LigBind: Identifying Binding Residues for Over 1000 Ligands with Relation-Aware Graph Neural Networks.

Identifying the interactions between proteins and ligands is significant for drug discovery and design. Considering the diverse binding patterns of ligands, the ligand-specific methods are trained per ligand to predict binding residues. However, most of the existing ligand-specific methods ignore shared binding preferences among various ligands and generally only cover a limited number of ligands with a sufficient number of known binding proteins. In this study, we propose a relation-aware framework LigBind with graph-level pre-training to enhance the ligand-specific binding residue predictions for 1159 ligands, which can effectively cover the ligands with a few known binding proteins. LigBind first pre-trains a graph neural network-based feature extractor for ligand-residue pairs and relation-aware classifiers for similar ligands. Then, LigBind is fine-tuned with ligand-specific binding data, where a domain adaptive neural network is designed to automatically leverage the diversity and similarity of various ligand-binding patterns for accurate binding residue prediction. We construct ligand-specific benchmark datasets of 1159 ligands and 16 unseen ligands, which are used to evaluate the effectiveness of LigBind. The results demonstrate the LigBind's efficacy on large-scale ligand-specific benchmark datasets, and it generalizes well to unseen ligands. LigBind also enables accurate identification of the ligand-binding residues in the main protease, papain-like protease and the RNA-dependent RNA polymerase of SARS-CoV-2. The web server and source codes of LigBind are available at http://www.csbio.sjtu.edu.cn/bioinf/LigBind/ and https://github.com/YYingXia/LigBind/ for academic use.

Relationship between negative coping style and fear of COVID-19 among Wuhan college students during the post-pandemic period: A moderated chain mediation model

Objectives After a long-term lockdown, particularly one in which human life is at risk, negative psychological consequences are expected. In this study, we aimed to explore the cause of stress and fear of coronavirus-19 (COVID-19) among Chinese college students in Wuhan during the latest strictest lockdown. Methods During the COVID-19 outbreak, 1,070 college students from Wuhan, aged 18–29 years, took part in an online survey. We used correlations, bootstrap tests, and other statistical analysis methods to analyze the data. Results Negative coping style significantly positively predicted fear of COVID-19, and stress had a significant mediating effect on the relationship between negative coping style and fear of COVID-19. In addition, rumination and stress had a chain-mediating effect on the relationship between negative coping style and fear of COVID-19. Perceived social support moderated the three paths of this serial mediation model. Conclusion Negative emotions, such as stress and fear of COVID-19, in college students are caused by both behavior (e.g., negative coping style) and cognition (e.g., rumination). Importantly, negative cognitive thinking (i.e., rumination) is often a malign consequence of a negative coping style. Thus, to improve students' mental health, students should be encouraged to engage in more positive behaviors and seek social support during periods of adherence to regular prevention and control measures.

Genomic Surveillance for SARS-CoV-2 Variants of Concern from Imported COVID-19 Cases - the Mainland of China, 2021.

Introduction: After the epidemic in Wuhan City was brought under control in 2020, local outbreaks of coronavirus disease 2019 (COVID-19) in the mainland of China were mainly due to imported COVID-19 cases. The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to generate new variants. Some have been designated as variants of concern (VOCs) by the World Health Organization (WHO). To better assess the role of imported SARS-CoV-2 surveillance and the prevalence of VOCs in 2021, the genomic surveillance data of SARS-CoV-2 from imported COVID-19 cases of 2021 in the mainland of China were analyzed. Methods: The analyses included the number of sequence submissions, time of sequence deposition, and time of detection of the VOCs in order to determine the timeliness and sensitivity of the surveillance. The proportions of VOCs were analyzed and compared with data from the Global Initiative of Sharing All Influenza Data (GISAID). Results: A total of 3,355 sequences of imported cases were submitted from 29 provincial-level administrative divisions, with differences in the number of sequence submissions and median time of sequence deposition. A total of 2,388 sequences with more than 90% genomic coverage were used for lineage analysis. The epidemic trend from Alpha to Delta to Omicron in imported cases was consistent with that in the GISAID. In addition, VOCs from imported cases were usually identified after WHO designation and before causing local outbreaks. Conclusions: The global distribution of SARS-CoV-2 VOCs changed rapidly in 2021. Robust genomic surveillance of the imported SARS-CoV-2 in the mainland of China is of great significance.

Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection.

Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.

High recurrence of lymphedema and influencing factors in discharged breast cancer patients during the COVID-19 pandemic: A multicenter, cross-sectional survey.

BACKGROUND: There has been a delay in the detection and treatment of lymphedema in breast cancer patients during the lockdown owing to quarantine and limited social activity. Moreover, this scenario has caused psychosocial issues in these patients. Given that there is scarce information on the prevalence and influence of lymphedema during the coronavirus disease (COVID-19) pandemic, we aimed to estimate the prevalence of lymphedema recurrence and its influencing factors among discharged breast cancer patients during the COVID-19 pandemic. METHODS: This was a multicenter, cross-sectional, hospital-based survey of discharged breast cancer patients was conducted during the COVID-19 pandemic in eight first-class hospitals in Wuhan, China. The Norman Questionnaire was used to assess lymphedema. Univariable and multivariable binary logistic regression analyses were performed to identify factors influencing moderate or severe lymphedema. Differences in living characteristics, anxiety, and depression were compared between the no/mild lymphedema group and the moderate/severe lymphedema groups. Preferences for lymphedema management during the pandemic were determined. RESULTS: Overall, 202 patients were included in this study, and 191 of them reported recurrent lymphedema (prevalence: 94.6%, 95% confidence interval [CI] 90.5% to 97.3%). Among them, 134 and 57 had mild and moderate/severe lymphedema, respectively. In 191 patients, the main symptoms were swelling (140; 69.3%) and pain (56, 27.7%). Multivariable regression showed that older age (odds ratio [OR], 1.06; 95% CI: 1.02-1.10), radical surgery (OR = 4.35, 95% CI: 1.54-12.50), and fully complete radiotherapy (OR = 2.62, 95% CI: 1.17-5.87, p = 0.019) were associated with an elevated risk of moderate/severe lymphedema. The moderate/severe lymphedema group experienced a higher rate of anxiety and depression than the no/mild lymphedema group did. Patients equally preferred treatment in the hospital and self-care at home. CONCLUSION: During the COVID-19 pandemic, high prevalence of lymphedema was observed in patients Age, radical surgery and fully completed radiotherapy were associated with increased risk of severer lymphedema. Meanwhile, the patients with severe lymphedema experienced psychological distress. While the Covid-19 pandemic was still raging, continuous efforts should be made to identify patient at risk of lymphedema and distribute feasible guidance and education for self-management in lymphedema.

SARS-CoV-2 cold-chain transmission: Characteristics, risks, and strategies.

Low temperature and certain humidity are conducive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for long-time survival and long-distance spread during logistics and trades. Contaminated cold-chain or frozen products and outer packaging act as the carrier of SARS-CoV-2, that infects the high-risk population who works in the ports, cold storage or seafood market. Since the coronavirus disease 2019 (COVID-19) pandemic worldwide, multiple localized outbreaks caused by SARS-CoV-2 contaminated imported cold-chain products have been reported in China, which brought challenges to COVID-19 prevention and control. Here, we review the evidences of SARS-CoV-2 cold-chain transmission from six confirmed cold-chain related COVID-19 outbreaks in China, especially in terms of SARS-CoV-2 whole-genome sequencing and virus isolation. In addition, we summarize the characteristics and mode of SARS-CoV-2 cold-chain transmission from both six COVID-19 outbreaks in China and the outbreaks suspected cold-chain transmission in other countries. Finally, we analyze the underlying risks of SARS-CoV-2 cold-chain transmission and propose the preventive countermeasures.

Risk assessment of public health emergencies concerned in the mainland of China, November 2021

Objective: To assess the risk of public health emergencies, both the indigenous ones and the imported ones, which might occur in the mainland of China in November 2021.

Analysis on genome variation of SARS-CoV-2 circulating in the world

Accordings to the Pango nomenclature, a total of 1 379 lineages of SARS-CoV-2 have been identified worldwide as of 20 September 2021. Some lineages have disappeared or are close to disappearing due to the replacement by the variants with higher transmissibility and/or immune escape ability. The World Health Organization (WHO) has defined 4 variants of concern (VOC), 5 variants of interest (VOI) and 11 variants belonging to variants under monitoring (VUM). At present, the Delta variant has replaced the Alpha variant as the predominant global pandemic strain, and it is also the main variant detected in imported cases and local epidemics recently in China. Meanwhile, the Gamma and Lambda variants reported in some countries of South America, the Mu variant reported in some countries of South America and North America, and the C.1.2 variant reported in South Africa have also attracted high attention worldwide. The paper summarizes the variation of SARS-CoV-2 genome and the research progress of key variants of SARS-CoV-2 and put forward the key points of further research based on the spread of SARS-CoV-2 variants.

Emergency Management of Medical Wastewater in Hospitals Specializing in Infectious Diseases: A Case Study of Huoshenshan Hospital, Wuhan, China.

Medical wastewater originating from hospitals specializing in infectious diseases pose a major risk to human and environmental health during pandemics. However, there have been few systematic studies on the management of this type of wastewater management. The function of the Huoshenshan Hospital as a designated emergency field hospital for the treatment of COVID-19 has provided lessons for the management measures of medical wastewater, mainly including: (1) Modern information technology, management schemes, and related standard systems provided the legislative foundation for emergency management of medical wastewater. (2) The three-tier prevention and control medical wastewater management system ensured the discharged wastewater met water quality standards, especially for the leak-proof sealed collection system of the first tier, and the biological and chemical treatment technology of the second tier. (3) The establishment of an effective three-tier medical wastewater quality monitoring accountability system. This system was particularly relevant for ensuring continuous data monitoring and dynamic analysis of characteristic indicators. (4) Information disclosure by government and public supervision promoted successful implementation of medical wastewater management and control measures. Public questionnaires (n = 212) further confirmed the effectiveness of information disclosure. The results of this study can act as methodological reference for the emergency management of wastewater in designated infectious disease hospitals under similar situations.

Microfluidic Chip with Two-Stage Isothermal Amplification Method for Highly Sensitive Parallel Detection of SARS-CoV-2 and Measles Virus.

A two-stage isothermal amplification method, which consists of a first-stage basic recombinase polymerase amplification (RPA) and a second-stage fluorescence loop-mediated isothermal amplification (LAMP), as well as a microfluidic-chip-based portable system, were developed in this study; these enabled parallel detection of multiplex targets in real time in around one hour, with high sensitivity and specificity, without cross-contamination. The consumption of the sample and the reagent was 2.1 µL and 10.6 µL per reaction for RPA and LAMP, respectively. The lowest detection limit (LOD) was about 10 copies. The clinical amplification of about 40 nasopharyngeal swab samples, containing 17 SARS-CoV-2 (severe acute respiratory syndrome coronavirus) and 23 measles viruses (MV), were parallel tested by using the microfluidic chip. Both clinical specificity and sensitivity were 100% for MV, and the clinical specificity and sensitivity were 94.12% and 95.83% for SARS-CoV-2, respectively. This two-stage isothermal amplification method based on the microfluidic chip format offers a convenient, clinically parallel molecular diagnostic method, which can identify different nucleic acid samples simultaneously and in a timely manner, and with a low cost of the reaction reagent. It is especially suitable for resource-limited areas and point-of-care testing (POCT).

Prevalence and Impact Factors of COVID-19 Vaccination Hesitancy Among Breast Cancer Survivors: A Multicenter Cross-Sectional Study in China.

Cancer patients are at a high risk of being infected with COVID-19 and have a poor prognosis after infection. Breast cancer is one of the most common cancers. Since vaccination is an effective measure to prevent the spread of COVID-19, we studied the vaccination rate among breast cancer survivors and analyzed their characteristics to provide evidence for boosting the vaccination rate. The researchers conducted a multicenter, cross-sectional study on 747 breast cancer survivors from six hospitals in Wuhan city between June 5, 2021, and June 12, 2021. The self-administrated questionnaires based on relevant studies were distributed. The researchers then compared differences in characteristics among vaccinated patients, hesitant patients, and non-vaccinated patients. Moreover, they performed univariable and multivariable logistic regression analyses to identify potential factors associated with vaccination hesitancy. The researchers assessed a total of 744 breast cancer survivors -94 cases in the vaccinated group, 103 in the planning group, 295 in the hesitancy group, and 252 in the refusal group. The vaccination rate was 12.63% (95% CI 10.25-15.02%) and 37.23% (95% CI 27.48-47.82%) patients reported adverse reactions. The vaccination hesitancy/refusal rate was 73.52% (95% CI 70.19-76.66%), which was independently associated with current endocrine or targeted therapy (odds ratio [OR] = 1.52, 95% CI 1.03-2.24), no notification from communities or units (OR = 2.46, 95% CI 1.69-3.59) and self-perceived feel (general vs. good, OR = 1.46, 95% CI 1.01-2.13; bad vs. good, OR = 4.75, 95% CI 1.85-12.16). In the hesitancy/refusal group, the primary reason was "I did not know who to ask whether I can get vaccinated" (46.07%), the person who would most influence decisions of patients was the doctor in charge of treatment (35.83%). Effective interaction between doctors and patients, simple and consistent practical guidelines on vaccination, and timely and positive information from authoritative media could combat misinformation and greatly reduce vaccine hesitancy among breast cancer survivors.