Faculty Bibliography

BACKGROUND/UNASSIGNED:Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide, yet current prediction tools do not fully capture sex differences in risk. Menopause further modifies women's risk of CHD, but underlying molecular mechanisms are not well understood. Proteomic profiling may provide new insights into these mechanisms. METHODS/UNASSIGNED:We analyzed 4,877 SomaScan™-based plasma proteins in 10,034 Atherosclerosis Risk in Communities (ARIC) participants. Using linear regression, we identified sex- and menopause-related differences in circulating protein concentrations. We performed pathway enrichment analyses to capture underlying biological mechanisms. To evaluate the associations between proteins and incident CHD and differences by sex or menopause status, we applied Cox regression. Finally, we used LASSO regression to identify proteins that improve CHD risk prediction beyond an established clinical model. RESULTS/UNASSIGNED:We observed significant differences in circulating proteins by sex and menopausal status, including early changes during the menopausal transition. We found protein associations with incident CHD differed markedly by sex and menopausal stage: eight proteins were associated with CHD in men, compared with 54 in women, and six and 17 proteins in peri‑ and postmenopausal women, respectively. In risk prediction analyses, adding sex-specific protein panels improved CHD prediction (ΔC-statistic=0.05 in men and 0.03 in women), with similar improvement across menopausal stages. CONCLUSIONS/UNASSIGNED:Proteomic profiles underlying CHD risk differ substantially by sex and menopausal stage. These findings suggest potential biological heterogeneity in CHD and support the study of sex- and menopause-related differences in underlying mechanisms.

UNLABELLED:The COVID-19 (C19) pandemic caused significant mortality often due to lung injury and systemic inflammation, but there is significant heterogeneity in severity, and the pathobiology is not well understood. We examined C19-induced pulmonary and inflammatory sequelae using a murine noninfectious model to further define the model's utility and to also understand the role of mediators such as heme oxgenase-1 (HO-1). K18-hACE2 male mice oropharyngeally aspirated C19-spike protein(SP) or equal volume control. After 72 h, pulmonary mechanics, bronchoalveolar lavage (BAL), plasma, snap-frozen right lung, and fixed/stained left lung for histologic injury assessment (Qupath) was collected. Cytokine elaboration in BAL and plasma was quantified (Luminex), and lung homogenates were probed for HO-1 and NLRP3 (Western). Statistical (SPSS and R) and pathways comparisons (Ingenuity Pathway Analysis) were made between control and C19-SP. C19-SP exposure significantly reduced inspiratory capacity and static lung compliance; tissue elastance and airway bronchoconstriction were increased. C19-SP exposure caused significant inflammation and thickened alveolar septae on histology. C19-SP exposure also led to inflammatory response in BAL and plasma with simultaneous activation of Type 1 and Type 2 pathways. NLRP3 and HO-1 protein expression is significantly increased after C19-SP. A noninfectious C19-SP murine model showed worsened lung parameters and increased inflammation. Increased expression of HO-1 and NLRP3 were associated with the inflammatory process after exposure to C19, consistent with findings in human cohorts. Further studies may focus on targeted knock in/knock down experiments and dose/time-course studies that probe the mechanistic relationship of HO-1 and NLRP3 in C19-related disease. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-58934-9.

INTRODUCTION:The Harambee randomised trial tested the extent to which integrating community-based care with microfinance improves viral suppression and retention in care among people with HIV in Kenya. METHODS:Using a two-arm parallel-cluster randomised controlled trial, we randomised 57 microfinance groups (29 to intervention, 28 to usual (facility-based) care) with 855 members living with HIV (407 in intervention, 448 in usual care). We enrolled n=300 frequency-matched, prospectively followed usual HIV care patients without microfinance. Delivered quarterly during community-based microfinance meetings, the intervention included clinical consultations, diabetes and/or hypertension management, distribution of antiretroviral therapy and non-communicable diseases medications, health education and facility referrals. The primary outcome was viral suppression (<400 HIV-RNA/mL before 1 January 2023; <200 HIV-RNA/mL on or after 1 January 2023) at 18 months. The secondary outcome was retention-in-care (attending >1 scheduled HIV care visit/quarter over 18 months). Between-arm comparisons were done using doubly-robust generalised estimating equations accounting for dropout and confounding (for comparisons to the non-randomised arm). RESULTS:At enrolment, 94% of participants were virally suppressed. Viral suppression at 18 months was not significantly different between microfinance group members receiving community care versus facility care (OR 1.23, 95% CI 0.51 to 2.95, p=0.64). Viral suppression at 18 months was higher among community-care microfinance members (OR 2.16, 1.48 to 3.19, p<0.001) and facility-care microfinance members (OR 1.42, 1.05 to 1.92, p=0.023), compared with matched facility-care patients not engaged in microfinance. There was evidence of better quarterly retention comparing microfinance group members receiving community care versus facility care (OR 3.79, 2.96 to 4.86, p<0.001). Retention was higher among community-care microfinance members (OR 9.13, 7.13 to 11.70, p<0.001) and facility-care microfinance members (OR 2.40, 2.03 to 2.85, p<0.001), compared with matched facility-care patients. CONCLUSION:More convenient services can improve retention in HIV care, while economic strengthening likely helps improve clinical HIV outcomes. Research to identify impact mechanisms and scale-up potential is needed. TRIAL REGISTRATION NUMBER:NCT04417127.

INTRODUCTION/UNASSIGNED:Falls impose a mounting burden on emergency care systems in ageing societies. Critical uncertainties remain regarding geographic disparities and future trajectories beyond demographic ageing. We examined patterns and projections of fall-related emergency department (ED) visits in Korea, one of the world's most rapidly ageing societies. METHODS/UNASSIGNED:We analysed 943 692 fall-related ED visits among adults aged ≥65 years from Korea's nationwide registry (2016-2023). Geographic disparities were characterised by area type (metropolitan vs non-metropolitan) and population density tertiles. Age-standardised and sex-standardised rates were calculated. Generalised additive models assessed non-linear temporal trends and pandemic-associated structural breaks. Future projections (2024-2040) were generated under three incidence scenarios, with component decomposition quantifying contributions from demographic ageing versus incidence rate changes. RESULTS/UNASSIGNED:A geographic paradox emerged: metropolitan and high-density areas exhibited higher visit rates, whereas non-metropolitan and low-density areas demonstrated greater clinical severity. Hospital admission rates followed a density gradient-46.7% in low-density, 44.0% in middle-density and 34.3% in high-density areas. Non-metropolitan areas showed disproportionate vertebral column injuries (17.4% vs 13.5%). Temporal trends revealed a pandemic-associated structural break followed by steep rebound from 2022. Projected visits will increase 2.0-fold to 4.1-fold by 2040. Demographic ageing alone guarantees doubling of burden. If pre-pandemic trends resume, rising intrinsic risk will contribute 67.9% of total increase, exceeding demographic effects (32.1%). CONCLUSION/UNASSIGNED:Korea faces a bifurcated geographic burden: metropolitan areas confront volume pressure, while non-metropolitan areas experience disproportionate severity. The future burden will be shaped by both unavoidable demographic ageing and potentially avertable increases in intrinsic fall risk. These findings have critical implications for rapidly ageing societies across East Asia facing comparable urban-rural disparities, necessitating regionally differentiated prevention and trauma care strategies that integrate capacity expansion with targeted risk reduction.

INTRODUCTION/BACKGROUND:Enrollment into clinical trials is challenging and has a major effect on the feasibility and the generalizability of a study. We used data from a previously completed hospital-based smoking cessation study to determine if enrollment rates varied by hospital admitting service, specifically comparing Medicine and Psychiatry departments. METHODS:We examined enrollment in the Financial Incentives for Smoking Cessation (FIESTA) study, which was conducted at the Veterans Affairs New York Harbor Healthcare System. FIESTA tested the effectiveness of financial incentives on smoking cessation among hospitalized patients. A total of 268 patients were eligible, with 182 enrolled in the original FIESTA study. In our secondary analysis, a LASSO approach was applied to the data set to create a model examining admitting service, age, sex, race and ethnicity, education, and number of cigarettes per day and their association with enrollment. RESULTS:The enrollment rates were higher for patients admitted to the Psychiatry service (80.2%) than to the Medicine and other services (59.9%). Patients with a high school education or less also had a higher enrollment rate (87.2%) than those with higher education (57.7%). Increasing age was associated with lower odds of enrollment (aOR = 0.97, 95% CI: 0.94, 0.99). Hispanic ethnicity appeared to associate with a higher odds of enrollment compared to non-Hispanic White (aOR = 2.52, 95% CI 1.11, 5.75). Higher odds of enrollment were observed among patients admitted to the Psychiatry service (aOR = 2.51, 95% CI: 1.23-5.12), while lower odds were observed among those with higher education (aOR = 0.17, 95% CI: 0.06-0.49). CONCLUSIONS:This research suggests that smoking cessation programs can effectively enroll a diverse patient population, including typically underrepresented groups such as those with lower education status and those with mental health diagnoses. Such enrollment efforts would enable studies to be more generalizable to the smoking population. Findings also emphasize the potential of urban hospital settings to support equitable enrollment efforts. The present work is a secondary analysis of the FIESTA RCT (NCT02506829). Future research should explore additional demographic factors, such as comorbidities and confidence in quitting, to better understand motivations for participation.

BACKGROUND/OBJECTIVE/OBJECTIVE:As genetic testing becomes routine, more individuals carrying pathogenic variants in breast cancer susceptibility genes in the absence of suggestive family history have been identified. Mutations in BRCA 1, BRCA 2, ATM, CHEK2, and PALB2 account for approximately 7-10% of breast cancers. Our aim was to identify differences in demographic factors, tumor characteristics, and surgical treatment between mutation carriers with and without a reported first-degree affected relative. METHODS:We retrospectively reviewed our Institution's IRB approved breast cancer database to identify patients enrolled between 1/2010 and 8/2025 who tested positive for BRCA1, BRCA2, ATM, CHEK2, or PALB2. Patients with prior breast cancer were excluded. Demographic, clinical, tumor, and surgical data were collected. Continuous variables were compared using t-tests and categorical variables using chi-square tests. RESULTS:Among 199 mutation carriers with breast cancer, 128 (64%) reported no first-degree affected relative (N1D) and 71 (36%) did (Y1D). At diagnosis, N1D patients were younger (p=0.001), more often presented with a palpable mass (p=0.003) and had higher rates of neoadjuvant chemotherapy (NAC) (p= 0.023). Mutation distribution did not differ, nor did overall histology, although N1D patients trended to have more invasive disease. Surgery type did not differ between groups (p=0.607). 55% of N1D patients had an affected second-degree relative. CONCLUSION/CONCLUSIONS:N1D patients presented at a younger age and were more likely to have clinically apparent invasive disease, along with higher rates of NAC. These findings likely reflect differences in screening rather than more aggressive tumor biology, as receptor subtype, triple-negative rates, and tumor grade were comparable across groups. Despite these differences, surgical management was similar, suggesting that operative planning is influenced more by genetic risk rather than by family history alone. Many N1D patients had an affected second-degree relative, indicating the need for comprehensive evaluation of family history. These findings support expanding genetic testing beyond family-based criteria to better identify high-risk individuals.

PURPOSE/OBJECTIVE:The aim of this study was to assess the interplay between 2 important viral infections and their management, herpes zoster ophthalmicus (HZO) and COVID-19. METHODS:A subanalysis from the Zoster Eye Disease Study, a prospective randomized controlled study examining prophylactic valacyclovir in HZO, and data collected on COVID-19 vaccination and infection from July 2020 were evaluated. Participants were included if enrolled from January 1, 2019, ensuring that their 18-month follow-up overlapped with the COVID-19 pandemic. Recurrence was defined as new or worsening stromal keratitis without ulceration, endothelial keratitis, iritis, dendritiform epithelial keratitis, or stromal keratitis with ulceration requiring a substantial increase or recommencement of topical steroid therapy. RESULTS:A total of 402 participants were included in the analysis. Attenuated zoster vaccination live was given to 35 (8.7%) and recombinant zoster vaccine to 40 (10.0%) before study commencement. No difference was observed in incidence or severity of COVID-19 infection in those with previous zoster vaccination, and no difference was observed in those treated with valacyclovir prophylaxis. COVID-19 infection occurred in 71 participants (17.7%) during the study period, and COVID-19 vaccination was received by 170 participants (42.3%). No association was observed between HZO recurrence and COVID-19 infection (P = 0.39) or vaccination (P = 0.75) during the 18-month follow-up. The study was powered to detect a hazard ratio of 1.19 for COVID-19 infection or vaccine-associated recurrence. CONCLUSIONS:No significant association was observed between zoster vaccination or valacyclovir use and COVID-19 incidence or severity. In addition, no significant increase in HZO recurrence was observed following COVID-19 infection or vaccination.

IMPORTANCE/UNASSIGNED:In Uganda and other low-income settings with prevalent mental health problems and limited resources, scalable professional development (PD) models are needed to strengthen teachers' capacity to apply evidence-based practices to support child mental health. OBJECTIVE/UNASSIGNED:To examine the short-term effectiveness of PD and PD with a teacher-wellness enhancement (PDT) compared with a control condition on teacher knowledge and use of evidence-based practices, teacher stress, and teacher stress management; implementation outcomes; and the differential outcomes between urban and rural primary schools in Uganda. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cluster randomized clinical trial was conducted in 47 urban and rural schools in Uganda between August 2021 and February 2025. Participating teachers in the schools were followed-up 24 months after the intervention, and the present trial focused on short-term teacher outcomes. Statistical analysis followed the intention-to-treat principle. INTERVENTIONS/UNASSIGNED:Schools and teachers were randomized to 1 of 3 conditions: PD, PDT, and control. The PD intervention (mWEL-PD or Mental Wellbeing and Empowering Lives of the School Community: Professional Development) consisted of 3 days of training and 8 one-hour coaching sessions in person for 2 to 3 months. The PDT intervention (mWEL-PD with a teacher-wellness enhancement) was provided as the PD program plus a 1-day workshop and 3 group support sessions. The control condition offered no intervention during year 1, but mental health knowledge and promotion materials and a 1-day teacher-wellness workshop were provided in year 2. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes for PD and PDT groups were knowledge and use of evidence-based practices. Teachers completed 15 self-report measures assessing 4 key outcomes: knowledge of evidence-based practices, use of evidence-based practices, teacher stress, and teacher stress management. Implementation outcomes, self-assessed after completion of the intervention, included teacher engagement in the intervention, teacher perception of acceptability and usefulness of the content, and teacher perception of the competence of the program facilitators. RESULTS/UNASSIGNED:A total of 47 schools with 509 teachers (mean [SD] age, 40.60 [11.12] years; 368 females [72.3%]) were included in the analysis. Among the schools, 15 (31.9%) were randomly assigned to the control, 16 (34.0%) to the PD, and 16 (34.0%) to the PDT groups. Among teachers, 165 (32.4%) were randomly assigned to the control, 187 (36.7%) to the PD, and 157 (30.8%) to the PDT groups. Teacher attendance at training and coaching sessions and ratings of relevance and facilitator competence were high in both urban and rural contexts. Compared with teachers in the PD group, those in the PDT group were more likely to attend all training days offered (120 of 187 [64.1%] in the PD group vs 127 of 157 [80.9%] in the PDT group) and participated in more coaching sessions (mean [SD] number, 4.58 [2.91] vs 6.09 [2.28]). Compared with teachers in the control condition, teachers in the PDT condition benefited on all 4 key outcomes: increased knowledge (standardized mean difference [SMD], 0.57; 95% CI, 0.26-0.88) and use (SMD, 0.36; 95% CI, 0.01-0.71) of evidence-based practices, increased stress management (SMD, 0.50; 95% CI, 0.19-0.80), and decreased stress (SMD, -0.27; 95% CI, -0.54 to 0.01). Benefits of PD were limited to knowledge of evidence-based practices (SMD, 0.33; 95% CI, 0.03-0.62). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This trial of a scalable teacher PD program delivered through existing educational infrastructure and resources demonstrates the program's feasibility, acceptability, and impact on self-reported teacher outcomes. The finding of short-term benefits for teacher practice and wellness suggests the potential of the PDT model for school-based mental health promotion. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04383327.

Social-class inequities in health arise from power imbalances in our political-economic system. However, through labor-union organizing, workers can build power to improve their life chances and health. In our review, we describe the rich historical, theoretical, and mechanistic evidence linking unions and health and critically evaluate the state of quantitative research on the topic. Most individual-level and ecological studies have estimated small beneficial or null union-health associations. However, as we describe, the studies are limited in number, particularly outside the Global North, and face many technical and conceptual challenges, including feedback loops between unions and societies' political-economic contexts. We conclude with recommendations for enhancing the rigor and utility of union-health research, including by richly contextualizing studies' findings and by answering questions raised by workers themselves. As social and economic inequities intensify and workers face heightening attacks on their well-being, unions remain crucial organizations for advancing health justice.