Transmissible Gastroenteritis Virus: An Update Review and Perspective.

Transmissible gastroenteritis virus (TGEV) is a member of the alphacoronavirus genus, which has caused huge threats and losses to pig husbandry with a 100% mortality in infected piglets. TGEV is observed to be recombining and evolving unstoppably in recent years, with some of these recombinant strains spreading across species, which makes the detection and prevention of TGEV more complex. This paper reviews and discusses the basic biological properties of TGEV, factors affecting virulence, viral receptors, and the latest research advances in TGEV infection-induced apoptosis and autophagy to improve understanding of the current status of TGEV and related research processes. We also highlight a possible risk of TGEV being zoonotic, which could be evidenced by the detection of CCoV-HuPn-2018 in humans.

Mediating effect of resilience between social support and compassion fatigue among intern nursing and midwifery students during COVID-19: a cross-sectional study.

AIMS: To examine the mediating effect of resilience between social support and compassion fatigue among intern nursing and midwifery students during COVID-19. BACKGROUND: Compassion fatigue has become exceedingly common among intern nursing and midwifery students, especially during the COVID-19 pandemic. Social support and resilience can help intern nursing and midwifery students control their negative emotions, reduce compassion fatigue, and increase their well-being. However, the mediating effect of resilience between social support and compassion fatigue remains unclear. DESIGN: A multicentre cross-sectional survey. METHODS: A total of 307 intern nursing and midwifery students were recruited from November 2020 to February 2021 in tertiary grade A hospitals in China. Structural equation modelling was applied to analyse the mediating effects of resilience between social support and compassion fatigue. The Social Support Rating Scale, the 10-item Connor-Davidson Resilience Scale, and the Chinese version of the Compassion Fatigue Short Scale were used to collect data. The hypothetical path model was tested by using IBM SPSS version 26.0 and AMOS version 26.0 software. RESULTS: Intern nursing and midwifery students had moderate compassion fatigue. Social support positively affected resilience (ß = 0.514, p < 0.01). Social support negatively affected compassion fatigue (ß = - 0.310, p < 0.01), while resilience negatively affected compassion fatigue (ß = - 0.283, p < 0.01). Resilience played a mediating role between social support and compassion fatigue. CONCLUSION: Social support can directly affect the compassion fatigue of intern nursing and midwifery students during COVID-19 and indirectly through resilience. Stronger resilience can reduce compassion fatigue. Accordingly, resilience-based interventions should be developed to reduce compassion fatigue.

Porcine Epidemic Diarrhea Virus: An Updated Overview of Virus Epidemiology, Virulence Variation Patterns and Virus-Host Interactions.

The porcine epidemic diarrhea virus (PEDV) is a member of the coronavirus family, causing deadly watery diarrhea in newborn piglets. The global pandemic of PEDV, with significant morbidity and mortality, poses a huge threat to the swine industry. The currently developed vaccines and drugs are only effective against the classic GI strains that were prevalent before 2010, while there is no effective control against the GII variant strains that are currently a global pandemic. In this review, we summarize the latest progress in the biology of PEDV, including its transmission and origin, structure and function, evolution, and virus-host interaction, in an attempt to find the potential virulence factors influencing PEDV pathogenesis. We conclude with the mechanism by which PEDV components antagonize the immune responses of the virus, and the role of host factors in virus infection. Essentially, this review serves as a valuable reference for the development of attenuated virus vaccines and the potential of host factors as antiviral targets for the prevention and control of PEDV infection.

Preliminary establishment of a rapid diagnosis method for detecting SARS-CoV-2 nucleic acid through recombinase polymerase amplification combined with a lateral flow dipstick

This study aimed to develop a rapid diagnostic method for the detection of SARS-CoV-2 nucleic acid based on recombinase polymerase amplification combined with a lateral flow dipstick (RPA-LFD), to provide technical support for the prevention and control of SARS-CoV-2 epidemics in basic hospitals and remote areas. According to the conserved nucleotide sequence of the N gene of SARS-CoV-2, the best recombinase polymerase amplification primers and lateral flow strip probes were designed, analyzed and screened in bioinformatics software. The reaction conditions for recombinase polymerase amplification were optimized, and the sensitivity and specificity of the established method were examined. The RPA-LFD assay for detecting SARS-CoV-2 performed best at 37 degrees C at 15 min. The lowest quantity of SARS-CoV-2 detected in a reaction was 100 fg. No cross-reaction with influenza virus, para-influenza virus, rhinovirus and adenovirus in the RPA-LFD assay was found. Thus, an easily performed, rapid diagnostic method for detecting SARS-CoV-2 with high sensitivity and specificity was established. In conclusion, our preliminary rapid diagnostic method for detecting SARS-CoV-2 with good sensitivity and specificity through RPA-LFD is worthy of further clinical application.

False beliefs and "healthy" skepticism: Understanding the multilevel and enduring challenges of misinformation

This dissertation is a study about how people make (mis)informed decisions in the contemporary media environment where there are growing concerns over misinformation, structural inequalities, and the power of platforms. This dissertation addresses two major questions. First, how do beliefs in misinformation develop as a function of multilevel mechanisms, not only as a result of individual identities, preferences, and media diets, but also as a result of mass media structures that impose contextual influences beyond individual choices? Second, how do we foster "healthy" skepticism that helps citizens detect misinformation on social media platforms, while avoiding perpetuating a contentious understanding of fake news that often leads to anti-democratic outcomes? Through four empirical studies, I use quasi-experiment, computational classification of social media and news texts, scale construction, and panel survey experiment to uncover the multilevel and enduring challenges of misinformation. In PART 1 (Chapter 1 & 2), I demonstrate that disparities in local newspaper context across communities uniquely influence people's beliefs about COVID-19 and politics. When living in a community without a local newspaper, people are less certain about and more likely to underestimate COVID-19 prevalence in their community, which in turn are associated with less social distancing. Further, lacking a local newspaper in one's community amplifies partisan selective exposure and makes it more likely for both Democrats and Republicans to believe in false claims made by national in-party elites. Turning from formation of misinformation beliefs to strategies to mitigate misinformation, In PART 2 (Chapter 3 & 4), I show that concerns over social media misinformation are frequently politicized in mainstream broadcast TV news and in Twitter and Facebook utterances. I contend that not all skepticism leads to a better-informed citizenry and theorize two types of skepticism towards social media misinformation: accuracy- vs. identity-motivated skepticism. I reveal that while accuracy-motivated skepticism decreases people's susceptibility to partisanship-congruent misinformation they later encounter, identity-motivated skepticism fuels biases in believing in congruent misinformation and makes content moderation by social media platforms less effective. Together, these findings seek to advance theory-building that deepens our understanding of how individuals, communities, and societies face the challenges brought by misinformation. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial.

BACKGROUND: We report on the safety and immunogenicity of V591, a measles vector-based SARS-CoV-2 vaccine candidate. METHODS: In this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial, healthy adults with no history of COVID-19 disease were assigned to intramuscular injection of V591 or placebo (4:1 ratio). In part 1, younger adults (18-55 years) received V591 median tissue culture infectious dose (TCID50)-levels of 1×105 or 1×106 or placebo, 56 days apart. In part 2, younger and older (>55 years) adults received a single dose of one of four (104/105/106/107) or one of two (105/106) V591 TCID50 levels, respectively, or placebo. PRIMARY OUTCOME: safety/tolerability. Secondary outcome: humoral immunogenicity. ClinicalTrials.gov: NCT04498247. FINDINGS: From August-December 2020, 444 participants were screened and 263 randomised (210 V591; 53 placebo); 262 received at least one and 10 received two doses of V591 or placebo. Adverse events were experienced by 140/209 (67.0%) V591 dose-group participants and 37/53 (69.8%) placebo-group participants following injection 1; most frequent were fatigue (57 [27.3%] vs 20 [37.7%]), headache (57 [27.3%] vs 19 [35.8%]), myalgia (35 [16.7%] vs 10 [18.9%]), and injection-site pain (35 [16.7%] vs 4 [7.5%]). No deaths nor vaccine-related serious adverse events occurred. At Day 29, no anti-SARS-CoV-2 spike serum neutralising antibody and IgG-responses were identified in placebo or the three lower V591 dose-groups; responses were detected with V591 1×107 TCID50, although titres were lower than convalescent serum. INTERPRETATION: V591 was generally well tolerated, but immunogenicity was insufficient to warrant continued development. FUNDING: Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Enhanced sampling protocol to elucidate fusion peptide opening of SARS-CoV-2 spike protein.

Large-scale conformational transitions in the spike protein S2 domain are required during host-cell infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although conventional molecular dynamics simulations have been extensively used to study therapeutic targets of SARS-CoV-2, it is still challenging to gain molecular insight into the key conformational changes because of the size of the spike protein and the long timescale required to capture these transitions. In this work, we have developed an efficient simulation protocol that leverages many short simulations, a dynamic selection algorithm, and Markov state models to interrogate the structural changes of the S2 domain. We discovered that the conformational flexibility of the dynamic region upstream of the fusion peptide in S2 is coupled to the proteolytic cleavage state of the spike protein. These results suggest that opening of the fusion peptide likely occurs on a submicrosecond timescale after cleavage at the S2' site. Building on the structural and dynamical information gained to date about S2 domain dynamics, we provide proof of principle that a small molecule bound to a seam neighboring the fusion peptide can slow the opening of the fusion peptide, leading to a new inhibition strategy for experiments to confirm. In aggregate, these results will aid the development of drug cocktails to inhibit infections caused by SARS-CoV-2 and other coronaviruses.

A computational study of cooperative binding to multiple SARS-CoV-2 proteins.

Structure-based drug design targeting the SARS-CoV-2 virus has been greatly facilitated by available virus-related protein structures. However, there is an urgent need for effective, safe small-molecule drugs to control the spread of the virus and variants. While many efforts are devoted to searching for compounds that selectively target individual proteins, we investigated the potential interactions between eight proteins related to SARS-CoV-2 and more than 600 compounds from a traditional Chinese medicine which has proven effective at treating the viral infection. Our original ensemble docking and cooperative docking approaches, followed by a total of over 16-micorsecond molecular simulations, have identified at least 9 compounds that may generally bind to key SARS-CoV-2 proteins. Further, we found evidence that some of these compounds can simultaneously bind to the same target, potentially leading to cooperative inhibition to SARS-CoV-2 proteins like the Spike protein and the RNA-dependent RNA polymerase. These results not only present a useful computational methodology to systematically assess the anti-viral potential of small molecules, but also point out a new avenue to seek cooperative compounds toward cocktail therapeutics to target more SARS-CoV-2-related proteins.

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.

Prediction of the Severity of the Coronavirus Disease and Its Adverse Clinical Outcomes.

This study aims to investigate blood and biochemical laboratory findings in patients with severe coronavirus disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes and to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Further, the patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin ratio, lactate dehydrogenase level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic curve revealed that the combination of IL-6 level, absolute lymphocyte count, and age is superior to a single factor as predictors for severe COVID-19, regardless of whether it is in terms of the area under the curve or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.

Prediction of adverse clinical outcomes in patients with coronavirus disease 2019.

OBJECTIVE: This study aims to investigate blood and biochemical laboratory findings in patients with coronavirus disease (COVID-19) and analyze the potential predictors of poor outcome in patients with COVID-19. METHODS: The clinical, laboratory, and outcome data of 87 patients with COVID-19 were collected and retrospectively analyzed. Only data collected at the time of admission were used in the analysis for predictors of poor outcome. These patients were divided into two groups: the adverse prognosis group (36 patients) and the non-adverse prognosis group (51 patients). The adverse prognosis of COVID-19 patients was defined as admission to the intensive care unit or death. RESULTS: On the univariate analysis, age, white blood cell (WBC) count, neutrophil counts, lymphocytes count, neutrophils-to-lymphocytes ratio (NLR), interleukin-6, albumin-to-globulin ratio (AGR), albumin, lactate dehydrogenase, glutamyl transpeptidase, and blood glucose were found to be the significant predictors. On the multivariate analysis, the predictors of poor outcome of patients with COVID-19 were NLR (OR = 2.741, [95% CI = 1.02 ~ 7.35], P = .045) and IL-6 (OR = 1.405, [95% CI = 1.04 ~ 1.89, P = .025]). The receiver operating characteristic (ROC) curve revealed that the AUC of NLR, interleukin-6, pneumonia severity index (PSI) score, and Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65) score were 0.883, 0.852, 0.824, and 0.782, respectively. CONCLUSION: High interleukin-6 (6 pg/mL, cuff value) and NLR (4.48, cuff value) can be used to predict poor outcomes in patients with COVID-19 on admission, thus can serve as a beneficial tool for timely identifying COVID-19 patients prone to poor outcome and reduce patient mortality through early intervention.