Faculty Bibliography

BACKGROUND/UNASSIGNED:The oral microbiome is vital for health, yet population-based evidence on how self-reported flossing relates to microbial communities remains limited. This study examined the association between self-reported dental flossing frequency and oral microbiome diversity in a nationally representative sample of U.S. adults. METHODS/UNASSIGNED:This cross-sectional analysis included 4,772 adults aged 30-69 from NHANES 2009-2012. Flossing frequency was categorized as non-users (0 days/week), some flossing (1-6 days/week), and daily users (7 days/week). Oral microbiome composition was profiled using 16S rRNA sequencing. α-diversity was calculated using Observed amplicon sequence variants (ASVs), Shannon, Inverse Simpson, and Faith's Phylogenetic Diversity (PD); β-diversity using Bray-Curtis and UniFrac distances. Survey-weighted linear regression and PERMANOVA were used with covariate adjustment. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Frequent flossing was associated with reduced microbial richness and phylogenetic diversity, potentially indicating a favorable shift toward a healthier microbial community.

MOTIVATION/BACKGROUND:Large-scale prospective cohort studies collect longitudinal biospecimens alongside time-to-event outcomes to investigate biomarker dynamics in relation to disease risk. The nested case-control (NCC) design provides a cost-effective alternative to full cohort biomarker studies while preserving statistical efficiency. Despite advances in joint modeling for longitudinal and time-to-event outcomes, few approaches address the unique challenges posed by NCC sampling, non-normally distributed biomarkers, and competing survival outcomes. RESULTS:Motivated by the TEDDY study, we propose "JM-NCC", a joint modeling framework designed for NCC studies with competing events. It integrates a generalized linear mixed-effects model for potentially non-normally distributed biomarkers with a cause-specific hazard model for competing risks. Two estimation methods are developed. fJM-NCC leverages NCC sub-cohort longitudinal biomarker data and full cohort survival and clinical metadata, while wJM-NCC uses only NCC sub-cohort data. Both simulation studies and an application to TEDDY microbiome dataset demonstrate the robustness and efficiency of the proposed methods. AVAILABILITY/BACKGROUND:Software is available at https://github.com/Zhaoyn-oss/JMNCC and archived on Zenodo at https://zenodo.org/records/18199759 (DOI: 10.5281/zenodo.18199759). SUPPLEMENTARY INFORMATION/BACKGROUND:Supplementary data are available at Bioinformatics online.

BACKGROUND:Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change. OBJECTIVE:To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss. METHODS:Post-hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared to a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone app. Personalized received algorithm-based scores (1 to 5) on predicted PPGR to foods logged (PPGR score; 1-2 indicating optimal; 3-5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as "high-PPGR quality" days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss. RESULTS:Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared to 1.9% among those with low adherence (p=0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (aOR=3.67, 95% CI: 1.63-8.50). Within Personalized, high PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (p<0.001). CONCLUSION/CONCLUSIONS:Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT03336411.

BACKGROUND:Chinese immigrants face numerous social determinants of health (SDOH) challenges that limit access to evidence-based diabetes self-management education and support programs (DSMES). To address these challenges, our team developed the LINK-IT intervention. This manuscript presents the study protocol for the LINK-IT trial. METHODS:The LINK-IT trial is a 12-month, 3-arm randomized controlled trial aiming to enroll 405 Chinese immigrants with T2D (HbA1c≥7%) from multiple community and clinical settings in New York City. A total of 405 participants will be randomly allocated to one of three groups (n = 135 per group): (1) video-based DSMES plus community health worker (CHW) support (VIDEO+CHW), (2) video-based DSMES only (VIDEO), or (3) wait-list control (CONTROL). The VIDEO+CHW group will receive 24 culturally and linguistically tailored DSMES videos (one per week for 24 weeks) delivered via text message links, along with biweekly (every other week) phone calls from trained CHWs to review video content, support goal setting, and address SDOH barriers. The VIDEO group will receive the same video intervention without CHW support. The CONTROL group will receive usual care and will be offered access to the videos upon study completion. The primary outcome is the change in HbA1c at 6 months. Secondary outcomes include changes in HbA1c at 12 months, self-efficacy for diabetes, dietary intake, physical activity, medication adherence and emotional support at 6 and 12 months. Data will be analyzed using an intention-to-treat approach with linear mixed-effects models. ETHICS AND DISSEMINATION/BACKGROUND:This study protocol has been approved by the Institutional Review Board of the NYU Grossman School of Medicine (S23-01274). All study procedures will adhere to the ethical principles outlined in the Declaration of Helsinki. Written or verbal informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and community events. TRIAL REGISTRATION/BACKGROUND:The LINK-IT trial was registered on March 20, 2024, on ClinicalTrials.gov under the identifier NCT06319716; https://clinicaltrials.gov/study/NCT06319716.

IMPORTANCE/UNASSIGNED:The oral microbiota may be involved in the development of pancreatic cancer, yet current evidence is largely limited to bacterial 16S amplicon sequencing and small retrospective case-control studies. OBJECTIVE/UNASSIGNED:To test whether the oral bacterial and fungal microbiome is associated with the subsequent development of pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from 2 epidemiological cohorts: the American Cancer Society Cancer Prevention Study-II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Among cohort participants who provided oral samples, those who prospectively developed pancreatic cancer were identified during follow-up. Control participants who remained free of cancer were selected by 1:1 frequency matching on cohort, 5-year age band, sex, race and ethnicity, and time since oral sample collection. Data were collected from August 2023 to September 2024, and data were analyzed from August 2023 to January 2025. EXPOSURES/UNASSIGNED:The oral bacterial and fungal microbiome were characterized via whole-genome shotgun sequencing and internal transcribed spacer (ITS) sequencing, respectively. The association of periodontal pathogens of the red complex (Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia) and orange complex (Fusobacterium nucleatum, F periodonticum, Prevotella intermedia, P nigrescens, Parvimonas micra, Eubacterium nodatum, Campylobacter shower, and C gracilis) with pancreatic cancer was tested via logistic regression. The association of the microbiome-wide bacterial and fungal taxa with pancreatic cancer was assessed by Analysis of Compositions of Microbiomes With Bias Correction 2 (ANCOM-BC2). Microbial risk scores (MRS) for pancreatic cancer were calculated from the risk-associated bacterial and fungal species. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Pancreatic cancer incidence. RESULTS/UNASSIGNED:Of 122 000 cohort participants who provided samples, 445 developed pancreatic cancer over a median (IQR) follow-up of 8.8 (4.9-13.4) years and were matched with 445 controls. Of these 890 participants, 474 (53.3%) were male, and the mean (SD) age was 67.2 (7.5) years. Three oral bacterial periodontal pathogens-P gingivalis, E nodatum, and P micra-were associated with increased risk of pancreatic cancer. A bacteriome-wide scan revealed 8 oral bacteria associated with decreased and 13 oral bacteria associated with increased risk of pancreatic cancer (false discovery rate-adjusted Q statistic less than .05). Of the fungi, genus Candida was associated with increased risk of pancreatic cancer. The MRS, based on 27 oral species, was associated with an increase in pancreatic cancer risk (multivariate odds ratio per 1-SD increase in MRS, 3.44; 95% CI, 2.63-4.51). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, oral bacteria and fungi were significant risk factors for pancreatic cancer development. Oral microbiota hold promise as biomarkers to identify individuals at high risk of pancreatic cancer, potentially contributing to personalized prevention.

BACKGROUND:levels. However, it remains unclear whether the CARE program also improves diabetes self-efficacy and psychosocial outcomes in the same study sample. OBJECTIVE:This is a secondary analysis to examine the potential efficacy of the CARE program on secondary outcomes, including diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress among Chinese Americans with T2D. METHODS:level of 7% or higher. Participants were recruited from various health care settings in New York City, including community health centers, private primary care providers, and NYU Langone Health and its affiliates, and were randomly assigned to either the CARE intervention group (n=30) or a waitlist control group (n=30). The intervention consisted of 2 culturally and linguistically tailored educational videos per week for 12 weeks, covering diabetes self-care topics such as healthy eating, physical activity, and medication adherence. These videos were delivered via the WeChat app. In addition, community health workers provided support calls to assist them in setting goals, problem-solving, and addressing social determinants of health barriers every 2 weeks. Secondary outcomes included patient self-reported diabetes self-efficacy, self-care activities, beliefs in diabetes self-care activities, and diabetes distress. Outcomes were assessed at baseline, 3 months, and 6 months. RESULTS:Participants had a mean age of 54.3 (SD 11.5) years and 62% (37/60) were male, 78% (47/60) were married, 58% (35/60) were employed, 70% (42/60) had a high school education or lower, and 88% (53/60) reported limited English proficiency. Intervention participants demonstrated statistically significant improvements in self-efficacy at 3 months (estimated difference in change: 8.47; 95% CI 2.44-14.5; adjusted P=.02), diabetes distress at 6 months (estimated difference in change: -0.43; 95% CI -0.71 to -0.15; adjusted P=.009), and adherence to a healthy diet at both 3 months (estimated difference in change: 1.61; 95% CI 0.46-2.75; adjusted P=.02) and 6 months (estimated difference in change: 1.64; 95% CI 0.48-2.81; adjusted P=.02). CONCLUSIONS:The culturally and linguistically tailored intervention showed promise in improving self-efficacy and diabetes self-care activities among Chinese Americans with T2D, warranting validation through a large-scale randomized controlled trial. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/study/NCT03557697.

RAGE and its intracellular effector molecule, the actin polymerase DIAPH1, mediate inflammation and the complications of diabetes. Using NMR spectroscopy and mass spectrometry, we built a structural model of the RAGE-DIAPH1 complex, revealing how binding of the cytoplasmic tail of RAGE (ctRAGE) to DIAPH1 stimulates its actin polymerization activity, which is inhibited by a small molecule antagonist of RAGE-DIAPH1 interaction, RAGE406R. The solution structure of the RAGE406R - ctRAGE suggests that RAGE406R prevents the formation of the RAGE-DIAPH1. FRET, actin polymerization assays, smooth muscle cell migration, and THP1 cell inflammation experiments, together with the in vivo interrogation of the effects of RAGE406R in mouse models of inflammation and diabetic wound healing, support this mode of RAGE-DIAPH1 antagonism. Finally, the treatment of macrophages differentiated from peripheral blood-derived mononuclear cells from humans with type 1 diabetes with RAGE406R reduces the mRNA expression of the chemokine CCL2, diminishing the expression of a key node in the inflammatory response.

Variations in the airway microbiome are associated with inflammatory responses in the lung and pulmonary disease outcomes. Regional changes in microbiome composition could have spatial effects on the metabolic environment, contributing to differences in the host response. Here, we profiled the respiratory microbiome (metagenome/metatranscriptome) and metabolome of a patient cohort, uncovering topographical differences in microbial function, which were further delineated using isotope probing in mice. In humans, the functional activity of taxa varied across the respiratory tract and correlated with immunomodulatory metabolites such as glutamic acid/glutamate and methionine. Common oral commensals, such as Prevotella, Streptococcus, and Veillonella, were more functionally active in the lower airways. Inoculating mice with these commensals led to regional increases in several metabolites, notably methionine and tyrosine. Isotope labeling validated the contribution of Prevotella melaninogenica in generating specific metabolites. This functional characterization of microbial communities reveals topographical changes in the lung metabolome and potential impacts on host responses.

BACKGROUND:Minoritized populations face many barriers to accessing evidence-based diabetes intervention. OBJECTIVES/OBJECTIVE:To evaluate the feasibility, acceptability, and potential efficacy of a social media-based intervention to improve glycemic control among Chinese Americans with type 2 diabetes. DESIGN/METHODS:A pilot randomized controlled trial (RCT) with 3-month and 6-month follow-ups. PARTICIPANTS/METHODS:Chinese Americans (n = 60, mean age 54.3 years old) with limited education (70.0% with high school or less) and low income (50.0% with annual household income < $25,000), and 88.3% have limited English proficiency. INTERVENTION/METHODS:Culturally and linguistically tailored diabetes videos (two videos/week for 12 weeks) delivered via social media and support calls from community health workers. MAIN MEASURES/METHODS:Primary outcomes include feasibility (video watch rate, biweekly call completion rate, and retention rates), acceptability (patient satisfaction), and HbA1c. Secondary health-related outcomes include body weight, BMI, physical activity, and dietary intake. Video watch rate and biweekly call completion rate were assessed at baseline and 3 months, while others were measured at baseline, 3 months, and 6 months. RESULTS:We observed high feasibility and acceptability of the intervention, with retention rates over 87%, an 89% video watch rate, 80% biweekly phone call completion, and a satisfaction rating of 9 out of 10. The intervention group showed a significantly greater increase in fruit intake compared to the control group (0.15 cups vs. - 0.44 cups, adj_p = 0.023) at 3 months. While no significant differences in other outcomes were observed between the groups, the intervention group showed significant improvements in key outcomes, including reduced HbA1c levels (- 1.08%, adj_p < 0.001), weight loss (- 5.15 lbs, adj_p = 0.004), lower BMI (- 0.83, adj_p = 0.023), and reduced starchy food intake (- 0.33 cups, adj_p = 0.033) at 6 months. CONCLUSIONS:The observed high feasibility and acceptability suggest the intervention's feasibility. However, due to the limited sample size, a larger-scale RCT is warranted to test the efficacy of the intervention. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03557697; https://clinicaltrials.gov/ct2/show/NCT03557697.