title: Temporary changes in clinical guidelines of gestational diabetes screening and management during COVID-19 outbreak: A narrative review

text: BACKGROUND AND AIMS: New clinical approaches are needed to minimize complications of gestational diabetes during the COVID-19 outbreak with timely screening and proper management. The present study aims to highlight changes in the clinical guideline for gestational diabetes during the pandemic. METHODS: In a narrative review, multiple databases were searched. Furthermore, online searches were conducted to identify guidelines or support documents provided by NGOs, local health authorities, and societies and organizations in the field of diabetes and obstetrics. RESULTS: We included five national guidelines that were published in English from Canada, the United Kingdom, Australia, New Zealand, and Australia health agencies. FBG, A1C, RPG were recommended as alternative tests instead of a 2-h oral glucose tolerance test (OGGT) for GDM screening at 24–28 weeks of gestation. Recommendations also included a deferral of postpartum screening till the end of the pandemic, or postponement of testing to 6–12 months after delivery, use telemedicine and telecare. CONCLUSIONS: Updated temporary changes in clinical guidelines are sensible and accommodates social distancing and minimizes risk of exposure to COVID-19. Despite many unsolved controversies in screening, treatment, and follow-up of gestational diabetes, it seems involvement with novel coronavirus have made a reach to a global agreement simpler.


The “Snotbarometer”: Epidemiological data on respiratory infections


title: Empfehlungen zur Durchführung einer Bronchoskopie in Zeiten der COVID-19-Pandemie

text: COVID-19, caused by coronavirus SARS-CoV-2 is a new and ongoing infectious disease affecting healthcare systems worldwide. Healthcare worker are at high risk for COIVD-19 and many have been infected or even died in countries severely affected by COVID-19 like China or Italy. Bronchoscopy causes cough and aerosol production and has to be considered a significant risk for the staff to get infected. Particular recommendations should guide to prevent spreading COVID-19 and to protect healthcare worker when performing a bronchoscopy.


title: Electrocardiographic Findings in COVID-19: Insights on Mortality and Underlying Myocardial Processes

text: INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. METHODS: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. RESULTS: 756 patients who presented to a large New York City teaching hospital with COVID-19 underwent an ECG. The mean age was 63.3 ± 16 years, 37% were women, 61% of patients were non-white, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (APC)s (odds ratio (OR)=2.57, 95% confidence interval (CI) 1.23-5.36, p=0.01), a right bundle branch block (RBBB) or intraventricular block (IVB) (OR=2.61, 95% CI 1.32-5.18, p=0.002), ischemic T-wave inversion (OR=3.49, 95% CI 1.56-7.80, p=0.002), and nonspecific repolarization (OR=2.31, 95% CI 1.27-4.21, p=0.006) increased the odds of death. ST elevation was rare (n=5, 0.7%). CONCLUSION: We found that patients with ECG findings of both left sided heart disease (APCs, IVB, repolarization abnormalities) and right sided disease (RBBB) have higher odds of death. ST elevation at presentation was rare.


title: The Influence Of Social Behavior On Competition Between Virulent Pathogen Strains

text: Infectious disease interventions like contact precautions and vaccination have proven effective in disease control and elimination. The priority given to interventions can depend strongly on how virulent the pathogen is, and interventions may also depend partly for their success on social processes that respond adaptively to disease dynamics. However, mathematical models of competition between pathogen strains with differing natural history profiles typically assume that human behaviour is fixed. Here, our objective is to model the influence of social behaviour on the competition between pathogen strains with differing virulence. We couple a compartmental Susceptible-Infectious-Recovered model for a resident pathogen strain and a mutant strain with higher virulence, with a differential equation of a population where individuals learn to adopt protective behaviour from others according to the prevalence of infection of the two strains and the perceived severity of the respective strains in the population. We perform invasion analysis, time series analysis and phase plane analysis to show that perceived severities of pathogen strains and the efficacy of infection control against them can greatly impact the invasion of more virulent strain. We demonstrate that adaptive social behaviour enables invasion of the mutant strain under plausible epidemiological scenarios, even when the mutant strain has a lower basic reproductive number than the resident strain. Surprisingly, in some situations, increasing the perceived severity of the resident strain can facilitate invasion of the more virulent mutant strain. Our results demonstrate that for certain applications, it may be necessary to include adaptive social behaviour in models of the emergence of virulent pathogens, so that the models can better assist public health efforts to control infectious diseases.


title: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

text: BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim(®)) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim(®) creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.


title: Percutaneous dilatational tracheostomy for saturating influx of COVID-19 patients: experience of military ENT physicians deployed in Mulhouse, France

text: Abstract Objectives: The main objective was to demonstrate the feasibility of percutaneous tracheostomy performed under difficult conditions by military ENT physicians during their deployment in the military intensive care field hospital of the French Military Medical Service in Mulhouse to confront the exceptional COVID-19 pandemic. The secondary objective was to assess reliability and safety for patient and caregivers, with a risk of iatrogenic viral contamination. Material and Methods: A single-center retrospective study was conducted between March 25 and April 25, 2020, in 47 COVID-19 patients requiring prolonged mechanical ventilation. The inclusion criterion was having undergone percutaneous tracheostomy. Results:18 consecutively included patients had successfully undergone percutaneous tracheostomy despite unfavorable anatomical conditions (short neck: 83.3%, overweight or obese: 88.9%). Median time to completion was 11 days after intubation, with an average duration of 7 minutes. The procedure was technically compliant in 83.3% of cases, and considered easy (on self-assessment) in 72.2%, with 2 minor per-procedural complications. No crossover to surgery was required. There was only 1 major post-procedural complication (late hemorrhage). Conclusion: This study showed the feasibility of percutaneous tracheostomy by an ENT physician under COVID-19 biohazard conditions. The technique was fast, easy and safe and met safety requirements for patient and staff.


title: Contingent assessment of the COVID-19 vaccine

text: The COVID-19 pandemic has not only had a negative impact on people’s health and life behavior, but also on economies around the world. At the same time, laboratories and institutions are working hard to obtain a COVID-19 vaccine, which we hope will be available soon. However, there has been no assessment of whether an individual and society value a vaccine monetarily, and what factors determine this value. Therefore, the objective of this research was to estimate the individual’s willingness to pay (WTP) for a hypothetical COVID-19 vaccine and, at the same time, find the main factors that determine this valuation. For this, we used the contingent valuation approach, in its single and double-bounded dichotomous choice format, which was based on a hypothetical market for a vaccine. The sample used was obtained through an online survey of n = 566 individuals from Chile. The main results showed that the WTP depends on the preexistence of chronic disease ([Formula: see text]), knowledge of COVID-19 ([Formula: see text]), being sick with COVID-19 ([Formula: see text]), perception of government performance ([Formula: see text]), employment status ([Formula: see text]), income ([Formula: see text]), health care ([Formula: see text]), adaptation to quarantine with children at home ([Formula: see text] and whether the person has recovered from COVID-19 ([Formula: see text]. According to our discrete choice model in double-bounded dichotomous format, it was concluded that the individuals’ WTP is US$184.72 (CI: 165.52-203.92; p < 0.01). This implies a social valuation of approximately US$2,232 million, corresponding to 1.09% of the GNP per capita.


title: Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?

text: The effects of smoking on Corona Virus Disease 2019 (COVID-19) are currently unknown. The purpose of this study was to systematically examine the prevalence of current smoking among hospitalized patients with COVID-19 in China, considering the high-population smoking prevalence in China (26.6%). A systematic review of the literature (PubMed) was performed on April 1. Thirteen studies examining the clinical characteristics of hospitalized COVID-19 patients in China and presenting data on the smoking status were found. The pooled prevalence of current smoking from all studies was calculated by random-effect meta-analysis. To address the possibility that some smokers had quit shortly before hospitalization and were classified as former smokers on admission to the hospital, we performed a secondary analysis in which all former smokers were classified as current smokers. A total of 5960 patients were included in the studies identified. The current smoking prevalence ranged from 1.4% (95% CI 0.0–3.4%) to 12.6% (95% CI 10.6–14.6%). An unusually low prevalence of current smoking was observed from the pooled analysis (6.5%, 95% CI 4.9–8.2%) as compared to population smoking prevalence in China. The secondary analysis, classifying former smokers as current smokers, found a pooled estimate of 7.3% (95% CI 5.7–8.9%). In conclusion, an unexpectedly low prevalence of current smoking was observed among patients with COVID-19 in China, which was approximately 1/4th the population smoking prevalence. Although the generalized advice to quit smoking as a measure to reduce health risk remains valid, the findings, together with the well-established immunomodulatory effects of nicotine, suggest that pharmaceutical nicotine should be considered as a potential treatment option in COVID-19.


title: Establishment of primary transgenic human airway epithelial cell cultures to study respiratory virus – host interactions

text: Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for FACS-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly(I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (RSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures thereby unlocking a unique potential for detailed molecular characterization of virus – host interactions in human respiratory epithelium.


title: COVID-19: key concepts for the surgeon

text: Abstract In view of the current pandemic by SARS-CoV-2 it deems essential to understand the key concepts about the infection: its epidemiological origin, presentation, clinical course, diagnosis and treatment (still experimental in many cases). The knowledge about the virus is still limited, but as the pandemic progresses and the physiopathology of the disease is understood, new evidence is being massively published. Surgical specialists are facing an unprecedented situation: they must collaborate in the ER or medical wards attending these patients, while still needing to make decisions about surgical patients with probable COVID-19. The present narrative review aims to summarize the most relevant aspects and synthetize concepts on COVID-19 for surgeons.


Chapter 10 Digestive disorders


title: COVID-19 and the March 2020 Stock Market Crash. Evidence from S&P1500

text: This paper investigates the US stock market performance during the crash of March 2020 triggered by COVID-19. We find that natural gas, food, healthcare, and software stocks earn high positive returns, whereas equity values in petroleum, real estate, entertainment, and hospitality sectors fall dramatically. Moreover, loser stocks exhibit extreme asymmetric volatility that correlates negatively with stock returns. Firms react in a variety of different ways to the COVID-19 revenue shock. The analysis of the 8K and DEF14A filings of poorest performers reveals departures of senior executives, remuneration cuts, and (most surprisingly) newly approved cash bonuses and salary increases.


title: Climate change and viral emergence: evidence from Aedes-borne arboviruses

text: Climate change is leading to increases in global temperatures and erratic precipitation patterns, both of which are contributing to the expansion of mosquito-borne arboviruses and the populations of the mosquitos that vector them. Herein, we review recent evidence of emergence and expansion of arboviruses transmitted by Aedes mosquitos that has been driven in part by environmental changes. We present as a case study of recent work from Córdoba, Argentina, where dengue has been actively emerging in the past decade. We review recent empirical and modeling studies that aim to understand the impact of climate on future expansion of arboviruses, and we highlight gaps in empirical studies linking climate to arbovirus transmission at regional levels.


title: Template-based coiled-coil antigens elicit neutralizing antibodies to the SARS-coronavirus

text: Abstract The Spike (S) glycoprotein of coronaviruses (CoV) mediates viral entry into host cells. It contains two hydrophobic heptad repeat (HR) regions, denoted HRN and HRC, which oligomerize the S glycoprotein into a trimer in the native state and when activated collapse into a six-helix bundle structure driving fusion of the host and viral membranes. Previous studies have shown that peptides of the HR regions can inhibit viral infectivity. These studies imply that the HR regions are accessible and that agents which can interact with them may prevent viral entry. In the present study, we have investigated an approach to generate antibodies that specifically recognize the HRN and HRC regions of the SARS-CoV spike (S) glycoprotein in order to evaluate whether these antibodies can inhibit viral infectivity and thus neutralize the SARS-CoV. In this regard, we incorporated HRN and HRC coiled-coil surface residues into a de novo designed two-stranded α-helical coiled-coil template for generating conformation-specific antibodies that recognize α-helices in proteins (Lu, S.M., Hodges, R.S., 2002. J. Biol. Chem. 277, 23515–23524). Eighteen surface residues from two regions of HRN and HRC were incorporated into the template and used to generate four anti-sera, HRN1, HRN2, HRC1, and HRC2. Our results show that all of the elicited anti-sera can specifically recognize HRN or HRC peptides and the native SARS-CoV S protein in an ELISA format. Flow cytometry (FACS) analysis, however, showed only HRC1 and HRC2 anti-sera could bind to native S protein expressed on the cell surface of Chinese hamster ovary cells, i.e., the cell surface structure of the S glycoprotein precluded the ability of the HRN1 or HRN2 anti-sera to see their respective epitope sites. In in vitro viral infectivity assays, no inhibition was observed for either HRN1 or HRN2 anti-serum, whereas both HRC1 and HRC2 anti-sera could inhibit SARS-CoV infection in a dose-dependent manner. Interestingly, the HRC1 anti-serum, which was a more effective inhibitor of viral infectivity compared to HRC2 anti-serum, could only bind the pre-fusogenic state of HRC, i.e., the HRC1 anti-serum did not recognize the six-helix bundle conformation (fusion state) whereas HRC2 anti-serum did. These results suggest that antibodies that are more specific for the pre-fusogenic state of HRC may be better neutralizing antibodies. Overall, these results clearly demonstrate that the two-stranded coiled-coil template acts as an excellent presentation system for eliciting helix-specific antibodies against highly conserved viral antigens and HRC1 and HRC2 peptides may represent potential candidates for use in a peptide vaccine against the SARS-CoV.


title: Effective infection prevention and control strategies in a large, accredited, psychiatric facility in Singapore

text: The Institute of Mental Health in Singapore continues to attempt to prevent the introduction of COVID-19, despite community transmission. Essential services are maintained and quarantine measures are currently unnecessary. To help similar organizations, strategies are listed along three themes: sustaining essential services, preventing infection, and managing human and consumable resources.


title: Molecular detection of human parechovirus in under-Five-Year-Old Children with gastroenteritis

text: Abstract Background Currently, RT-PCR is used widely and considered to be a convenient, useful, and powerful method for molecular diagnosis, to detect pathogens from clinical specimens. Objectives In this work we describe the development of an in-house Real-time Taqman PCR assay for quantification of HPeV in stool specimens. Study designs A total of 137 fecal specimens previously screened for rotavirus and adenovirus were tested for HPeV virus. Results A total of 11 out of 137 (8%) episodes of acute gastroenteritis were associated with HPeV genomic detection with median viral load 14678±28927 genomes/mg fecal specimens. There was no significant difference in the detection rate between male and female (54.5% (6/11) vs. 45.5% (5/11). Among the 11 HPeV-positive cases, 2 were also positive for other viral pathogens, including rotavirus (n=2). Conclusion In conclusion, the development of a laboratory designed Real Time PCR TaqMan assay for quantitative detection of HPeV and the optimization and standardization of this assay using stool of children with acute gastroenteritis are described.


title: Preventive replacement policies with time of operations, mission durations, minimal repairs and maintenance triggering approaches

text: When a mission arrives at a random time and lasts for a duration, it becomes an interesting problem to plan replacement policies according to the health condition and repair history of the operating unit, as the reliability is required at mission time and no replacement can be done preventively during the mission duration. From this viewpoint, this paper proposes that effective replacement policies should be collaborative ones gathering data from time of operations, mission durations, minimal repairs and maintenance triggering approaches. We firstly discuss replacement policies with time of operations and random arrival times of mission durations, model the policies and find optimum replacement times and mission durations to minimize the expected replacement cost rates analytically. Secondly, replacement policies with minimal repairs and mission durations are discussed in a similar analytical way. Furthermore, the maintenance triggering approaches, i.e., replacement first and last, are also considered into respective replacement policies. Numerical examples are illustrated when the arrival time of the mission has a gamma distribution and the failure time of the unit has a Weibull distribution. In addition, simple case illustrations of maintaining the production system in glass factories are given based on the assumed data.


title: China’s rural electricity market—a quantitative analysis

text: Abstract The objective of this paper is to quantify the development of the rural electricity market at county level and below in China. A sectorial energy demand analysis and forecasting model was developed to analyze six Chinese provinces with different economic backgrounds. Historical data for over 20 years were collected on rural economic development, households, population, per capita income, community infrastructure development, capital investment, electricity consumption, output values in agriculture sector, and township and village enterprises (TVEs). This paper concludes that by 2010, annual electricity demand will increase at a rate between −1.40% and 15.60% (depending on the sectors and provinces). It also recommends a preferred order for future rural electricity investment: Jiangsu, Hebei, Henan, Shaanxi, Liaoning and Xinjiang, i.e. from the most to the least developed provinces, if the investment objectives are to find the best market return and the greatest impact on rural market development.


title: 13th ERS Lung Science Conference. The most important take home messages: News from the Underground

text: The 13th ERS Lung Science Conference (LSC) was organised to bring academics together from all over the world to present and discuss the latest developments regarding lung infection and immunity. The conference took place in breathtaking Estoril, Portugal; however, it wasn’t the beautiful surroundings that were our main motivation to attend, but instead the scientific merit of the conference and the chance to create new scientific collaborations. The scientific programme [1] was packed with the most up-to-date content in the field of lung infection and immunity and included some of the top researchers within this exciting area. Moreover, the convenient size of the LSC offered the opportunity to renew and intensify friendships and collaborations. In particular, for researchers at the start of their career, this is a great feature and we therefore warmly recommend the LSC to ERS Juniors Members!


title: Genetic studies of diseases: Predicting siRNA efficiency

text: Since the identification of RNA-mediated interference (RNAi) in 1998, RNAi has become an effective tool to inhibit gene expression. The inhibition mechanism is triggered by introducing a short interference double-stranded RNA (siRNA,19~27 bp) into the cytoplasm, where the guide strand of siRNA (usually antisense strand) binds to its target messenger RNA and the expression of the target gene is blocked. RNAi has been widely applied in gene functional analysis, and as a potential therapeutic strategy in viral diseases, drug target discovery, and cancer therapy. Among the factors which may compromise inhibition efficiency, how to design siRNAs with high efficiency and high specificity to its target gene is critical. Although many algorithms have been developed for this purpose, it is still difficult to design such siRNAs. In this review, we will briefly discuss prediction methods for siRNA efficiency and the problems of present approaches.


title: Isolation and characterization of Korean porcine deltacoronavirus strain KNU16-07

text: Porcine deltacoronavirus (PDCoV) has emerged in several pig-raising countries and has been a causative pathogen associated with diarrheal diseases in South Korea since 2014. In the present study, we were able to isolate and cultivate a Korean PDCoV strain (KNU16-07) in cell culture and investigate its pathogenicity. PDCoV-inoculated piglets showed watery diarrhea accompanied by acute enteritis in the natural host. Sequencing analysis demonstrated the genetic stability of KNU16-07 for at least thirty serial passages.


title: Dynamic template-assisted strategies in fragment-based drug discovery

text: Fragment-based methods for drug discovery are increasingly popular because they provide drug leads with greater ligand efficiency than conventional high-throughput screening. However, established methods for fragment detection do not address the central question in fragment-based ligand discovery: how can a primary ligand be optimally extended by a secondary fragment? Dynamic screening methods solve this issue by using a protein target as a template for ligand assembly, thus yielding high-affinity binders from low-affinity fragments. This review summarizes recent work on dynamic screening methodology, which resulted in the development of several high-affinity binders for various targets. Strengths and limitations of the published approaches are discussed and possible contributions of dynamic screening methodology to the drug discovery process are highlighted.


title: The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD‐L1 levels on CNS cells

text: Central nervous system (CNS) cells locally modulate immune responses using numerous molecules that are not fully elucidated. Engagement of programmed death‐1 (PD‐1), expressed on activated T cells, by its ligands (PD‐L1 or PD‐L2) suppresses T‐cell responses. Enhanced CNS PD‐1 and PD‐L1 expression has been documented in inflammatory murine models; however, human CNS data are still incomplete. We determined that human primary cultures of astrocytes, microglia, oligodendrocytes, or neurons expressed low or undetectable PD‐L1 under basal conditions, but inflammatory cytokines significantly induced such expression, especially on astrocytes and microglia. Blocking PD‐L1 expression in astrocytes using specific siRNA led to significantly increased CD8 T‐cell responses (proliferation, cytokines, lytic enzyme). Thus, our results establish that inflamed human glial cells can express sufficient and functional PD‐L1 to inhibit CD8 T cell responses. Extensive immunohistochemical analysis of postmortem brain tissues demonstrated a significantly greater PD‐L1 expression in multiple sclerosis (MS) lesions compared with control tissues, which colocalized with astrocyte or microglia/macrophage cell markers. However, more than half of infiltrating CD8 T lymphocytes in MS lesions did not express PD‐1, the cognate receptor. Thus, our results demonstrate that inflamed human CNS cells such as in MS lesions express significantly elevated PD‐L1, providing a means to reduce CD8 T cell responses, but most of these infiltrating immune cells are devoid of PD‐1 and thus insensitive to PD‐L1/L2. Strategies aimed at inducing PD‐1 on deleterious activated human CD8 T cells that are devoid of this receptor could provide therapeutic benefits since PD‐L1 is already increased in the target organ. © 2011 Wiley‐Liss, Inc.


title: Discovery of antitumor lectins from rainforest tree root transcriptomes

text: Glycans are multi-branched sugars that are displayed from lipids and proteins. Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival. Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy. Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death. This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence. Remarkably, ML6 displays antitumor activity that is >10(5) times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells. This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors. Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies. Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.


title: Emerging Practice Patterns in Vascular Surgery During the COVID-19 Pandemic

text: OBJECTIVE: Ever since the first positive test was identified on January 21, 2020, Washington State has been on the frontlines of the COVID-19 pandemic. Based on information obtained from Italian surgeons in Milan and given concerns regarding rising case numbers in Washington state, we implemented new vascular surgery guidelines, which canceled all non-emergent surgical procedures and involved significant changes to our inpatient and outpatient workflow. The consequences of these decisions are not yet understood. METHODS: The division of vascular surgery at Harborview Medical Center immediately instituted new vascular surgery COVID-19 practice guidelines on March 17, 2020. Subsequent clinic, operative, and consult volume was collected over the next 4 weeks and compared to historical averages. Washington state case/death numbers and UW Medicine hospital case volumes were collected from publicly available sources. RESULTS: Since March 10, 2020, the number of confirmed positive COVID-19 cases within the UW Medicine system has increased 1867%, with floor and intensive care unit bed utilization increasing by 120% and 215%, respectively. After instituting our new COVID-19 guidelines, our average weekly clinical volume decreased by 96.5% (43.1 patients to 1.5 per week), our average weekly surgical volume decreased by 71.7% (from 15 cases to 4.25 per week), and our inpatient consultation volume decreased to 1.81 consults per day. 60% of consultations were completed as telemedicine “e-consults” in which the patient was never evaluated in-person. Trainee surgical volume has also decreased by 86.4% for the vascular surgery fellow and 84.8% for the integrated resident. CONCLUSIONS: The COVID-19 pandemic has changed every aspect of “normal” vascular surgical practice in a large academic institution. New practice guidelines effectively reduced operating room utilization and decreased staff and trainee exposure to potential infection, with changes to clinic volume not resulting in an immediate rise in emergency department/inpatient consultations or acute surgical emergencies. These changes, although preserving resources, are also reducing trainee exposure and operative volume significantly, which requires new modes of education delivery. Lessons learned during the COVID-19 pandemic, if analyzed, will help us prepare for the next crisis.


title: Medical students’ preference for returning to the clinical setting during the COVID‐19 pandemic

text: OBJECTIVES: The Covid‐19 pandemic has led to widespread disruptions in the clinical education of medical students. In managing students’ return to the clinical setting, medical schools face the challenge of balancing education, service, and risk considerations. To compound this challenge, medical students may prefer not to re‐enter during a period of great uncertainty, leading to substantive downstream sequelae on individual, institutional, and national levels. Understanding students’ views on resuming clinical experiences, therefore, is an important consideration. The purpose of this study was to assess medical students’ preference for re‐entering the clinical setting during a pandemic, and to explore personal and environmental characteristics associated with that preference. METHODS: We conducted an electronic survey of currently enrolled medical students of Duke‐NUS Medical School in Singapore, less than a month into the pandemic. Survey items were aligned with a conceptual framework related to medical students’ preference for returning to the clinical setting. The framework consisted of three domains: 1) non‐modifiable demographic information, 2) factors thought to be modifiable through the course of medical education, including burnout, tolerance for ambiguity, motivation, and professionalism, and 3) students’ perception of Covid‐19 infection risk to self. RESULTS: Approximately one third of 179 students preferred not to return to the clinical setting. Results of a multivariable analysis indicated that compared to this group, the two‐thirds of students favouring return showed evidence of greater autonomous (or internal) motivation, a greater sense of professional responsibility, and a lower self‐perception of harbouring risk to patients. CONCLUSIONS: Students’ preference regarding return to the clinical environment stems from the interplay of several key factors, and is substantively associated with perceptions of professional responsibility and their own potential risk to the healthcare system. Mindfully considering and addressing these issues may help medical schools in their preparation for returning students to the clinical setting.


title: Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring

text: A library of phosphonic acid analogs of phenylalanine substituted with fluorine, chlorine and trifluoromethyl moieties on the aromatic ring was synthesized and evaluated for inhibitory activity against human (hAPN) and porcine (pAPN) aminopeptidases. Fluorogenic screening indicated that these analogs are micromolar or submicromolar inhibitors, both enzymes being more active against hAPN. In order to better understand the mode of the action of the most active compounds, molecular modeling was used. It confirmed that aminophosphonic portion of the enzyme is bound nearly identically in the case of all the studied compounds, whereas the difference in activity results from the placement of aromatic side chain of an inhibitor. Interestingly, both enantiomers of the individual compounds are usually bound quite similarly.


title: Characterization of an Immunodominant Epitope in the Endodomain of the Coronavirus Membrane Protein

text: The coronavirus membrane (M) protein acts as a dominant immunogen and is a major player in virus assembly. In this study, we prepared two monoclonal antibodies (mAbs; 1C3 and 4C7) directed against the transmissible gastroenteritis virus (TGEV) M protein. The 1C3 and 4C7 mAbs both reacted with the native TGEV M protein in western blotting and immunofluorescence (IFA) assays. Two linear epitopes, 243YSTEART249 (1C3) and 243YSTEARTDNLSEQEKLLHMV262 (4C7), were identified in the endodomain of the TGEV M protein. The 1C3 mAb can be used for the detection of the TGEV M protein in different assays. An IFA method for the detection of TGEV M protein was optimized using mAb 1C3. Furthermore, the ability of the epitope identified in this study to stimulate antibody production was also evaluated. An immunodominant epitope in the TGEV membrane protein endodomain was identified. The results of this study have implications for further research on TGEV replication.


title: A 'fly-by' killing with a primordial cellular weapon

text: Autophagy has been suggested—on the basis of in vitro studies—to be involved in defense against bacterial challenge. A study in drosophila now shows the importance of autophagy in vivo and links a pattern recognition receptor to the autophagy pathway.


title: Etiology, seasonality, and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon

text: Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital, and to correlate disease severity and the presence of virus. Over a 1‐year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16‐year old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real‐time RT‐PCR. Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co‐infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%), and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom. This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. J. Med. Virol. 88:1874–1881, 2016. © 2016 Wiley Periodicals, Inc.


title: Disease Transmission and Networks

text: While epidemiological models have traditionally assumed that diseases spread by the mass action principle, actual contact networks within social groups do not meet this assumption. Theoretical models have shown that disease dynamics could vary considerably under different types of contact networks, but these models face challenges in terms of their evaluation due to the difficulty of collecting empirical data. The honeybee colony with its elaborate social organization and large repertoire of diseases provides an ideal setting to explore how the structure of the contact network contributes to the transmission of a disease.


title: The Role of Internists During Epidemics, Outbreaks, and Bioterrorist Attacks

text: Internists are well-positioned to play significant roles in recognizing and responding to epidemics, outbreaks, and bioterrorist attacks. They see large numbers of patients with various health problems and may be the patients’ only interaction with the medical community for symptoms resulting from infectious diseases and injuries from radiation, chemicals, and/or burns. Therefore, Internists must understand early warning signs of different bioterrorist and infectious agents, proper reporting channels and measures, various ways that they can assist the public health response, and roles of different local, state, and federal agencies. In addition, it is important to understand effects of a public health disaster on clinic operations and relevant legal consequences.


title: COVID-19: A case report from Bangladesh perspective

text: Abstract A 34-year-old man without any significant medical history or comorbidities, suddenly developed fever, and shortness of breath, thereby admitted to the emergency department of a tertiary care hospital, Dhaka, Bangladesh. He had neither a history of traveling to Coronavirus disease (COVID) prone areas nor a direct contact of COVID positive patients. His chest X-ray revealed ground-glass opacity in the right middle and lower zone of the lung. The first polymerase chain reaction (PCR) test on throat and nasal swabs for the COVID upon admission was negative. Based on the chest X-ray result, RT-PCR was done again resulted positive. The patient was primarily treated with chloroquine and azithromycin. On full recovery, he was discharged from the hospital on day 12, after two subsequent throat swab samples tested negative by PCR (24 hours apart). He was encouraged to maintain home quarantine for at least the next 14 days. SARS-CoV-2 RNA by swab remained negative and the blood sample shows the presence of antibody (both IgM and IgG) in his follow-up visit (after 7 days of hospital discharge).


Fatal lower respiratory tract disease with human corona virus NL63 in an adult haematopoietic cell transplant recipient


title: Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

text: The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction.


title: Chapter 24 Nanosensor networks for health-care applications

text: Abstract Functionalized transistors provide effective sensors for a variety of viruses (Zika, severe acute respiratory syndrome), toxins (botulinum), cancers (breast and prostate), and disease or injury biomarkers (troponin, cerebrospinal fluid). A hallmark of this approach is high specificity, rapid response (<5minutes), and ability to be integrated with wireless data transmission capabilities. The ultimate goal is hand-held point-of-care detection that can streamline patient diagnosis.


title: An Investigation of the Effect of COVID-19 on OCD in Youth in the Context of Emotional Reactivity, Experiential Avoidance, Depression and Anxiety

text: In addition to the serious physical and medical effects on individuals, the COVID-19 pandemic is likely to have short- and long-term psycho-social consequences, especially for young people. Nowadays, with psychological problems becoming more widely recognized in adolescents, it is possible that the fear and anxiety caused by the pandemic will trigger various anxiety disorders, OCD and similar negative outcomes. Considering that psychological qualities such as emotional reactivity and experiential avoidance observed in adolescents may increase the risk of such psycho-social disorders, in this study the relationship between fear of COVID-19 and OCD was investigated in a Turkish sample of 598 adolescents, and the mediating role of emotional reactivity, experiential avoidance and depression-anxiety in this relationship was examined. The data collection was performed online rather than in person because of the COVID-19 threat. A structural equation model was used to determine the direct and indirect predictive effects between variables in data analysis. The results of the study show that the effect of COVID-19 fear on OCD is mediated by emotional reactivity, experiential avoidance and depression-anxiety. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11469-020-00322-z) contains supplementary material, which is available to authorized users.


title: A Multidimensional Model of Public Health Approaches Against COVID-19

text: COVID-19 is appearing as one of the most fetal disease of the world’s history and has caused a global health emergency. Therefore, this study was designed with the aim to address the issue of public response against COVID-19. The literature lacks studies on social aspects of COVID-19. Therefore, the current study is an attempt to investigate its social aspects and suggest a theoretical structural equation model to examine the associations between social media exposure, awareness, and information exchange and preventive behavior and to determine the indirect as well as direct impact of social media exposure on preventive behavior from the viewpoints of awareness and information exchange. The current empirical investigation was held in Pakistan, and the collected survey data from 500 respondents through social media tools were utilized to examine the associations between studied variables as stated in the anticipated study model. The findings of the study indicate that social media exposure has no significant and direct effect on preventive behavior. Social media exposure influences preventive behavior indirectly through awareness and information exchange. In addition, awareness and information exchange have significant and direct effects on preventive behavior. Findings are valuable for health administrators, governments, policymakers, and social scientists, specifically for individuals whose situations are like those in Pakistan. This research validates how social media exposure indirectly effects preventive behavior concerning COVID-19 and explains the paths of effect through awareness or information exchange. To the best of our knowledge, there is no work at present that covers this gap, for this reason the authors propose a new model. The conceptual model offers valuable information for policymakers and practitioners to enhance preventive behavior through the adoption of appropriate awareness strategies and information exchange and social media strategies.


Shared Ventilation: Toward Safer Ventilator Splitting in Resource Emergencies


COVID‐19 and impact of personal protective equipment use: From occupational to generalized skin care need


title: Risk Factors for Viral RNA Shedding in COVID-19 Patients

text: The median time from symptoms onset to viral RNA shedding was 19 days. Patients with CHD comorbidity or decreased albumin levels experienced delays in clearance of SARS-CoV-2 RNA.


title: Exploring the epidemic transmission network of SARS in-out flow in mainland China

text: The changing spatiotemporal patterns of the individual susceptible-infected-symptomatic-treated-recovered epidemic process and the interactions of information/material flows between regions, along with the 2002–2003 Severe Acute Respiratory Syndrome (SARS) epidemiological investigation data in mainland China, including three typical locations of individuals (working unit/home address, onset location and reporting unit), are used to define the in-out flow of the SARS epidemic spread. Moreover, the input/output transmission networks of the SARS epidemic are built according to the definition of in-out flow. The spatiotemporal distribution of the SARS in-out flow, spatial distribution and temporal change of node characteristic parameters, and the structural characteristics of the SARS transmission networks are comprehensively and systematically explored. The results show that (1) Beijing and Guangdong had the highest risk of self-spread and output cases, and prevention/control measures directed toward self-spread cases in Beijing should have focused on the later period of the SARS epidemic; (2) the SARS transmission networks in mainland China had significant clustering characteristics, with two clustering areas of output cases centered in Beijing and Guangdong; (3) Guangdong was the original source of the SARS epidemic, and while the infected cases of most other provinces occurred mainly during the early period, there was no significant spread to the surrounding provinces; in contrast, although the input/output interactions between Beijing and the other provinces countrywide began during the mid-late epidemic period, SARS in Beijing showed a significant capacity for spatial spreading; (4) Guangdong had a significant range of spatial spreading throughout the entire epidemic period, while Beijing and its surrounding provinces formed a separate, significant range of high-risk spreading during the mid-late period; especially in late period, the influence range of Beijing’s neighboring provinces, such as Hebei, was even slightly larger than that of Beijing; and (5) the input network had a low-intensity spread capacity and middle-level influence range, while the output network had an extensive high-intensity spread capacity and influence range that covered almost the entire country, and this spread and influence indicated that significant clustering characteristics increased gradually. This analysis of the epidemic in-out flow and its corresponding transmission network helps reveal the potential spatiotemporal characteristics and evolvement mechanism of the SARS epidemic and provides more effective theoretical support for prevention and control measures.


title: Prophylactic negative pressure wound therapy for closed laparotomy wounds: a systematic review and meta-analysis of randomised controlled trials

text: Surgical site infections are a common source of post-operative morbidity and contribute significantly to healthcare costs. Patients undergoing emergency laparotomy and/or bowel surgery are particularly at risk. Prophylactic negative pressure wound therapy (NPWT) has been shown to reduce wound infection. However, to date, there has been a lack of consensus around its use for closed laparotomy wounds. We conducted a systematic review of randomised controlled trials comparing the use of prophylactic negative pressure wound therapy with standard dressings for closed laparotomy incisions. The primary outcome was incidence of incisional surgical site infection (SSI) at 30 days post-operatively. Secondary outcomes included superficial and deep SSI, skin dehiscence, fascial dehiscence and length of stay. A total of 2182 publications were identified, of which, following review of titles, abstracts and full texts, five studies met the criteria for inclusion. Across these studies, 467 patients were randomised to NPWT and 464 to standard dressings. Overall SSI rate was 18.6% (n = 87/467) versus 23.9% (n = 111/464) in the NPWT and standard dressing groups, respectively (Odds ratio 0.71, 95% CI 0.52–0.99, p = 0.04*). Deep SSI incidence was the same in both groups (2.6%). Both skin dehiscence and fascial dehiscence were slightly higher in the standard dressing group ((4.2%, n = 11/263 versus 3.1% (n = 8/261) and (0.9% (n = 3/324) versus 0.6% (n = 2/323)), respectively. This study observed that NPWT reduces the overall SSI for closed laparotomy wounds. It supports data recommending the use of prophylactic NPWT dressings, especially in high-risk patients in both emergency and elective circumstances.


title: Investigation of a Potential Zoonotic Transmission of Orthoreovirus Associated with Acute Influenza-Like Illness in an Adult Patient

text: Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.


title: The Covid-19 pandemic in Denmark: Big lessons from a small country

text: Abstract Denmark, a Scandinavian country of 5.8 million people has weathered the Covid-19 crisis with a relatively low rate of infection and death. Denmark has also become one of the first European countries to partially re-open its society. We offer the perspective that the combination of rapid response from the government, trust and a high level of confidence in government by Danish citizens, and the importance of social heritage contributed to the effective management of the coronavirus crisis.


Environmental chemistry is most relevant to study coronavirus pandemics


title: Comparative metrics of neurosurgical scientific journals: What do they mean to readers?

text: BACKGROUND: In regard to scientific information, are we effectively reaching the universe of physicians in the 21st century, all of whom have different backgrounds, practice environments, educational experiences, and varying degrees of research knowledge? METHODS: A comparison of the top nine neurosurgery journals based on various popular citation indices and also on the digital metric, Readers (Users)/month, was compiled from available metrics and from internet sources. RESULTS: Major differences in the ranking of the Readers (Users)/month metrics compared to ranking of the various citation indices were found. It is obvious that the citation indices do not measure the number of readers of a publication. Which metric should be used in judging the value of a scientific paper? The answer to that question relates to what the interest of the reader has in the scientific information. It appears that the academic scientist may have a different reason for reading a scientific publication than a physician caring for a patient. CONCLUSIONS: There needs to be more than one type of metric that measures the value and “Impact” of a scientific paper based on how physicians learn.


title: Viruses in bats and potential spillover to animals and humans

text: In the last two decades, several high impact zoonotic disease outbreaks have been linked to bat-borne viruses. These include SARS coronavirus, Hendra virus and Nipah virus. In addition, it has been suspected that ebolaviruses and MERS coronavirus are also linked to bats. It is being increasingly accepted that bats are potential reservoirs of a large number of known and unknown viruses, many of which could spillover into animal and human populations. However, our knowledge into basic bat biology and immunology is very limited and we have little understanding of major factors contributing to the risk of bat virus spillover events. Here we provide a brief review of the latest findings in bat viruses and their potential risk of cross-species transmission.


title: Anti-inflammatory activity of electron-deficient organometallics

text: We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η(6)-p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η(5)-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (3), [Os/Ru(η(6)-p-cymene)(benzene-1,2-dithiolato)] (4/5) and [Ir(η(5)-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action.


title: Epitope mapping by random peptide phage display reveals essential residues for vaccinia extracellular enveloped virion spread

text: BACKGROUND: A33 is a type II integral membrane protein expressed on the extracellular enveloped form of vaccinia virus (VACV). Passive transfer of A33-directed monoclonal antibodies or vaccination with an A33 subunit vaccine confers protection against lethal poxvirus challenge in animal models. Homologs of A33 are highly conserved among members of the Orthopoxvirus genus and are potential candidates for inclusion in vaccines or assays targeting extracellular enveloped virus activity. One monoclonal antibody directed against VACV A33, MAb-1G10, has been shown to target a conformation-dependent epitope. Interestingly, while it recognizes VACV A33 as well as the corresponding variola homolog, it does not bind to the monkeypox homolog. In this study, we utilized a random phage display library to investigate the epitope recognized by MAb-1G10 that is critical for facilitating cell-to-cell spread of the vaccinia virus. RESULTS: By screening with linear or conformational random phage libraries, we found that phages binding to MAb-1G10 display the consensus motif CEPLC, with a disulfide bond formed between two cysteine residues required for MAb-1G10 binding. Although the phage motif contained no linear sequences homologous to VACV A33, structure modeling and analysis suggested that residue D115 is important to form the minimal epitope core. A panel of point mutants expressing the ectodomain of A33 protein was generated and analyzed by either binding assays such as ELISA and immunoprecipitation or a functional assessment by blocking MAb-1G10 mediated comet inhibition in cell culture. CONCLUSIONS: These results confirm L118 as a component of the MAb-1G10 binding epitope, and further identify D115 as an essential residue. By defining the minimum conformational structure, as well as the conformational arrangement of a short peptide sequence recognized by MAb-1G10, these results introduce the possibility of designing small molecule mimetics that may interfere with the function of A33 in vivo. This information will also be useful for designing improved assays to evaluate the potency of monoclonal and polyclonal products that target A33 or A33-modulated EV dissemination.


title: Case of Hemorrhagic Cardiac Tamponade in a Patient with COVID-19 Infection

text: • There are protean manifestations of cardiac involvement with COVID 19; • Hemorrhagic pericardial effusion may be the sole cardiac manifestation of COVID 19.


title: Deceiving SARS-CoV-2 molecular-tropism clues – A combinational contemporary strategy

text: Several attempts to control the dreadfulness of SARS-CoV-2 are still underway. Based on the literature evidences we have speculated a prospective contemporary remedy, which was categorized into Specificity, Remedy, and a Conveyor. In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 from prepone targets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificial surfactant system as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery. Overall we postulate focused insights by employing a combinational contemporary strategy to steer towards a prospective direction on combating SARS-CoV-2.


title: IL‐35: A potential therapeutic target for controlling hepatitis B virus infection

text: Interleukin (IL)‐35, a recently identified cytokine of the IL‐12 family, is a potent immunosuppressive cytokine secreted by regulatory T (Treg) cells and the newly reported regulatory B (Breg) cells. IL‐35 functions as a crucial immunosuppressive factor in immune‐mediated diseases, and the predominant mechanism of suppression is its ability to suppress T cell proliferation and effector functions. The pathogenic processes of the non‐cytopathic hepatitis B virus (HBV) infection‐related liver diseases are immune‐mediated, including liver damage and viral control. It has been found that IL‐35 is detectable in peripheral CD4(+) T cells in chronic HBV‐infected patients, whereas it is undetectable in healthy individuals. There is growing evidence that cytokine‐mediated immune responses play a pivotal role in determining the clinical outcome during HBV infection. It is particularly important to investigate the effects of IL‐35 in the immunopathogenesis of chronic HBV infection. In this study, the recent understanding of this issue is discussed.


title: Do COVID-19 Conspiracy Theory Beliefs Form a Monological Belief System?

text: Along with criticisms of the U.S. government's response to the COVID-19 pandemic, the disruptions to home, work, and school life resulting from social distancing orders recommended by public health experts, as well as the uncertainty about how long the disruptions will be necessary and when (if ever) we will have a vaccine, have come COVID-19 conspiracy theories (CTs).


title: The aging lung

text: There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.


title: Definitive diagnosis in suspected Middle East Respiratory Syndrome Coronavirus cases

text: We evaluated the microbiological diagnosis in 14 patients with epidemiological and clinical suspicion of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) attended in a non-endemic area between June 2015 and January 2017. While no MERS-CoV was detected, other respiratory viruses were identified in 12 cases and Mycoplasma pneumoniae in 1 case.


title: Statistical Explorations and Univariate Timeseries Analysis on COVID-19 Datasets to Understand the Trend of Disease Spreading and Death

text: “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, the novel coronavirus, is responsible for the ongoing worldwide pandemic. “World Health Organization (WHO)” assigned an “International Classification of Diseases (ICD)” code—“COVID-19”-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with “Middle East Respiratory Syndrome (MERS-CoV)”, “Severe Acute Respiratory Syndrome (SARS-CoV)”, and now with this new virus, namely “SARS-CoV-2”, or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a “spread factor (f)”, and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in “ourworldindata.org (Oxford University database)”, and newly simulated datasets, following the analysis of different univariate “Long Short Term Memory (LSTM)” models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months—January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.


title: Synthesis of β-amino-α-trifluoromethyl alcohols and their applications in organic synthesis

text: Abstract A comprehensive overview on methods applied for syntheses of β-amino-α-trifluoromethyl alcohols, including stereocontrolled variants, is presented. In addition, reported cases of the exploration of β-amino-α-trifluoromethyl alcohols for the preparation of trifluoromethylated peptidomimetics and other biologically active, fluorinated compounds are discussed. Attractive opportunities for their applications as organocatalysts are also presented.


title: Service-learning in response to the coronavirus disease 2019 pandemic: Emerging lessons from the Department of Family Medicine and Public Health at the University of Botswana

text: The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted many lives worldwide. Training programmes in academic institutions have also been affected by the pandemic. Teaching and learning family medicine and public health medicine in the COVID-19 era require adjustments to training activities. At the University of Botswana, the pandemic presented an opportunity to steer training programmes in the Department of Family Medicine and Public Health Medicine more towards service-learning. The department collaborated with the Ministry of Health and Wellness as well as the District Health Management teams in the national response to the pandemic as essential service providers. The increased demands for service provision were balanced with educational opportunities for trainees during the COVID-19 public health emergency. Including structured ongoing reflections for trainees involved in the COVID-19 response helps to connect service and the academic curriculum. KEYWORDS: COVID-19; coronavirus; service-learning; pandemic; Botswana.


title: Kawasaki disease: a matter of innate immunity

text: Kawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person‐to‐person and does not occur in clusters within households, schools or nurseries. KD is a self‐limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen‐associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD‐specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe‐associated molecular patterns (MAMPs), as shown by liquid chromatography‐tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe‐derived innate immune stimulants and that it is not a typical infectious disease.


title: Inhibition of norovirus replication by morpholino oligomers targeting the 5′-end of the genome

text: Noroviruses are an important cause of non-bacterial epidemic gastroenteritis, but no specific antiviral therapies are available. We investigated the inhibitory effect of phosphorodiamidiate morpholino oligomers (PMOs) targeted against norovirus sequences. A panel of peptide-conjugated PMOs (PPMOs) specific for the murine norovirus (MNV) genome was developed, and two PPMO compounds directed against the first AUG of the ORF1 coding sequence near the 5′-end of the genome proved effective in inhibiting MNV replication in cells. A consensus PPMO (designated Noro 1.1), designed to target the corresponding region of several diverse human norovirus genotypes, decreased the efficiency of protein translation in a cell-free luciferase reporter assay and inhibited Norwalk virus protein expression in replicon-bearing cells. Our data suggest that PPMOs directed against the relatively conserved 5′-end of the norovirus genome may show broad antiviral activity against this genetically diverse group of viruses.


title: mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3

text: Rapamycin and its derivatives are specific inhibitors of mammalian target of rapamycin (mTOR) kinase and, as a result, are well-established immunosuppressants and antitumorigenic agents. Additionally, this class of drug promotes gene delivery by facilitating lentiviral vector entry into cells, revealing its potential to improve gene therapy efforts. However, the precise mechanism was unknown. Here, we report that mTOR inhibitor treatment results in down-regulation of the IFN-induced transmembrane (IFITM) proteins. IFITM proteins, especially IFITM3, are potent inhibitors of virus–cell fusion and are broadly active against a range of pathogenic viruses. We found that the effect of rapamycin treatment on lentiviral transduction is diminished upon IFITM silencing or knockout in primary and transformed cells, and the extent of transduction enhancement depends on basal expression of IFITM proteins, with a major contribution from IFITM3. The effect of rapamycin treatment on IFITM3 manifests at the level of protein, but not mRNA, and is selective, as many other endosome-associated transmembrane proteins are unaffected. Rapamycin-mediated degradation of IFITM3 requires endosomal trafficking, ubiquitination, endosomal sorting complex required for transport (ESCRT) machinery, and lysosomal acidification. Since IFITM proteins exhibit broad antiviral activity, we show that mTOR inhibition also promotes infection by another IFITM-sensitive virus, Influenza A virus, but not infection by Sendai virus, which is IFITM-resistant. Our results identify the molecular basis by which mTOR inhibitors enhance virus entry into cells and reveal a previously unrecognized immunosuppressive feature of these clinically important drugs. In addition, this study uncovers a functional convergence between the mTOR pathway and IFITM proteins at endolysosomal membranes.


Biocontrol risks


Detection and Monitoring of SARS Coronavirus in the Plasma and Peripheral Blood Lymphocytes of Patients with Severe Acute Respiratory Syndrome


title: Chapter 7 Diseases of the ear

text: Abstract In children with normal hearing, inflammatory disorders caused by infections of the middle ear (otitis media) are the most common ear illnesses. Many of older adults experience some level of hearing loss. Several factors can lead to either a partial loss or the total inability to hear (deafness) including exposure to noise, a hereditary predisposition, chronic infections, traumas, medications, and aging.


title: Assessment of the quality of systematic reviews on COVID‐19: A comparative study of previous coronavirus outbreaks

text: Several systematic reviews (SRs) have been conducted on the COVID‐19 outbreak, which together with the SRs on previous coronavirus outbreaks, form important sources of evidence for clinical decision and policy making. Here, we investigated the methodological quality of SRs on COVID‐19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Online searches were performed to obtain SRs on COVID‐19, SARS, and MERS. The methodological quality of the included SRs was assessed using the AMSTAR‐2 tool. Descriptive statistics were used to present the data. In total, of 49 SRs that were finally included in our study, 17, 16, and 16 SRs were specifically on COVID‐19, MERS, and SARS, respectively. The growth rate of SRs on COVID‐19 was the highest (4.54/month) presently. Of the included SRs, 6, 12, and 31 SRs were of moderate, low, and critically low quality, respectively. SRs on SARS showed the optimum quality among the SRs on the three diseases. Subgroup analyses showed that the SR topic (P < .001), the involvement of a methodologist (P < .001), and funding support (P = .046) were significantly associated with the methodological quality of the SR. According to the adherence scores, adherence to AMSTAR‐2 items sequentially decreased in SRs on SARS, MERS, and COVID‐19. The methodological quality of most SRs on coronavirus outbreaks is unsatisfactory, and those on COVID‐19 have higher risks of poor quality, despite the rapid actions taken to conduct SRs. The quality of SRs should be improved in the future. Readers must exercise caution in accepting and using the results of these SRs.


title: Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

text: BACKGROUND: Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH(2)-terminal kinase (JNK) METHODS: Human bronchial epithelial cells (BEAS-2B) or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. RESULTS: S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1). We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser(63/73)-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. CONCLUSION: S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun to the il8 promoter.


title: Coexistence of multiple genotypes of porcine epidemic diarrhea virus with novel mutant S genes in the Hubei Province of China in 2016

text: The emergence of highly virulent porcine epidemic diarrhea virus (PEDV) variants in China caused huge economic losses in 2010. Since then, large-scale sporadic outbreaks of PED caused by PEDV variants have occasionally occurred in China. However, the molecular diversity and epidemiology of PEDV in different provinces has not been completely understood. To determine the molecular diversity of PEDV in the Hubei Province of China, we collected 172 PED samples from 34 farms across the province in 2016 and performed reverse transcription polymerase chain reaction (RT-PCR) by targeting the nucleocapsid (N) gene. Seventy-four samples were found to be PEDV-positive. We further characterized the complete spike (S) glycoprotein genes from the positive samples and found 21 different S genes with amino acid mutations. The PEDV isolates here presented most of the genotypes which were found previously in field isolates in East and South-East Asia, North America, and Europe. Besides the typical Genotypes I and II, the INDEX groups were also found. Importantly, 58 new amino acids mutant sites in the S genes, including 44 sites in S1 and 14 sites in S2, were first described. Our results revealed that the S genes of PEDV showed variation and that diverse genotypes of PEDV coexisted and were responsible for the PED outbreaks in Hubei in 2016. This work highlighted the complexity of the epidemiology of PEDV and emphasized the need for reassessing the efficacy of classic PEDV vaccines against emerging variant strains and developing new vaccines to facilitate the prevention and control of PEDV in fields. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-017-4021-8 and is accessible for authorized users.


title: COVID‐19 breakthroughs: separating fact from fiction

text: The newly recognised coronavirus SARS‐CoV‐2, causative agent of COVID‐19, has caused a pandemic with huge ramifications for human interactions around the globe. As expected, research efforts to understand the virus and curtail the disease are moving at a frantic pace alongside the spread of rumours, speculations and falsehoods. In this article, we aim to clarify the current scientific view behind several claims or controversies related to COVID‐19. Starting with the origin of the virus, we then discuss the effect of ibuprofen and nicotine on the severity of the disease. We highlight the knowledge on fomites and SARS‐CoV‐2 and discuss the evidence and explications for a disproportionately stronger impact of COVID‐19 on ethnic minorities, including a potential protective role for vitamin D. We further review what is known about the effects of SARS‐CoV‐2 infection in children, including their role in transmission of the disease, and conclude with the science on different mortality rates between different countries and whether this hints at the existence of more pathogenic cohorts of SARS‐CoV‐2.


title: Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2′.


title: Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes

text: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.


title: Characterization of divergent and atypical canine coronaviruses from Sweden

text: Field canine coronaviruses (CCVs) identified during a series of outbreaks of gastroenteritis in Swedish dogs were subjected to genetic analysis involving the open reading frame 1b (ORF1b) and the membrane (M) and spike (S) protein genes. Four field viruses originating from the Stockholm region presented identical sequences and segregated separately from other CCVs characterized so far and from GOT/05, the variant recovered in Western Sweden. A recombinant origin of the fifth virus identified in the Stockholm region is suggested. In addition, the five viruses originating from the same geographical area displayed atypical 5′ S gene sequences.


On the crucial role of multilingual biomedical databases on epidemic events (SARS-CoV-2 analysis)


title: Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals

text: IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires. DOI: http://dx.doi.org/10.7554/eLife.14228.001


title: Veterans’ Response to an Automated Text Messaging Protocol During the COVID-19 Pandemic

text: The US Department of Veterans Affairs (VA) is using an automated short message service (SMS) application named ‘Annie’ as part of their COVID-19 response with a protocol for coronavirus precautions, which can help the Veteran monitor symptoms and can advise the Veteran when to contact their VA care team or a nurse triage line. We surveyed 1,134 Veterans on their use of the Annie application and coronavirus precautions protocol. Survey results support what is likely a substantial resource savings for the VA, as well as non-VA community healthcare. Moreover, the majority of Veterans reported at least one positive sentiment (felt more connected to VA, confident, or educated and/or felt less anxious) by receiving the protocol messages. The findings from this study have implications for other healthcare systems to help manage a patient population during the coronavirus pandemic.


title: Nipah virus: Impact, origins, and causes of emergence

text: Nipah virus is an emerging zoonotic pathogen that causes severe febrile encephalitis resulting in death in 40% to 75% of human cases. Nipah virus is considered a biosafety level-4 pathogen and is listed as a select agent with high risk for public health and security due to its high mortality rate in people and the lack of effective vaccines or therapies. The natural reservoir for Nipah virus and related members of the genus Henipavirus are fruit bats of the genus Pteropus. Nipah virus emerged in Malaysia in 1998 as a porcine neurologic and respiratory disease that spread to humans who had contact with live, infected pigs. Research reviewed in this paper suggests that anthropogenic factors, including agricultural expansion and intensification, were the underlying causes of its emergence. Nipah virus has caused five subsequent outbreaks between 2001 and 2005 in Bangladesh. Here, it appears to have spilled over directly from bats to humans, and person-to-person transmission is evident suggesting a heightened public health risk.


title: Human SCARB2-Mediated Entry and Endocytosis of EV71

text: Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus.


On the usefulness of point-of-care antibody tests for SARS-CoV-2 in community screening settings


title: Unrealistic Optimism in the Time of Coronavirus Pandemic: May It Help to Kill, If So—Whom: Disease or the Person?

text: Objective: The results of numerous empirical studies have showed the occurrence of so-called unrealistic optimism. Thus, we aimed to investigate whether in the situation of an imminent coronavirus pandemic, people would still perceive themselves as being less exposed to the disease than others. Methods: Survey studies were conducted to examine the level of unrealistic optimism. Participants (n = 171, 67.3% of women) in a subjective way judged the risk of their coronavirus infection and the likelihood that this would happen to an average student of the same sex from their class. The survey was conducted in three waves: prior to the announcement of the first case of coronavirus (2–3 March), immediately after that announcement (5–6 March), and a few days later (9–10 March). Results: We showed that women estimated the chances of being infected as significantly higher (M = 4.52, SD = 2.079; t = 2.387; p = 0.018; Cohen’s d = 0.393) than men (M = 3.71, SD = 2.042). The phenomenon of unrealistic optimism was observed especially in men (as compared to other male participants) as it appeared in all three measures (M (you) = 3.95 vs. M (other male student) = 4.63; M = 3.71 vs. M = 4.68, and M = 4.46 vs. M = 5.38 in phase one, two, and three, respectively; p ≤ 0.006 for all comparison), but also in women in the last two measures (M (you) = 4.55 vs. M (other female student) = 4.95, and M = 4.99 vs. M = 5.38 in phase 2 and 3, respectively; p ≤ 0.012 for both comparisons). Conclusions: The study revealed a fairly general occurrence of unrealistic optimism, which was mainly observed in men as it appeared in all three measures, but also in women in the last two measures. This result is important for health experts who are responsible for making people comply with regulations concerning social distancing, putting masks on to stop infection, and staying at home. It is possible that unrealistically optimistic people will behave much less in line with the aforementioned recommendations, causing coronavirus to spread widely.


title: Human herpesvirus 6 and multiple sclerosis: A study of t cell cross‐reactivity to viral and myelin basic protein antigens

text: Several reports have suggested an association of human herpesvirus 6 (HHV‐6) with multiple sclerosis. Autoreactive T lymphocytes directed against myelin components seem to contribute to the pathogenesis of the disease. It has been suggested that molecular mimicry between viral and self‐antigens might be one of the mechanisms that determine the onset of several autoimmune diseases. Following this hypothesis, the purpose of the present study was to evaluate if HHV‐6 could play a role in activating T cells capable of cross‐reaction with an important myelin component, the myelin basic protein. T cell lines were established from 22 multiple sclerosis patients and from 16 healthy controls, and their capability to react to both virus and myelin basic protein antigens was compared. The analysis of T cell cross‐reactivity in patients and controls did not show significant differences in the HHV‐6 ability to activate myelin basic protein‐reactive T cells. Similarly, the evaluation of the humoral immune response to HHV‐6 in patients and controls did not mirror any abnormality in the HHV‐6 status in multiple sclerosis patients. Therefore, although the findings of activity in vitro of T cell lines with dual specificity are consistent with the hypothesis of molecular mimicry, the lack of differences in cross‐reactivity between patients and controls do not support molecular mimicry as an important mechanism in the physiopathology of this disease. J. Med. Virol. 68: 268–272, 2002. © 2002 Wiley‐Liss, Inc.


title: Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation

text: The COVID‐19 coronavirus is now spreading worldwide. Its pathogen, SARS‐CoV‐2, has been shown to use angiotensin‐converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS‐CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age‐dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. A shockingly common enrichment of viral infection pathways was found among ACE2 anti‐expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID‐19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.


title: Reply to Comments on 'Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China’

text: Coronovirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronovirus 2 (SARS‐CoV‐2) infection has been ranging in China throughout the world now. The World Health Organiztion declared the COVID‐19 crisis a global pandemic. The previous our case of co‐infection of SARS‐CoV‐2 and HIV has raised the interests of the HIV research community(1). This article is protected by copyright. All rights reserved.


title: Alliances for scientific success

text: The diverse histories of China's cities strongly influence their collaboration patterns.


Progressive CT findings and positive RT-PCR again of recovered and discharged patients with COVID-19