Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine (preprint)

SARS-CoV-2 has the ability to evade immunity, resulting in breakthrough infections even after vaccination. Similarly, zoonotic coronaviruses pose a risk of spillover to humans. There is an urgent need to develop a pre-emptive pan-coronavirus vaccine that can induce systemic and mucosal immunity. Here, we employed a combination of immune-informatics approaches to identify shared immunodominant linear B- and T-cell epitopes from SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs), as well as zoonotic coronaviruses. Epitope-guided vaccine were designed and the attenuated coxsackievirus B3 vectored intranasal vaccines rCVB3-EPI and rCVB3-RBD-trimer were constructed. The immunogenicity of these candidate vaccines was evaluated using Balb/c mice. The results demonstrated effective immune responses, including the production of SARS-CoV-2-specific IgG and sIgA antibodies, as well as T cell-mediated responses. However, further verification is required to assess cross-reactivity with various variants. Our intranasal pre-emptive pan-coronavirus vaccine design framework offers an appealing candidate for future vaccine development.

Causal Associations Between Ulcerative Colitis and COVID-19: A Bidirectional Mendelian Randomization Study (preprint)

Background Corona Virus Disease 2019(COVID-19) has put human health and medical resources under strain since 2019. However, it’s still equivocal whether ulcerative colitis (UC) and COVID-19 have a bidirectional causal relationship, so we attempted to clarify this issue using two-sample mendelian randomization (two-sample MR) analysis.Methods To explore the relationship between ulcerative colitis and COVID-19, we obtained summary statistics from the GWAS database and used single nucleotide polymorphisms (SNPs) as a genetic tool. The inverse-variance weighted (IVW) method was chosen as the primary analytical method for two-sample Mendelian randomization analysis, complemented by a combination of MR-egger. Further validation using sensitivity analysis such as Q-test, MR-PRESSO, MR-Egger intercepts method.Result All forward MR analyses demonstrated that UC has a significant susceptibility and severity to COVID-19, 1. COVID-19 vs population: IVW (OR = 1.053; CI, 1.012–1.096; P = 0.009) and MR Egger (OR = 1.015; CI, 0.946–1.089; P = 0.672). 2.hospitalized vs population: IVW (OR = 1.080; CI, 1.004–1.162; P = 0.037) and MR Egger (OR = 1.009; CI, 0.882–1.153; P = 0.898). 3. very severe respiratory confirmed vs population: IVW (OR = 1.187; CI, 1.018–1.384; P = 0.027) and MR Egger (OR = 1.104; CI, 0.801–1.521; P = 0.554). In the bidirectional MR study, the P values (P > 0.05) obtained by several methods were not statistically significant.Conclusion There is significant evidence that UC is both a risk factor for COVID-19 and may increase the risk of COVID-19. However, there is no reverse causal relationship between the two diseases.

A new model for investigating the effective factors in the development of modern clinical and health services in the time of COVID-19

Excessive information exposure and misleading information in controlling COVID-19 disease have affected the dimensions of people's lives and caused mental health problems. Healthcare effectiveness is a critical subject worldwide. Thus, engaging resources in the progress and use of e-health technologies are very crucial, especially in the COVID-19 era. Due to the sensitivity of this issue and the world health organization's attention to developing new clinical and health services in the pandemic, this article introduces and presents a new model. This new model investigates the factors influencing the development of modern clinical and health services during the pandemic era. Also, this research presents a new model to investigate the technological, management, environmental, social, and cultural factors and perceived usefulness and ease of use influencing the development of modern clinical and health services throughout COVID-19. The questionnaire survey technique is utilized for gathering data. The authors contacted about 300 potential respondents. To statistically analyze the questionnaires, Smart-PLS 3.2 software is used. The outcomes illustrate a great strength of the suggested model. The results demonstrate that technological, management, social, cultural, and environmental factors positively affect perceived usefulness and ease of use. They also show that perceived usefulness and ease of use are significant factors in developing modern clinical and health services.

Strategic alliances and firms' chances to survive "black swans” in B2B industries

Purpose>This study aims to propose that, in business-to-business (B2B) industries, number of strategic alliances firms established before a "black swan” event enhances their chances to survive the black swan, and the enhancements take place through moderation effects. Changes in firms' core structures – their stated goals, authority structure, core technologies and marketing strategies – to adapt to business jolts have adverse effects on firm performance. Firms' existing B2B strategic alliances moderate the effects negatively by outsourcing different goals, authority structures, core technologies and marketing strategies to partners who fit the changed environment.Design/methodology/approach>This study collected quantitative data and analyzed the data with the regression method.Findings>Using data from Chinese firms in five technology industries during the 2007–2009 economic crisis, this study finds that firms' internal adaptation is negatively correlated with their performance during economic crises, and B2B strategic alliances negatively moderate this relationship.Research limitations/implications>First, this study focuses on B2B strategic alliances, and it is not clear whether the findings apply to B2C industries, where strategic alliances may not be common. Perhaps firms can use other means of survival in addition to strategic alliances in B2C industries. Second, this study does not differentiate between fast-moving and slow-moving industries, and it is not clear whether strategic alliances play the same role in both industries. Third, this study does not differentiate firm ages and sizes. It remains unclear how large, established and small, young firms differ when facing crises. Finally, this study is based on the Chinese setting, and it is not clear whether the findings apply to other markets as well. These issues should be explored in future studies.Practical implications>Changing firms' core structures harms their performance during black swan crises because such crises are unpredictable, and planned changes may not adapt firms to crises. Managers should not attempt to change their core structures during crises. B2B strategic alliances provide an effective means for firms to survive crises.Originality/value>This paper makes two contributions to the existing literature: First, this paper demonstrates that changes of one of the four core structures of a firm to cope with black swan events have negative impacts on firm performance. Second, this paper identifies the importance of holding a variety of strategic alliances previously to the black swan events to reduce the negative impacts of changing core structures.

Cost-effectiveness of the second COVID-19 booster vaccination in the United States (preprint)

ABSTRACT Background: On March 29, 2022, the United States (US) authorized the second booster dose of COVID-19 vaccine for individuals aged 50 years and older. To date, the cost-effectiveness of the second booster strategy remains unassessed. Methods: We developed a decision-analytic SEIR-Markov model by five age groups (0-4yrs with 18,827,338 individuals, 5-11yrs with 28,584,443 individuals, 12-17yrs with 26,154,652 individuals, 18-49yrs with 138,769,369 individuals, and 50+yrs with 119,557,943 individuals) to evaluate the cost-effectiveness of the second COVID-19 booster vaccination (administered 4 months after the first booster dose) over an evaluation period of 180 days in the US, from a healthcare system perspective. Results: Implementing the second booster strategy among individuals aged 50+ years would cost US$807 million but reduce direct medical care costs by $1,128 million, corresponding to a benefit-cost ratio of 1.40. This strategy would also result in a gain of 1,048 QALYs during the 180 days, indicating it was cost-saving. Probabilistic sensitivity analysis demonstrated that the probability of being cost-effective with the strategy was 68%. Further, vaccinating individuals aged 18-49 years with the second booster would result in an additional gain of $1,566 million and 2,276 QALYs. Expanding vaccination to individuals aged 12-17 years would result in an additional gain of $15 million and 89 QALYs. Coverage of the first booster vaccination in age groups under 12 was too low to consider the administration of the second booster. If the social interaction between all age groups was severed, vaccination expansion to 18-49yrs and 12-17yrs would no longer be cost-effective. Conclusion: The second booster strategy was likely to be effective and cost-effective in reducing the disease burden of the COVID-19 pandemic. Expanding the second booster strategy to 18-49yrs and 12-17yrs remains cost-effective due to their social contacts with the older age group. Keywords: COVID-19; Second booster; Cost-effective analysis; SEIR-Markov model; Age groups

Network pharmacology analysis on mechanisms of xuanfei baidu prescription in treatment of SARS, MERS and COVID-19

Objective: To explore the effective components, target and signal pathway of Xuanfei Baidu Prescription in treatment of coronavirus infection, and to explain its mechanism of action. Methods A network of Character, taste, and meridian of Xuanfei Baidu Prescription was constructed using Cytoscape. Effective components and related targets of Xuanfei Baidu Prescription were selected by using TCMSP database, SwissADME database, and Swiss Target Prediction database. Disease targets of SARS, MERS and COVID-19 were collected using GeneCards database and CTD database. Drug targets and disease targets were intersected, and Cytoscape software was used to construct the network diagram. Using String database, the network model of protein-protein interaction (PPI) was constructed for potential targets. Metascape database was used for GO and KEGG enrichment analysis of potential targets, and Cytoscape was used to construct the network diagram. Results The results showed that 10 ingredients in Xuanfeibaidu Prescription are associated with the Lung meridian. 167 active components and 242 potential targets were screened out. The core drugs were Glycyrrhiza uralensis Fisch.,Ephedrae Herba, Artemisia annua L, Verbena officinalis L., Polygonum cuspidatum Sieb. et Zucc.. The core components were quercetin, stigmasterol, kaempferol, luteolin, isorhamnetin. The core targets were AKT1, IL-6, TP53, VEGFA, TNF. The possible mechanism of action is related to several signaling pathways such as PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, and so on. Conclusion This study explored the potential common mechanism of Xuanfei Baidu Prescription on SARS, MERS and COVID-19, reflecting the multi-component, multi-target and multi-pathway characteristics of TCM.

Flexible Scheduling Model of Bus Services between Venues of the Beijing Winter Olympic Games

Traditional buses travel on fixed routes and areas, which cannot satisfy the flexible demands of athletes in the context of COVID-19 and the closed-loop traffic management policy during the 2022 Beijing Winter Olympic Games (BWOG). This study predicts the travel demands based on the characteristics of athletes' daily travel demands and then presents a flexible bus service scheduling model for cross-region scheduling among Beijing, Yanqing, and Zhangjiakou to provide high-level service. The flexible bus service is point-to-point and avoids unnecessary contact, which reduces the risk of spreading COVID-19 and ensures athletes' safety. In this study, the flexible bus scheduling model is established to optimize scheduling schemes, whose object is to minimize the cost of the system based on some realistic constraints. These constraints consider not only the preferred time windows of athletes' demand but also the vehicle's capacity, depot, minimum load factor, total demands, etc. In addition, a genetic-simulated annealing hybrid algorithm (GSAHA) is designed to solve the model based on the characteristics of the genetic algorithm (GA) and simulated annealing. To assess the feasibility and efficiency of the model and algorithm, a case study is conducted in the Beijing-Yanqing area. Furthermore, the travel time of the flexible bus is compared to that of the traditional bus, according to the results of the case study. Moreover, the sensitivity of the model and algorithm are analyzed. The experimental results show that the proposed model and algorithm can dispatch buses with superior flexibility and high-level services during the BWOG. [ FROM AUTHOR]

Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2

Monoclonal antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting mAb by regulatory authority. However, the continuous virus evolution requires diverse mAb options to combat variants. Here we describe two fully human mAbs, amubarvimab (BRII-196) and romlusevimab (BRII-198) that bind to non-competing epitopes on the receptor binding domain (RBD) of spike protein and effectively neutralize SARS-CoV-2 variants. A YTE modification was introduced to the fragment crystallizable (Fc) region of both mAbs to prolong serum half-life and reduce effector function. The amubarvimab and romlusevimab combination retained activity against most mutations associated with reduced susceptibility to previously authorized mAbs and against variants containing amino acid substitutions in their epitope regions. Consistently, the combination of amubarvimab and romlusevimab effectively neutralized a wide range of viruses including most variants of concern and interest in vitro. In a Syrian golden hamster model of SARS-CoV-2 infection, animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic.

Impact of the COVID-19 pandemic on research on marine plastic pollution – A bibliometric-based assessment

Fighting the COVID-19 pandemic has led to a dramatic increase in plastic waste, which has had a huge impact on the environment, including the marine environment. This work is aimed to evaluate the pattern of national research cooperation, research hotspots, and research evolution before and during the epidemic by systematically reviewing the publications on marine plastic pollution during 2015-2019 (before the pandemic) 2020-2022 (during the pandemic) using the Systematic Literature Review and Latent Semantic Analysis. The results show (i) Compared to pre-pandemic, publications on marine pollution during the COVID-19 pandemic declined briefly and then increased sharply. (ii) Compared with before the pandemic, the national cooperation model has changed during the pandemic, and four major research centers have been formed: Central European countries centered on Italy;Nordic countries centered on United Kingdom;South Korea;Asia and Africa centered on India A developing country and a Pacific Rim country centered on United States and China. (iii) The knowledge map of keyword clustering does not change significantly before and during the COVID-19: ecosystem, spatial distribution, environmental governance and biodegradation. However, there are differences in the sub-category research of the four types of keywords. (iv) The impact of marine plastics on organisms and the governance of marine plastic pollution have become a branch of knowledge that has evolved rapidly during the pandemic. The governance of marine plastic pollution and microplastics are expected to become an important research direction.

Photocatalytic Chemical Crosslinking for Profiling RNA–Protein Interactions in Living Cells

The dynamic interactions between RNAs and proteins play crucial roles in regulating diverse cellular processes. Proteome‐wide characterization of these interactions in their native cellular context remains desirable but challenging. Herein, we developed a photocatalytic crosslinking (PhotoCAX) strategy coupled with mass spectrometry (PhotoCAX‐MS) and RNA sequencing (PhotoCAX‐seq) for the study of the composition and dynamics of protein‐RNA interactions. By integrating the blue light‐triggered photocatalyst with a dual‐functional RNA–protein crosslinker (RP‐linker) and the phase separation‐based enrichment strategy, PhotoCAX‐MS revealed a total of 2044 RBPs in human HEK293 cells. We further employed PhotoCAX to investigate the dynamic change of RBPome in macrophage cells upon LPS‐stimulation, as well as the identification of RBPs interacting directly with the 5′ untranslated regions of SARS‐CoV‐2 RNA. [ FROM AUTHOR] Copyright of Angewandte Chemie International Edition is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

mRNA-based COVID-19 booster vaccination is highly effective and cost-effective in Australia (preprint)

Background: Australia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days. Methods: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2nd dose) in those aged [≥]16 years in Australia from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000. Findings: Compared with 2-doses of COVID-19 vaccines without a booster, Australia's booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days. Interpretation: The COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness.

Preliminary evaluation of a new initiative to centralize colorectal cancer care during the COVID-19 epidemic in Shanghai, China: a retrospective study

Background A novel colorectal cancer center (CCC) was developed in the Shanghai Tenth People’s hospital of Tongji University during the COVID-19 epidemic. In this study, we aimed to evaluate the CCC model in terms of three aspects. Methods This retrospective study used data from the Shanghai Tenth People’s hospital patient databases. The research hypothesis was that the CCC reduces preoperative waiting time (PWT), length of hospital stay (LOS), and costs of hospitalization, without reducing the quality of surgery. Thus, we compared the time, cost, and quality between March 1 to December 31, 2019, and March 1 to December 31, 2020. Descriptive and inferential analyses of patient demographic characteristics, time, postoperative outcomes, and inpatient costs were conducted. Results A total of 965 hospitalizations for colorectal cancer (CRC) were identified—415 in 2019 and 550 in 2020. In the CCC, PWT declined by 26.2 hours (P<0.01). Patients in the CCC express group only needed to wait for 24.5 hours before undergoing surgery, with a shorter LOS than the normal group (P<0.01). None of the patients had any symptoms of COVID-19 or were high-risk COVID-19 contacts, and the incidence of immediate postoperative complications was low. The mean total inpatient cost (TIC) for all patients with CRC was 78,309.824 Chinese Yuan in 2020, which was slightly lower than that in 2019. Conclusions This study found that the centralized management model for CRC care could help patients save the PWT, LOS and costs of hospitalization during the COVID-19 epidemic.

Eliminating Mother-to-Child Transmission of Syphilis: Chinese Practice before and during COVID-19 Pandemics.

Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, WHO launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100 000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are great challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, point out that we have made remarkable achievements due to the national health policy support and strong leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19 and adopting safe, rapid, early and high-quality clinical care to ensure that 100% of pregnant women receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are key measures to determine the effect of MTCT of syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.

TransMUSE: Transferable Traffic Prediction in MUlti-Service EdgeNetworks (preprint)

The Covid-19 pandemic has forced the workforce to switch to working from home, which has put significant burdens on the management of broadband networks and called for intelligent service-by-service resource optimization at the network edge. In this context, network traffic prediction is crucial for operators to provide reliable connectivity across large geographic regions. Although recent advances in neural network design have demonstrated potential to effectively tackle forecasting, in this work we reveal based on real-world measurements that network traffic across different regions differs widely. As a result, models trained on historical traffic data observed in one region can hardly serve in making accurate predictions in other areas. Training bespoke models for different regions is tempting, but that approach bears significant measurement overhead, is computationally expensive, and does not scale. Therefore, in this paper we propose TransMUSE, a novel deep learning framework that clusters similar services, groups edge-nodes into cohorts by traffic feature similarity, and employs a Transformer-based Multi-service Traffic Prediction Network (TMTPN), which can be directly transferred within a cohort without any customization. We demonstrate that TransMUSE exhibits imperceptible performance degradation in terms of mean absolute error (MAE) when forecasting traffic, compared with settings where a model is trained for each individual edge node. Moreover, our proposed TMTPN architecture outperforms the state-of-the-art, achieving up to 43.21% lower MAE in the multi-service traffic prediction task. To the best of our knowledge, this is the first work that jointly employs model transfer and multi-service traffic prediction to reduce measurement overhead, while providing fine-grained accurate demand forecasts for edge services provisioning.

COVID-19: Exercise Behavior of College Students Communicating at Home (preprint)

Background: During the outbreak and spread of COVID-19, the extension of college students' time spent studying at home changed their physical exercise behavior and affected the physical activity behavior of the whole family. Methods: A questionnaire survey was conducted among 1,582 college students using a specific measurement scale. A total of 305 urban college students were selected as research subjects. SPSS24.0 and AMOS24.0 were used for statistical analysis. Results: During the COVID-19 transmission period, the pair correlation coefficients of exercise behavior, exercise attitude, and family exercise conditions were 0.63, 0.36, and 0.25, respectively. The influence on family exercise behavior is as follows: college students' exercise behavior (0.403), family exercise support (0.329), and college students' exercise attitude (0.257). The most significant influence on family exercise support is college students' exercise attitude (0.509). The regression model of family exercise behavior standardization had 0.74 and 0.44 explanatory power to family exercise behavior and family exercise support, respectively. Conclusions: The individual-level interventions were assessed by considering the interaction between individual exercise behavior and individual factors. In addition, the exercise environment exhibited a regulatory role and should be controlled. At the interpersonal level, the communication of the college students regarding exercise behavior was bidirectional. Exercise support for family members is an important factor affecting two-way communication and has a significant effect. With the development of the exercise behavior theory, the interaction between individuals is the origin of the spread of group behavior. The data suggest that instead of one-way influence two-way influence mechanisms should be proposed to assess the transformation from the individual to group exercise behavior.