Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern (preprint)

SARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.

Pandemic and prejudice: Results from a national survey experiment

Do health and economic shocks exacerbate prejudice towards racial/ethnic minority groups? We investigate this question in the wake of the COVID-19 pandemic by collecting nationally representative survey data with an embedded experiment. Results show that priming COVID-19 salience has an immediate impact: compared to the control group, respondents in the treatment group reported increased prejudice towards East Asian and Hispanic colleagues. East Asians in the treatment group faced higher prejudicial responses from Americans living in counties with higher COVID-19 infections and those who lost jobs due to COVID-19, and fewer prejudicial responses in counties with a higher concentration of Asians. These results point to the salience of COVID-19 fueled health and economic insecurities in shaping prejudicial attitudes, specifically towards East Asians. County-level socioeconomic factors did not moderate the increased prejudicial attitudes toward Hispanics in the workplace. These findings highlight a dimension of prejudice, intensified during the pandemic, which has been largely underreported and therefore missing from the current discourse on this important topic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

A Personalized Learning Service Compatible with Moodle E-Learning Management System

Among the numerous learning management platforms, Moodle is free, open-source software supporting expanding and modularized system functions and services to facilitate online courses or online resources and interactive activities. This study enhanced a personalized learning service for the Moodle e-learning management system, which synchronizes the user’s identity according to the user information database of the third-party user management platform system. According to the user’s demand to provide a personalized e-course, including personalized learning process, e-materials, and learning path to improve learning efficiency. This study adopted the pre-test and post-test achievement to compare the benefit of the personalized e-learning platform. Research samples were students in the “programming” course at the Technology University in central Taiwan. The experiment results indicate: (i) The average post-test result after using the proposed platform was higher than the average pre-test result (before using the proposed platform). (ii) The learning effect gap in the post-test between students was less than in the pre-test result. Hence, the proposed personalized e-learning platform was beneficial.

Alternative splicing and alternative polyadenylation define tumor immune microenvironment and pharmacogenomic landscape in clear cell renal carcinoma

Two major posttranscriptional mechanisms—alternative splicing (AS) and alternative polyadenylation (APA)—have attracted much attention in cancer research. Nevertheless, their roles in clear cell renal carcinoma (ccRCC) are still ill defined. Herein, this study was conducted to uncover the implications of AS and APA events in ccRCC progression. Through consensus molecular clustering analysis, two AS or APA RNA processing phenotypes were separately constructed with distinct prognosis, tumor-infiltrating immune cells, responses to immunotherapy, and chemotherapy. The AS or APA score was constructed to quantify AS or APA RNA processing patterns of individual ccRCCs with principal-component analysis. Both high AS and APA scores were characterized by undesirable survival outcomes, relatively high response to immunotherapy, and low sensitivity to targeted drugs, such as sorafenib and pazopanib. Moreover, several small molecular compounds were predicted for patients with a high AS or APA score. There was a positive correlation between AS and APA scores. Their interplay contributed to poor prognosis and reshaped the tumor immune microenvironment. Collectively, this study is the first to comprehensively analyze two major posttranscriptional events in ccRCC. Our findings uncovered the potential functions of AS and APA events and identified their therapeutic potential in immunotherapy and targeted therapy. Graphical This study for the first time uncovered the potential roles of two major posttranscriptional mechanisms—alternative splicing (AS) and alternative polyadenylation (APA) events—and their crosstalk in the tumor immune microenvironment, clinical outcomes, and therapeutic responses of ccRCC, which could assist in exploiting personalized therapeutic strategies for ccRCC.

Dynamic Zero-Covid strategy curtails mutagenesis and emergence of new variants of the SARS-CoV-2 (preprint)

Within the local outbreak period of SARS-CoV-2 Delta variant in Nanjing and Yangzhou, China, we analyzed the mutation process of the Delta variants in 520 cases, as well as the production, spread and elimination of new mutant strains under the non-pharmaceutical interventions (NPI) strategy. The investigation on distribution of COVID-19 cases and phylogenetic analysis of SARS-CoV-2 genome sequences attributed to tracking the transmission chains, transmission chains were terminated by the isolation of the COVID-19 patients and quarantine of close-contracts, suggesting the importance of NPI in prompting some mutations to disappear and stopping the transmission of new variants. Dynamic zero-Covid strategy has been implemented successfully to against the second-largest local epidemic caused by an imported COVID-19 case in China.

The status of anxiety state among cancer patients and their relatives during coronavirus disease 2019 (COVID-19) in Hubei, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, tumor patients and their families might suffer from greater psychological stress as a result of anxiety or other psychological disorders. We conducted an online study during the epidemic to explore the mental state of tumor patients and their families during this extraordinary time. METHODS: A cross-sectional survey was carried out. Questionnaires were distributed through the WeChat "Questionnaire Star" network. The snowball sampling technique was adopted and further promoted by subjects who had completed the questionnaire. RESULTS: A total of 1,030 valid questionnaires were collected. There were 609 (59.13%) tumor patients and 421 (40.87%) family members. One hundred and fifty-six (15.15%) subjects had anxiety, among which 65 (6.31%) had moderate to severe anxiety. Single-factor analysis indicated that age (>60 years old), the farmer occupation, and a high sleep disorder assessment score were risk factors for anxiety, while the latter two might also be independent risk factors, as suggested by multi-factor analysis. Infrequent contact with doctors was an independent risk factor for cancer patients, while uninterrupted anti-tumor therapy was an independent protective factor. 40.19% of the subjects expressed a need for psychosocial support during the COVID-19 period. CONCLUSIONS: The COVID-19 outbreak resulted in tumor patients and their relatives experiencing greater psychological pressure than usual, and patients were more worried about anti-tumor treatment and disease progression impacted by the epidemic. Both groups had a significant need for psychosocial help.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019 (preprint)

Background The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a six-month follow-up of functional status of COVID-19 survivors.Methods We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a six-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 5 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a six-month follow-up after discharge.Results We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At six-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95%CI 1.33 - 12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95%CI 1.06 - 10.81, p = 0.039).Conclusions A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a six-month follow-up; intervention strategies are required.