Causal Mediation Model Research Articles

Medical mistrust and vaccine-hesitant attitudes explain SARS-CoV-2 vaccination disparities in a mixed-serostatus cohort.

To understand the extent of racial disparities in SARS-CoV-2 vaccination among PWH and those vulnerable to HIV infection and to estimate the contributions of medical mistrust and vaccine-hesitant attitudes to these disparities. Quantitative data analyses in a racially and gender diverse, mixed-serostatus prospective cohort, the MACS/WIHS Combined Cohort Study. Interviewer-assisted questionnaires assessed SARS-CoV-2 vaccination, medical mistrust, and vaccine-hesitant attitudes from March 2021-September 2022 (n=3948). Longitudinal analyses assessed effects of sociodemographics on medical mistrust and vaccine-hesitant attitudes. A hierarchical multivariable logistic regression assessed effects of these co-factors on SARS-CoV-2 vaccination. Causal mediation models assessed whether a) medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, and b) vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 non-vaccination. Participants' mean age was 56.7; 55.3% were Black, 52.6% cisgender female, 62.6% PWH. 10.1% reported never receiving SARS-CoV-2 vaccinations (13.4% of Black and 4.5% of white participants). Black-identified participants had higher odds of non-vaccination than white participants (aOR = 1.72; 95% CI: 1.08, 2.72). Medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, accounting for 46.0% of the effect (p < 0.0001). Vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 non-vaccination to the extent that 57.7% (95% CI: 25.3%, 90.1%) of the disparity would be eliminated if vaccine-hesitant attitudes among Black respondents were reduced to levels reported among other racial groups. Findings indicate a profound need to build trustworthy healthcare environments to combat medical mistrust and vaccine-hesitant attitudes in Black communities in the U.S, including those affected by HIV.

Associations of various healthy dietary patterns with biological age acceleration and the mediating role of gut microbiota: results from the China Multi-Ethnic Cohort study.

To investigate the associations between dietary patterns and biological aging, identify the most recommended dietary pattern for coping with biological aging and explore the potential mediating role of gut microbiota in less-developed ethnic minority regions (LEMRs). This prospective cohort study included 8288 participants aged 30-79 years from the China Multi-Ethnic Cohort study (CMEC). Anthropometric measurements and clinical biomarkers were utilized to construct biological age based on Klemera and Doubal's method (KDM-BA) and KDM-BA acceleration (KDM-AA). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Six dietary patterns were constructed: plant-based diet index (PDI), healthful plant-based diet index (hPDI), unhealthful plant-based diet index (uPDI), healthy diet score (HDS), Dietary Approaches to Stop Hypertension (DASH), and alternative Mediterranean diets (aMED). Follow-up adjusted for baseline analysis were employed to assess the associations between dietary patterns and KDM-AA. Additionally, quantile G-computation was utilized to evaluate the significant beneficial and harmful food groups. In the subsample of 764 participants with gut microbiota data obtained through 16S rRNA gene sequencing, we used causal mediation model to explore the mediating role of gut microbiota in the associations between dietary patterns and KDM-AA. The results showed that all dietary patterns were associated with KDM-AA. Transitioning from non-compliance to compliance, DASH exhibited the strongest negative association with KDM-AA [β = -0.91, 95%CI (-1.19, -0.63)]. The component analyses revealed that tea and soybean products were the significant beneficial food groups, while salt, preserved vegetables, red and processed meats were identified as the major harmful food groups. In mediation analysis, the decreased abundance of Synergistetes phylum and Pyramidobacter genus possibly mediated the negative associations between plant-based diets and KDM-AA (5.61%-9.19%). Overall, healthy dietary patterns, especially DASH, are negatively associated with biological aging in LEMRs. The Synergistetes and Pyramidobacter may mediate the associations between plant-based diets and biological aging. Developing appropriate strategies may promote healthy aging in LEMRs.

Association between healthy lifestyle and frailty in adults and mediating role of weight-adjusted waist index: results from NHANES

BackgroundThe relationship between healthy lifestyle and frailty remains unclear. Healthy weight is crucial for overall well-being, but using body mass index (BMI) to evaluate weight management is inefficient. This study clarifies the association between healthy lifestyle or its factors (non-smoking, moderate drinking, healthy weight, healthy diet, sufficeint physical activity, and non-sedentary) and frailty, and the feasibility of using the weight-adjusted waist index (WWI) reflecting central obesity as an intermediate indicator.MethodsThis study included 4,473 participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Healthy lifestyle quality was assessed by summing the scores of each healthy lifestyle factor. Frailty was assessed using a 49-item frailty index (FI), categorizing participants into robust, pre-frail, and frail. Logistic regression to investigate the association between healthy lifestyle or its factors, WWI, and frailty. Smooth curve fitting and threshold effect analyses were used to elucidate the nonlinear association. Subgroup and two other sensitivity analyses were conducted to confirm the stability of the results. A causal mediation model examined the proportion of frailty mediated by WWI.ResultsThe study identified 13.98% of the participants as frail. Optimal healthy lifestyle and frailty were negatively associated (OR: 0.39, 95%CI: 0.27–0.58). Five healthy lifestyle factors (non-smoking, healthy weight, healthy diet, sufficient physical activity, and non-sedentary) were associated with a lower prevalence of frailty, with odds ratios (OR) ranging from 0.48 to 0.61. We also analyzed the association between a healthy lifestyle and WWI (OR: 0.32, 95%CI: 0.27–0.37), WWI and frailty (OR: 1.85, 95%CI: 1.59–2.16). A positive association between WWI and FI was observed beyond the inflection point (9.99) (OR: 0.03, 95%CI: 0.02–0.03). Subgroup and sensitivity analyses confirmed stable associations between healthy lifestyle, WWI, and frailty. WWI partially mediated the association between a healthy lifestyle and frailty (mediating ratio = 20.50–20.65%).ConclusionsAn optimal healthy lifestyle and positive healthy lifestyle factors are associated with a lower incidence of frailty. WWI may mediate the relationship between a healthy lifestyle and frailty.

The mediating effect of blood biomarkers in the associations between inflammatory bowel disease and incident psychiatric disorders: a prospective cohort study.

Despite the growing evidence of an association between inflammatory bowel disease (IBD) and psychiatric disorders, there has been limited research exploring the underlying mediating role of blood biomarkers on the gut-brain axis. This study aimed to examine the association between IBD and the risk of incident psychiatric disorders and investigate whether and how blood biomarkers mediate this association. This prospective cohort study using data from the UK Biobank included participants without psychiatric diagnoses at baseline. The case cohort consisted of participants with a hospital-based diagnosis of IBD at baseline. The primary outcome was all psychiatric disorders. Secondary outcomes included 11 major psychiatric disorders. Cox regression models estimated adjusted hazard ratios (HRs) for psychiatric outcomes. Causal mediation models investigated the potential mediation effects of blood biomarkers. Among 491,131 participants, patients with IBD exhibited higher risks of overall psychiatric disorders (HR 1.23 [95% CI 1.13-1.33]), substance misuse (1.23 [1.09-1.38]), depression (1.36 [1.22-1.52]), anxiety (1.15 [1.01-1.30]) and post-traumatic stress disorder (1.87 [1.00-3.51]) compared with non-IBD participants. The association with incident substance misuse was only among patients with Crohn's disease (CD, 1.47 [1.23-1.76]), but not ulcerative colitis (UC, 1.01 [0.84-1.21]). Mediation analysis revealed 16, 14, 15, and 6 biomarkers partially mediated the associations for all psychiatric disorders, substance misuse, depression, and anxiety, respectively. Six blood markers showed the strongest mediating effects: neutrophil count (12.04%), C-reactive protein (10.29%), systemic immune-inflammatory index (8.94%), erythrocyte distribution width (16.51%), erythrocyte count (9.76%), and albumin (9.15%). Moreover, several blood mediators of CD identified in association with incident substance misuse may explain the risk discrepancy between IBD subtype. The blood biomarkers of inflammation, blood oxygen-carrying capacity, and metabolism mediate the effect of IBD on the risk of psychiatric outcomes and could be considered as a therapeutic target.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with βFLI→SBP = 0.081, P < 0.001 versus βSBP→FLI = 0.020, P = 0.031; βFLI→DBP = 0.082, P < 0.001 versus βDBP→FLI = -0.006, P = 0.480 for CEMC, and βFLI→SBP = 0.057, P < 0.001 versus βSBP→FLI = -0.001, P = 0.727; βFLI→DBP = 0.061, P < 0.001, versus βDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

The role of depression and use of alcohol and other drugs after partner suicide in the association between suicide bereavement and suicide: cohort study in the Danish population.

Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide. Linkage of nationwide, longitudinal data from Denmark for the period 1980-2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide. Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36-1.86) and of depression (ORadj 1.16, 95% CI 1.09-1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78-0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55-4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%-3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls. Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.

The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study.

: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Well-being among parents of youth with multiple sclerosis: a preliminary longitudinal study.

In 2021, the annual rate of pediatric-onset multiple sclerosis (POMS) in Israel among children was 1.5, and 4.5% among youth aged 14-18, out of a total of 5,000 multiple sclerosis cases nationwide. Children diagnosed with POMS often display various deficiencies across psychological, cognitive, sensory, and physical areas. As such, POMS poses significant challenges for parents' well-being, with heightened emotional, financial, and physical strains linked to both the immediate and long-term care requirements of their children. In this preliminary study, we examined changes over three time-points in two measures of well-being: satisfaction with life and psychological distress. In addition, the role of perceived social support (PSS) and coping flexibility was examined through a multilevel causal mediation model which suggested that PSS 1 month post-diagnosis would predict coping flexibility at 6 months post-diagnosis, which in turn would predict parents' life satisfaction and psychological distress at 12 months post-diagnosis. The research was conducted at a tertiary university-affiliated children's hospital in central Israel. Preliminary data were obtained from 36 parents at three times-points. Participants provided demographic information and filled out the following standardized self-report questionnaires: the Diener's Satisfaction with Life Scale, Kessler's inventory for measuring psychological distress (K6), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Perceived Ability to Cope with Trauma Scale (PACT) for measuring coping flexibility. Over time (12 months), parents reported stable levels of PSS, coping flexibility, satisfaction with life, and psychological distress. In addition, mothers reported significantly greater PSS from friends than did fathers. Regarding the causal mediation model, greater PSS from friends at T1 was significantly associated with an increase in coping flexibility from T1 to T2. In turn, an increase in coping flexibility was associated with a decrease in psychological distress from T1 to T3 (after controlling for PSS). Yet the causal mediation path via coping flexibility to satisfaction with life was not significant. This preliminary study emphasizes the important role of both PSS and coping flexibility for the well-being of parents whose children are affected by POMS, a subject that merits heightened consideration among healthcare professionals dealing with long-term chronic diseases.

Nutritional Status and Physical Exercise Are Associated with Cognitive Function in Chinese Community-Dwelling Older Adults: The Role of Happiness.

We aim to assess the relationship between nutrition status, physical exercise, and cognitive function and particularly examine how happiness modifies and mediates the relationship, among 699 seniors aged 60 and above in Shanghai, China. Linear regression models were used to validate the effects of nutrition and exercise on cognitive function and to test their interaction effects with happiness. When the interactions were significant, stratified analyses in sub-groups were conducted. Mediation effects of happiness were examined using two-step causal mediation models. We confirmed that better nutrition (p < 0.001) and exercise (p = 0.009) were significantly associated with less cognitive decline. Furthermore, the effects of nutrition and exercise on cognitive decline were significant in the unhappy (happiness < 20) (p < 0.001) and younger (age < 74) sub-groups (p = 0.015). Happiness partially mediated 11.5% of the negative association of cognitive decline with nutrition (p = 0.015) and 23.0% of that with exercise (p = 0.017). This study suggests that happiness moderates and partially mediates the effects of exercise and nutrition on cognitive status. The beneficial effects of exercise and nutrition were stronger in less happy or younger seniors. Future intervention studies are required to confirm this path relationship.

Maternal obesity and childhood asthma risk: Exploring mediating pathways.

Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways. To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk. We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m2) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma. Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed. Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.

Decomposing the Black-White Racial Disparity in Severe Maternal Morbidity Risk: The Role of Hypertensive Disorders of Pregnancy.

To our knowledge, no studies have explicitly studied the role of hypertensive disorders of pregnancy (HDP) in racial disparities in severe maternal morbidity (SMM). Using causal mediation models, we estimated the proportion of the non-Hispanic (NH) Black-White racial disparity in risk of SMM that is explained through the pathway of HDP. We linked 2006-2019 Georgia hospital discharge records with vital statistics birth and fetal death records for NH Black and NH White birthing persons. We used G-estimation of a structural nested mean model to decompose the absolute racial disparity in the incidence of SMM into pathways operating through HDP. NH Black birthing people experienced an excess 56 SMM events (95% confidence interval [CI] = 52, 59) per 10,000 delivery hospitalizations compared with NH White birthing people. If counterfactual disparity measure estimation assumptions hold, the estimated absolute disparity remaining after blocking the causal pathways through HDP was 41 SMM events per 10,000 deliveries (95% CI = 38, 44), suggesting that 26% (95% CI = 12, 40) of the absolute racial disparity would be eliminated if there was no contribution of HDP to SMM risk. Our results are consistent with the hypothesis that intervening to prevent HDP is an important (yet incomplete) pathway for reducing the excess risk among NH Black pregnancies compared with NH White pregnancies.

The psychological legacy of past obesity and early mortality: evidence from two longitudinal studies

BackgroundWe test a novel ‘weight scarring’ hypothesis which suggests that past obesity is associated with impairments in current psychological well-being and this increases risk of negative physical health outcomes associated with obesity. Across two nationally representative studies, we tested whether past obesity is associated with current psychological outcomes and whether these psychological outcomes explain the association between past obesity and subsequent early mortality.MethodsData were from the National Health and Nutrition Examination Survey (NHANES) (n = 29,047) and the Health and Retirement Study (HRS) (n = 11,998). Past obesity was defined based on maximum lifetime weight in NHANES and the highest weight from past study waves in the HRS. Across both studies, current depressive symptoms were analysed. A set of 10 additional well-being measures were combined to produce an ‘index of impaired well-being’ in HRS. Subsequent all-cause mortality was examined using National Deaths Index records in NHANES and household interviews in HRS. Linear or logistic regression, Cox proportional hazard regression, and causal mediation models were used.ResultsWe found that past obesity was associated with greater current depressive symptoms after controlling for current weight status and in analyses limited to those who were no longer classified as having obesity in NHANES (β = 0.17; 95% CI: 0.13, 0.22) and HRS (β = 0.20; 95% CI: 0.08, 0.31). In HRS, past obesity was also associated with a range of current negative psychological outcomes, including an index of impaired psychological well-being (β = 0.16; 95% CI: 0.05, 0.27). Past obesity was associated with a higher risk of early mortality in both NHANES and HRS (HR = 1.31; 95% CI: 1.16, 1.48 and HR = 1.34; 95% CI: 1.20, 1.50, respectively). Depressive symptoms explained 6% (95% CI: 0.01, 0.10) and 5% (95% CI: 0.01, 0.09) of the association between past obesity and premature mortality in NHANES and HRS, respectively. Impaired psychological well-being partly mediated the association between past obesity and premature mortality by 10% (95% CI: 0.04, 0.16) in HRS.ConclusionsOur findings suggest that there may be a psychological legacy of past obesity that is associated with raised mortality risk. Ensuring people with obesity receive psychological support even after experiencing weight loss may be important.

Age-associated mortality is partially mediated by TERT promoter mutation status in differentiated thyroid carcinoma

Background Age at diagnosis (AAD) and telomerase reverse transcriptase (TERT) promoter mutations are prognostic factors in differentiated thyroid carcinoma (DTC), and the prevalence of the mutations increases with AAD. Considering this correlation, we investigated whether an interaction between AAD and the mutations is present and whether the mutation mediates the effect of AAD on the mortality rate in DTC. Methods The study included 393 patients with DTC who were followed-up after thyroidectomy at a single medical center in Korea from 1994 to 2004. Multivariable Cox regression was used to investigate the interaction of AAD and TERT promoter mutation. Mediation analysis was conducted using a regression-based causal mediation model. Results The age-associated mortality rate increased progressively in all DTC patients and wild-type TERT group (WT-TERT) with a linear trend (p &lt; 0.001) contrary to mutant TERT group (M-TERT) (p = 0.301). Kaplan-Meier curves declined progressively with increasing AAD in the entire group, but the change was without significance in M-TERT. The effect of AAD on mortality was not significant (adjusted HR: 1.07, 95% CI 0.38–3.05) in M-TERT. An interaction between AAD and TERT promoter mutation (p = 0.005) was found in a multivariable Cox regression. TERT promoter mutations mediated the effect of AAD on the mortality rate by 36% in DTC in a mediation analysis. Conclusions Considering the mediation of TERT promoter mutation on the effect of AAD on mortality, inclusion of TERT promoter mutation in a stage classification to achieve further individualized prediction in DTC is necessary.

Causal evidence of healthy diets, long-term PM2.5 exposure, and kidney function decline in adults: An observational study

BackgroundEvidence of a causal relationship between long-term PM2.5 exposure and reduced kidney function is lacking in developing countries, and the potential moderating role and mechanisms of healthy dietary patterns remain unexplored. MethodsParticipants in this study were drawn from a national cohort from China. We used high-resolution, near real-time data to calculate PM2.5 exposure, blood biomarker data to assess kidney function, and detailed food surveillance data to assess dietary patterns. We used rigorously tested instrumental variable models to examine the causal effects of air pollution and the moderating role of healthy diet, and causal mediation models to explore potential mechanisms. ResultsThis study included 4447 adults with an average eGFRmdrd(CN) of 82.13 mL/min/1.73 m2. Each unit increase in PM2.5 was associated with a decrease in eGFRmdrd(CN) of -0.7 mL/min/1.73 m2 (95% confidential interval: -1.1– -0.3). Healthy dietary patterns was found able to mitigate the harm of PM2.5. Males are more susceptible to the effects of PM2.5 than females. PM2.5-related lipoprotein cholesterol variation was found one of the pathways in which PM2.5 impair kidney function. ConclusionsThe findings reveal that PM2.5 exposure would impair kidney function, especially for males. Embracing healthy dietary patterns can help alleviate the harm. Long-term exposure to PM2.5 may impair kidney function by causing variations in lipoprotein cholesterol.

Uric acid mediated the relationship between obesity and hypertension in children and adolescents: A population‑based cohort study

Background and aimObesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents. Methods and resultsA total of 7525 subjects aged 6–16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (β1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (β2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4–22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9–18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension. ConclusionsIt is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents.

Breaking through ingrained beliefs: revisiting the impact of the digital economy on carbon emissions

The impact of the digital economy on carbon emissions has become a topic of contention due to the paucity of guiding theoretical and empirical research. This study presents a comprehensive causal mediation model based on an expanded structural equation model. Leveraging extensive big data analysis and data sourced from developing nations, this research aims to elucidate the precise impact of the digital economy on carbon emissions and unravel the underlying mechanism. The findings unequivocally demonstrate the pivotal role played by the digital economy in mitigating carbon emissions. Even after subjecting the conclusions to a battery of robustness and endogeneity tests, their validity remains intact. The mechanism analysis reveals that the digital economy effectively curbs carbon emissions through low-carbon technological innovation and industrial diversification. The disproportionate dominance of digital industrialization is a significant factor contributing to the emergence of the “Digital Economy Paradox”. Consequently, this paper not only introduces a novel analytical perspective that systematically comprehends the carbon impact of the digital economy but also presents fresh empirical evidence that advocates for the transformation and development of a low-carbon economy.

Exploring the Carbon-Mitigation Effect of High-Speed Railway and Its Underlying Mechanism

Existing studies on high-speed railway (HSR) and carbon dioxide (CO2) emissions have focused on analyzing their net effect, paying less attention to HSR’s impact mechanism on CO2 emissions. This paper investigates the influence and underlying mechanism of HSR on CO2 emissions. We apply a time-varying difference-in-differences approach to panel data from 283 cities in China between 2003 and 2016 to analyze HSR’s carbon-mitigation effects. A causal three-path mediation model and bootstrap method are utilized to analyze how HSR contributes to CO2 mitigation. The results show that HSR operations have significant carbon-mitigation effects, especially in the eastern regions and large cities of China. Moreover, the carbon-mitigation effect of HSR tends to amplify over time. Mechanism analysis showed that HSR’s carbon-mitigation effects are realized through four pathways: transportation substitution, economic agglomeration, industrial structuring, and technological innovation, with the last one contributing the most. This paper provides practical policy recommendations for the next phase of carbon governance in China.

The Relationship of Neighborhood Disadvantage, Biological Aging, and Psychosocial Risk and Resilience Factors in Heart Failure Incidence Among Black Persons: A Moderated Mediation Analysis.

Deprived living environments contribute to greater heart failure (HF) risk among non-Hispanic Black persons, who disproportionately occupy disadvantaged neighborhoods. The mechanisms for these effects are not fully explicated, partially attributable to an insufficient understanding of the individual factors that contribute additional risk or resilience to the impact of neighborhood disadvantage on health. The objective of this study was, therefore, to clarify the complex pathways over which such exposures act to facilitate more targeted, effective interventions. Given the evidence for a mediating role of biological age and a moderating role of individual psychosocial characteristics in the neighborhood disadvantage-HF link, we tested a moderated mediation mechanism. Using multilevel causal moderated mediation models, we prospectively examined whether the association of neighborhood disadvantage with incident HF mediated through accelerated biological aging, captured by the GrimAge epigenetic clock, is moderated by hypothesized psychosocial risk (negative affect) and resilience (optimism) factors. Among a sample of 1,448 Black participants in the shared Jackson Heart Study-Atherosclerosis Risk in Communities cohort (mean age 64.3 years), 334 adjudicated incident hospitalized HF events occurred over a median follow-up of 18 years. In models adjusted for age and sex, the indirect (GrimAge-mediated) effect of neighborhood disadvantage was moderated by psychosocial risk such that for every standard deviation increase in negative affect the hazards of HF was 1.18 (95% confidence interval = 1.05, 1.36). No moderated mediation effect was detected for optimism. Findings support the necessity for multilevel interventions simultaneously addressing neighborhood and individual psychosocial risk in the reduction of HF among Black persons.

A microbial causal mediation analytic tool for health disparity and applications in body mass index

BackgroundEmerging evidence suggests the potential mediating role of microbiome in health disparities. However, no analytic framework can be directly used to analyze microbiome as a mediator between health disparity and clinical outcome, due to the non-manipulable nature of the exposure and the unique structure of microbiome data, including high dimensionality, sparsity, and compositionality.MethodsConsidering the modifiable and quantitative features of the microbiome, we propose a microbial causal mediation model framework, SparseMCMM_HD, to uncover the mediating role of microbiome in health disparities, by depicting a plausible path from a non-manipulable exposure (e.g., ethnicity or region) to the outcome through the microbiome. The proposed SparseMCMM_HD rigorously defines and quantifies the manipulable disparity measure that would be eliminated by equalizing microbiome profiles between comparison and reference groups and innovatively and successfully extends the existing microbial mediation methods, which are originally proposed under potential outcome or counterfactual outcome study design, to address health disparities.ResultsThrough three body mass index (BMI) studies selected from the curatedMetagenomicData 3.4.2 package and the American gut project: China vs. USA, China vs. UK, and Asian or Pacific Islander (API) vs. Caucasian, we exhibit the utility of the proposed SparseMCMM_HD framework for investigating the microbiome’s contributions in health disparities. Specifically, BMI exhibits disparities and microbial community diversities are significantly distinctive between reference and comparison groups in all three applications. By employing SparseMCMM_HD, we illustrate that microbiome plays a crucial role in explaining the disparities in BMI between ethnicities or regions. 20.63%, 33.09%, and 25.71% of the overall disparity in BMI in China-USA, China-UK, and API-Caucasian comparisons, respectively, would be eliminated if the between-group microbiome profiles were equalized; and 15, 18, and 16 species are identified to play the mediating role respectively.ConclusionsThe proposed SparseMCMM_HD is an effective and validated tool to elucidate the mediating role of microbiome in health disparity. Three BMI applications shed light on the utility of microbiome in reducing BMI disparity by manipulating microbial profiles.6ppc1U8Yu1nT7JqzesB9dWVideo

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β=-1.1; 95% CI, -2.2 to -0.02; P=.05) and language scores (β=-2.1; 95% CI, -3.3 to -0.8; P=.002). An increase by 1g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P=.06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P=.001), after adjustment for birth weight z-score. For children with birth weight<25th percentile, a 1g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P=.02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P=.004). Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. Clinicaltrials.gov identifier: NCT02371460.