Faculty Bibliography

Despite well-studied benefits of preventive parenting programs for early child development, various real-world barriers may impede families from engaging in those programs. The current study aims to provide new insights into family engagement by examining enrollment, retention, and involvement and their predictors in an evidence-based universal pediatric primary care parenting program for families with young children. Data (n = 204) were from an ongoing longitudinal randomized controlled trial of PlayReadVIP in Flint, MI. Families (66% Black, 35% White, low socioeconomic status) had high enrollment and retention in the program. As exploratory analyses, random forest models, a machine learning method, identified a multitude of sociodemographic, psychosocial, and contextual predictors of retention and involvement in PlayReadVIP across the first 9 months. As confirmatory analyses, multiple regressions showed that COVID-19 significantly hindered retention (odds ratio = .04; b =  - .30) and involvement (b =  - .31) and that higher parenting self-efficacy was associated with lower retention (odds ratio = .76). Furthermore, the association between COVID-19 and family engagement was moderated by household income, suggesting that families with the highest economic risks were less likely to attend and be actively involved in sessions during the pandemic. This study addresses important research gaps by focusing on multiple aspects of family engagement in a pediatric program during infancy, assessing whether experiencing contextual adversity hinders or motivates engagement, and employing a machine learning method. These findings have crucial implications for designing and implementing early childhood prevention parenting programs to more effectively engage families with higher needs.

BACKGROUND:Midkine is a heparin-binding growth factor that is overexpressed in most human malignancies, including breast cancer. While elevated midkine levels have been associated with tumor progression and aging, its role as a predictive biomarker for breast cancer risk in healthy individuals remains unclear. We previously showed that higher midkine expression in estrogen receptor-positive (ER +) breast cancer in younger (< 55) women is associated with shorter disease-free survival. We investigated whether serum midkine levels in premenopausal women are associated with subsequent risk of ER + breast cancer. METHODS:We conducted a prospective, nested case-control study within the New York University Women's Health Study (NYUWHS). Serum midkine levels were measured in baseline blood samples from 249 premenopausal women who developed ER + breast cancer more than 10 years after blood collection and 249 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across quartiles and continuous midkine levels, adjusting for key breast cancer risk factors. RESULTS:Higher circulating midkine levels were associated with a marginally statistically significant lower risk of ER + breast cancer. Compared to the lowest quartile, women in the highest quartile had an OR of 0.55 (95% CI: 0.30-0.99; P for trend = 0.10). A doubling in midkine was associated with a 34% reduction in risk (OR = 0.66; 95% CI: 0.42-1.02). The inverse association was generally consistent across subgroups. CONCLUSION/CONCLUSIONS:These findings suggest that higher baseline serum midkine levels in premenopausal women are associated with a reduced long-term risk of ER + breast cancer. This challenges prior assumptions about midkine's uniformly pro-tumorigenic role and suggests it may be a context-dependent biomarker in breast cancer development.

BACKGROUND:Betel quid is a widely consumed substance that has been associated with higher mortality and increased risk of several diseases. RESEARCH QUESTION/OBJECTIVE:Is betel quid use associated with increased respiratory disease mortality, particularly in COPD? STUDY DESIGN AND METHODS/METHODS:A prospective cohort included 20,033 individuals 18 to 75 years of age living in Araihazar, Bangladesh. A total of 476 deaths resulting from respiratory disease were recorded during follow-up between October 2000 and April 2024. Data on baseline demographics, lifestyle factors, and betel nut use were ascertained using standardized questionnaires. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations between betel consumption practices and the risk of death due to respiratory disease while adjusting for age, BMI, educational attainment, sex, and cigarette smoking history. RESULTS:Cohort members who had ever consumed betel were at increased risk of death due to respiratory disease (HR, 1.38; 95% CI, 1.13-1.69), including COPD (HR, 1.56; 95% CI, 1.19- 2.05) but not lung cancer (HR, 1.24; 95% CI, 0.81-1.89). We observed a dose-response relationship between indicators of betel use intensity and COPD mortality; compared with those who never used betel, the HR was 1.46 (95% CI, 1.10-1.94) and 2.47 (95% CI, 1.64-3.74) for those who did use betel with low and high levels of consumption, respectively. The association did not differ appreciably by other characteristics and remained apparent in female individuals (HR, 3.63; 95% CI, 2.01-6.59) and people who have never smoked (HR, 3.44; 95% CI, 1.85-6.39). The population attributable fraction for betel use was 16.3% for deaths from COPD. INTERPRETATION/CONCLUSIONS:Betel quid consumption was associated with increased mortality from respiratory disease, including COPD, in this cohort. Efforts to bolster clinical and public awareness are warranted to help combat the global health emergency posed by betel quid consumption.

IMPORTANCE/UNASSIGNED:Chronic exposure to arsenic in drinking water has been associated with increased chronic disease mortality. However, there is limited evidence on associations between reduced exposure and mortality risk. OBJECTIVE/UNASSIGNED:To examine whether reductions in arsenic exposure, measured using urinary arsenic levels, are associated with lower mortality from chronic diseases, including cancer and cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A prospective cohort of 11 746 adults was enrolled between 2000 and 2002 in Araihazar, Bangladesh, with levels of well-water arsenic ranging from less than 1 µg/L to 864 µg/L (mean, 102 µg/L), exceeding the Bangladesh standard of 50 µg/L. Arsenic levels declined over time as a result of community mitigation. Mortality was tracked through 2022. Analyses included 10 977 participants with calculable changes in urinary arsenic levels. EXPOSURES/UNASSIGNED:Urinary arsenic levels were measured up to 5 times per participant through 2018. Participants were categorized based on changes in urinary arsenic levels. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Adjusted hazard ratios (aHRs) and 95% CIs for mortality from chronic diseases, including cancer and CVD. RESULTS/UNASSIGNED:Among 10 977 participants (57% female; mean age, 37.0 [SD, 10.1] years), mean urinary arsenic levels declined from 283 (SD, 314) to 132 (SD, 161) µg/g creatinine from 2000 to 2018. Each IQR decrease in urinary arsenic (197 µg/g creatinine) was associated with 22% lower chronic disease mortality (aHR, 0.78 [95% CI, 0.75-0.82]), 20% lower cancer mortality (aHR, 0.80 [95% CI, 0.73-0.87]), and 23% lower CVD mortality (aHR, 0.77 [95% CI, 0.73-0.81]). Time-varying Cox and restricted cubic spline analyses showed larger reductions were associated with lower mortality, while increases were linked to higher risk. Compared with participants with consistently high urinary arsenic levels (above the baseline median of 199 µg/g creatinine [n = 1757]), those whose levels declined below the median (n = 3757) had lower mortality from chronic diseases (aHR, 0.46 [95% CI, 0.39-0.53]), including cancer (aHR, 0.51 [95% CI, 0.35-0.73]) and CVD (aHR, 0.43 [95% CI, 0.34-0.53]), similar to those consistently below the median (n = 4959) (aHR, 0.43-0.49). Findings were similar in propensity score-matched analyses. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These findings support an association between reduced arsenic exposure and improved health outcomes in populations exposed to contaminated drinking water.

Genome-wide association studies (GWAS) have identified more than 200 risk loci for breast cancer. However, target genes and their encoded proteins in these loci remain largely unknown. In this study, we utilized genetic prediction models for 1349 circulating proteins derived from individuals of African (n = 1871) and European (n = 7213) ancestry to investigate genetically predicted protein levels in association with breast cancer risk among females of African (n = 40,138), Asian (n = 137,677), and European (n = 247,173) ancestry. We identified 51 blood protein biomarkers associated with breast cancer risk, overall or by subtypes, at a false discovery rate (FDR) < 0.05, including 27 proteins encoded by genes located at least 1 Mb away from any of the known risk loci identified in GWAS. Of them, 32 proteins showed significant associations with breast cancer risk at the Bonferroni-corrected significance level (p < 2.45 × 10^-4). Of the 24 proteins located at GWAS-identified risk loci, associations for 14 proteins were significantly attenuated after adjustment for the index risk variant of each respective locus, suggesting that these proteins may be target proteins for the risk loci. Encoding gene expression levels in normal breast tissue could be genetically predicted for 23 of the 51 identified proteins, and 13 encoding genes were associated with breast cancer risk in the same direction (p < .05). Our study identified potential protein targets of GWAS risk loci and biomarkers for breast cancer risk and provided additional insights into breast cancer genetics and etiology.

The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.

Prior research links prenatal exposure to organophosphate (OP) pesticides to adverse health outcomes via molecular mechanisms, such as oxidative stress, neurotransmitter disruption, and mitochondrial dysfunction. This study investigates such mechanisms by assessing the relationships between prenatal OP pesticide exposure and targeted urinary maternal metabolomic profiles using data from the New York University Children's Health and Environment Study (NYU CHES) cohort (n = 890). Urine samples were collected at three time points during pregnancy (T

BACKGROUND:Bile acids are produced in the liver and are important for lipid digestion. Higher circulating bile acid levels, however, have been linked to metabolic disorders, inflammation, and gut microbiota dysbiosis, which have been implicated in liver carcinogenesis. To date, few epidemiological studies have explored the association between circulating bile acids and liver cancer risk. METHODS:We conducted a nested case-control study among 12 prospective cohort studies located in the United States. Fifteen pre-diagnostic circulating bile acids were measured from blood samples among 872 individuals who developed liver cancer and 872 matched control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable-adjusted conditional logistic regression analysis of circulating bile acid levels and liver cancer risk. RESULTS:Primary conjugated bile acid concentrations were positively associated with higher risk of liver cancer (OR per doubling in concentrations [log2] of glycocholic acid, 95% CI: 1.32, 1.24-1.40; glycochenodeoxycholic acid: 1.33, 1.24-1.43; taurocholic acid: 1.28, 1.22-1.35; and taurchenodeoxycholic acid: 1.32, 1.24-1.39). Secondary conjugated bile acids were also positively associated with liver cancer risk (doubling of concentrations OR ranged from 1.11 to 1.22). Unconjugated bile acid concentrations were generally not associated with liver cancer risk, except lithocholic acid (OR per doubling: 1.27, 1.16-1.39). When analyses were separated into the two main subtypes of liver cancer, hepatocellular carcinoma (HCC; 438 cases/438 controls) and intrahepatic cholangiocarcinoma (ICC; 111 cases/111 controls), significant heterogeneity was observed for primary conjugated bile acid concentrations (all p-values < 0.001) that showed positive significant associations with HCC but not ICC. CONCLUSIONS:These results suggest that bile acids may be important markers of HCC risk and contribute to hepatocarcinogenesis; however, further research using serial measurements is needed.

OBJECTIVE:Research into risk factors for subjective cognitive complaints (SCCs) may offer insight into the etiology and prevention of Alzheimer's disease. Ultra-processed foods (UPFs) contain food additives that improve palatability and processed raw materials. Evidence is limited on the role of mid-life UPF intake in the development of late-life SCCs. METHODS:We included 5119 participants who responded to the 2018 or 2020 follow-up of the New York University Women's Health Study, a prospective cohort of 14,274 women recruited in New York City, United States, in 1985-91. Data on diet were collected at baseline using a validated modified Block food frequency questionnaire. Energy-adjusted total intake of UPFs and subgroups of UPFs, defined following the nova guidelines, were estimated using the residual method. RESULTS:The odds ratios (ORs) and 95 % confidence intervals (CIs) for reporting ≥2 SCCs were 1.15 (0.94-1.39), 1.06 (0.87-1.30), 1.20 (0.99-1.46), and 1.24 (1.02-1.51) for women in the 2nd, 3rd, 4th, and 5th quintiles of energy-adjusted UPF intake, respectively, compared to those in the bottom quintile (p-trend = 0.02). The associations were similar in sensitivity analyses using Multiple Imputation and Inverse Probability Weighting to account for potential selection bias. CONCLUSIONS:Higher UPF intakes in midlife were associated with higher odds of late-life SCCs in women.

BACKGROUND/UNASSIGNED:Per- and polyfluoroalkyl substances (PFAS) have been associated with numerous deleterious health outcomes including liver damage. However, whether exposure to PFAS is associated with liver cancer risk remains unclear. METHODS/UNASSIGNED:percentile incremental increase. RESULTS/UNASSIGNED:percentile increase:0.68, 0.50-0.92; p-interaction=0.005). Analyses separating liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma, showed no evidence of heterogeneity, although associations were stronger but not significant for HCC. No evidence of interaction was observed by time to diagnosis, time period of blood draw, body mass index, alcohol intake, ethnicity, or diabetes status. CONCLUSIONS/UNASSIGNED:In the largest study to date, none of the measured circulating PFAS were associated with liver cancer risk; however, PFOA associations appeared to differ by sex and further research is needed to explore these apparent differences by sex. https://doi.org/10.1289/EHP16980.