Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space.

Computational tools for integrative analyses of diverse single-cell experiments are facing formidable new challenges including dramatic increases in data scale, sample heterogeneity, and the need to informatively cross-reference new data with foundational datasets. Here, we present SCALEX, a deep-learning method that integrates single-cell data by projecting cells into a batch-invariant, common cell-embedding space in a truly online manner (i.e., without retraining the model). SCALEX substantially outperforms online iNMF and other state-of-the-art non-online integration methods on benchmark single-cell datasets of diverse modalities, (e.g., single-cell RNA sequencing, scRNA-seq, single-cell assay for transposase-accessible chromatin use sequencing, scATAC-seq), especially for datasets with partial overlaps, accurately aligning similar cell populations while retaining true biological differences. We showcase SCALEX's advantages by constructing continuously expandable single-cell atlases for human, mouse, and COVID-19 patients, each assembled from diverse data sources and growing with every new data. The online data integration capacity and superior performance makes SCALEX particularly appropriate for large-scale single-cell applications to build upon previous scientific insights.

Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans.

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.

Exploring Strategies for Improving Green Open Spaces in Old Downtown Residential Communities from the Perspective of Public Health to Enhance the Health and Well-Being of the Aged.

Based on the trend of global aging, people are paying more and more attention to the health of the elderly and the improvement of green open spaces. However, few studies have focused on strategies to improve green spaces in response to this trend. Especially, with the outbreak of COVID-19, an urgent need to develop a sustainable system strategy to improve the health of the elderly in residential communities in old districts has emerged. Traditional improvement strategies based on current situation evaluation often focus on the most prominent practical problems. Therefore, the objective of this study was to provide theoretical research and practical improvement strategies for green open spaces in old downtown residential communities to improve the health and well-being of the elderly. In response to this problem, this research proposes an alternative method based on causality (FDM-DANP-mV model), by extracting 23 green open space elements that affect the health of the elderly and dividing them into three dimensions, to form a preliminary evaluation framework. On this basis, the more effective and feasible standard elements are screened out, and the influence relationship behind the elements is clarified. Then, the sustainable development strategy is systematically discussed in three practical cases. This allows for the analysis of the present situation to not only identify the current significant problems but also to capture the source of the influence behind the real problems based on the clarification of the dominant influence relationship. The actual value of this study is to provide a key design decision basis for the improvement of the green open spaces in old downtown residential communities, aiming at avoiding waste to the greatest extent under the premise of limited resources and gradually promoting the improvement of the urban built environment to promote the health and well-being of the elderly.

Environmental Design Strategies to Decrease the Risk of Nosocomial Infection in Medical Buildings Using a Hybrid MCDM Model.

The prevention and control of nosocomial infection (NI) are becoming increasingly difficult, and its mechanism is becoming increasingly complex. A globally aging population means that an increasing proportion of patients have a susceptible constitution, and the frequent occurrence of severe infectious diseases has also led to an increase in the cost of prevention and control of NI. Medical buildings' spatial environment design for the prevention of NI has been a hot subject of considerable research, but few previous studies have summarized the design criteria for a medical building environment to control the risk of NI. Thus, there is no suitable evaluation framework to determine whether the spatial environment of a medical building is capable of inhibiting the spread of NI. In the context of the global spread of COVID-19, it is necessary to evaluate the performance of the existing medical building environment in terms of inhibiting the spread of NI and to verify current environmental improvement strategies for the efficient and rational use of resources. This study determines the key design elements for the spatial environment of medical buildings, constructs an evaluation framework using exploratory factor analysis, verifies the complex dominant influence relationship, and prioritizes criteria in the evaluation framework using the decision-making trial and evaluation laboratory- (DEMATEL-) based analytical network process (ANP) (DANP). Using representative real cases, this study uses the technique for order preference by similarity to ideal solution (TOPSIS) to evaluate and analyze the performance with the aspiration level of reducing the NI risk. A continuous and systematic transformation design strategy for these real cases is proposed. The main contributions of this study include the following: (1) it creates a systematic framework that allows hospital decision-makers to evaluate the spatial environment of medical buildings; (2) it provides a reference for making design decisions to improve the current situation using the results of a performance evaluation; (3) it draws an influential network relation map (INRM) and the training of influence weights (IWs) for criteria. The sources of practical problems can be identified by the proposed evaluation framework, and the corresponding strategy can be proposed to avoid the waste of resources for the prevention of epidemics.

The psychological impact on patients with memory disorders and their caregivers during COVID-19.

BACKGROUND: COVID-19 is erupting globally. Mass quarantine had been implemented all around China which could influence the psychological status of patients with memory disorders and their caregivers. AIM: To investigate the psychological impact of mass quarantine on patients with memory disorders and their caregivers in China. METHODS: We completed a cross-sectional study in 787 patients and their caregivers registered from 2010 to 2019 in Memory Clinic, The First Affiliated Hospital of Chongqing Medical University, by telephone interviews. The performance in neuropsychiatric symptoms (NPSs), sleep, nutrition, chronic diseases of patients, and the burden of care, anxiety and depression of caregivers was assessed by six assessment scales (MNA-SF, PSQI, NPI, RSS, PHQ-9 and GAD-7). RESULTS: Only 68 (8.6%) patients worried about the outbreak of COVID-19. The prevalence of NPSs among all subjects was nearly 60.0%. Approximately 50.0% of the caregivers reported distress. More than 70.0% of patients remained stable in NPSs. However, anxiety, depression, aberrant motor disorder and delusion were exacerbated (22.9%, 18.6%, 17.1% and 16.8%, respectively). Appetite and eating disorder led alleviation rate by 25.8% while disappearing rate of agitation led by 5.8%. 7.5% of caregivers manifested depressive symptoms while 4.9% expressed anxiety symptoms, and 40.8% showed care burden. The coefficients of RSS and PHQ-9, RSS and GAD-7, RSS and NPI-D, PHQ-9 and GAD-7 were 0.7, 0.5, 0.5 and 0.6, respectively (p < 0.01). CONCLUSION: Changes in NPSs during COVID-19 were observed in some patients with memory disorders and their caregivers, and adherence to medication contributed to the stabilization of NPSs.

Homo-harringtonine (HHT) - A highly effective drug against coronaviruses and the potential for large-scale clinical applications (preprint)

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins (~16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.