Accurate prediction of molecular properties and drug targets using a self-supervised image representation learning framework

The clinical efficacy and safety of a drug is determined by its molecular properties and targets in humans. However, proteome-wide evaluation of all compounds in humans, or even animal models, is challenging. In this study, we present an unsupervised pretraining deep learning framework, named ImageMol, pretrained on 10 million unlabelled drug-like, bioactive molecules, to predict molecular targets of candidate compounds. The ImageMol framework is designed to pretrain chemical representations from unlabelled molecular images on the basis of local and global structural characteristics of molecules from pixels. We demonstrate high performance of ImageMol in evaluation of molecular properties (that is, the drug's metabolism, brain penetration and toxicity) and molecular target profiles (that is, beta-secretase enzyme and kinases) across 51 benchmark datasets. ImageMol shows high accuracy in identifying anti-SARS-CoV-2 molecules across 13 high-throughput experimental datasets from the National Center for Advancing Translational Sciences. Via ImageMol, we identified candidate clinical 3C-like protease inhibitors for potential treatment of COVID-19. Predicting the properties of a molecule from its structure with high accuracy is a crucial problem in digital drug design. Instead of sequence features, Zeng and colleagues use an image representation of a large collection of bioactive molecules to pretrain a model that can be fine-tuned on specific property prediction tasks.

Safety of Inactivated and mRNA COVID-19 Vaccination among Patients Treated for Hypothyroidism: a Population-based Cohort Study

Background: Thyroiditis and Graves’ disease have been reported after COVID-19 vaccination. Patients with hypothyroidism due to various etiologies may be at risk of thyroid-specific outcomes. We aimed to evaluate the risks of thyroid-specific outcomes and adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this population-based cohort from Hong Kong Hospital Authority electronic health records with Department of Health vaccination records linkage, levothyroxine users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine) or CoronaVac (inactivated vaccine) between 23 February and 9 September 2021. Propensity score (PS) weighting with inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics among the three groups, which included age, sex, history of COVID-19, health care utilization, comorbidities, baseline thyroid-stimulating hormone (TSH) level (within the 6 months before the index date), and recent use of medications including anti-hypertensive, anti-diabetic and lipid-lowering agents. Study outcomes were dosage reduction or escalation in levothyroxine, emergency department visit, unscheduled hospitalization, adverse events of special interest (AESI) according to World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Results: In total, 47,086 levothyroxine users were identified (BNT162b2: n=12,310;CoronaVac: n=11,353;unvaccinated: n=23,423). After PS weighting, all baseline characteristics had standardised differences of less than 0.2, implying a balance of covariates among the three groups. COVID-19 vaccination was not associated with increased risks of levothyroxine dosage reduction (BNT162b2: HR=0.971, 95% CI 0.892–1. 058;CoronaVac: HR=0.968, 95% CI 0.904–1. 037) or escalation (BNT162b2: HR=0.779, 95% CI 0.519–1.169;CoronaVac: HR=0.715, 95% CI 0.481–1. 062). Besides, COVID-19 vaccination was not associated with a higher risk of emergency department visits (BNT162b2: HR=0.944, 95% CI 0.700-1.273;CoronaVac: HR=0.851, 95% CI 0.647-1.120) or unscheduled hospitalization (BNT162b2: HR=0.905, 95% CI 0.539-1.520;CoronaVac: HR=0.735, 95% CI 0.448-1.207). There were two (0. 016%) deaths and six (0. 062%) AESI recorded for BNT162b2 recipients, and one (0. 009%) and three (0. 035%) for CoronaVac recipients, respectively. Sensitivity analyses were performed by stratifying the groups according to age, sex and pre-vaccination thyroid status. The results were largely consistent with the main analysis. Conclusion: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.Presentation: No date and time listed

Analysis of regional differences and decomposition of carbon emissions in China based on generalized divisia index method

The achievement of China's carbon dioxide (CO2) emission reduction target is of great significance in the face of global climate change. Accurate identification of key factors that affect CO2 emissions can provide theoretical support to policymakers when designing related policies. Compared to the traditional method, the generalized Divisia index method (GDIM) can capture the influence of multiple scale factors on carbon emissions, providing new tools for studying the decomposition of carbon emissions. The article proposed a GDIM-based decomposition method to analyze the drivers that influence CO2 emissions in China from 2000 to 2017. The results indicate that investment activity is the primary element in promoting China's carbon emissions, followed by energy use and economic activities. On the contrary, investment carbon intensity is the vital inhibitory factor, followed by GDP carbon intensity. Specifically, the positive driving force of investment and energy use is gradually weakening, while the contribution of economic activities is continuously strengthening. The effectiveness of carbon emission reduction in the Northeast, East, and Southwest is actively promoting China's carbon emission reduction, while the effectiveness of CO2 emission reduction in the Northwest is not performing well. The findings provide support and reference for carbon emission control in China. (C) 2022 Elsevier Ltd. All rights reserved.

A Family-based Child Health Education Curriculum for Refugee Families

Background: Refugees are at risk for low health literacy and high rates of illness and hospitalization. A partnership between medical professionals at Yale and two New-Haven, CT-based refugee resettlement organizations aimed to create and implement a family-based, interactive pediatric healthcare curriculum with a goal of increasing childhood health knowledge among refugee families. Methods: Seven 1-hour, in-person classes and 1 virtual class were taught by pediatric residents with real-time translation in Pashto, Dari, Arabic, Swahili, and Kinyarwanda on the topics of child nutrition, safety, parenting, and oral health. Each class incorporated play-based activities for toddlers-a My Healthy Plate puzzle, street-crossing simulation, teeth-brushing demonstration, and block play-which were integrated into parental discussion with visual aids. Knowledge acquisition and satisfaction was assessed using pre- and posttests. Results: 67 adult participants had an 85% response rate. Average knowledge test scores increased in 5 of 7 classes, reaching significance in a class on parenting (mean 52% vs 90%, paired t-test p = 0.03) and child safety (mean 80% vs 97%, p = 0.04). 100% of respondents (67% response rate) reported increased understanding of the topic and would recommend the class to a friend. There were 5 participants for the virtual class. Conclusion: Child health education classes conducted for refugee families can improve knowledge of pediatric healthcare topics and provide positive experiences. A close relationship between healthcare providers and community refugee organizations has the potential to improve health education in refugee families. Future studies will assess efficacy and satisfaction of virtual classes during the COVID-19 pandemic.

Effect of ontological insecurity on vaccination behavior against COVID-19: a hospital-based cross-sectional study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has brought great uncertainty to our society and it may have disrupted people's ontological security. Consequently, this hospital-based study concerns the impact of ontological insecurity on vaccination behavior against COVID-19. STUDY DESIGN: This cross-sectional study was conducted among hospital inpatients. METHODS: A questionnaire survey addressing inpatient ontological insecurity and vaccination behavior against COVID-19 was administered in Taizhou, China. A total of 1223 questionnaires were collected; specifically, 1185 of them were credible, for a validity rate of 96.9%. RESULTS: The score of ontological insecurity was 13.27 ± 7.84, which was higher in participants who did not recommend vaccination for others than those who did (12.95 ± 8.25 vs 14.00 ± 6.78, P = 0.022). There was no difference between the vaccinated and unvaccinated groups (13.22 ± 7.96 vs 13.35 ± 7.67, P = 0.779). Lower ontological insecurity (odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.08-1.81) and being inoculated with COVID-19 vaccines (OR = 2.17, 95% CI: 1.67-2.82) were significantly associated with recommendation of COVID-19 vaccines to others after adjusting for sex, age, education, and occupation. Associations between low ontological insecurity and recommendations for COVID-19 vaccines were observed in men, adults aged 18-59 years, non-farmers, and vaccine recipients. CONCLUSIONS: This study suggests that the ontological insecurity of participants affects their behavior of recommending the COVID-19 vaccination to others rather than getting vaccinated themselves. This promotion of vaccination can be considered from the perspective of improving ontological security in China.

Forecast and analysis of the ePidemics (rend of COVID-19 in the United States by TRP-SEAMRD model

The traditional SEIR (susceptible-exposed-infectious-recovered/removed) model is a simplified dynamical predictive model which does not consider the impact of changes in the anti-epidemic policy. We take the US anti-epidemic policy and the incubation period characteristic of COVID-19 into account to propose the TRP-SEAMRD(test-restricted-phased SEAMRD) model for the pandemic in US. The model fits well with the figures of COVID-19 infections, recovery and death in the United States during February ~ August 2020. According to the data generated from the model, some of the characteristics of COVID- 19 can be ed. Based on the TRP-SEAMRD model, we can analyze the impact of the improper anti¬epidemic policy at the early stage of the epidemic. The effect of the subsequent “stay at home”epidemic controlling measures is also considered and analyzed. Finally, future development of the pandemic in the US under different degrees of social control is simulated,offering a reference for formulating scientific anti¬epidemic measures. © 2020, Editorial Department of Journal of University of Science and Technology of China. All rights reserved.

Deep learning for drug repurposing: Methods, databases, and applications

Drug development is time-consuming and expensive. Repurposing existing drugs for new therapies is an attractive solution that accelerates drug development at reduced experimental costs, specifically for Coronavirus Disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensively obtaining and productively integrating available knowledge and big biomedical data to effectively advance deep learning models is still challenging for drug repurposing in other complex diseases. In this review, we introduce guidelines on how to utilize deep learning methodologies and tools for drug repurposing. We first summarized the commonly used bioinformatics and pharmacogenomics databases for drug repurposing. Next, we discuss recently developed sequence-based and graph-based representation approaches as well as state-of-the-art deep learning-based methods. Finally, we present applications of drug repurposing to fight the COVID-19 pandemic and outline its future challenges. This article is categorized under: Data Science > Artificial Intelligence/Machine Learning

Debate on mandatory COVID-19 vaccination.

BACKGROUND: Since January 2020, worldwide public health has been threatened by COVID-19, for which vaccines have been adopted from December 2020. DISCUSSION: Although vaccines demonstrate effectiveness against this disease, vaccine hesitancy reveals concerns towards short-term and long-term side effects or adverse reactions such as post-inoculation death. Mandatory vaccination is used to provide herd immunity, but is refutable due to infringement of human rights and autonomy. Furthermore, the evidence testifies that vaccination cannot guarantee prevention of infection or re-infection, resulting in public resentment against this coercive measure, whilst post-inoculation anxiety continues. PERSPECTIVE: This discussion suggests a holistic approach, involving the collective efforts of governments, medical experts and individuals, through basic preventive measures and alternative therapy to live with COVID-19 in a healthy and resourceful manner.

Effects of SARS‑CoV‑2 on testicular function

Objective: To describe the clinical characteristics of the male reproductive system of COVID‑19 patients and to explore the presence of SARS‑CoV‑2 in semen. Methods: Case series of 112 male patients with confirmed COVID‑19 who were admitted to Renmin Hospital of Wuhan University from January to March, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. SARS‑CoV‑2 RNA levels were measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on HPA database were investigated. Results: The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in testis. A total of 3 severe COVID‑19 patients (2.7%) presented with orchidoptosis, while no patient experienced other symptoms or signs related to the male reproductive system. The analysis of SARS‑CoV‑2 RNA in semen included 17 patients with fertility needs. In the semen SARS‑CoV‑2 analysis, all 17 patients were negative for the N gene and ORF1ab gene. Conclusion: The online datasets indicated the potential impairment of the testicular function by SARS‑CoV‑2. However, this study suggestes that male patients have few reproductive symptoms and signs, and SARS‑CoV‑2 was not present in the semen of patients with confirmed COVID‑19. In view of the potential impairment, the long‑term follow‑up for male COVID‑19 patients with fertility needs is of great significance. © 2022, Editorial Board of Medical Journal of Wuhan University. All right reserved.

Mask reuse during the COVID-19 pandemic: a national survey in Taiwan

Background The use of masks is an effective measure to prevent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection;however, mask reuse is not recommended. Studies examining the factors associated with mask reuse during the coronavirus disease (COVID-19) pandemic are limited. This nationwide survey aimed to determine the prevalence and factors associated with mask reuse among Taiwanese citizens during the pandemic. Methods From May 18 through May 31, 2020, a computer-assisted telephone interview system was used to randomly select Taiwanese citizens who were interviewed for COVID-19 preventive behaviors and knowledge on the usage of masks. Multivariate logistic regression was used to identify factors associated with mask reuse during the COVID-19 pandemic. Moreover, generalized estimating equations (GEE) were used to analyze the rate of mask reuse among participants before and during the pandemic. Results For a total of 1,075 participants, the overall mean age was 57.4 years, and 82.2% of participants reported mask reuse during the COVID-19 pandemic. After controlling for other covariates, participants who had a greater knowledge on mask usage or had a high supply of masks were less likely to reuse masks during the pandemic. GEE analysis showed that compared with the participants' mask wearing behaviors before the COVID-19 pandemic, they were more likely to reuse masks during the pandemic. Conclusions The rate of mask reuse among the general population during the pandemic was significantly higher than that before the pandemic. Individuals were less likely to reuse masks if they had adequate knowledge on mask usage or had a high supply of masks. Since mask reuse is associated with a higher risk of COVID-19 due to the possibility of wearing SAS-CoV-2-contaminated masks, it is imperative to educate people on the correct usage of masks. Further, the government should provide sufficient masks to the general population to decrease the reuse of masks. Key messages Mask reuse increased during the COVID-19 pandemic due to the shortage in supply. It is imperative to educate people about the correct usage of masks.

Effects of Micronutrients or Conditional Amino Acids on COVID-19-Related Outcomes: An Evidence Analysis Center Scoping Review

Recent narrative reviews have described the potential efficacy of providing individuals infected with coronavirus disease 2019 (COVID-19) with additional micronutrients to reduce disease severity. Although there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19-related health outcomes. A literature search of the MEDLINE database and hand search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and 8 studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In 6 of the 8 included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared with sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists must rely on clinical expertise and indirect evidence to guide medical nutrition therapy for patients infected with COVID-19.

The role of probiotics in coronavirus disease-19 infection in Wuhan: A retrospective study of 311 severe patients

PURPOSE: Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. METHODS: In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. RESULTS: In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. CONCLUSIONS: Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.

<b>Malnutrition Care during the COVID-19 Pandemic: Considerations for Registered Dietitian Nutritionists</b> Evidence Analysis Center

Recent evidence examining adults infected with COVID-19 has indicated a significant impact of malnutrition on health outcomes. Individuals who have multiple comorbidities, are older adults, or who are malnourished are at increased risk of being admitted to the intensive care unit and of mortality from COVID-19 infections. Hence, nutrition care to identify and address malnutrition is critical in treating and preventing further adverse health outcomes from COVID-19 infection. This document provides guidance and practice considerations for Registered Dietitian Nutritionists (RDNs) providing nutrition care for adults with suspected or confirmed COVID-19 infection in the hospital, outpatient, or homecare settings. In addition, this document discusses and provides considerations for RDNs working with individuals at risk of malnutrition secondary to food insecurity during the COVID-19 pandemic.