Multivariable Linear Regression Models Research Articles

Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes.

To develop targeted treatments, it is crucial to identify the full spectrum of genetic drivers in melanoma, including those in non-coding regions. However, recent efforts to explore non-coding regions have primarily focused on gene-adjacent elements such as promoters and non-coding RNAs, leaving intergenic distal regulatory elements largely unexplored. We used Hi-C chromatin contact data from melanoma cells to map distal, non-coding, promoter-interacting regulatory elements genome-wide in melanoma. Using this "promoter-interaction network", alongside whole-genome sequence and gene expression data from the Pan Cancer Analysis of Whole Genomes, we developed multivariate linear regression models to identify distal somatic mutation hotspots that affect promoter activity. We identified eight recurrently mutated hotspots that are novel, melanoma-specific, located in promoter-interacting distal regulatory elements, alter transcription factor binding motifs, and affect the expression of genes (e.g., HSPB7, CLDN1, ADCY9 and FDXR) previously implicated as tumour suppressors/oncogenes in various cancers. Our study suggests additional non-coding drivers beyond the well-characterised TERT promoter in melanoma, offering new insights into the disruption of complex regulatory networks by non-coding mutations that may contribute to melanoma development. Furthermore, our study provides a framework for integrating multiple levels of biological data to uncover cancer-specific non-coding drivers.

Associations Between Every day and Medical Setting-Based Discrimination and Religious and Sociodemographic Characteristics of Muslim Americans: Findings from a National Survey.

We investigated the associations between sociodemographic factors, religiosity traits, and the perception of discrimination among Muslim Americans in both everyday life and medical settings. A self-administered web-based questionnaire, comprising validated measures of discrimination and religiosity, was completed by a convenience sample of English-speaking adult Muslim Americans, recruited through both in-person and online channels. Among the 1281 respondents, less than half were born in the USA (46%), and a significant portion displayed visible religious markers, such as wearing a hijab or having a beard (61%). Only 154 (12%) reported never experiencing everyday discrimination, while 358 (28%) reported not experiencing discrimination in medical settings. In a multivariable linear regression model, greater perceived everyday discrimination (β = 1.053, p < 0.01) was positively associated with greater discrimination in medical settings. Participants more comfortable self-identifying as Muslim in hospital settings (β = -0.395, p < 0.05) were less likely to perceive healthcare discrimination. Those visibly expressing their religiosity (β = 0.779, p < 0.01) and those with greater intrinsic religiosity (β = 0.231, p < 0.05) were more likely to encounter everyday discrimination. Conversely, older participants (β = -0.015, p < 0.05), adult immigrants to the US (β = -0.375, p < 0.05), those in better health (β = -0.157, p < 0.05), and those more comfortable identifying as Muslim (β = -0.305, p < 0.05) had lower perceptions of everyday discrimination. This study underscores the significance of the relationship between religiosity characteristics and experiences of both hospital and everyday discrimination for Muslim Americans.

Exploring the Relationship Between Hospital Patient Safety Culture and Performance on Measures of Hospital-Acquired Conditions

Objective The aim of the study is to examine the relationship between hospital perceptions of patient safety culture and the incidence of hospital-acquired conditions (HACs) included in Medicare’s HAC Reduction Program utilizing updated and standardized metrics. Methods The pooled cross-sectional study design utilized the 2018 and 2021 datasets from (1) the Agency for Healthcare Research and Quality’s Hospital Survey on Patient Safety Culture (HSOPS), (2) the American Hospital Association’s annual survey, and (3) the Center for Medicare and Medicaid’s Hospital Compare dataset. The final analytic sample included 131 acute care, nonfederal, U.S. facilities. Multivariable linear regression models were used to compare the HSOPS domains of patient safety culture to CMS’s HAC metrics. Results Controlling for hospital structural and patient-mix characteristics, hospitals with higher staff-reported ratings of overall patient safety culture (‘overall perceptions of patient safety’ and ‘patient safety grade’) had significantly lower rates of HACs, including total HAC rate, catheter-associated urinary tract infections, and central line-associated blood stream infections (P’s &lt; 0.000–0.044). Higher HSOPS domain scores were variably associated with lower HAC rates, with consistently significant associations found for domains related to nonpunitive, open communication (P’s &lt; 0.05). Conclusions Our relatively robust results suggest that while patient safety culture may not be the only strategy necessary to improve HAC rates, it needs to be aligned with other efforts to improve quality and safety. This underscores the importance of cultivating a culture of psychological safety that promotes open feedback and communication about errors.

A pilot cross-sectional investigation of symptom clusters and associations with patient-reported outcomes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with long-term disability and poor quality of life (QoL). Cardinal ME/CFS symptoms (including post-exertional malaise, cognitive dysfunction and sleep disturbances) have been observed in Post COVID-19 Condition (PCC). To gain further insight into the potential role of ME/CFS as a post-COVID-19 sequela, this study investigates associations between symptoms and patient-reported outcomes, as well as symptom clusters. Participants included Australian residents aged between 18 and 65 years formally diagnosed with ME/CFS fulfilling the Canadian or International Consensus Criteria or PCC meeting the World Health Organization case definition. Validated, self-administered questionnaires collected participants' sociodemographic and illness characteristics, symptoms, QoL and functional capacity. Associations between symptoms and patient-reported outcomes were investigated with multivariate linear regression models. Hierarchical cluster analysis was performed to identify symptom clusters. Most people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) were female (n = 48/60, 80.0% and n = 19/30, 63.3%, respectively; p = 0.12). PwME/CFS were significantly younger (x̄=41.75, s = 12.91 years) than pwPCC (x̄=48.13, s =10.05 years; p =0.017). Autonomic symptoms (notably dyspnoea) were associated with poorer scores in most patient-reported outcome domains for both cohorts. None of the four symptom clusters identified were unique to ME/CFS or PCC. Clusters were largely delineated by the presence of gastrointestinal and neurosensory symptoms, illness duration, ME/CFS criteria met and total symptoms. Illness duration may explain differences in symptom burden between pwME/CFS and pwPCC. PCC diagnostic criteria must be refined to distinguish pwPCC at risk of long-term ME/CFS-like illness and subsequently deliver necessary care and support.

Who is consuming ultra-processed food in Canada? A cross-sectional analysis of the 2018/2019 International Food Policy Study.

High consumption of ultra-processed foods and drinks (UPF) has been linked to poor diet quality and an increased risk of non-communicable diseases. To inform public policies and interventions aimed at reducing UPF intake in Canada, updated information on UPF intake among different sociodemographic groups is needed. This study, using data from 5,872 adults aged 18 years and older from the International Food Policy Study (2018-2019), aims to estimate the dietary energy contribution of UPF and assess its variation among sociodemographic subgroups. All foods and drinks reported in a single 24-hour dietary recall were classified using the Nova system. We estimated the mean proportion of total daily energy from UPF and subcategories of UPF in the overall sample and among sociodemographic subgroups. Multivariable linear regression models evaluated the association between sociodemographic characteristics with the proportion of total daily energy from UPF. On average, adults consumed 45.2% of their total daily energy from UPF. UPF consumption was slightly higher among males than females (49.4% vs. 47.6%, p=0.039) and younger adults aged 19-30 years compared with older adults aged 51-64 years (50.0% vs. 47.2%, p=0.029), adjusting for a range of sociodemographic factors. Overall, UPF consumption was relatively high among adults in all sociodemographic subgroups, highlighting the need for policies to decrease UPF consumption in the entire population.

Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study

BackgroundThe recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring.MethodsBased on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring.ResultsCompared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72).ConclusionsOur results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

B-158 Association between multiple heavy metals exposure and blood lipid levels: evidence from a cross-sectional study of Korean adults

Abstract Background Metals are ubiquitous in our environment and enter human body via various pathways, such as air, soil, food, water, etc. Increasing studies have found that metals are important risk factors in developing dyslipidemia. However, there is no consensus regarding the effects of co-exposure to multiple metals on blood lipid levels. We investigated both the joint and individual effects of this metal mixture exposure on human blood lipid levels. Methods Blood concentrations of four human toxic metals (Pb, Cs, Hg, and Cd) in 2,798 general populations from Korea were simultaneously determined as a measure of exposure. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of four blood metals and metals mixture with lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Results The mean age of the overall study population was 41.2 ± 9.85 years, and 66.9% were men. The prevalence of overweight or obesity, diabetes, and hypertension in the population was 62.5, 6.8, and 13.9%, respectively. In the multivariable linear regression model, the blood Cs was positively associated with TC and LDL-C(p &amp;lt; 0.05, all), and the blood Pb was positively associated with serum TG (p &amp;lt; 0.05, all). Also, the blood Cd was positively associated with serum HDL-C (p &amp;lt; 0.05, all). We did not identify any other obvious interaction between metals on the lipid profiles using a bivariate exposure-response function in BKMR. Conclusions Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Cs and Pb, should be a priority for the general population. However, future studies with a larger number of heavy metals are still needed to focus on the detrimental effects of single metals on lipid profiles as well as to identify key components.

Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches

BackgroundThe Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumptions of linear regression models are usually violated, which may result in failure to detect associations with variables of interest.MethodsAlternative approaches to analyzing the results of these cognitive batteries include transformations (standardization, square root, or log transformation) of the scores in the multivariate linear regression (MLR) model, the use of nonlinear beta-binomial regression (which is not dependent on the assumption of normality), or Tobit regression, which adds a latent variable to account for bounded data. We aim to empirically compare the model performance of all proposed approaches using four large randomized controlled trials (ORIGIN, TRANSCEND, COMPASS, and NAVIGATE-ESUS), and using as metrics the Akaike information criterion (AIC). We also compared the treatment effects for the methods that have the same unit of measure (i.e., untransformed MLR, beta-binomial, and Tobit).ResultsThe beta-binomial consistently demonstrated superior model performance, with the lowest AIC values among nearly all the approaches considered, followed by the MLR with square root and log transformations across all four studies. Notably, in ORIGIN, a substantial AIC reduction was observed when comparing the untransformed MLR to the beta-binomial, whereas other studies had relatively small AIC reductions. The beta-binomial model also resulted in a significant treatment effect in ORIGIN, while the untransformed MLR and Tobit regression showed no significance. The other three studies had similar and insignificant treatment effects among the three approaches.ConclusionWhen analyzing discrete and bounded outcomes, such as cognitive scores, as continuous variables, a beta-binomial regression model improves model performance, avoids spurious significance, and allows for a direct interpretation of the actual cognitive measure.Trials registrationORIGIN (NCT00069784). Registered on October 1, 2003; TRANSCEND (NCT00153101). Registered on September 9, 2005; COMPASS (NCT01776424). Registered on January 24, 2013; NAVIGATE-ESUS (NCT02313909). Registered on December 8, 2014.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study

BackgroundObesity poses a significant global health challenge, with profound implications for women’s reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients.MethodsWe conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses.ResultsAnti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20–30 and 30–35 years. Among women aged 20–35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia.ConclusionsAn age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Community Benefit and Tax-Exemption Levels at Non-Profit Hospitals Across U.S. States.

To assess the association between state policies and sociodemographic characteristics and state mean fair share spending at non-profit hospitals. Fair share spending is a hospital's charity care and community investment less the estimated value of their tax-exempt status. Hospitals with non-profit status in the United States are exempt from paying taxes. In return, they are expected to provide community benefits by subsidizing medical care for those who cannot pay and investing in the health and social needs of their community. We used a multivariable linear regression model to determine the association of state-level sociodemographics and policies with state-level mean fair share spending in 2019. Fair share spending data was obtained from the Lown Institute. We found no association between the percentage of people living in poverty, in rural areas, or U.S. region and fair share spending. Similarly, there was no association found for state minimum community benefit and reporting requirements. The state percentage of racial/ethnic minorities was associated with higher mean fair share spending [+$1.48 million for every 10% increase (95% CI: 0.01 to 2.96 million)]. Medicaid expansion status was associated with a 6.9-million-dollar decrease (95% CI: -10.4 to -3.3 million). State-level community benefit policies have been ineffective at raising community benefit spending to levels comparable to the value of non-profit hospital tax-exempt status.

Modelling personal temperature exposure using household and outdoor temperature and questionnaire data: Implications for epidemiological studies

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman’s ρ: 0.86–0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74–0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R2summer: 0.92; R2winter: 0.68–0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at ∼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings.

Normative Profile of Retinal Nerve Fiber Layer Thickness and Lamina Cribrosa-Related Parameters in a Healthy Non-Glaucoma Cynomolgus Monkey Colony.

The purpose of this study was to investigate the normal range of ophthalmic parameters and the correlations between systematic and ocular parameters and retinal nerve fiber layer (RNFL) thickness among a healthy non-glaucoma cynomolgus monkey colony. All included monkeys were given detailed ophthalmic examinations, including anterior and posterior segments. Furthermore, univariate and multivariate linear regression models were conducted to estimate the relationship between systemic and ophthalmic parameters and global RNFL thickness. A total of 349 non-glaucoma monkeys (18.69 ± 2.88 years old) were collected. The global RNFL thickness was 94.61 ± 10.13 µm, and sex-specific differences existed in all sectors. The decreasing trend of RNFL is as follows: inferotemporal, superotemporal, inferonasal, superonasal, temporal, and nasal. For lamina cribrosa (LC)-related parameters, cup depth (P < 0.01), LC thickness (P = 0.014), and Bruch's membrane opening (BMO) - minimum rim width 2 (P = 0.002) were greater in the male group. However, LC depth (P = 0.02), anterior laminar insertion depth-1 (P = 0.009), and mean anterior laminar insertion depth (P = 0.029) of female monkeys were greater than those of male monkeys. In multivariate linear regression, only older age was significantly related to reduced global RNFL thickness (P < 0.001). Our findings suggest the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkeys and humans. Therefore, the impact of this difference on outcomes should be fully considered in laboratory animal studies. Our findings are also significant in terms of developing a normative optical coherence tomography (OCT) database in nonhuman primates (NHPs). We found that the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkey colonies and humans should be thoroughly taken into account in laboratory animal studies.

Predictors of participant compliance with ecological momentary assessment among individuals with chronic pain who are using cannabis and opioids

BackgroundCannabis may be an alternative or adjunct to opioid therapy for chronic pain. However, there are limited data on patterns of opioid medication and medical cannabis use. The current study investigated the feasibility of using Ecological Momentary Assessment (EMA) to assess patterns of prescription opioids and medical cannabis among individuals experiencing chronic pain. MethodThe study included 133 participants recruited online. Participants were 42.6 (SD = 13.9) years old on average and the majority were men (57.9 %) and Non-Hispanic White (63.2 %). Participants completed a baseline assessment, followed by 30-days of EMA data collection with four randomly prompted past-hour surveys and one daily diary per day, and a follow-up survey that assessed perceived EMA burden. Simple and multivariable linear regression models were estimated to investigate participant predictors of the proportion of EMA surveys completed (past-hour surveys and daily diaries in separate models). ResultsCompliance rates for EMAs prompts were 89.7 % for daily diaries and 63.3 % for past-hour surveys. In multivariable regression, participants holding a graduate degree completed a lower proportion of daily diaries (b = −0.109, SE = 0.052, p < .05) and past-hour surveys (b = −0.148, SE = 0.071, p < .05), compared to those with less than a 4-year degree. Participants completing a higher proportion of daily diaries reported greater ease of use at follow-up (b = 0.050, SE = 0.022, p < .05) and those completing a higher proportion of past-hour surveys desired higher rewards (b = 0.066, SE = 0.033, p < .05). ConclusionsStudy results confirm the feasibility of using EMA methods to assess patterns of prescription opioids and medical cannabis among individuals experiencing chronic pain.

APOE4 and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer's Pathology: New Findings from the ADNI.

Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD. We analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed. Prior infections were associated with greater HCI [β=0.15, 95% CI: 0.03, 0.27, p=0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p=0.01) compared to 0.11 (p=0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β=-0.01 (p=0.02) and β=-0.01 (p=0.04), respectively. Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a "multi-hit" mechanism in AD development.

Participant Personal Characteristics and Adherence to Oral Capsules: A Secondary Analysis of a Randomized Placebo-Controlled Trial of Antenatal Probiotics.

Adherence to study interventions is critical to the conduct of randomized controlled trials (RCTs). The relationships between participant characteristics and intervention adherence are understudied in pregnant populations. The purpose of this study was to conduct a secondary analysis of adherence to study capsules in a double-masked, placebo-controlled RCT of a probiotic intervention to reduce antenatal Group B Streptococcus colonization, in relationship to participant characteristics. We analyzed the relationship between capsule adherence rates and demographic characteristics among 81 RCT participants. Categorical variables were reported using counts and percentages, and continuous variables were expressed as means along with their standard deviations. For the univariate analyses, we compared demographic variables with adherence scores. A multivariate linear regression model was used to identify predictors of adherence. Average adherence was similar for control and probiotic group participants (P =.86) Univariate analysis showed that average adherence increased directly with age, education, and income. Participants who were partnered or living with others had higher average adherence compared with those who were single and living alone. Asian and White participants had the highest and Black participants had the lowest average, and there was no difference based on Hispanic ethnicity. Adjusting for all the variables in the regression, participants who identified as Black were significantly less likely to adhere to capsules than White participants, and those who were married or living with partners were more likely to adhere than the single participants. Diverse participants are critically important to RCTs. This secondary analysis provides evidence that participant characteristics and the social determinants of health play an important role in adherence to self-administered interventions in RCTs, although more research is needed. Our findings suggest that intentional consideration of RCT participant characteristics may allow for the development and tailoring of strategies to enhance intervention adherence. The study was registered on ClinicalTrials.gov (NCT03696953) on January 10, 2018.

Hormones, Stress, and Heart Disease in Transgender Women with HIV in LITE Plus

Cardiovascular disease (CVD) is a leading cause of death among transgender women and people with HIV. Exogenous estrogen and psychosocial stressors are known risk factors for CVD. Yet, few studies have used biomarkers to examine the role of stress in CVD risk among transgender women with HIV (TWHIV). This analysis examined whether stress moderates relationships between gender-affirming hormone therapy (GAHT) duration and CVD risk among TWHIV. This cross-sectional analysis of baseline data from an observational cohort of 108 Black and Latina TWHIV in Boston, New York, and Washington, DC, enrolled December 2020 to June 2022, measured sociodemographics, medical diagnoses, medications, smoking history, and perceived stress via interviewer-administered surveys. Physiological stress was measured with 14 biomarkers to calculate allostatic load indices (ALI). Forty participants provided saliva samples used to calculate cortisol awakening response and cortisol daily decline. The 2018 American College of Cardiology Revised Pooled Cohort Equation estimated 10-year CVD risk. Data were analyzed in 2024. GAHT duration was positively associated with CVD risk scores in bivariate regression. In multivariable linear regression models (adjusting for age, income, education), only age and ALI remained significantly associated with CVD risk scores (β 1.13, CI: 1.05, 1.21). No stress measure significantly interacted with GAHT duration to affect CVD risk scores. In visual plots, GAHT duration increased CVD risk scores only for TWHIV experiencing the highest ALI. Stress plays an important role in CVD in TWHIV. More research is needed on non-GAHT factors, which influence CVD health among transgender women.

Insulin Resistance in Hypercalciuric Calcium Kidney Stone Patients

Rational and ObjectiveDiabetes and uric acid kidney stones are strongly associated. Patients with calcium kidney stones also have higher risk of developing diabetes compared to non-kidney stone patients yet this has not been further investigated. We aimed to characterize insulin resistance in calcium kidney stone patients. Study DesignObservational Setting & PopulationThis study was performed in the University of Chicago Clinical Research Center. Kidney stone patients (N=42) were selected for having idiopathic hypercalciuria and calcium stones with no other medical conditions and controls (N=27) were healthy. ExposuresAll participants presented to the Clinical Research Center in a fasting state and at least 2 timed fasting blood and urine were collected prior to a fixed breakfast. Six additional timed blood and urine collections were performed after breakfast. OutcomesWe compared fasting and fed indices of insulin resistance between the groups. Analytic ApproachWe used t-tests and multivariable linear regression models. A sensitivity analysis removing all patients who had ever been on a thiazide diuretic was also performed. ResultsIn separate multivariable linear models, kidney stone patients had higher fasting serum insulin (24 (3 to 46pmol/L), p=0.03) and higher homeostatic model of insulin resistance (HOMA-IR) (1.0 (0.2 to 1.8), p=0.02). In separate multivariable linear models, kidney stone patients had higher fed serum glucose (10 (2 to 18mg/dL), p=0.01). Results were similar in a sensitivity analysis removing all patients who had ever been on a thiazide diuretic. There were no differences in urine composition based on HOMA-IR levels. LimitationsSingle institution. Small sample size limited subanalyses by different calcium stone types. ConclusionsCalcium kidney stone patients without diabetes or other medical conditions demonstrated signs of insulin resistance compared to healthy matched controls.

Super-large diameter slurry shield tunnel encountering boulder formation: Detection, treatment and data analysis

Boulders pose substantial challenges in coastal urban tunnel engineering. This study, for the first time, utilizes extensive closely spaced borehole data from 3486 drilling points obtained during actual tunnelling through boulder strata to evaluate the effectiveness of microtremor detection, analyze variations in operational parameters, and assess the efficiency of blasting treatment. Additionally, leveraging borehole data, a 3D reconstruction of the soil-boulder-bedrock stratum was developed, and the stratum content ratio at the excavation face was derived. A multivariate linear regression model was established to explore the relationship between boulder geology and construction parameters. The results demonstrated that microtremor surveys effectively identified boulder distributions by analyzing horizontal-to-vertical spectral ratio curves and differences in surface wave phase velocity. Field drilling confirmed the high accuracy of microtremor predictions, particularly in areas with dense or thick boulder layers. Post-blasting secondary drilling revealed boulder fragments smaller than 30 cm, meeting the operational requirements for shield cutter and crusher systems. The presence of boulders was found to increase thrust, torque, and overturning moments, as well as cause abnormal cutter wear. Blasting significantly reduced the standard deviation of operational data, demonstrating its effectiveness in stabilizing tunnelling performance. Regression analysis showed a strong correlation between geological conditions and tunnelling parameters, with results indicating that blasting operations effectively mitigate the adverse impacts of boulders on shield tunnelling performance. This study aims to provide valuable insights and references for future engineering projects encountering similar complex geological conditions.

Patterns and Determinants of Micronutrient Dietary Biomarkers and Their Associations with Dietary Intakes in Young Children

BackgroundCirculating dietary biomarkers are not direct proxies for intake, as the biomarkers reflect not only food and supplement consumption but also nutrient absorption, metabolism, and tissue distribution. Therefore, along with nutrient intake, several other upstream factors can impact dietary biomarker concentrations, including demographic, medical history, and genetic factors. ObjectivesThe aim of this study was to explore the dietary and nondietary determinants of circulating levels of vitamins A, C, D, and E among children aged 6 mo–4 y. MethodsPlasma retinol, β-carotene, ascorbic acid, 25(OH)D, α-tocopherol, and γ-tocopherol were measured in 2887 samples from 1490 children enrolled in The Environmental Determinants of Diabetes in the Young study. Dietary intake was assessed with 3-d food records. Associations of genetic and environmental factors with biomarker concentrations were examined using multivariable linear regression models with random intercepts. ResultsAll biomarkers except retinol were positively associated with intake of the same nutrient. Inverse associations were identified between recent gastrointestinal infection and β-carotene, ascorbic acid, and α-tocopherol, whereas recent respiratory infection was associated inversely with plasma retinol. Several genetic determinants of biomarker status were identified, validating previously reported findings. For some genetic and environmental exposures, we found evidence of statistical interaction with same-nutrient intake, indicating that the association between intake and biomarker concentration is dependent on the level or status of these other exposures. For example, the association between β-carotene intake and concentration is weaker among children with a recent respiratory infection. ConclusionsOur findings suggest that nondietary exposures including childhood infections can alter micronutrient metabolism. This summary of micronutrient determinants will facilitate improved design of future analyses exploring the role of diet in childhood chronic disease etiology through a better understanding of relevant potential confounders and mediators of the diet–outcome relationships.