Pathway-enhanced Transformer-based model for robust enumeration of cell types from the cell-free transcriptome (preprint)

Analysis cell types origin of cell-free RNA can enhance the resolution of liquid biopsies, thereby deepening the understanding of molecular and cellular changes in development and disease processes. Existing deconvolution methods typically rely on meticulously curated gene expression profiles or employ deep neural network with vast and complex solution spaces that are difficult to interpret. These approaches fail to leverage the synergistic and co-expression effects among genes in biological signaling pathways, compromising their generalizability and robustness. To address this issue, we have developed 'Deconformer', a Transformer-based deconvolution model that integrates biological signaling pathways at the embedding stage. Compared to popular methods on multiple datasets, Deconformer demonstrates superior performance and robustness, and is capable of tracking the developmental process of the placenta. Additionally, Deconformer's self-attention mechanism has identified a connection between platelet activation, dependencies with other pathways, and the severity of COVID-19. We believe that Deconformer will enable and accelerate the precise analysis of a wide range of cell-free RNA, describing disease progression and severity from the perspectives of originating cell fractions and pathway dependencies.

Prevention and treatment of ventilator-associated pneumonia in COVID-19

Ventilator-associated pneumonia (VAP) is the most common acquired infection in the intensive care unit. Recent studies showed that the critical COVID-19 patients with invasive mechanical ventilation have a high risk of developing VAP, which result in a worse outcome and an increasing economic burden. With the development of critical care medicine, the morbidity and mortality of VAP remains high. Especially since the outbreak of COVID-19, the healthcare system is facing unprecedented challenges. Therefore, many efforts have been made in effective prevention, early diagnosis, and early treatment of VAP. This review focuses on the treatment and prevention drugs of VAP in COVID-19 patients. In general, prevention is more important than treatment for VAP. Prevention of VAP is based on minimizing exposure to mechanical ventilation and encouraging early release. There is little difference in drug prophylaxis from non-COVID-19. In term of treatment of VAP, empirical antibiotics is the main treatment, special attention should be paid to the antimicrobial spectrum and duration of antibiotics because of the existence of drug-resistant bacteria. Further studies with well-designed and large sample size were needed to demonstrate the prevention and treatment of ventilator-associated pneumonia in COVID-19 based on the specificity of COVID-19.

Optimal Control and Stability Analysis of an SEIR Model with Infectious Force in Latent Period.

In this paper, an SEWIR epidemic model with the government control rate and infectious force in latent period is proposed. The conditions to the existence and uniqueness of disease-free and endemic equilibrium points in the SEWIR model are obtained. By using the Hurwitz criterion, the locally asymptotic stability of disease-free and endemic equilibrium points is proved. We show the global asymptotic stability of the disease-free equilibrium point by the construction of Lyapunov function and LaSalle invariance principle. The globally asymptotic stability of the endemic equilibrium is verified by numerical simulation. Several optimal control strategies are proposed on controlling infectious diseases.

Infectivity and antigenicity of SARS-CoV-2 B.1.617 variants (preprint)

SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants was enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.

Risk and Protective Factors for Anxiety Disorder During COVID-19 Pandemic (preprint)

Background: COVID-19 is a global pandemic and an anxiety-provoking event. Therefore, a study was conducted to identify potential risk and protective factors related to anxiety during COVID-19 pandemic.Methods: We collected information on demographic data and lifestyles by conducting a web-based survey of 19,802 participants from 34 provinces in China during COVID-19 pandemic. Level of anxiety was evaluated using the Self-Rating Anxiety Scale. We used ordinal multivariable logistic regression to estimate the associations of anxiety level with potential risk and protective factors, and further developed a new score to simplify the assessment of anxiety disorder during COVID-19 crisis.Results: Among 19,802 participants (mean [SD] age, 25.3 [8.1], years; 10,121 [51.1%] men), we found that those who were front-line medical personnel, suffered from chronic diseases, with present symptom of SARS-CoV-2 infection or contact history had 112%, 93%, 40% and 15% increase risk of higher anxiety level; while those with knowledge about personal protective measures or wore masks had 75% and 29% lower risk of higher anxiety level respectively. We developed a risk score by calculating the sum of single score of 17 factors. Each one increase of the risk score was associated with a 297% increase in anxiety index score. In categorical analysis, low risk (the risk score between 1 to 2), the moderate risk group (the risk score of 3) and high risk group (the risk score ≥4) had a -0.40 (95% CI: -1.55, 0.76), 1.44 (95% CI: 0.27, 2.61) and 9.18 (95% CI: 8.04, 10.33) increase in anxiety index score, and a 26% (95% CI: -7%, 72%), 172% (95% CI: 100%, 270%), and 733% (95% CI: 516%, 1026%) higher risk of anxiety disorder respectively, when compared with the very low risk group (the risk score of 0). The AUC was 0.73 (95% CI: 0.72, 0.74) for the model fitted the developed risk score, with the cut-off point of 3.5.Conclusions: These findings revealed protective and risk factors associated with anxiety disorder, and propose a practical and simple method of identifying people who are at an increased risk of anxiety disorder during COVID-19 pandemic.

A Couple with Different Symptoms after Simultaneously 2019-nCoV Infected (preprint)

Background 2019-nCoV has posed a significant threat to human health since the epidemic began. So far, there is no definite safe and effective drug treatment. Proper management can help prevent mild patients from becoming severe. We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV and analyze the changes in the diagnosis and treatment process. Case presentation We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV in Shandong, China，describe their clinical course，characteristics and detection results in detail, and analyze the changes in the diagnosis and treatment process. The wife was mainly affected by respiratory system and had ever experienced high fever for several days. The husband's condition is lighter than his wife，mainly manifested as digestive tract symptoms，but it took longer than his wife for the nucleic acid of nasopharynx swab for 2019-nCoV to turn negative. Conclusions   In the course of the disease both of the couple had hypokalemia which was easy to be corrected. CRP and ESR were consistent with the changes of the disease during the 2019-nCoV infection, which were good indicators to reflect the severity and development of the disease. Two months after discharge, both of them showed negative IgM antibody and positive IgG antibody.