Multi-scenario surveillance of respiratory viruses in aerosols with a sub-single molecule spatial resolution (preprint)

Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-CoV-2 and various respiratory viruses with a sensitivity of 10 copies/mL. When seamlessly integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single molecule spatial resolution of 0.83 copies/m3 for airborne virus surveillance. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.

CircRNA-Pro: A Novel Toolkit for High-Precision Detection of Differentially Expressed Circular RNAs and Translatable Circular RNAs (preprint)

With the increasing discovery of circular RNAs (circRNAs) and their critical roles in gene regulation and disease progression, there is a growing need for more accurate and efficient tools for circRNAs research. In response, we have developed an integrated software suite specifically for circRNAs. This all-in-one tool specializes in detecting differentially expressed circRNAs, including those with the potential to be translated into proteins, and allows for comparing against relevant databases, thereby enabling comprehensive circRNA profiling and annotation. To enhance the accuracy in detecting differentially expressed circRNAs, we incorporated three different software algorithms and cross-validated their results through mutual verification. Additionally, this toolkit improves the effectiveness in identifying translatable circRNAs by optimizing Ribo-seq alignment and verifying against public circRNA databases. The performance of circRNA-pro has been evaluated through its application to public RNA-seq and Ribo-seq datasets on breast cancer and SARS-CoV-2 infected cells, and the results obtained have been validated against previous literature and databases. Overall, our integrated toolkit provides a reliable workflow for circRNA research, facilitating insights into their diverse roles across life sciences.

Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis (preprint)

BackgroundAfter the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. MethodsWe conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. ResultsOur study included 274 records obtained from 147 household studies, contact tracing studies or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods. Specifically, we found that Omicron had the shortest pooled estimates for the incubation period (3.63 days, 95%CI: 3.25-4.02 days), serial interval (3.19 days, 95%CI: 2.95-3.43 days), and realized generation time (2.96 days, 95%CI: 2.54-3.38 days) whereas the ancestral lineage had the highest pooled estimates for each of them. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. We found considerable heterogeneities (I2 > 80%) when pooling the estimates across different virus lineages, indicating potential unmeasured confounding from population factors (e.g., social behavior, deployed interventions). ConclusionOur study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves.

An investigation of the incidence of post-traumatic stress disorder, turnover intention and psychological resilience among medical staff in a public hospital in China during the outbreak of the omicron variant in the COVID-19 pandemic in 2022.

Objective: To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods: Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points; the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results: The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected; in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD; the differences were statistically significant (all P < 0.05). Conclusion: Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

Impact of Home Literacy Environment on Literacy Development of Children with Intellectual Disabilities: A Moderated Mediation Model

Research on the effects of the home literacy environment (HLE) on the literacy development of children with intellectual disabilities (ID) is limited, and relevant results are inconsistent. This study aimed to explore the influence of the HLE on the literacy development of children with ID, and the role of the reading interest and parent-child relationship in this process. The subjects of this study were 381 children with ID from special needs schools in 7 regions of China, including 234 boys and 147 girls aged 6-15 years. This study adopted the network survey method, and parents of these children completed the surveys of the HLE, literacy development, reading interest, and parent-child relationship. The results revealed that the HLE significantly influenced the literacy development of children with ID, and the reading interest partially mediated this effect. In this mediating process, the regression relationship between the HLE and the reading interest was positively regulated by the parent-child relationship. This study suggests that improving the HLE and parent-child relationship is beneficial for the reading interest and literacy development of children with ID.

Investigating the Dynamics of Social Norm Emergence within Online Communities (preprint)

Although the effects of the social norm on mitigating misinformation are identified, scant knowledge exists about the patterns of social norm emergence, such as the patterns and variations of social tipping in online communities with diverse characteristics. Accordingly, this study investigates the features of social tipping in online communities and examines the correlations between the tipping features and characteristics of online communities. Taking the side effects of COVID-19 vaccination as the case topic, we first track the patterns of tipping features in 100 online communities, which are detected using Louvain Algorithm from the aggregated communication network on Twitter between May 2020 and April 2021. Then, we use multi-variant linear regression to explore the correlations between tipping features and community characteristics. We find that social tipping in online communities can sustain for two to four months and lead to a 50% increase in populations who accept the normative belief in online communities. The regression indicates that the duration of social tipping is positively related to the community populations and original acceptance of social norms, while the correlation between the tipping duration and the degrees among community members is negative. Additionally, the network modularity and original acceptance of social norms have negative relationships with the extent of social tipping, while the degree and betweenness centrality can have significant positive relationships with the extent of tipping. Our findings shed light on more precise normative interventions on misinformation in digital environments as it offers preliminary evidence about the timing and mechanism of social norm emergence.

Innate and adaptive immune response in SARS-CoV-2 infection-Current perspectives

Coronavirus disease 2019 (COVID-19) has been a global pandemic, caused by a novel coronavirus strain with strong infectivity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the in-depth research, the close relationship between COVID-19 and immune system has been dug out. During the infection, macrophages, dendritic cells, natural killer cells, CD8+ T cells, Th1, Th17, Tfh cells and effector B cells are all involved in the anti-SARS-CoV-2 responses, however, the dysfunctional immune responses will ultimately lead to the excessive inflammation, acute lung injury, even other organ failure. Thus, a detailed understanding of pertinent immune response during COVID-19 will provide insights in predicting disease outcomes and developing appropriate therapeutic approaches. In this review, we mainly clarify the role of immune cells in COVID-19 and the target-vaccine development and treatment.

Characterization of Oral Bacterial and Fungal Microbiome in Recovered COVID-19 Patients (preprint)

COVID-19 has emerged as a global pandemic, challenging the world’s economic and health systems. Human oral microbiota comprises the second largest microbial community after the gut microbiota and is closely related to respiratory tract infections; however, oral microbiomes of patients who have recovered from COVID-19 have not yet been thoroughly studied. Herein, we compared the oral bacterial and fungal microbiota after clearance of SARS-CoV-2 in 23 COVID-19 recovered patients to those of 29 healthy individuals. Our results showed that both bacterial and fungal diversity were nearly normalized in recovered patients. However, the relative abundance of some specific bacteria and fungi, primarily opportunistic pathogens, decreased in recovered patients (RPs), while the abundance of butyrate-producing organisms increased in these patients. Moreover, these differences were still present for some organisms at 12 months after recovery, indicating the need for long-term monitoring of COVID-19 patients after virus clearance.

ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2 (preprint)

Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism may associate with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and spike protein and between ApoE and also the SARS-CoV-2 primary receptor ACE2. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.Results ApoE gene polymorphism (ε4 carries genotypes VS non-ε4 carries genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI: 1.18–1.76) and progression (P < 0.00001, OR = 1.85, 95% CI: 1.50–2.28) of COVID-19. ApoE interacts with both the spike protein and ACE2 but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1–7.Conclusions ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin–angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

Impact of improved stroke green channel process on the delay of intravenous thrombolysis in patients with acute cerebral infarction during the COVID-19 pandemic: An observational study

Objective This study analyzed the impact of the improved stroke green channel process on the delay of intravenous thrombolysis in patients with acute cerebral infarction under coronavirus disease 2019 (COVID-19) prevention and control measures. Methods We included 57 patients from the stroke center of the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine before the improvement of the stroke green channel process (March–July 2019), as well as 94 patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak (March–July 2020) and 68 patients during the Omicron variant outbreak (March–July 2022) after the improvement of stroke green channel process. The door-to-needle time (DNT), door-to-imaging time (DIT), and door-to-test completion time were compared among the three groups. We analyzed the impact of this process improvement in the emergency green channel during the pandemic on the delay of intravenous thrombolysis. Results This study included a total of 229 patients with acute cerebral infarction who went through the green channel for intravenous thrombolysis (57 in the pre-pandemic group, 94 in the SARS-CoV-2 outbreak group, and 68 in the Omicron outbreak group). The percentages of patients undergoing intravenous thrombolysis in the pre-pandemic, SARS-CoV-2 outbreak, and Omicron outbreak groups differed significantly (19.32%, 22.27%, and 28.94%, respectively, P = 0.029). Compared to the pre-pandemic group, the National Institutes of Health Stroke Scale (NIHSS) score at admission was significantly higher in the Omicron outbreak group (7.71 ± 7.36 in the Omicron outbreak group vs. 5.00 ± 4.52 in the pre-pandemic group) (P = 0.026) but not in the SARS-CoV-2 outbreak group (4.79 ± 5.94 in the SARS-CoV-2 outbreak group vs. 5.00 ± 4.52 in the pre-pandemic group, P = 0.970). Significantly higher proportions of patients undergoing emergency intravenous thrombolysis came to the hospital by ambulance in the SARS-CoV-2 and Omicron outbreak groups compared to the pre-pandemic group (38.6% in the pre-pandemic group, 51.1% in the SARS-CoV-2 outbreak group, and 82.4% in the Omicron outbreak group, P < 0.001). Compared to the pre-pandemic group, the DIT was significantly higher in the SARS-CoV-2 outbreak group (22.42 ± 7.62 min in the SARS-CoV-2 outbreak group vs. 18.91 ± 8.23 min in the pre-pandemic group, P =0.031) but not the Omicron outbreak group (20.35 ± 10.38 min in the Omicron outbreak group vs. 18.91 ± 8.23 min in the pre-pandemic group, P = 0.543). The door-to-test completion time was significantly longer in the SARS-CoV-2 and Omicron outbreak groups compared to that in the pre-pandemic group (78.37 ± 25.17 min in the SARS-CoV-2 outbreak group, 92.60 ± 25.82 min in the Omicron outbreak group vs. 65.11 ± 22.35 min in the pre-pandemic group, P < 0.001);however, the DNT in the SARS-CoV-2 and Omicron outbreak groups did not differ significantly from those in the pre-pandemic group (both P > 0.05). Conclusion During the two periods of the COVID-19 outbreak (SARS-CoV-2 and Omicron), after the improvement of the green channel for intravenous thrombolysis, there might be some delay in in-hospital DIT during the SARS-CoV-2 outbreak, however, the in-hospital delay indicator DNT for intravenous thrombolysis were not affected.

An investigation of the incidence of post-traumatic stress disorder, turnover intention and psychological resilience among medical staff in a public hospital in China during the outbreak of the omicron variant in the COVID-19 pandemic in 2022

Objective To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points;the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected;in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD;the differences were statistically significant (all P < 0.05). Conclusion Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China：a case-ascertained study (preprint)

Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. We collected detailed information on 323 pediatric cases and their 951 household members, all received consecutively intensive RT-PCR testing. We estimated the transmission parameters. Both secondary infection attack rates (SARI) and secondary clinical attack rates (SARC) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. The mean incubation period and serial interval of Omicron variant were estimated to be 4.6±2.1 days and 3.9±3.7 days. The overall SARI and SARC among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. Full vaccination and booster vaccination of inactivated vaccines were 14.8% (5.8%-22.9%) and 18.9% (9.0%-27.7%) effective against Omicron infection and 21.5% (10.4%-31.2%) and 24.3% (12.3%-34.7%) effective against symptomatic disease. Overall, we found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Household transmission of SARS-CoV-2 during the Omicron wave in Shanghai, China:a case-ascertained study (preprint)

Background Since late 2021, the highly transmissible SARS-CoV-2 Omicron variant has driven a new surge of infections across the world. We used a case-ascertained study to determine the features of household transmission of SARS-CoV-2 Omicron variant in Shanghai, China. Methods We collected detailed information on 323 pediatric cases and their 951 household members in April 2022 during the Omicron outbreak. All household members received consecutively intensive RT-PCR testing for SARS-CoV-2 and routine symptom monitoring within 14 days after exposure to a confirmed case. We described the characteristics of study participants and estimated the transmission parameters. Both secondary infection attack rates (SAR I ) and secondary clinical attack rates (SAR C ) among adult household contacts were computed, through which the transmission heterogeneities in infectivity and susceptibility were characterized and the vaccine effectiveness were estimated. Results We estimated the mean incubation period of SARS-CoV-2 Omicron variant to be 4.6 (median: 4.4, IQR: 3.1-6.0) days and the mean serial interval to be 3.9 (median:4.0, IQR: 1.4-6.5) days. The overall SAR I and SAR C among adult household contacts were 77.11% (95% confidence interval [CI]: 73.58%-80.63%) and 67.03% (63.09%-70.98%). We found higher household susceptibility in females, while infectivity was not significantly different in primary cases by age, sex, vaccination status and clinical severity. The estimated VEs of full vaccination was 14.8% (95% CI: 5.8%-22.9%) against Omicron infection and 21.5% (95% CI: 10.4%-31.2%) against symptomatic disease. The booster vaccination was 18.9% (95% CI: 9.0%-27.7%) and 24.3% (95% CI: 12.3%-34.7%) effective against infection and symptomatic disease, respectively. Conclusions We found high household transmission during the Omicron wave in Shanghai due to asymptomatic and pre-symptomatic transmission in the context of city-wide lockdown, indicating the importance of early detection and timely isolation of SARS-CoV-2 infections and quarantine of close contacts. Marginal effectiveness of inactivated vaccines against Omicron infection poses great challenge for prevention and control of the SARS-CoV-2 Omicron variant.

Response of Natural Gas Consumption to Temperature and Projection under SSP Scenarios during Winter in Beijing

The present study investigates the response of natural gas consumption to temperature on the basis of observations during heating season (middle November–middle March) for the period 2002–2021 in Beijing, China, and then estimates temperature-related changes in the gas consumption under future scenarios by using climate model simulations from the Coupled Model Intercomparison Project Phase 6. Observational evidence suggests that the daily natural gas consumption normalized by gross domestic product is linearly correlated with the daily average temperature during heating season in the past two decades in Beijing. Hence, a linear regression model is built to estimate temperature-related changes in the natural gas consumption under future scenarios. Corresponding to a rising trend in the temperature, the natural gas consumption shows a decrease trend during 2015–2100 under both the SSP245 and the SSP585 scenarios. In particular, the temperature would increase rapidly from early 2040s to the end of 21st century under the SSP585 scenario, leading to an obvious reduction in the natural gas consumption for heating in Beijing. Relative to that in the present day (1995–2014), the natural gas consumption would show a reduction of approximately 9% (±4%) at the end of 21st century (2091–2100) under the SSP245 scenario and approximately 22% (±7%) under the SSP585 scenario.

HiFuse: Hierarchical Multi-Scale Feature Fusion Network for Medical Image Classification (preprint)

Medical image classification has developed rapidly under the impetus of the convolutional neural network (CNN). Due to the fixed size of the receptive field of the convolution kernel, it is difficult to capture the global features of medical images. Although the self-attention-based Transformer can model long-range dependencies, it has high computational complexity and lacks local inductive bias. Much research has demonstrated that global and local features are crucial for image classification. However, medical images have a lot of noisy, scattered features, intra-class variation, and inter-class similarities. This paper proposes a three-branch hierarchical multi-scale feature fusion network structure termed as HiFuse for medical image classification as a new method. It can fuse the advantages of Transformer and CNN from multi-scale hierarchies without destroying the respective modeling so as to improve the classification accuracy of various medical images. A parallel hierarchy of local and global feature blocks is designed to efficiently extract local features and global representations at various semantic scales, with the flexibility to model at different scales and linear computational complexity relevant to image size. Moreover, an adaptive hierarchical feature fusion block (HFF block) is designed to utilize the features obtained at different hierarchical levels comprehensively. The HFF block contains spatial attention, channel attention, residual inverted MLP, and shortcut to adaptively fuse semantic information between various scale features of each branch. The accuracy of our proposed model on the ISIC2018 dataset is 7.6% higher than baseline, 21.5% on the Covid-19 dataset, and 10.4% on the Kvasir dataset. Compared with other advanced models, the HiFuse model performs the best. Our code is open-source and available from https://github.com/huoxiangzuo/HiFuse.