, in fact, constitute a group particularly vulnerable to the spread of an infectious disease, both because they have an average level of health lower than that of the general population, and because they live forced in cramped, overcrowded, poorly ventilated environments, in which it is not always possible to observe the general hygiene rules. For these reasons, during the ongoing pandemic emergency, it could be even more difficult to concretely protect the right to health of this portion of the population.


title: First detection of novel enterovirus G recombining a torovirus papain‐like protease gene associated with diarrhoea in swine in South Korea

text: Enterovirus species G (EV‐G) comprises a highly diversity of 20 genotypes that is prevalent in pig populations, with or without diarrhoea. In the present study, a novel EV‐G strain (KOR/KNU‐1811/2018) that resulted from cross‐order recombination was discovered in diagnostic faecal samples from neonatal pigs with diarrhoea that were negative for swine enteric coronaviruses and rotavirus. The recombinant EV‐G genome possessed an exogenous 594‐nucleotide (198‐amino acid) sequence, flanked by two viral 3C(pro) cleavage sites at the 5′ and 3′ ends in its 2C/3A junction region. This insertion encoded a predicted protease similar to the porcine torovirus papain‐like cysteine protease (PLCP), which was recently found in the EV‐G1, ‐G2, and ‐G17 genomes. The complete KNU‐1811 genome shared 73.7% nucleotide identity with a prototype EV‐G1 strain, but had 83.9%–86.7% sequence homology with the global EV‐G1‐PLCP strains. Genetic and phylogenetic analyses demonstrated that the Korean recombinant EV‐G's own VP1 and inserted foreign PLCP genes are most closely related independently to contemporary chimeric G1‐PLCP and G17‐PLCP strains respectively. These results implied that the torovirus‐derived PLCP gene might have undergone continuous nucleotide mutations in the respective EV‐G genome following its independent acquisition through naturally occurring recombination. Our results advance the understanding of the genetic evolution of EV‐G driven by infrequent viral recombination events, by which EV‐G populations laterally gain an exotic gene encoding a virulence factor from heterogeneous virus families, thereby causing clinical disease in swine.


title: The Ebola epidemic is ongoing in West Africa and responses from China are positive

text: The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. On August 8, 2014, the World Health Organization (WHO) declared the cross-country Ebola outbreak a Public Emergency of International Concern. China has had no confirmed cases of Ebola. In this paper, virologic characteristics, pathogenesis, clinical manifestations, laboratory examination and prophylactic vaccines and therapeutic drugs of Ebola are summarized. Importantly, active responses and actions from China are introduced. Moreover, the key issues in the future prevention and control of Ebola were also addressed.


title: Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow 2 fever virus structural proteins and BALB/c (H2(d)) mice model

text: Immunomics research uses in silico epitope prediction, as well as in vivo and in vitro approaches. We inoculated BALB/c (H2(d)) mice with 17DD yellow fever vaccine to investigate the correlations between approaches used for epitope discovery: ELISPOT assays, binding assays, and prediction software. Our results showed a good agreement between ELISPOT and binding assays, which seemed to correlate with the protein immunogenicity. PRED(BALB/c) prediction software partially agreed with the ELISPOT and binding assay results, but presented low specificity. The use of prediction software to exclude peptides containing no epitopes, followed by high throughput screening of the remaining peptides by ELISPOT, and the use of MHC-biding assays to characterize the MHC restrictions demonstrated to be an efficient strategy. The results allowed the characterization of 2 MHC class I and 17 class II epitopes in the envelope protein of the YF virus in BALB/c (H2(d)) mice.


title: Influenza virus-induced oxidized DNA activates inflammasomes

text: Summary Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. While the oxidized DNA enhanced influenza virus-induced IL-1β secretion, inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1β secretion. In addition, we show that influenza virus stimulates IL-1β secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammaseome activation, and reveal the importance of influenza virus-induced oxidized DNA in inflammasomes activation.


title: Artificial intelligence for rapid identification of the coronavirus disease 2019 (COVID-19)

text: The coronavirus disease 2019 (COVID-19) outbreak that originated in Wuhan, China has rapidly propagated due to widespread person-to-person transmission and has resulted in over 1,133,758 cases in 197 countries with a total of 62,784 deaths as of April 5, 2020. Laboratory confirmation of SARS-CoV-2 is performed with a virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test. This test can take up to two days to complete, and, due to the possibility of false negatives, serial testing may be required to reliably exclude infection. A current supply shortage of RT-PCR test kits compounds the shortcomings of entrusting diagnosis to the PCR test alone and underscores the urgent need to provide alternative methods for the rapid and accurate diagnosis of SARS-CoV-2 patients. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value to fully exclude infection, because of the normal radiologic findings in some early disease patients. In this study, we use artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history, and/or laboratory testing to more accurately and rapidly diagnose SARS-CoV-2 (+) patients. We included 905 RT-PCR confirmed patients. 419 (46.2%) tested positive for SARS-CoV-2 by laboratory-confirmed real-time RT-PCR assay and next-generation sequencing, while 486 patients (53.8%) tested negative (confirmed by at least two additional negative RT-PCR tests and clinical observation). The proposed AI system achieved an AUC of 0.92 and performed equally well in sensitivity compared to a senior thoracic radiologist on a testing set of 279 cases. The AI system also improved the detection of RT-PCR positive SARS-CoV-2 patients who presented with normal CTs, correctly identifying 17/25 (68%) patients, whereas all 25 RT-PCR SARS-CoV-2-positive CT-normal patients were classified as SARS-CoV-2 negative by radiologists.


title: SAMHD1's protein expression profile in humans

text: The deoxynucleoside triphosphate triphosphohydrolase and 3′ → 5′ exonuclease SAMHD1 restricts HIV‐1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue‐resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV‐susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV‐restrictive activity. Surprisingly, stimulation of these primary cells with IFN‐α, IFN‐γ, IL‐4, IL‐6, IL‐12, IL‐18, IL‐27, or TNF‐α affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL‐1β moderately down‐regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross‐sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle‐dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.


Efficient Transduction of Dendritic Cells Using Coronavirus-Based Vectors


title: Prosthetic aortic valve endocarditis complicated by COVID‐19 and hemorrhage

text: The novel coronavirus, now termed SARS‐CoV‐2, has caused a significant global impact in the space of 4 months. Almost all elective cardiac surgical operations have been postponed with only urgent and emergency operations being considered in order to maximise resource utilisation. We present a case of a 69‐year old lady with an infected prosthetic aortic valve for consideration of urgent inpatient surgery. Despite being asymptomatic and testing negative initially for COVID‐19 RT‐PCR swab, further investigations with CT revealed suspicious findings. She subsequently tested positive on a repeat swab and unfortunately deteriorated rapidly with complications including gastro‐intestinal and intracerebral haemorrhage.


title: The effect of Baihu Decoction (白虎汤) on blood glucose levels in treating systemic inflammatory response syndrome

text: In this paper we investigated the mechanisms of Baihu Decoction ((白虎汤, BH) and Baihu with Radix Ginseng (BHG) in treating systemic inflammatory response syndrome (SIRS) and sepsis in humans and animals. By reviewing published data on the effects of BH and BHG and the control of blood glucose in treating SIRS and sepsis, we found that (1) BH and BHG were beneficial in the treatment of SIRS and sepsis in humans and animals; (2) BH and BHG also had great effect in lowering blood glucose level; and (3) the tight control of blood glucose during critical illness substantially improved the outcome. Considering these data together, we hypothesize that one of the major mechanisms of BH and BHG in treating SIRS and sepsis is to lower the blood glucose level. The findings also suggest that the application of BH and BHG can extend to many acute illnesses and injuries, which commonly cause hyperglycemia.


title: COVID-19: review and hematologic impact

text: Abstract In the last decades, coronaviruses have been a major threat to public health worldwide. SARS-CoV-2 is the third known coronavirus that causes fatal respiratory diseases in humans. The initial clinical features of SARS-CoV-2 infection are quite nonspecific and not all suspected patients can be tested to exclude or confirm the diagnosis. Increasing scientific evidence has shown that abnormalities in routine laboratory tests, particularly hematological tests, have the potential to indicate, in a quick, practical and economical way, the need for specific laboratory tests for the diagnosis of SARS-CoV-2 infection, besides assisting in the prognosis of the disease and in the optimization of its clinical monitoring. In order to address in a simple and practical way the various aspects related to SARS-CoV-2 infection, this review reports the history of the virus, the epidemiology and pathophysiology of COVID-19, with emphasis on its laboratory diagnosis, particularly in hematological changes found during the course of the disease.