In China, several expressways have been designed as prefabricated box culverts with hinge connections, which have different structural features from the prefabricated culverts in other countries. The difference would contribute to the culvert-soil interaction of prefabricated box culverts, which could affect the earth pressure on the culvert. Based on the field test and numerical simulation method, a hinged prefabricated box culvert (HPBC) with a span of 4 m and a rise of 4 m was investigated, which was applied to the Xi-Yu expressway in China. The objective of this research was to investigate the vertical earth pressure on the top slab of the HPBC culvert at different backfill heights through the field tests. The FLAC3D software was employed to conduct further analysis of the effects of backfill height, backfill modulus, and foundation modulus on the vertical earth pressure on the top slab of HPBC. The differences between the HPBC and monolithic box culvert (MBC) were also examined. Furthermore, a revised method for calculating the vertical earth pressure on the top slab was put proposed and compared with the AASHTO method for calculating earth pressure on the top of culverts and the values taken from the Chinese culvert design code. The proposed method is capable of improving the accuracy of the earth pressure approach, making it more representative of actual conditions. Subsequently, the sensitivity analysis of backfill height, backfill modulus and foundation modulus to the vertical earth pressure concentration coefficient of the top slab was carried out by using the principle of orthogonal array analysis and the modified calculation method proposed in this paper. The findings of this study offer valuable insights into the determination of culvert top earth pressure of HPBC.

UNASSIGNED: In virtual bioequivalence (VBE) assessments, pharmacokinetic models informed with in vitro data and verified with small clinical trials\' data are used to simulate otherwise unfeasibly large trials. Simulated VBE trials are assessed in a frequentist framework as if they were real despite the unlimited number of virtual subjects they can use. This may adequately control consumer risk but imposes unnecessary risks on producers. We propose a fully Bayesian model-integrated VBE assessment framework that circumvents these limitations.
UNASSIGNED: We illustrate our approach with a case study on a hypothetical paliperidone palmitate (PP) generic long-acting injectable suspension formulation using a validated population pharmacokinetic model published for the reference formulation. BE testing, study power, type I and type II error analyses or their Bayesian equivalents, and safe-space analyses are demonstrated.
UNASSIGNED: The fully Bayesian workflow is more precise than the frequentist workflow. Decisions about bioequivalence and safe space analyses in the two workflows can differ markedly because the Bayesian analyses are more accurate.
UNASSIGNED: A Bayesian framework can adequately control consumer risk and minimize producer risk . It rewards data gathering and model integration to make the best use of prior information. The frequentist approach is less precise but faster to compute, and it can still be used as a first step to narrow down the parameter space to explore in safe-space analyses.

The number of Methicillin-resistant Staphylococcus aureus (MRSA) cases in communities and hospitals is on the rise worldwide. In this work, a nonlinear deterministic model for the dynamics of MRSA infection in society was developed to visualize the significance of awareness in interventions that could be applied in the prevention of transmission with and without optimal control. Positivity and uniqueness were verified for the proposed corruption model to identify the level of resolution of infection factors in society. Furthermore, how various parameters affect the reproductive number R 0 and sensitivity analysis of the proposed model was explored through mathematical techniques and figures. The global stability of model equilibria analysis was established by using Lyapunov functions with the first derivative test. A total of seven years of data gathered from a private hospital consisting of inpatients and outpatients of MRSA were used in this model for numerical simulations and for observing the dynamics of infection by using a non-standard finite difference (NSFD) scheme. When optimal control was applied as a second model, it was determined that increasing awareness of hand hygiene and wearing a mask were the key controlling measures to prevent the spread of community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA). Lastly, it was concluded that both CA-MRSA and HA-MRSA cases are on the rise in the community, and increasing awareness concerning transmission is extremely significant in preventing further spread.

UNASSIGNED: This study introduces a novel method for developing an advanced exposure conceptual model tailored for health risk assessment, focusing on microenvironments.
UNASSIGNED: The research was conducted at a major smelter in China to assess the health risks associated with trace metals (TMs) pollutants in the facility and the surrounding soil.
UNASSIGNED: Deterministic risk assessment indicated that cobalt, cadmium, antimony, manganese, arsenic, plumbum, and mercury (Co, Cd, Sb, Mn, As, Pb, and Hg) necessitated further evaluation through probabilistic risk assessment to assess potential health risks to residents. The 95% quantile concentrations of other TMs were found to be within acceptable health risk limits. For the probabilistic risk assessment, exposure parameters such as body weight, respiration rate, and exposure duration were collected using a questionnaire. This targeted assessment of the residential microenvironment revealed it as the site of the highest carcinogenic (CR) and non-carcinogenic risks (NCR), with values ranging from 2.84×10-5 to 6.7×10-5 and 1.59 to 5.57, respectively.
UNASSIGNED: The primary contaminants posing the greatest health risks in residential and industrial areas have been identified as As, Pb, and Mn. The probabilistic health risk model, which focuses on microenvironmental factors, yields more precise results and offers a valuable tool for managing soil health risks.

UNASSIGNED: It has been recognized that HIV-related stigma hinders efforts in testing, treatment, and prevention. In this systematic review, we aimed to summarize available findings on the association between HIV-related stigma and age, social support, educational status, depression, employment status, wealth index, gender, residence, knowledge about HIV, marital status, duration since diagnosis, and disclosure status using a large number of studies.
UNASSIGNED: Electronic databases including Scopus, Medline/PubMed, Web of Sciences (WOS), Cochrane Library, Google Scholar, and Open Research Dataset Challenge were systematically searched until 15 April 2023. We included all kinds of HIV-stigma studies, regardless of language, publishing date, or geographic location. The inclusion criteria were met by 40 studies, with a total of 171,627 patients. A mixed-effect model was used to pool estimates and evaluate publication bias, as well as to conduct sensitivity analysis.
UNASSIGNED: Factors such as older age, social support, greater education, higher socioeconomic status, good knowledge of HIV, and longer years of living with HIV significantly lowered the likelihood of HIV-related stigma. Contrarily, factors such as depression, residing in rural areas, female respondents, and non-disclosure of HIV status were significantly associated with a high risk of HIV-related stigma.
UNASSIGNED: To combat systemic HIV-associated stigma, it is crucial to develop wholesome and comprehensive social methods by raising community-level HIV awareness. In addition to activism, local economic development is also crucial for creating thriving communities with a strong social fabric.

This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model\'s effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.

Tuberculosis (TB) remains a significant global health concern, necessitating effective control strategies. This article presents a mathematical model to evaluate the comparative effectiveness of medical mask usage and case detection in TB control. The model is constructed as a system of ordinary differential equations and incorporates crucial aspects of TB dynamics, including slow-fast progression, medical mask use, case detection, treatment interventions and differentiation between symptomatic and asymptomatic cases. A key objective of TB control is to ensure that the reproduction number, R c , remains below unity to achieve TB elimination or persistence if R c exceeds 1. Our mathematical analysis reveals the presence of a transcritical bifurcation when the R c = 1 signifies a critical juncture in TB control strategies. These results confirm that the effectiveness of case detection in diminishing the endemic population of symptomatic individuals within a TB-endemic equilibrium depends on exceeding a critical threshold value. Furthermore, our model is calibrated using TB yearly case incidence data per 100 000 population from Indonesia, India, Lesotho and Angola. We employed the bootstrap resampling residual approach to assess the uncertainty inherent in our parameter estimates which provides a comprehensive distribution of the parameter values. Despite a declining trend in new incidence, these four countries exhibit a reproduction number greater than 1, indicating persistent TB cases in the presence of ongoing TB control programmes. We employ the partial rank correlation coefficient in conjunction with the Latin hypercube sampling method to conduct a global sensitivity analysis of the R c parameter for each fitted parameter in every country. We find that the medical mask use is more sensitive to reduce R c compared with the case detection implementation. To further gain insight into the necessary control strategy, we formulated an optimal control and studied the cost-effectiveness analysis of our model to investigate the impact of case detection and medical mask use as control measures in TB spread. Cost-effectiveness analysis demonstrates that combining these interventions emerges as the most cost-effective strategy for TB control. Our findings highlight the critical importance of medical masks and their efficacy coupled with case detection in shaping TB control dynamics, elucidating the primary parameter of concern for managing the control reproduction number. We envisage our findings to have implications and be vital for TB control if implemented by policymakers and healthcare practitioners involved in TB control efforts.

UNASSIGNED: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown.
UNASSIGNED: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR).
UNASSIGNED: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran\'s Q tests. FDR correction was used to correct the p-values.
UNASSIGNED: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane\'s Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results.
UNASSIGNED: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.

Chemical reaction networks are powerful tools for modeling cell signaling and its disruptions in diseases like cancer. Realistic chemical reaction networks involve hundreds of proteins and reactions, resulting in a model depending on a consistently large number of kinetic parameters. Since finely calibrating all the parameters would require an unrealistic amount of data, proper sensitivity analysis is required to identify a subset of parameters for which fine tuning is needed and thus provide a fundamental tool for the qualitative analysis of the network. We present a multidisciplinary approach for computing a set of synthetic sensitivity indices. These indices rank the kinetic parameters, based on the impact that errors in their values would have on the protein concentration profile at equilibrium. Our tests on a chemical reaction network devised for colorectal cells demonstrate the effectiveness of the considered sensitivity indices in different scenarios including in-silico drug dosage and novel therapeutic target discovery. The Matlab code for computing the synthetic sensitivity indices and the data concerning the network for colorectal cells are available at https://github.com/theMIDAgroup/CRN_sensitivity.

The interaction between the immune system and the brain, crucial for blood-brain barrier integrity, is a potential factor in migraine development. Although there\'s evidence of a connection between immune dysregulation and migraine, a clear causal link has been lacking. To bridge this knowledge gap, we performed a two-sample Mendelian randomization (MR) analysis of 731 immune cell phenotypes to determine their causality with migraine, of which parameters included fluorescence, cell abundance, count, and morphology. Sensitivity and pleiotropy checks validated our findings. After applying a false discovery rate correction, our MR study identified 35 of 731 immune phenotypes with a significant causal link to migraine (p < 0.05). Of these, 24 showed a protective effect (inverse variance weighting : p < 0.05, odds ratio <1), and 11 were risk factors (inverse variance weighting : p < 0.05, odds ratio >1). Although limited by population sample size and potential population-specific genetic variations, our study uncovers a significant genetic link between certain immune cell markers and migraine, providing new insights into the disorder\'s pathophysiology. These discoveries are crucial for developing targeted biomarkers and personalized treatments. The research enhances our understanding of immune cells\' role in migraine and may substantially improve patient outcomes and lessen its socio-economic impact.