High-dimensional mediation analysis for continuous outcome with confounders using overlap weighting method in observational epigenetic study.

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Association between childhood trauma and Internet gaming disorder: a moderated mediation analysis with depression as a mediator and psychological resilience as a moderator.

BACKGROUND: The effect of childhood trauma on Internet gaming disorder remains unclear. In this study, we examined this association in Chinese students and explored the possible associated roles of psychological resilience and depression. METHODS: In total, 8,579 students from Hunan Province, China, provided information regarding their sociodemographic factors, history of childhood trauma, any symptoms of depression, psychological resilience, and characteristics of Internet gaming disorder for this cross-sectional study. The impact of childhood trauma on Internet gaming disorder, as well as the extent to which it was mediated by depression and moderated by psychological resilience was evaluated. RESULTS: The influence of childhood trauma on Internet gaming disorder was partially mediated by depression (B = 0.07, 95% CI [0.04, 0.05], p < 0.001), with psychological resilience acting as a mitigating factor (B = -0.002, 95% CI [13.74, 21.72], p < 0.001). Psychological resilience also moderated the association between childhood trauma and depression (B = - 0.003, 95% CI [22.17, 28.10], p < 0.001). Our moderated mediation model elucidated psychosocial mechanisms, revealing the underlying link between childhood trauma and Internet gaming disorder. It also demonstrated the partial mediating role of depression and modulating role of psychological resilience among Chinese students. CONCLUSIONS: Education and interventions, along with effective social support, should be provided to enhance students' psychological resilience and prevent childhood trauma and depression.

The relationship between fear of cancer recurrence and death anxiety among Chinese cancer patients: the serial mediation model.

AIMS: This study aims to investigate the association between fear of cancer recurrence (FCR) and death anxiety (DA) among Chinese cancer patients, while considering the mediating effects of experiential avoidance (EA) and meaning in life (MIL). METHODS: From February to June 2023, convenience sampling was used to select newly diagnosed cancer patients in a tertiary Cancer Hospital in Chinese Hunan Province as the survey objects. A total of 436 cancer patients completed the Fear of Cancer Recurrence Inventory, the Meaning in Life Questionnaire, the Acceptance and Action Questionnaire-II, and the Templer's death anxiety scale. Descriptive analysis and Pearson correlation analysis were conducted using SPSS 28.0 software. Serial mediation analysis was performed by Hayes' PROCESS macro. RESULTS: Gender, age, educational level, marital status, residence, occupation, per capita monthly household income, tumor type, and cancer stage were controlled in the model. The results revealed that fear of cancer recurrence had a significant direct effect on death anxiety (Effect = 0.075, 95% CI: 0.064 to 0.087). Additionally, three indirect pathways were identified: (1) through experiential avoidance (Effect = 0.037, 95% CI: 0.026 to 0.049), (2) through meaning in life (Effect = 0.022, 95% CI: 0.014 to 0.031), and (3) through the serial mediators involving meaning in life and experiential avoidance (Effect = 0.016, 95% CI: 0.010 to 0.023). The total indirect effect of the three mediation paths was 63.56%. CONCLUSION: Fear of cancer recurrence is a significant psychological distress experienced by cancer patients, which not only directly contributes to death anxiety but also may triggers changes, such as experiential avoidance and meaning in life. Ultimately, this comprehensive psychological distress leads to death anxiety.

Gardening and subjective cognitive decline: a cross-sectional study and mediation analyses of 136,748 adults aged 45+ years.

BACKGROUND: Given the benefits of gardening for physical and psychological health, we explored whether gardening was associated with lower risks of subjective cognitive decline (SCD), a precursor of dementia, and SCD-related functional limitations. METHODS: Included in this cross-sectional study were 136,748 participants aged 45 + years old from the Behavioral Risk Factor Surveillance System 2019 survey, who were then categorized into three groups according to self-reported exercise status: non-exercisers, gardeners, and other exercisers. SCD was assessed via a questionnaire, and SCD-related functional limitations were referred to as having difficulties in engaging in household or social activities due to SCD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the associations of gardening with SCD and SCD-related functional limitations, adjusted for age, sex, socioeconomic status, lifestyle factors, and health status. Mediation analyses were conducted to examine whether the observed association between gardening and SCD was mediated by energy expenditure (MET-hours/week), depression status, and consumption of fruits and vegetables. RESULTS: Overall, 11.1% and 5.4% of participants self-reported experiencing SCD and SCD-related functional limitations, respectively. The adjusted OR for gardeners vs. non-exercisers, was 0.72 (95% CI 0.62-0.83) for SCD and 0.57 (95% CI 0.44-0.73) for SCD-related functional limitations. The observed association between gardening and SCD was explained by higher energy expenditure (39.0%), lower likelihood of having depression (21.5%), and higher consumption of fruits and vegetables (3.4%) (P<0.05 for all). Similar patterns were observed for SCD-related functional limitations. CONCLUSION: In this nationally representative sample, gardening was associated with better cognitive status, which may be mainly attributed to better depression status and energy expenditure.

Intolerance of uncertainty and negative emotions among high school art students during COVID-19 pandemic: a moderated mediation analysis.

Objectives: A number of high school art students experience negative emotions during their preparation for the art college entrance examination, characterized by worries and fear of uncertainty. Therefore, how individual difference factors, such as intolerance of uncertainty, affect the negative emotions of students needs to be examined. Inspired by the integrative model of uncertainty tolerance, the current study seeks to explain the association between intolerance of uncertainty and negative emotions by testing the potential mediating role of psychological capital and the moderating role of family functioning. Patients and methods: A total of 919 Chinese high school art students (Mage = 18.50 years, range = 16-22) participated from November 2022 to December 2022. Convenience sampling strategies were used. The participants were asked to complete the measures of intolerance of uncertainty scale, psychological capital questionnaire, depression anxiety stress scale, and family adaptability and cohesion evaluation scale. The data were analyzed using Pearson's r correlations and moderated mediation analysis. Results: Results showed that intolerance of uncertainty was positively associated with negative emotions but negatively associated with psychological capital, which in turn, was negatively associated with negative emotions. Psychological capital mediated the indirect link of intolerance of uncertainty with negative emotions. Family functioning buffered the impact of psychological capital on negative emotions. Conclusion: This study can enhance our understanding of the intolerance of uncertainty on negative emotions and provide insights on interventions for high school art students' negative emotions for educators. The interventions targeting intolerance of uncertainty, psychological capital and family functioning may be beneficial in reducing the effect of intolerance of uncertainty on negative emotions faced by high school art students.

Association between serum copper and blood glucose: a mediation analysis of inflammation indicators in the NHANES (2011-2016).

Background: The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. Methods: The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. Results: Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 µg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. Conclusion: Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.

Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses.

Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10-1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction.IMPACT STATEMENTWhat is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood.What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD.What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Widening Educational Inequalities in Physical Health Due to the Obesity Trend?-A Mediation Analysis Using the German Socio-Economic Panel Study.

Objectives: This study examined the contribution of obesity to the development of educational inequalities in physical health. Methods: We used data from the German Socio-Economic Panel for the period 2002-2020. Physical health was measured with the modified SF12-questionnaire. Logistic regression analyses were applied to estimate time trends. The Relative Index of Inequality (RII) and the Slope Index of Inequality (SII) were calculated to examine educational inequalities. The role of obesity as a mediator was analyzed using the Karlson-Holm-Breen (KHB) method. Results: Over time, educational inequalities in obesity as well as impaired physical health widened in men and women, particularly among those aged 30-49 years. For individuals with a low level of education at this age, the probability of impaired physical health increased significantly by 7.7%-points in women and 9.4%-points in men. Of this increase, 25.9% for women and 14.8% for men could be attributed to the increase in obesity. Conclusion: Our findings suggest that the steeper rise in obesity among individuals with a low level of education partly explains the observed widening in educational inequalities in physical health.

Direct and indirect treatment effects in the presence of semicompeting risks.

Semicompeting risks refer to the phenomenon that the terminal event (such as death) can censor the nonterminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either directly following the treatment or indirectly through the nonterminal event. We consider 2 strategies to decompose the total effect into a direct effect and an indirect effect under the framework of mediation analysis in completely randomized experiments by adjusting the prevalence and hazard of nonterminal events, respectively. They require slightly different assumptions on cross-world quantities to achieve identifiability. We establish asymptotic properties for the estimated counterfactual cumulative incidences and decomposed treatment effects. We illustrate the subtle difference between these 2 decompositions through simulation studies and two real-data applications in the Supplementary Materials.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Prediction and mediation analysis for treatment responses to combined cognitive and physical training for older adults.

Diminished cognitive and physical functions negatively affect the daily functions of individuals. Although combined cognitive and physical training prevents instrumental activities of daily living (IADL) disability in older adults, no predictive model or mediation analysis of IADL after combined training exists. This study aims to employ prediction and mediation analysis to identify the predictors of IADL performance and to elucidate the mediators of the association between baseline global cognition and subsequent IADL performance following combined cognitive and physical training. This study involved 177 participants aged 60 years and older who underwent combined training. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Color Trails Test, Word List, and a dual task; physical function with the Timed Up and Go (TUG) test; daily function with the Lawton IADL Scale. We conducted regression analyses to identify the predictors of IADL performance, and mediation analysis to examine whether DSST and TUG mediate the relationship between MoCA and IADL. The pre-intervention DSST and TUG were significant independent predictors of post-intervention IADL. The association between the pre-intervention MoCA and post-intervention IADL was mediated by pre-intervention DSST and TUG. This study highlighted the importance of measuring and improving processing speed and functional mobility before and during interventions to enhance IADL outcomes.Trial registration: NCT03619577, 23/07/2018; NCT04689776, 29/12/2020.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Mendelian randomisation and mediation analysis of self-reported walking pace and coronary artery disease.

The aim of this study was to assess the causal relationship between habitual walking pace and cardiovascular disease risk using a Mendelian randomisation approach. We performed both one- and two-sample Mendelian randomisation analyses in a sample of 340,000 European ancestry participants from UK Biobank, applying a range of sensitivity analyses to assess pleiotropy and reverse causality. We used a latent variable framework throughout to model walking pace as a continuous exposure, despite being measured in discrete categories, which provided more robust and interpretable causal effect estimates. Using one-sample Mendelian randomisation, we estimated that a 1 mph (i.e., 1.6 kph) increase in self-reported habitual walking pace corresponds to a 63% (hazard ratio (HR) = 0.37, 95% confidence interval (CI), 0.25-0.55, P = 2.0 × 10-6) reduction in coronary artery disease risk. Using conditional analyses, we also estimated that the proportion of the total effect on coronary artery disease mediated through BMI was 45% (95% CI 16-70%). We further validated findings from UK Biobank using two-sample Mendelian randomisation with outcome data from the CARDIoGRAMplusC4D consortium. Our findings suggest that interventions that seek to encourage individuals to walk more briskly should lead to protective effects on cardiovascular disease risk.

A cohort study of self-perception of ageing and all-cause mortality among older adults in China: a multiple mediators analysis.

BACKGROUND: Positive self-perception of aging (SPA) is a well-known predictor of longevity, while how and to what extent SPA is linked with all-cause mortality among older adults is still unclear. This study aims to elucidate the relationship between positive SPA and all-cause mortality and its potential mediators among Chinese older adults. METHODS: This is a 20-year dynamic cohort study conducted among 22,957 older adults aged ≥ 65 years old from a nationally representative sample. Positive SPA was measured using a validated 7-item scale. Potential mediators including health behaviors and social participation were collected using a self-reported questionnaire. Cox proportional hazards regression models were conducted to examine the association between positive SPA and all-cause mortality. A mediation analysis was conducted to determine whether health behaviors and social participation mediated the association between SPA and all-cause mortality. RESULTS: Throughout follow-up (median [interquartile range], 46 [21-84] months), all-cause mortality was 87.4%. Compared with older adults with the lowest quartile positive SPA, hazard ratio(HR) of all-cause mortality among older adults with the second, third, and fourth quartile of positive SPA was 0.96(95%CI:0.93-1.00), 0.93(95%CI:0.90-0.99), and 0.92(95%CI:0.87-0.96) respectively after controlling for all potential mediators and covariates. The mediation analysis showed that regular daily vegetable intake, physical activity, and high social participation explained 41.1-48.5% of the variance in the association between positive SPA and all-cause mortality. CONCLUSIONS: In this cohort study, we found that high positive SPA was associated with decreased all-cause mortality directly, and indirectly through healthy lifestyle behaviors and social participation. These findings suggest that interventions targeted at promoting or maintaining positive SPA may contribute to healthy ageing among older adults in China.

Association between the executive dysfunction and balance function in patients with stroke.

INTRODUCTION: A previous study has shown an association between executive dysfunction (ED) and balance function in patients with stroke. However, it is unclear what factors mediate the association between ED and balance function. Therefore, the aim of this study was to investigate the association between ED and balance function and to identify mediating factors using mediation analysis. METHODS: This study had a cross-sectional design. The study included 107 patients with stroke. This study was divided into two groups (ED and non-ED) using trail making test (TMT) part B. Two groups were compared for balance function (timed up and go test [TUGT] and Berg balance scale [BBS]) and other variables using paired test. In addition, partial correlation analysis with age, cognitive function as a control factor, and mediation analysis were also performed. RESULTS: The ED group (N = 55) had significantly lower TUGT and BBS scores than the non-ED group (N = 52). TMT part B correlated with TUGT (ρ = 0.41), BBS (ρ = -0.33), and Brunnstrom recovery stage (BRS) lower limb (ρ = -0.22). The TUGT model of mediation analysis showed a significant indirect effect as a result of mediation of the BRS lower limb between TMT part B and TUGT. The BBS model showed a significant indirect effect as a result of mediation of the activities of daily living (ADL) motor function between TMT part B and BBS. CONCLUSIONS: ED and balance function were associated, and the degree of paralysis and ADL motor function were associated with them in patients with stroke.

Dissecting the colocalized GWAS and eQTLs with mediation analysis for high-dimensional exposures and confounders.

To leverage the advancements in genome-wide association studies (GWAS) and quantitative trait loci (QTL) mapping for traits and molecular phenotypes to gain mechanistic understanding of the genetic regulation, biological researchers often investigate the expression QTLs (eQTLs) that colocalize with QTL or GWAS peaks. Our research is inspired by 2 such studies. One aims to identify the causal single nucleotide polymorphisms that are responsible for the phenotypic variation and whose effects can be explained by their impacts at the transcriptomic level in maize. The other study in mouse focuses on uncovering the cis-driver genes that induce phenotypic changes by regulating trans-regulated genes. Both studies can be formulated as mediation problems with potentially high-dimensional exposures, confounders, and mediators that seek to estimate the overall indirect effect (IE) for each exposure. In this paper, we propose MedDiC, a novel procedure to estimate the overall IE based on difference-in-coefficients approach. Our simulation studies find that MedDiC offers valid inference for the IE with higher power, shorter confidence intervals, and faster computing time than competing methods. We apply MedDiC to the 2 aforementioned motivating datasets and find that MedDiC yields reproducible outputs across the analysis of closely related traits, with results supported by external biological evidence. The code and additional information are available on our GitHub page (https://github.com/QiZhangStat/MedDiC).

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis.

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Medical Error Prevalence, Nursing Power, and Structural Empowerment: A Serial Mediation Analysis.

Aim: To investigate how structural empowerment and power may contribute to and predict the reduction of medical errors. Background: Medical errors threaten patient well-being, leading to adverse outcomes. Improving work conditions holds promise for reducing medical errors among nurses. Methods: A multisite correlational cross-sectional design was utilized. Data were completed by 375 nurses from four hospitals in Jordan. Data collection occurred between September and November 2023 using sociodemographic, structural empowerment, and medical error questionnaires. The study employed descriptive statistics, Pearson r correlation, and serial mediation analysis. Informed consent was obtained from each participant. Results: Pearson r correlation revealed significant negative correlations between medical error and structural empowerment, formal power, and informal power. The conceptual framework was significant and predicted 16% of the variance in medical errors. The mediation analysis confirmed that formal power and informal power mediate the relationship between structural empowerment and medical error. Conclusions and Implications. This study sheds light on the intricate connection of structural empowerment, formal and informal power, and their collective impact on reducing medical errors. Understanding and addressing these dynamics allows nurses and administrators to achieve a culture of patient safety. Reduction of medical errors is paramount to a safe healthcare environment that prioritizes patient outcomes. Strategies should be fostered to enhance structural empowerment, refine formal power structures, and leverage the positive aspects of informal networks.