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Background: Long-lasting nonpharmaceutical interventions (NPIs) suppressed the infection of COVID-19 but came at a substantial economic cost and the elevated risk of the outbreak of respiratory infectious diseases (RIDs) following the pandemic. Policymakers need data-driven evidence to guide the relaxation with adaptive NPIs that consider the risk of both COVID-19 and other RIDs outbreaks, as well as the available healthcare resources., Methods: Combining the COVID-19 data of the sixth wave in Hong Kong between May 31, 2022 and August 28, 2022, 6-year epidemic data of other RIDs (2014-2019), and the healthcare resources data, we constructed compartment models to predict the epidemic curves of RIDs after the COVID-19-targeted NPIs. A deep reinforcement learning (DRL) model was developed to learn the optimal adaptive NPIs strategies to mitigate the outbreak of RIDs after COVID-19-targeted NPIs are lifted with minimal health and economic cost. The performance was validated by simulations of 1000 days starting August 29, 2022. We also extended the model to Beijing context., Findings: Without any NPIs, Hong Kong experienced a major COVID-19 resurgence far exceeding the hospital bed capacity. Simulation results showed that the proposed DRL-based adaptive NPIs successfully suppressed the outbreak of COVID-19 and other RIDs to lower than capacity. DRL carefully controlled the epidemic curve to be close to the full capacity so that herd immunity can be reached in a relatively short period with minimal cost. DRL derived more stringent adaptive NPIs in Beijing., Interpretation: DRL is a feasible method to identify the optimal adaptive NPIs that lead to minimal health and economic cost by facilitating gradual herd immunity of COVID-19 and mitigating the other RIDs outbreaks without overwhelming the hospitals. The insights can be extended to other countries/regions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporosis (OP) is commonly encountered, which is a kind of systemic injury of bone mass and microstructure, leading to brittle fractures. With the aging of the population, this disease will pose a more serious impact on medical, social, and economic aspects, especially postmenopausal osteoporosis (PMOP). This study is aimed at figuring out potential therapeutic targets and new biomarkers in OP via bioinformatics tools. After differentially expressed gene (DEG) analysis, we successfully identified 97 upregulated and 172 downregulated DEGs. They are mainly concentrated in actin binding, regulation of cytokine production, muscle cell promotion, chemokine signaling pathway, and cytokine-cytokine receiver interaction. According to the diagram of protein-protein interaction (PPI), we obtained 10 hub genes: CCL5, CXCL10, EGFR, HMOX1, IL12B, CCL7, TBX21, XCL1, PGR, and ITGA1. Expression analysis showed that Egfr, Hmox1, and Pgr were significantly upregulated in estrogen-treated osteoporotic patients, while Ccl5, Cxcl10, Il12b, Ccl7, Tbx21, Xcl1, and Itga1 were significantly downregulated. In addition, the analysis results of Pearson's correlation revealed that CCL7 has a strong positive association with IL12b, TBX21, and CCL5 and so was CCL5 with IL12b. Conversely, EGFR has a strong negative association with XCL1 and CXCL10. In conclusion, this study screened 10 hub genes related to OP based on the GEO database, laying a biological foundation for further research on new biomarkers and potential therapeutic targets in OP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Mengdie Hu et al.)

The accumulation of susceptible populations for respiratory infectious diseases (RIDs) when COVID-19-targeted non-pharmaceutical interventions (NPIs) were in place might pose a greater risk of future RID outbreaks. We examined the timing and magnitude of RID resurgence after lifting COVID-19-targeted NPIs and assessed the burdens on the health system. We proposed the Threshold-based Control Method (TCM) to identify data-driven solutions to maintain the resilience of the health system by re-introducing NPIs when the number of severe infections reaches a threshold. There will be outbreaks of all RIDs with staggered peak times after lifting COVID-19-targeted NPIs. Such a large-scale resurgence of RID patients will impose a significant risk of overwhelming the health system. With a strict NPI strategy, a TCM-initiated threshold of 600 severe infections can ensure a sufficient supply of hospital beds for all hospitalized severely infected patients. The proposed TCM identifies effective dynamic NPIs, which facilitate future NPI relaxation policymaking.

The COVID-19 pandemic has caused a dramatic surge in demand for personal protective equipment (PPE) worldwide. Many countries have imposed export restrictions on PPE to ensure the sufficient domestic supply. The surging demand and export restrictions cause shortage contagions on the global PPE trade network. Here, an integrated network model is developed, which integrates a metapopulation model and a threshold model, to investigate the shortage contagion patterns. The metapopulation model captures disease contagion across countries. The threshold model captures the shortage contagion on the global PPE trade network. Due to the Pareto distribution in global exports, the shortage contagion pattern is mainly determined by the export restriction policies of the top exporters. Export restrictions exacerbate the shortages of PPE and cause the shortage contagion to transmit even faster than the disease contagion. To some extent, export restrictions can provide benefits for self-sufficient countries, at the sacrifice of immediate economic shocks at not-self-sufficient countries. With export restrictions, a large amount of PPE is hoarded instead of being distributed to where it is most needed, particularly at the early stage. Cooperation between countries plays an essential role in preventing global shortages of PPE regardless of the production level. Except for promoting global cooperation, governments and international organizations should take actions to reduce supply chain barriers and work together to increase global PPE production., Competing Interests: The authors declare no conflict of interest., (© 2021 Wiley‐VCH GmbH.)

MutS homolog 2 (MSH2) is a crucial participant in human DNA repair, and lots of the studies functionally associated with it were begun with hereditary nonpolyposis colorectal cancer (HNPCC). MSH2 has also been reported to take part in the progresses of various tumors' formation. With the help of GTEx, CCLE, and TCGA pan-cancer databases, the analysis of MSH2 gene distribution in both tumor tissues and normal control tissues was carried out. Kaplan-Meyer survival plots and COX regression analysis were conducted for the assessment into the MSH2's impact on tumor patients' clinical prognosis. In an investigation to the association of MSH2 expression with immune infiltration level of various tumors and a similar study on tumor immune neoantigens, microsatellite instability was subsequently taken. It was found that high expression of MSH2 is prevalent in most cancers. MSH2's efficacy on clinical prognosis as well as immune infiltration in tumor patients revealed a fact that expression of MSH2 in prostate adenocarcinoma (PRAD), brain lower-grade glioma (LGG), breast-invasive carcinoma (BRCA), and head and neck squamous cell carcinoma (HNSC) posed a significant correlation with the immune cell infiltration level of patients. Likewise as above, MSH2's expression comes in a similar trend with tumor immune neoantigens and microsatellite instability. MSH2's expression in the majority of tumors is a direct factor to the activation of tumor-associated pathways as well as immune-associated pathways. MSH2's early screening or even therapeutic target role for sarcoma (SARC) diagnosis is contributing to the efficiency of early screening and overall survival in SARC patients., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Hai Yao et al.)

Objectives: The aim of the study was to reconstruct the complete transmission chain of the COVID-19 outbreak in Beijing's Xinfadi Market using data from epidemiological investigations, which contributes to reflecting transmission dynamics and transmission risk factors., Methods: We set up a transmission model, and the model parameters are estimated from the survey data via Markov chain Monte Carlo sampling. Bayesian data augmentation approaches are used to account for uncertainty in the source of infection, unobserved onset, and infection dates., Results: The rate of transmission of COVID-19 within households is 9.2%. Older people are more susceptible to infection. The accuracy of our reconstructed transmission chain was 67.26%. In the gathering place of this outbreak, the Beef and Mutton Trading Hall of Xinfadi market, most of the transmission occurs within 20 m, only 19.61% of the transmission occurs over a wider area (>20 m), with an overall average transmission distance of 13.00 m. The deepest transmission generation is 9. In this outbreak, there were 2 abnormally high transmission events., Conclusions: The statistical method of reconstruction of transmission trees from incomplete epidemic data provides a valuable tool to help understand the complex transmission factors and provides a practical guideline for investigating the characteristics of the development of epidemics and the formulation of control measures., Competing Interests: Conflict of interest statement All authors have no conflict of interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite broad agreement on the negative consequences of vaccine inequity, the distribution of COVID-19 vaccines is imbalanced. Access to vaccines in high-income countries (HICs) is far greater than in low- and middle-income countries (LMICs). As a result, there continue to be high rates of COVID-19 infections and deaths in LMICs. In addition, recent mutant COVID-19 outbreaks may counteract advances in epidemic control and economic recovery in HICs. To explore the consequences of vaccine (in)equity in the face of evolving COVID-19 strains, we examine vaccine allocation strategies using a multistrain metapopulation model. Our results show that vaccine inequity provides only limited and short-term benefits to HICs. Sharper disparities in vaccine allocation between HICs and LMICs lead to earlier and larger outbreaks of new waves. Equitable vaccine allocation strategies, in contrast, substantially curb the spread of new strains. For HICs, making immediate and generous vaccine donations to LMICs is a practical pathway to protect everyone., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

During the COVID-19 pandemic, more than ever, data science has become a powerful weapon in combating an infectious disease epidemic and arguably any future infectious disease epidemic. Computer scientists, data scientists, physicists and mathematicians have joined public health professionals and virologists to confront the largest pandemic in the century by capitalizing on the large-scale 'big data' generated and harnessed for combating the COVID-19 pandemic. In this paper, we review the newly born data science approaches to confronting COVID-19, including the estimation of epidemiological parameters, digital contact tracing, diagnosis, policy-making, resource allocation, risk assessment, mental health surveillance, social media analytics, drug repurposing and drug development. We compare the new approaches with conventional epidemiological studies, discuss lessons we learned from the COVID-19 pandemic, and highlight opportunities and challenges of data science approaches to confronting future infectious disease epidemics. This article is part of the theme issue 'Data science approaches to infectious disease surveillance'.

Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI. Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis. Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39-5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE's ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment. Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Cao and Jiang.)

COVID-19 is the most severe pandemic globally since the 1918 influenza pandemic. Effectively responding to this once-in-a-century global pandemic is a worldwide challenge that the international community needs to jointly face and solve. This study reviews and discusses the key measures taken by major countries in 2020 to fight against COVID-19, such as lockdowns, social distancing, wearing masks, hand hygiene, using Fangcang shelter hospitals, large-scale nucleic acid testing, close-contacts tracking, and pandemic information monitoring, as well as their prevention and control effects. We hope it can help improve the efficiency and effectiveness of pandemic prevention and control in future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Nonpharmaceutical interventions (NPIs) for contact suppression have been widely used worldwide, which impose harmful burdens on the well-being of populations and the local economy. The evaluation of alternative NPIs is needed to confront the pandemic with less disruption. By harnessing human mobility data, we develop an agent-based model that can evaluate the efficacies of NPIs with individualized mobility simulations. Based on the model, we propose data-driven targeted interventions to mitigate the COVID-19 pandemic in Hong Kong without city-wide NPIs. We develop a data-driven agent-based model for 7.55×10 6 Hong Kong residents to evaluate the efficacies of various NPIs in the first 80 days of the initial outbreak. The entire territory of Hong Kong has been split into 4905 500×500m 2 grids. The model can simulate detailed agent interactions based on the demographics data, public facilities and functional buildings, transportation systems, and travel patterns. The general daily human mobility patterns are adopted from Google's Community Mobility Report. The scenario without any NPIs is set as the baseline. By simulating the epidemic progression and human movement at the individual level, we propose model-driven targeted interventions which focus on the surgical testing and quarantine of only a small portion of regions instead of enforcing NPIs in the whole city. The effectiveness of common NPIs and the proposed targeted interventions are evaluated by 100 extensive simulations. The proposed model can inform targeted interventions, which are able to effectively contain the COVID-19 outbreak with much lower disruption of the city. It represents a promising approach to sustainable NPIs to help us revive the economy of the city and the world.

As part of ongoing efforts to contain the coronavirus disease (COVID-19) pandemic, understanding the role of asymptomatic patients in the transmission system is essential for infection control. However, the optimal approach to risk assessment and management of asymptomatic cases remains unclear. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) epidemic propagation model. The model was constructed based on epidemiological characteristics of COVID-19 in China and accounting for the heterogeneity of social contact networks. The early community outbreaks in Wuhan were reconstructed and fitted with the actual data. We used this model to assess epidemic control measures for asymptomatic cases in three dimensions. The impact of asymptomatic cases on epidemic propagation was examined based on the effective reproduction number, abnormally high transmission events, and type and structure of transmission. Management of asymptomatic cases can help flatten the infection curve. Tracing 75% of the asymptomatic cases corresponds to a 32.5% overall reduction in new cases (compared with tracing no asymptomatic cases). Regardless of population-wide measures, household transmission is higher than other types of transmission, accounting for an estimated 50% of all cases. The magnitude of tracing of asymptomatic cases is more important than the timing; when all symptomatic patients were traced, tested, and isolated in a timely manner, the overall epidemic was not sensitive to the time of implementing the measures to trace asymptomatic patients. Disease control and prevention within families should be emphasized during an epidemic. Note to Practitioners -This article addresses the urgent need to assess the risk of another COVID-19 outbreak caused by asymptomatic cases and to find the optimal, most practical approach to asymptomatic case management. Previous studies mostly focused on the clinical and statistical characteristics of asymptomatic cases; few have evaluated the impact of asymptomatic case measures using mathematical modeling at the community scale. This study proposed a Susceptible, Exposed, Infectious, No symptoms, Hospitalized and reported, Recovered, Death (SEINRHD) propagation model based on local community structures and social contact networks, according to the development characteristics and trend of COVID-19 in a Chinese community. The conclusion provides theoretical support for emergency work of relevant departments in different periods of an epidemic. In the early stages of the epidemic, timely detection and isolation of symptomatic patients should be a priority. Where there are surplus resources for epidemic prevention, the authorities should consider increasing the proportion of asymptomatic patients being traced. Epidemic prevention measures among family members should be a primary focus of attention. This combination of strategies can help reduce the rate of viral transmission and result in extinguishing the epidemic.

2020 was an unprecedented year, with rapid and drastic changes in human mobility due to the COVID-19 pandemic. To understand the variation in commuting patterns among the Chinese population across stable and unstable periods, we used nationwide mobility data from 318 million mobile phone users in China to examine the extreme fluctuations of population movements in 2020, ranging from the Lunar New Year travel season ( chunyun ), to the exceptional calm of COVID-19 lockdown, and then to the recovery period. We observed that cross-city movements, which increased substantially in chunyun and then dropped sharply during the lockdown, are primarily dependent on travel distance and the socio-economic development of cities. Following the Lunar New Year holiday, national mobility remained low until mid-February, and COVID-19 interventions delayed more than 72.89 million people returning to large cities. Mobility network analysis revealed clusters of highly connected cities, conforming to the social-economic division of urban agglomerations in China. While the mass migration back to large cities was delayed, smaller cities connected more densely to form new clusters. During the recovery period after travel restrictions were lifted, the netflows of over 55% city pairs reversed in direction compared to before the lockdown. These findings offer the most comprehensive picture of Chinese mobility at fine resolution across various scenarios in China and are of critical importance for decision making regarding future public-health-emergency response, transportation planning and regional economic development, among others., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be associated with higher susceptibility of COVID-19 infection and adverse outcomes. We compared ACEI/ARB use and COVID-19 positivity in a case-control design, and severity in COVID-19 positive patients., Methods: Consecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1 January and 28 July 2020 for COVID-19 real time-PCR (RT-PCR) tests were included. Baseline demographics, past comorbidities, laboratory tests and use of different medications were compared between COVID-19 positive and negative patients. Severe endpoints for COVID-19 positive patients were 28-day mortality, need for intensive care admission or intubation., Results: This study included 213 788 patients (COVID-19 positive: n = 2774 patients; negative: n = 211 014). In total, 162 COVID-19 positive patients (5.83%) met the severity outcome. The use of ACEI/ARB was significantly higher amongst cases than controls (n = 156/2774, 5.62 vs. n = 6708/211014, 3.17%; P < 0.0001). Significant univariate predictors of COVID-19 positivity and severe COVID-19 disease were older age, higher Charlson score, comorbidities, use of ACEI/ARB, antidiabetic, lipid-lowering, anticoagulant and antiplatelet drugs and laboratory tests (odds ratio >1, P < 0.05). The relationship between the use of ACEI/ARB and COVID-19 positivity or severe disease remained significant after multivariable adjustment. No significant differences in COVID-19 positivity or disease severity between ACEI and ARB use were observed (P > 0.05)., Conclusion: There was a significant relationship between ACEI/ARB use and COVID-19 positivity and severe disease after adjusting for significant confounders., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs. ASF has led to major economic losses and adverse impacts on livelihoods of stakeholders involved in the pork food system in many European and Asian countries. While the epidemiology of ASF virus (ASFV) is fairly well understood, there is neither any effective treatment nor vaccine. In this paper, we propose a novel method to model the spread of ASFV in China by integrating the data of pork import/export, transportation networks, and pork distribution centers. We first empirically analyze the overall spatiotemporal patterns of ASFV spread and conduct extensive experiments to evaluate the efficacy of a number of geographic distance measures. These empirical analyses of ASFV spread within China indicate that the first occurrence of ASFV has not been purely dependent on the geographical distance from existing infected regions. Instead, the pork supply-demand patterns have played an important role. Predictions based on a new distance measure achieve better performance in predicting ASFV spread among Chinese provinces and thus have the potential to enable the design of more effective control interventions.

Recent studies have reported numerous predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk scores available for prompt risk stratification. The objective is to develop a simple risk score for predicting severe COVID-19 disease using territory-wide data based on simple clinical and laboratory variables. Consecutive patients admitted to Hong Kong's public hospitals between 1 January and 22 August 2020 and diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8 September 2020. An external independent cohort from Wuhan was used for model validation. COVID-19 testing was performed in 237,493 patients and 4442 patients (median age 44.8 years old, 95% confidence interval (CI): [28.9, 60.8]); 50% males) were tested positive. Of these, 209 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression: gender, age, diabetes mellitus, hypertension, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, stroke, dementia, liver diseases, gastrointestinal bleeding, cancer, increases in neutrophil count, potassium, urea, creatinine, aspartate transaminase, alanine transaminase, bilirubin, D-dimer, high sensitive troponin-I, lactate dehydrogenase, activated partial thromboplastin time, prothrombin time, and C-reactive protein, as well as decreases in lymphocyte count, platelet, hematocrit, albumin, sodium, low-density lipoprotein, high-density lipoprotein, cholesterol, glucose, and base excess. The model based on test results taken on the day of admission demonstrated an excellent predictive value. Incorporation of test results on successive time points did not further improve risk prediction. The derived score system was evaluated with out-of-sample five-cross-validation (AUC: 0.86, 95% CI: 0.82-0.91) and external validation (N = 202, AUC: 0.89, 95% CI: 0.85-0.93). A simple clinical score accurately predicted severe COVID-19 disease, even without including symptoms, blood pressure or oxygen status on presentation, or chest radiograph results.

Objectives: We aimed to explore the collective wisdom of preprints related to COVID-19 by comparing and synthesizing them with results of peer-reviewed publications., Methods: PubMed, Google Scholar, medRxiv, bioRxiv, arXiv, and SSRN were searched for papers regarding the estimation of four epidemiological parameters of COVID-19: the basic reproduction number, incubation period, infectious period, and case-fatality-rate. Distributions of parameters and timeliness of preprints and peer-reviewed papers were compared. Four parameters in two groups were synthesized by bootstrapping, and their validities were evaluated by simulated cumulative cases of the susceptible-exposed-infectious-recovered-dead-cumulative (SEIRDC) model., Results: A total of 106 papers were included for analysis. The distributions of four parameters in two literature groups were close, and the timeliness of preprints was better. Synthesized estimates of the basic reproduction number (3.18, 95% CI 2.85-3.53), incubation period (5.44 days, 95% CI 4.98-5.99), infectious period (6.25 days, 95% CI 5.09-7.51), and case-fatality-rate (4.51%, 95% CI 3.41%-6.29%) were obtained. Simulated cumulative cases of the SEIRDC model matched well with the onset cases in China., Conclusions: The validity of the COVID-19 parameter estimations of the preprints was on par with that of peer-reviewed publications, and synthesized results of literatures could reduce the uncertainty and be used for epidemic decision-making., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The emergence of coronavirus disease 2019 (COVID-19) has infected more than 62 million people worldwide. Control responses varied across countries with different outcomes in terms of epidemic size and social disruption. This study presents an age-specific susceptible-exposed-infected-recovery-death model that considers the unique characteristics of COVID-19 to examine the effectiveness of various non-pharmaceutical interventions (NPIs) in New York City (NYC). Numerical experiments from our model show that the control policies implemented in NYC reduced the number of infections by 72% [interquartile range (IQR) 53-95] and the number of deceased cases by 76% (IQR 58-96) by the end of 2020. Among all the NPIs, social distancing for the entire population and protection for the elderly in public facilities is the most effective control measure in reducing severe infections and deceased cases. School closure policy may not work as effectively as one might expect in terms of reducing the number of deceased cases. Our simulation results provide novel insights into the city-specific implementation of NPIs with minimal social disruption considering the locations and population characteristics.

Information spread on social media has been extensively studied through both model-driven theoretical research and data-driven case studies. Recent empirical studies have analyzed the differences and complexity of information dissemination, but theoretical explanations of its characteristics from a modeling perspective are underresearched. To capture the complex patterns of the information dissemination mechanism, we propose a resistant linear threshold (RLT) dissemination model based on psychological theories and empirical findings. In this article, we validate the RLT model on three types of networks and then quantify and compare the dissemination characteristics of the simulation results with those from the empirical results. In addition, we examine the factors affecting dissemination. Finally, we perform two case studies of the 2019 novel Corona Virus Disease (COVID-19)-related information dissemination. The dissemination characteristics derived by the simulations are consistent with the empirical research. These results demonstrate that the RLT model is able to capture the patterns of information dissemination on social media and thus provide model-driven insights into the interpretation of public opinion, rumor control, and marketing strategies on social media.

Motivated by the importance of individual differences in risk perception and behavior change in people's responses to infectious disease outbreaks (particularly the ongoing COVID-19 pandemic), we propose a heterogeneous disease-behavior-information transmission model, in which people's risk of getting infected is influenced by information diffusion, behavior change, and disease transmission. We use both a mean-field approximation and Monte Carlo simulations to analyze the dynamics of the model. Information diffusion influences behavior change by allowing people to be aware of the disease and adopt self-protection and subsequently affects disease transmission by changing the actual infection rate. Results show that (a) awareness plays a central role in epidemic prevention, (b) a reasonable fraction of overreacting nodes are needed in epidemic prevention (c) the basic reproduction number R&#95;{0} has different effects on epidemic outbreak for cases with and without asymptomatic infection, and (d) social influence on behavior change can remarkably decrease the epidemic outbreak size. This research indicates that the media and opinion leaders should not understate the transmissibility and severity of diseases to ensure that people become aware of the disease and adopt self-protection to protect themselves and the whole population.

Hand-foot-and-month disease (HFMD), especially the enterovirus A71 (EV-A71) subtype, is a major health problem in Beijing, China. Previous studies mainly used regressive models to forecast the prevalence of HFMD, ignoring its intrinsic age groups. This study aims to predict HFMD of EV-A71 subtype in three age groups (0-3, 3-6 and > 6 years old) from 2011 to 2018 using residual-convolutional-recurrent neural network (CNNRNN-Res), convolutional-recurrent neural network (CNNRNN) and recurrent neural network (RNN). They were compared with auto-regressio, global auto-regression and vector auto-regression on both short-term and long-term prediction. Results showed that CNNRNN-Res and RNN had higher accuracies on point forecast tasks, as well as robust performances in long-term prediction. Three deep learning models also had better skills in peak intensity forecast, and CNNRNN-Res achieved the best results in the peak month forecast. We also found that three age groups had consistent outbreak trends and similar patterns of prediction errors. These results highlight the superior performance of deep learning models in HFMD prediction and can assist the decision-makers to refine the HFMD control measures according to age groups.

Background: Children aged under 5 years are particularly vulnerable to influenza infection. In this study, we aim to estimate the number and incidence of influenza among young children and estimate the impact of childhood vaccination in different scenarios from 2013/14 to 2016/17 seasons., Methods: The number and incidence rate of influenza infections among children aged under 5 years in Beijing was estimated by scaling up observed surveillance data. Then, we used a susceptible-exposed-infected-recovery (SEIR) model to reproduce the weekly number of influenza infections estimated in Beijing during the study seasons, and to estimate the number and proportion of influenza-attributed medically attended acute respiratory infections (I-MAARI) averted by vaccination in each season. Finally, we evaluated the impact of alternative childhood vaccination programs with different coverage and speed of vaccine distribution., Results: The estimated average annual incidence of influenza in children aged under 5 years was 33.9% (95% confidence interval (CI): 27.5%, 47.2%) during the study period. With the actual coverage during the included seasons at around 2.9%, an average of 3.9% (95%CI: 3.5%, 4.4%) I-MAARI was reduced compared to a no-vaccination scenario. Reaching 20%, 40%, 50%, 60%, 80% and 100% vaccine coverage would lead to an overall I-MAARI reduction of 25.3%, 42.7%, 51.9%, 57.0%, 65.3% and 71.2%. At 20% coverage scenario, an average of 28.8% I-MAARI will be prevented if intensive vaccination implemented in 2 months since the vaccine released., Conclusion: In Beijing, the introduction of a program for vaccinating young children, even at relatively low vaccine coverage rates, would considerably reduce I-MAARI, particularly if the vaccines can be quickly delivered.

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-DL-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

Introduction: In order to improve the prediction accuracy of dengue fever incidence, we constructed a prediction model with interactive effects between meteorological factors, based on weekly dengue fever cases in Guangdong, China from 2008 to 2016., Methods: Dengue fever data were derived from statistical data from the China National Notifiable Infectious Disease Reporting Information System. Daily meteorological data were obtained from the China Integrated Meteorological Information Sharing System. The minimum temperature for transmission was identified using data fitting and the Ross-Macdonald model. Correlations and interactive effects were examined using Spearman's rank correlation and multivariate analysis of variance. A probit regression model to describe the incidence of dengue fever from 2008 to 2016 and forecast the 2017 incidence was constructed, based on key meteorological factors, interactive effects, mosquito-vector factors, and other important factors., Results: We found the minimum temperature suitable for dengue transmission was ≥18°C, and as 97.91% of cases occurred when the minimum temperature was above 18 °C, the data were used for model training and construction. Epidemics of dengue are related to mean temperature, maximum/minimum and mean atmospheric pressure, and mean relative humidity. Moreover, interactions occur between mean temperature, minimum atmospheric pressure, and mean relative humidity. Our weekly probit regression prediction model is 0.72. Prediction of dengue cases for the first 41 weeks of 2017 exhibited goodness of fit of 0.60., Conclusion: Our model was accurate and timely, with consideration of interactive effects between meteorological factors., Competing Interests: The authors have declared that no competing interests exist.

Background: The benefit of school-based influenza vaccination policy has not been fully addressed in Beijing., Objectives: To evaluate the benefit of school-based influenza vaccination policy launched in Beijing., Methods: Using existing surveillance and immunization data, we developed a dynamic transmission model to assess the impact of influenza vaccination in school-going children. The outcome was defined as the averted number of medically attended influenza illnesses and the prevented disease fraction to all children aged 5-14 years for the 2013/14, 2014/15, and 2015/16 seasons., Results: We estimated that during the three consecutive influenza seasons, the averted number of medically attended influenza illnesses among children aged 5-14 years was around 104 000 (95% CI: 101 000-106 000), 23 000 (95% CI: 22 000-23 000), and 21 000 (95% CI: 21 000-22 000), respectively. Corresponding prevented fractions to all children aged 5-14 years were 76.3%, 38.5%, and 43.9%., Conclusions: In Beijing, school-based vaccinations reduced a substantial number of medically attended influenza illnesses despite seasonal variation in the prevented fraction. This is strong supportive evidence for the continuation of school-based vaccination programs to reduce the influenza burden in this age group., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

An increasing number of studies indicate that microRNAs (miRNAs) may exert an oncogenic or tumor suppressive role in diverse types of cancer. MicroRNA (miR)-142-3p has been detected to be downregulated in a number of cancer types, and it may function as a tumor suppressor. However, the expression profile and potential role of miR-142-3p in gastric cancer remain unknown. In the present study, the expression of miR-142-3p in numerous gastric cancer samples was investigated. It was observed that miR-142-3p was markedly downregulated in cancer tissues compared with normal tissues. Furthermore, a low expression level of miR-142-3p was associated with higher tumor stages. The overexpression of miR-142-3p was able to inhibit the proliferation, invasion and migration of gastric cancer cells. A further investigation into the mechanism underlying the effect of miR-142-3p identified cyclin T2 (CCNT2) as a target of miR-142-3p in gastric cancers. miR-142-3p may exert its tumor suppressor role partially by downregulating CCNT2. These results suggested that the abnormal downregulation of miR-142-3p and the subsequent increase in CCNT2 expression may have an important role in gastric cancer carcinogenesis.

Antibiotic-loaded carriers were developed to fill cavities and locally deliver antibiotics following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate (PMMA), has many disadvantages including that it does not promote bone regeneration or conduction. Vancomycin-loaded bone-like hydroxyapatite/poly amino acid (V-BHA/PAA) was successfully fabricated by a homogeneous method, certified as biosafe and known to promote osteogenesis. To evaluate its drug-release features, the quantity of the vancomycin in the elution was obtained every 2 days after in vitro simulated body fluid immersion. The drug concentration in the elution was determined to obtain the drug-release curve. The in vitro drug release was a three-phase process with two release peaks. Its antibacterial activity was evaluated in vitro using an antibacterial zone assay, antibacterial inhibition, and scanning electron microscopy (SEM) observation. Scaffolds of V-BHA/PAA were implanted into a rabbit model of chronic osteomyelitis. The antibacterial activity of the material was evaluated in vivo by gross observations, X-ray, and histological and ultrastructural observations. During the first 48 h, the vancomycin release was more rapid, followed by a period of sustained slow release. Use of V-BHA/PAA could achieve relatively long-term vancomycin delivery of 38 days in vitro and 42 days in vivo. V-BHA/PAA showed a significant and consistent bactericidal effect toward both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in vitro and in vivo. Moreover, the bactericidal effect was stronger than that of vancomycin-loaded polymethyl meth acrylate (V-PMMA). The duration of the antibacterial effect of V-BHA/PAA toward both S. aureus and MRSA exceeded 28 days in vitro, while that of V-PMMA lasted only 14 days. The curative rate for V-BHA/PAA in the chronic osteomyelitis model was 75% for regular S. aureus and 66.67% for MRSA infection, which significantly exceeded that of V-PMMA (50% and 41.67%, respectively). Vancomycin released from the V-BHA/PAA scaffold was significantly superior to that delivered by V-PMMA., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Hypertension is a severe threat to human being's health due to its association with many comorbidities. Many research works have explored hypertension's prevalence and treatment. However, few considered impact of patient's socioeconomic status and geographical disparities. We intended to fulfill that research gap by analyzing the association of the prevalence of hypertension and three important comorbidities with various socioeconomic and geographical factors. We also investigated the prevalence of those comorbidities if the patient has been diagnosed with hypertension. We obtained a large collection of medical records from 29 hospitals across China. We utilized Bayes' Theorem, Pearson's chi-squared test, univariate and multivariate regression methods and geographical detector methods to analyze the association between disease prevalence and risk factors. We first attempted to quantified and analyzed the spatial stratified heterogeneity of the prevalence of hypertension comorbidities by q-statistic using geographical detector methods. We found that the demographic and socioeconomic factors, and hospital class and geographical factors would have an enhanced interactive influence on the prevalence of hypertension comorbidities. Our findings can be leveraged by public health policy makers to allocate medical resources more effectively. Healthcare practitioners can also be benefited by our analysis to offer customized disease prevention for populations with different socioeconomic status., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Antibiotic-loaded carriers were developed because of their ability to fill cavities and deliver antibiotics locally following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate, has many shortcomings, such as heat production, non-bioresorbable and lack of bone regeneration or conduction. Bone-like hydroxyapatite/poly(amino acid) scaffolds have been shown to have controllable biodegradability, nontoxicity, some osteogenic and osteoconductive properties, which has great potential as a carrier for local delivery of antibiotics. Vancomycin-loaded bone-like hydroxyapatite/poly(amino acid) was successfully fabricated by a homogeneous method using a diffusion control system. In this study, bone regeneration using this scaffold was observed both in vitro and in vivo., Methods: In vitro tests, MG63 cells were incubated with the vancomycin-loaded scaffold to observe its effects on the activation of osteoblasts. In vivo tests, the scaffolds were implanted into rabbit models of chronic osteomyelitis, including regular and methicillin-resistant Staphylococcus aureus. The effects were evaluated by gross observation, X-ray and histological observation., Results: After incubating with the scaffold, MG63 cells exhibited good proliferative activity, and increased calcium and alkaline phosphatase synthesis compared with blank control group. In vivo tests, the experimental group showed increased bone growth in infectious bone defects compared with the control groups, regardless of the type of Staphylococcus aureus., Conclusion: Vancomycin-loaded bone-like hydroxyapatite/poly(amino acid) scaffold has good potential for the repair of infectious bone defects because of its ability to deliver antibiotics and promote bone regeneration., (© The Author(s) 2015.)

Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R₀, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period.

Background: Hypertension, an important risk factor for the health of human being, is often accompanied by various comorbidities. However, the incidence patterns of those comorbidities have not been widely studied., Aim: Applying big-data techniques on a large collection of electronic medical records, we investigated sex-specific and age-specific detection rates of some important comorbidities of hypertension, and sketched their relationships to reveal the risk for hypertension patients., Methods: We collected a total of 6,371,963 hypertension-related medical records from 106 hospitals in 72 cities throughout China. Those records were reported to a National Center for Disease Control in China between 2011 and 2013. Based on the comprehensive and geographically distributed data set, we identified the top 20 comorbidities of hypertension, and disclosed the sex-specific and age-specific patterns of those comorbidities. A comorbidities network was constructed based on the frequency of co-occurrence relationships among those comorbidities., Results: The top four comorbidities of hypertension were coronary heart disease, diabetes, hyperlipemia, and arteriosclerosis, whose detection rates were 21.71% (21.49% for men vs 21.95% for women), 16.00% (16.24% vs 15.74%), 13.81% (13.86% vs 13.76%), and 12.66% (12.25% vs 13.08%), respectively. The age-specific detection rates of comorbidities showed five unique patterns and also indicated that nephropathy, uremia, and anemia were significant risks for patients under 39 years of age. On the other hand, coronary heart disease, diabetes, arteriosclerosis, hyperlipemia, and cerebral infarction were more likely to occur in older patients. The comorbidity network that we constructed indicated that the top 20 comorbidities of hypertension had strong co-occurrence correlations., Conclusions: Hypertension patients can be aware of their risks of comorbidities based on our sex-specific results, age-specific patterns, and the comorbidity network. Our findings provide useful insights into the comorbidity prevention, risk assessment, and early warning for hypertension patients.

Many outbreaks of A(H1N1)pdm09 influenza have occurred in schools with a high population density. Containment of school outbreaks is predicted to help mitigate pandemic influenza. Understanding disease transmission characteristics within the school setting is critical to implementing effective control measures. Based on a school outbreak survey, we found almost all (93.7%) disease transmission occurred within a single grade, only 6.3% crossed grades. Transmissions originating from freshmen exhibited a star-shaped network; other grades exhibited branch- or line-shaped networks, indicating freshmen have higher activity and are more likely to cause infection. R0 for freshmen, calculated as 2.04, estimated as 2.76, was greater than for other grades (P < 0.01). Without intervention, the estimated number of cases was much greater when the outbreak was initiated by freshmen than by other grades. Furthermore, the estimated number of cases required to be under quarantine and isolation for freshmen was less than that of equivalent other grades. So we concluded that different grades have different transmission mode. Freshmen were the main facilitators of the spread of A(H1N1)pdm09 influenza during this school outbreak, so control measures (e.g. close contact isolation) priority used for freshmen would likely have effectively reduced spread of influenza in school settings.

Background: Hand, foot, and mouth disease (HFMD) mostly affects the health of infants and preschool children. Many studies of HFMD in different regions have been published. However, the epidemiological characteristics and space-time patterns of individual-level HFMD cases in a major city such as Beijing are unknown. The objective of this study was to investigate epidemiological features and identify high relative risk space-time HFMD clusters at a fine spatial scale., Methods: Detailed information on age, occupation, pathogen and gender was used to analyze the epidemiological features of HFMD epidemics. Data on individual-level HFMD cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify the spatial autocorrelation of HFMD incidence. Spatial filtering combined with scan statistics methods were used to detect HFMD clusters., Results: A total of 157,707 HFMD cases (60.25% were male, 39.75% were female) reported in Beijing from 2008 to 2012 included 1465 severe cases and 33 fatal cases. The annual average incidence rate was 164.3 per 100,000 (ranged from 104.2 in 2008 to 231.5 in 2010). Male incidence was higher than female incidence for the 0 to 14-year age group, and 93.88% were nursery children or lived at home. Areas at a higher relative risk were mainly located in the urban-rural transition zones (the percentage of the population at risk ranged from 33.89% in 2011 to 39.58% in 2012) showing High-High positive spatial association for HFMD incidence. The most likely space-time cluster was located in the mid-east part of the Fangshan district, southwest of Beijing., Conclusions: The spatial-time patterns of Beijing HFMD (2008-2012) showed relatively steady. The population at risk were mainly distributed in the urban-rural transition zones. Epidemiological features of Beijing HFMD were generally consistent with the previous research. The findings generated computational insights useful for disease surveillance, risk assessment and early warning.

A novel influenza A (H1N1) has been spreading worldwide. Early studies implied that international air travels might be key cause of a severe potential pandemic without appropriate containments. In this study, early outbreaks in Mexico and some cities of United States were used to estimate the preliminary epidemic parameters by applying adjusted SEIR epidemiological model, indicating transmissibility infectivity of the virus. According to the findings, a new spatial allocation model totally based on the real-time airline data was established to assess the potential spreading of H1N1 from Mexico to the world. Our estimates find the basic reproductive number R0 of H1N1 is around 3.4, and the effective reproductive number fall sharply by effective containment strategies. The finding also implies Spain, Canada, France, Panama, Peru are the most possible country to be involved in severe endemic H1N1 spreading., (© Science China Press and Springer-Verlag Berlin Heidelberg 2010.)

Studying spatio-temporal evolution of epidemics can uncover important aspects of interaction among people, infectious diseases, and the environment, providing useful insights and modeling support to facilitate public health response and possibly prevention measures. This paper presents an empirical spatio-temporal analysis of epidemiological data concerning 2321 SARS-infected patients in Beijing in 2003. We mapped the SARS morbidity data with the spatial data resolution at the level of street and township. Two smoothing methods, Bayesian adjustment and spatial smoothing, were applied to identify the spatial risks and spatial transmission trends. Furthermore, we explored various spatial patterns and spatio-temporal evolution of Beijing 2003 SARS epidemic using spatial statistics such as Moran's I and LISA. Part of this study is targeted at evaluating the effectiveness of public health control measures implemented during the SARS epidemic. The main findings are as follows. (1) The diffusion speed of SARS in the northwest-southeast direction is weaker than that in northeast-southwest direction. (2) SARS's spread risk is positively spatially associated and the strength of this spatial association has experienced changes from weak to strong and then back to weak during the lifetime of the Beijing SARS epidemic. (3) Two spatial clusters of disease cases are identified: one in the city center and the other in the eastern suburban area. These two clusters followed different evolutionary paths but interacted with each other as well. (4) Although the government missed the opportunity to contain the early outbreak of SARS in March 2003, the response strategies implemented after the mid of April were effective. These response measures not only controlled the growth of the disease cases, but also mitigated the spatial diffusion., (© Science China Press and Springer-Verlag Berlin Heidelberg 2010.)