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Nonmonotonic rate-dependent adhesion of hydrogels
Hydrogel adhesion underlies a wide range of biological and engineering functions, yet its rate dependence remains poorly understood. Classical adhesive systems exhibit a monotonic increase in adhesion strength with separation rate, a behavior attributed to bond stress relaxation. Here, we show that hydrogels fundamentally deviate from this paradigm. Using atomic force microscopy-based indentation over six orders of magnitude in retraction rate, we find that the pull-off force first decreases and then increases, revealing a distinctly nonmonotonic rate dependence in hydrogels. To explain this behavior, we develop a quantitative model that couples the deformation of the hydrogel with a rate-dependent traction carried by interfacial bonds with distinct association and dissociation kinetics. The model reproduces the full pull-off force spectrum exhibiting the nonmonotonic behavior and predicts the evolution of the contact radius during detachment. In situ confocal microscopy measurements of contact-area dynamics confirm these predictions, providing independent validation of the kinetic mechanism. Together, the experiments and theory reveal that hydrogel adhesion is governed by a competition between time-dependent bond formation, which strengthens adhesion at slow rates, and limited bond relaxation, which enhances traction at fast rates. This interplay produces a broad intermediate regime in which reduced contact time suppresses bond buildup and weakens adhesion. Our findings identify a previously unrecognized adhesion regime in polymeric materials and provide a unified framework for understanding and designing hydrogel interfaces whose performance depends sensitively on rate, contact history, and interfacial bonding kinetics.
Abstract TH814: Independent Genetic Effects of <i>GLP1R</i> Locus on Body Mass Index and Type 2 Diabetes
Background: The glucagon-like peptide-1 receptor ( GLP1R ) gene has been implicated in metabolic regulation. GLP1R antagonists (GLP1-RAs) have been developed to treat type 2 diabetes (T2D) and obesity, and demonstrated broad clinical benefits in multiple cardiometabolic conditions. Recent genome-wide association studies (GWAS) have identified multiple GLP1R variants associated with T2D and body mass index (BMI), but the extent to which these associations represent independent genetic signals remains unclear. Methods: We conducted fine-mapping of the GLP1R locus (± 500 kb) among 431,107 participants of European ancestry in the Million Veteran Program (MVP). Linear regression was used to identify sentinel variant associated with BMI, adjusting for age, sex, and ten principal components (PCs). Conditional analysis additionally adjusting for the primary BMI sentinel variant was performed to identify a secondary sentinel variant. Logistic regression models evaluated associations of each BMI variant with T2D risk: Model 1 adjusted for age, sex, and PCs; Model 2 additionally adjusted for BMI to test mediation; and Model 3 further adjusted for the alternate sentinel variant. Results: Two independent variants at the GLP1R locus were identified. The primary sentinel variant rs12213929, located upstream of GLP1R in the DNAH8 region, was most strongly associated with BMI (β = 0.11; 95% CI 0.08-0.14; p = 1.9×10 -17 ). After conditioning on rs12213929, the secondary sentinel rs112102888 remained significant (β = 0.11; 95% CI 0.08-0.14; p = 2.6×10 -14 ), confirming two independent BMI signals. Both variants were also associated with T2D. For rs12213929, the association with T2D (OR = 1.03; 95% CI 1.02-1.04; p = 1.5×10 -9 ) persisted after adjustment for BMI and rs112102888, indicating a BMI-independent effect. In contrast, the rs112102888-T2D association (OR = 1.02; 95% CI 1.01-1.03; p = 0.0029) was attenuated following BMI adjustment (p = 0.59), implying BMI-mediated effects. Conclusions: Fine-mapping identified two independent variants in GLP1R locus associated with BMI and T2D. The rs12213929-T2D association appears BMI-independent, whereas the rs112102888-T2D association is largely BMI-mediated. These findings highlight distinct genetic mechanisms linking GLP1R to adiposity and T2D which underscore the role of GLP1R in metabolic disease and may explain the cardiometabolic benefits of GLP1-RAs independent from weight-loss.
Abstract WE566: Barriers and Facilitators to Post-Stroke Rehabilitation Among Stroke Survivors and Caregivers in India
Introduction: Stroke is the second leading cause of death and third leading cause of disability among non-communicable diseases. Rehabilitation is vital in restoring motor function and independence, and caregivers are essential to this process. Compared to high income countries, low- and middle-income countries (LMICs) have conducted limited studies on the needs of stroke survivors and caregivers. The aim of this study is to understand the barriers and facilitators that impact access to and utilization of rehabilitation services in coastal Karnataka, India. Methods: This cross-sectional study used two questionnaires, the Indian Stroke Scale and an internally validated questionnaire. Stroke survivors who were 18 years or older, experienced one or more ischemic or hemorrhagic strokes 6 months to 36 months prior to enrollment, and were admitted to Kasturba Hospital in Manipal were included. Caregivers of eligible stroke survivors were included. Matched pair recruitment was not always feasible. This study included 54 stroke survivors and 51 caregivers. Data from both cohorts was analyzed separately using descriptive statistics. Results: Among stroke survivors, 41 (76%) were male with an average age of 58.4 years (SD: 13.9). For most participants (65%), their spouse served as the primary caregiver, and the majority (76%) lived in rural areas. Following hospital admission, only 59% of stroke survivors participated in physical therapy, and 15% were receiving physical therapy at the time of the study. Among caregivers, 26 (51%) were male with an average age of 42.9 years (SD: 10.7). Awareness of stroke symptoms prior to hospitalization was low, with only 6 stroke survivors (11%) and 8 caregivers (16%) reporting prior knowledge. For both groups, family support was the most prevalent facilitator to rehabilitation care. Barriers included lack of reliable transport (stroke survivors), long waiting room times (caregivers) and cost of care (caregivers). Conclusion: Stroke rehabilitation remains markedly underutilized in this population, and caregivers showed low awareness of stroke symptoms, which can contribute to delayed recognition of stroke. Strengthening post-discharge counseling, community-based rehabilitation, and caregiver education could improve long-term outcomes for stroke survivors in LMIC settings. Future studies should evaluate scalable interventions that enhance rehabilitation continuity and caregiver preparedness.
Abstract TU190: Comparison of the Olink and Alamar Paired Antibody-based Plasma Proteomics: The Dallas Heart Study
Introduction: Plasma proteomics provide valuable insights into circulating biomarkers of disease risk associated molecular pathways. However, challenges persist for low abundance proteins which are often biologically active. Newer assays, such as the Alamar NULISA assay, have improved sensitivity, but data regarding their performance characteristics relative to established large-scale assays such as Olink are limited. Methods: Among 179 participants in the multi-ethnic and community-based Dallas Heart Study who participated in the third study phase (2020-2024), we measured proteomics using two paired antibody-based methods (Alamar Biosciences inflammation panel; Olink Explore HT). For proteins represented in both datasets with values above limit of detection in at least half the population, we calculated cross-platform Spearman correlations. Blind duplicates were run for 9 samples and data was used to calculate coefficient of variation (CV) for each protein in both datasets. Finally, we tested associations of protein level with HF case/control status in a subset of 118 participants (59 paired case/control samples) using linear regression models adjusted for age, sex, and eGFR. The Benjamini-Hochberg method was used for multiple testing correction. Results: Mean age was 64±10 years, 59% were female, and 76% reported Black race. There were 248 proteins measured by Alamar and 2,352 proteins measured by Olink, of which 225 were captured by both platforms. Of these 225 proteins, all were detectable in >50% of samples by Alamar and 181 by Olink (Figure A). The median inter-assay correlation for these 181 proteins was 0.77 (Figure B). Assay variability was similar for both platforms (CV 7.5% for Olink, 6.9% for Alamar). After multiple testing correction, 9 proteins were associated with HF case/control status using Alamar data and 5 using Olink data (FDR adjusted p < 0.05; Figure C). Conclusions: Protein values from these two paired antibody-based proteomics methods are highly correlated, with the Alamar panel demonstrating greater protein detectability across samples despite similar assay variability. The increased sensitivity should be weighed against the decrease in protein coverage when deciding which platform to use for analyses.
Bioinspired periodic mesoporous tin oxides enable steady nonequilibrium chemical sensing for enhanced gas discrimination
Periodic porous structures with interconnected pore channels and high specific surface area are widely spread in natural world. These structures guarantee rapid mass transportation and efficient biochemical reactions within organisms, thereby satisfying the requirements of complex life activities. Inspired by the periodic porous membrane and breathing process of the mammalian respiratory system, a steady nonequilibrium chemical sensing process is established to achieve high-accuracy gas discrimination based on artificial periodic porous structures consisting of metal oxide semiconductors and pulse heating (PH) technique. Owing to its highly accessible mesopores and enormous solid–gas interfaces, periodic mesoporous tin oxide (P-mSnO 2 ) facilitates gas diffusion during PH cycles and enhances the catalytic reaction between gas molecules and P-mSnO 2 . As a result, the P-mSnO 2 based sensor exhibits stable and enhanced overshoot peaks in gas sensing response curves, thus achieving superior discrimination accuracy (99.8%) for six gases under the assistance of convolutional neural network (CNN). Furthermore, the mechanism underlying the distinct shapes of the gas response curves is uncovered, revealing that gas adsorption capacity, gas diffusion coefficient, catalytic reaction barrier, and transferred electron numbers are crucial factors. This work lays the foundation for the development of single-sensor artificial olfactory intelligence and the exploration of periodic porous structures in diverse frontier fields.
Abstract 76: Consistency of Meeting Physical Activity Guidelines and Long-term Risk of Cardiovascular Disease
Background: The long-term consistency of meeting physical activity guidelines may be critical for cardiovascular health, yet its independent contribution beyond total physical activity amount remains unclear. Methods: A total of 225,264 adults from 3 large prospective cohorts (Health Professionals Follow-up Study, 1988-16; Nurses’ Health Study, 1988-2018; Nurses’ Health Study II, 1991-2017) were included. Leisure-time physical activity was assessed biennially using validated questionnaires and expressed in metabolic equivalent (MET)-hours per week. Consistency was defined as the percentage of follow-up years meeting the recommended level (≥7.5 MET-hours/week) and was updated at each questionnaire cycle across three decades of follow-up. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cardiovascular disease (CVD), myocardial infarction (MI), and stroke. Results: Over up to 30 years of follow-up, 24,766 CVD cases were documented. In traditional dose–response analyses, the lowest CVD risk was observed at 50.7 MET-hours/week (HR = 0.73; 95% CI, 0.70–0.77). After considering long-term consistency, consistently maintaining the guideline-recommended level at moderate intensity (median = 11.6 MET-hours/week) was associated with a 23% lower CVD risk (HR = 0.77; 95% CI, 0.72–0.84) compared with individuals with low activity (<7.5 MET-hours/week) and very low consistency. Consistently maintaining higher levels of physical activity was not associated with additional risk reduction (HRs [95% CIs]: 0.78 [0.73–0.83], 0.80 [0.75–0.85], 0.77 [0.73–0.82], and 0.77 [0.73–0.82] for median levels of 18.7, 26.0, 36.3, and 60.7 MET-hours/week, respectively). Similar associations were observed for MI and stroke and were consistent after adjustment for body mass index and across subgroups defined by age, gender, smoking status, and dietary quality. Conclusions: Traditional dose-response analysis suggested that 50.7 MET-hours/week was needed for optimal mortality benefit. After incorporating long-term consistency, we found that maintaining a moderate level around 11.6 MET-hours/week over three decades was sufficient to achieve the optimal benefit in CVD risk reduction.
Abstract MPWE27: Weekday Temporal Step Accumulation Patterns and Hypertensive Disorders of Pregnancy
Introduction: Physical Activity (PA) during pregnancy is known to reduce the risk of hypertensive disorders of pregnancy (HDP). However, little is known regarding how daily PA patterns, particularly the timing of step accumulation, affect HDP risk. Given the growing interest in PA timing, this study aims to examine weekday step accumulation patterns during pregnancy and their associations with HDP. Hypothesis: We hypothesize that pregnant individuals who accumulate steps later in the day will have a greater reduction of HDP risk compared to those who accumulate steps earlier, relative to those with the low overall step counts. Methods: A total of 500 women participated in the Pregnancy 24/7 multi-site cohort study. Demographics (age, parity, socioeconomic status) were collected via questionnaire. Pre-pregnancy BMI was calculated using measured height and pre-pregnancy weight abstracted from medical charts. HDP diagnoses were abstracted from medical charts and confirmed by the study obstetricians. Step counts were recorded using thigh-worn accelerometers worn continuously for 7 full days during each trimester. Daily steps were grouped into morning (6 am – 12 pm), afternoon (12 – 6 pm), and evening (6 pm – 12 am). Group-based multivariable trajectory modeling identified four weekday step patterns: Low (n = 143), Middle-Early day (n = 130; ME), Middle-Later day (n = 139; ML), and High (n = 59). Multivariable logistic regression estimated HDP odds ratios using the low pattern as the referent group, sequentially adjusting for demographics and pre-pregnancy BMI. Results: Of 464 participants (mean age: 30.7 ± 4.5 years; mean pre-pregnancy BMI: 27.2 ± 6.5 kg/m 2 ), estimated mean daily steps across trajectory groups were 4,293 (Low), 7,041 (ME), 6,847 (ML), and 10,119 (High). The estimated means of weekday temporal step counts by trajectory group are illustrated in the Figure. Compared to the Low group, the odds of HDP were lower in all groups (OR [95% CI], ME: 0.861 [0.469 – 1.573]; ML: 0.443 [0.225 – 0.845]; and High: 0.522 [0.216 – 1.164]). All associations were attenuated after adjusting for pre-pregnancy BMI (Figure). Conclusions: Weekday step accumulation patterns during pregnancy were associated with reduced odds of HDP, particularly among those with steps accumulated later in the day. Further research is encouraged to investigate the associations between the timing of PA and various pregnancy health outcomes.
Abstract WE547: Patient Perspectives of Life’s Essential 8 Cardiovascular Health Questionnaire and Cardiovascular Health Score
Introduction/Background: The American Heart Association’s Life’s Essential 8 (LE8) is a cardiovascular health (CVH) framework assigning scores to eight CVH metrics, inversely associated with cardiovascular disease (CVD) risk. We aimed to assess patient perspectives on completing LE8 questionnaires and receiving LE8 scores as a means to promote behavior change. This evaluation used an inductive, data-driven qualitative approach. Objectives: To identify: (1) patient perspectives on completing LE8 questionnaires, and (2) how best to provide LE8 CVH scores to motivate improvements in CVH. Methods: This qualitative observational study recruited adult patients who completed the LE8 questionnaire, had video conferencing access, and were fluent in English. Participants were invited to semi-structured interviews about their experience with the LE8 questionnaire and perceptions of the resulting score. Transcripts were coded independently by three researchers to develop preliminary codebooks. A finalized codebook was created with input from the entire study team and was applied to all transcripts in Dedoose. Codes were grouped into themes, and thematic frequency was calculated based on the number of quotes per theme. Results were ranked by prevalence. The process was applied to each research question. Results: Four overarching themes were identified per question (Table 1). For question one, the most common theme was “logistical interpretation of the questionnaire and results.” Many participants reported not noticing their LE8 CVH score in the after-visit summary. However, most found the questionnaire easy to complete and the score understandable when seen. For question two, the most common theme was “retrieval of CVH score results and accessibility.” Participants preferred receiving their LE8 score by text, email, or phone—separate from the after-visit summary. They recommended including a short summary explaining the score’s meaning and suggested actions. Conclusion: This initiative highlights the need to optimize LE8 delivery. While patients found the questionnaire easy to complete, they suggested reducing redundancy and allowing updates to prior responses. Most did not recall seeing their score in the after-visit summary and preferred separate, direct communication. Patients also expressed a desire to review their score with clinicians. Incorporating LE8 discussions into clinic visits may enhance engagement and improve CVH outcomes.
Endocrine gland growth as the developmental switch for insect diapause
Many animals rely on diapause to survive unfavorable seasons, but how environmental cues are transduced into endocrine changes remains poorly understood. In insects, reproductive diapause is triggered when juvenile hormone (JH) production from the corpora allata (CA) is suppressed, yet the regulatory basis of this suppression is unclear. Here, we show in the cabbage beetle ( Colaphellus bowringi ) that seasonal photoperiod controls CA growth, which in turn sets the gland’s capacity for JH biosynthesis and reproductive fate. Under long-day (LD), diapause-inducing conditions, the CA and its nuclei are smaller than those under short-day (SD), reproductive conditions. To uncover the mechanism, we generated photoperiod-resolved CA transcriptomes and compared them with whole-body profiles, identifying hundreds of CA-enriched and photoperiod-responsive transcripts, including many associated with DNA replication. From these datasets, we selected 54 candidate transcriptional regulators for RNAi screening. This screen uncovered two key factors, retained ( retn ) and ventral veins lacking ( vvl ), which act in the CA to promote DNA replication, gland growth, and JH production. Mechanistically, retn functions upstream of vvl , and together, they activate extra macrochaetae ( emc ), which encodes a downstream transcription factor that further promotes CA growth. Silencing retn , vvl , or emc reduced CA and nuclear size, lowered hemolymph JH titers, and induced diapause-like ovarian arrest and lipid accumulation. Application of the JH analog methoprene reversed these effects. Our findings provide genetic evidence that endocrine organ growth itself is a causal switch for seasonal diapause, revealing how photoperiod-responsive transcriptional cascades can shape endocrine plasticity to mediate seasonal adaptation.
Abstract TH969: High Left Ventricular Mass on Cardiac Magnetic Resonance Imaging is Associated with Incident Frailty in Community-dwelling Adults
Introduction: Cardiovascular disease (CVD) and frailty share pathophysiology and risk factors. Markers of subclinical CVD on cardiac magnetic resonance imaging (CMR) have been associated with adverse CVD events. However, the data are limited on whether these markers may be associated with incident frailty. We sought to determine whether measures of myocardial structure and function on CMR are associated with incident frailty in community-dwelling adults. Methods: The study sample included Framingham Heart Study (FHS) Offspring and Omni 1 cohort participants who attended both a baseline (2005-2008) and a follow-up study visit (2011-2014), underwent CMR (1.5-T system, Gyroscan NT, Philips Healthcare), and were free of prevalent frailty at baseline. All CMR measures (left ventricular (LV) mass, end systolic volume, end diastolic volume, and ejection fraction, and left atrial volume) were 1) standardized by sex (per 1 standard deviation (SD) increment) and 2) categorized into >90 th (“high”) versus ≤90 th percentile. The 90th percentile (P90) cut points were calculated by sex and age group (≥65 versus <65 years) using a healthy referent sample (free of hypertension, heart failure, and coronary heart disease). Incident frailty assessed at follow-up was defined using a 37-item Framingham Rockwood Frailty Index (FHS-FI; ≤0.1 non-frail, >0.1 to 0.21 prefrail, and >0.21 frail). Multivariable-adjusted logistic regression models were constructed to examine the association between each CMR marker and incident frailty. Results: Of 1,224 participants (mean age 64 ± 8 years, 52% women), 165 (13%) developed incident frailty over 5.7±0.5 years). In multivariable adjusted models (Table), a 1 SD increment of LV mass was associated with 23% higher odds of incident frailty. Participants with high LV mass had a 59% increase in odds of frailty as compared to those with LV mass ≤90 th percentile, although this finding did not achieve statistical significance (95% CI: 1.00-2.55, p=0.05). Conclusion: High LV mass was significantly associated with increased odds of frailty in community-dwelling adults, independent of prevalent CVD and associated risk factors. Further studies of the association between CMR measures and frailty are warranted, as they may provide insight into the mechanisms linking subclinical CVD to frailty.
Abstract TU244: Negative Affective Responsivity is Differentially Related to Postprandial Changes in Pulse Pressure Augmentation Between Hispanic or Latine and non-Hispanic White Young Adults
Latine and Hispanic Americans (LHA) experience poorer cardiometabolic outcomes than their non-Hispanic White (NHW) counterparts, potentially due to differential psychosocial stress exposure. Altered postprandial hemodynamic responses may reflect subclinical cardiometabolic risk and serve as an early link between psychosocial stress and poor cardiometabolic outcomes. Purpose: To determine if meal-induced changes in arterial dynamics are differentially related to daily psychosocial stress in healthy young LHA and NHW adults. We hypothesized that LHA participants would show blunted postprandial reductions in pulse pressure augmentation compared to NHW participants, which would be related to greater stressor exposure and stressor-related negative emotions. Methods: Twenty-three healthy young adults (12 LHA/11 NHW; 8M/15F; 23±3 y; 24±3 kg/m 2 ) completed 7-day diaries capturing exposure to daily stressors and stressor-related negative emotions. Augmentation pressure (AP) and augmentation index (AIx) were then assessed via pulse wave analysis pre and post-ingestion of a liquid mixed meal (62% carbohydrate, 22% fat) providing energy equivalent 20% of basal metabolic rate (324±42 kcal). Repeated measures mixed-effects ANOVAs examined the effects of ethnicity and meal ingestion on AP and AIx. Mixed linear regression models tested whether ethnicity-dependent daily stress processes influenced meal-induced changes (Δ0-60 min postprandial) in AP and AIx. Where a significant interaction was observed, within-group partial correlation analyses were performed. Analyses were controlled for sex and the regression model including stressor-related negative emotion was also adjusted for total stressor exposure. Results: There were no group differences in stressor exposure or related negative emotions ( p ≥0.35). The meal induced a significant decrease in AIx ( p =0.045), independent of ethnicity ( p =0.11), but did not significantly affect AP ( p =0.12). There was a significant interactive effect of ethnicity and stressor-related negative emotions on AIx (estimate=-1.28±0.53, p =0.030), but not AP ( p =0.068). Stressor-related negative emotions were significantly associated with postprandial changes in AIx among LHA (r=0.72, p =0.046) and not NHW (r=-0.22, p =0.64). Conclusions: These data suggest that stress-related negative emotional responsiveness is associated with blunted postprandial hemodynamic adjustments in LHA adults, which may contribute to increased cardiometabolic risk.
Abstract TU103: Adherence to the Mediterranean diet and some related serum metabolites are strongly associated with epigenetic biomarkers of aging in Mediterranean subjects
Background and aims: The Mediterranean diet (MedDiet) is a healthy dietary pattern that has been consistently associated with reduced cardiovascular disease incidence. Likewise, higher adherence to the MedDiet has been related to beneficial effects on cardiometabolic health, reducing serum inflammatory and oxidative stress biomarkers (i.e GlycA and branched chain amino acids-BCAAs). In addition, a higher adherence to the MedDiet has been associated with higher serum polyunsaturated fatty acids (PUFAs), mainly Omega-3. However, few studies in Mediterranean populations have investigated these associations with epigenetic biomarkers of aging. Our objective was to analyze the association between MedDiet adherence and several generations of epigenetic biomarkers of aging and to examine the relationship between serum GlycA and BBCAs and the aging biomarkers in Mediterranean subjects. Methods: We analyzed participants from two Mediterranean Spanish populations recruited in Valencia. Cohort 1 consisted of high cardiovascular risk subjects aged 55-75 y (n=426), and Cohort 2 (n=200) consisted of healthy subjects from the general population (18-80y). Likewise, DNA was isolated from blood, and DNA methylation was analyzed with the EPICv1 array. After quality control and normalization, several generations of biomarkers of aging were computed using the UCLA and Biolearn platforms for both populations. We focused on Horvath, PhenoAge, GrimAge, DunedinPACE, and CausAge clocks. Adherence to the MedDiet was measured with the validated 17-item MEDAS score (only in cohort 1). Multivariate adjusted regression models were computed. Results and conclusions: In the high cardiovascular risk cohort, the adherence to MedDiet was inversely associated with all the biomarkers of aging examined (Horvath, PhenoAge, GrimAge1, GrimAge2, DunedinPACE, and CausAge). In the adjusted model (with adherence to MeDiet as continuous variable), the most significant associations were for GrimAge1 (P<0.001), GrimAge2 (P=0.001), CausAge (P=0.002), and DunedinPACE (P=0.019). Likewise, in this high-cardiovascular risk cohort we found strong inverse associations of serum PUFA, mainly % of Omega-3 with biomarkers of aging (even after adjustment for MedDiet adherence). In the general population we also observed the strong inverse association between PUFAs and the biomarkers of aging (all P<0.05). Direct associations between GlycA and serum BBCAs with epigenetic biomarkers of aging were detected (P<0.05).
m6A epigenetic modification of viral RNA is critical for the transmission cycle of mosquito-borne flaviviruses
Arboviruses maintain alternative transmission routes between arthropods and vertebrates through precise dual-host adaptation of their viral genome. However, how epigenetic modifications impact flavivirus transmission cycle remains obscure. Depleting the m6A modification complex revealed that m6A modifications preferentially facilitate mosquito-borne flaviviruses (MBFs) propagation in vertebrates but not in mosquitoes. Stem loop I (SLI) deletion in the MBF 3’ UTR decreased m6A expression and viral propagation in vertebrates but not in mosquitoes, indicating viral genome component–epigenetic modification interplay. Mechanistically, m6A modification in stress granules was found to be driven by dynamic SLI–cellular G3BP1 interaction. The m6A-methylated viral genome is ejected by G3BP1 and undergoes viral assembly. Chemical perturbation of m6A modification via METTL3 inhibition potently blocked MBF proliferation in mice and abolished mouse–mosquito viral transmission. Overall, m6A modification is indispensable for efficient arthropod-to-vertebrate transmission of MBF, highlighting its potential as a target for antiviral and transmission-control strategies.
Abstract 54: Body Weight, Human Gut Microbiome, Blood Metabolome, and incident Type 2 Diabetes- A Multi-Omics Integration Study
Background: Few prospective human studies have characterized interrelationships between body weight, gut microbiome, plasma metabolome, and incident type 2 diabetes (T2D). Aims: To identify microbial profiles associated with adiposity, derive its responsive metabolomic signatures, and evaluate their associations with future weight change and incident T2D. Methods: Shotgun stool metagenomes were profiled in the Men’s Lifestyle Validation Study (MLVS; n=924). Body mass index (BMI)-associated microbial species were identified after adjusting for age, total energy, physical activity, alcohol and smoking, and were synthesized into a composite microbiome score. We evaluated its association with waist-to-hip ratio (WHR) and DEXA-measured fat mass in MLVS and validated its association with BMI in female Mind–Body Study (MBS; n=807). Next, the score was examined for its association with prevalent T2D in the multiethnic Micro-Cardio consortium (n=8,117). Prospectively, we tested its predictability of 2-year BMI increase and incident T2D risk in the Micro-N (n=3,318). To further characterize the downstream metabolism of this microbial profile, we linked it to >300 LC–MS metabolites in the MLVS and derived a microbiome-informed multi-metabolite score, which was validated in the MBS. We examined the metabolomic score for incident T2D risk in a prospective cohort, the Nurses’ Health Study (NHS; n=1,057). Results: We identified 23 microbial species associated with BMI in MLVS. The 23-species composite score was correlated with higher BMI (High vs.Low: MLVS β=3.45; MBS β=4.37 both P<0.001), and also correlated with WHR (r=0.45) and fat mass (r=0.73). Additionally, higher microbiome score consistently predicted 2-year BMI increase (β=0.22, P =0.003) and predicts incident T2D in Micro-N (HR [high vs. low] = 2.19, P=0.01), as well as prevalent T2D in the Micro-Cardio (HR [per SD] =1.19, P<0.001). A 32-plasma metabolite signature was responsive to this microbial profile in MLVS (r=0.66) and validated in MBS (r=0.38), and also predicted incident T2D in NHS (RR=2.18, P<0.0001) independent of baseline BMI. Conclusions: We identified and validated a gut microbiome score predictive of adiposity across multiple cohorts, showing consistent associations with plasma metabolomic signatures and increased risk of T2D. This highlights a potential role of the gut microbiome in weight regulation and T2D development, providing new insights into microbiome-informed strategies for T2D prevention.
Abstract TH887: Modifiable Risk Factors for Dementia and Their Association with Cognitive Performance and Brain Structure Among Hispanic/Latino Individuals in Early and Middle Adulthood
Introduction: Few studies have examined the association of modifiable risk factors for dementia with cognitive performance and brain structure in early and middle adulthood, when underlying functional and structural changes in the brain may begin, and the potential for risk reduction and prevention is high. Hypothesis: We hypothesized that cardiovascular risk factors are associated with cognitive performance and MRI-derived brain volumes in Hispanic/Latino individuals in early and middle adulthood (25-49 years of age). Methods: We used data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the SOL-INCA-MRI ancillary study. We included adults aged 25-49 years examined with cognitive tests at baseline (2008-2011, n=2330). These tests were z-score standardized and averaged to derive a global cognition (GC) score. We also included adults aged 35-49 years with MRI brain volumes quantified 10 years after baseline (2018-2022, n=219): total brain (TBV), total gray matter (TGMV), total cortical gray (TCGV), hippocampal (HV), and white matter hyperintensity (log-WMHV). These volumes were residualized to total cranial volume and z-score standardized. Cardiovascular risk factors measured at HCHS/SOL baseline for cognition and/or visit 2 (2014-2017) for brain volumes included self-reported smoking status, alcohol use level, diet quality (Alternative Healthy Eating Index 2010), and physical activity (Global Physical Activity Questionnaire), body mass index (BMI), systolic and diastolic blood pressure (mm Hg), fasting blood glucose (mg/dL), and non-HDL Cholesterol (mg/dL). We fitted survey linear regression models to test the association between cardiovascular risk factors and cognitive performance and brain volumes, accounting for sociodemographic factors. Results: In multivariable regression models, current smoking (vs. never/former; GC: -0.10 [-0.17, -0.02]) and overweight status (vs. normal weight; GC: -0.11 [-0.21, -0.01]) were associated with lower cognitive performance. Current smoking status (vs. never/former; TGMV: -0.35 [-0.68, -0.03]), and higher diastolic blood pressure (TGMV: -0.02 [-0.03, -0.00]) were associated with smaller brain volumes and/or larger log-WMHV. Conclusion: Modifiable risk factors, including smoking, overweight status, and high blood pressure, were associated with lower cognitive performance and/or smaller brain volumes in a relatively young Hispanic/Latino population.
Abstract TU196: Lipid Catabolism and Cytokine Signaling Show Divergent Associations with 30-year Incidence of Coronary Artery Disease in Type 1 Diabetes
Prior studies of biomarkers for coronary artery disease (CAD) in the high-risk type 1 diabetes (T1D) population focused on candidate proteins but such analyses may miss the complex systemic process underlying atherosclerosis. High-throughput proteomics facilitate a systems approach to identify pathways associated with risk. Thus, we hypothesized that protein networks are associated with 30-year incident CAD (CAD death, myocardial infarction, coronary revascularization/blockage≥50%) in the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset (<17 yrs) T1D (n=421 with available stored serum specimens prior to first CAD, mean age 30 yrs, T1D duration range 7-42 yrs at baseline). We measured 184 circulating proteins (Olink Proteomics CVD II and CVD III panels) in each participant’s earliest serum sample. Protein modules were identified using weighted co-expression network analysis. Pathway enrichment analysis was performed using all proteins on the panels as background. Prospective associations between modules (per eigenvalue standard deviation) and CAD incidence were estimated in Cox models adjusted for covariates concurrent with the serum sample, including age, sex, sample visit, smoking, blood pressure and lipid lowering medications, eGFR, and HbA1c. Associations between individual proteins (per 2-fold increment) and CAD incidence were also estimated. We identified 3 modules: Module 1 (Brown, 33 proteins) was primarily enriched for “lipid catabolic process”, Module 2 (Turquoise, 56 proteins) for "cytokine-cytokine receptor interaction”, and Module 3 (Blue, 33 proteins) for "platelet alpha granule”. Incident CAD occurred in 151 participants (36.2%). Module 1 was associated with reduced CAD (HR=0.82, 95% CI:0.70-0.96, p=0.014), Module 2 with increased CAD (HR=1.35, 95% CI:1.06-1.72, p=0.017), and Module 3 was not associated. Alpha-1-Microglobulin/Bikunin Precursor (AMBP, HR=2.68, 95% CI:1.64-4.29, p<0.0001) in Module 2 was the top individual protein associated with CAD. While not members of any module, LDL receptor protein (HR= 1.49, 95% CI: 1.22-1.82, p=0.0001) and fatty acid binding protein 4 (FABP4, HR=1.39, 95% CI: 1.17-1.66, p=0.0002) were also associated with CAD. In conclusion our results suggest opposing pathways may influence CAD in T1D, including a protective role of lipid catabolism and detrimental role of cytokine signaling, which warrant further study to determine if they improve risk prediction beyond clinical risk factors.
Unveiling the sensitivity and significance of the Ni oxidation state for alkaline hydrogen oxidation electrocatalysis
The development of nonprecious-metal-based hydrogen oxidation reaction (HOR) electrocatalysts remains as the bottleneck for achieving high-performance, platinum group metal-free (PGM-free) alkaline/anion exchange membrane fuel cells. Numerous efforts have been dedicated toward enhancing the HOR activity of Ni catalysts due to the lack of alternative choices. However, mechanistic insights relating to electrocatalytic activity and degradation remain a matter of debate, and proposed models tend to lack conclusive experimental evidence. Here, we studied the state of Ni catalysts using scanning transmission electron microscopy and electron energy loss spectroscopy, together with in situ high energy resolution fluorescence detected X-ray absorption spectroscopy. The results revealed that a metallic Ni surface is crucial for effectively catalyzing the HOR, and that the formation of α-Ni(OH) 2 at potentials positive of +0.3 V vs. RHE leads to deactivation of the catalyst. Further analysis with theoretical calculations revealed a strong interaction between the Ni surface and graphene, resulting in a tightly sealed carbon shell that protects the Ni surface. The analysis further indicates that HOR occurs on graphene-protected Ni@C catalysts through the transport of hydrogen and protons across the carbon shell, particularly at self-healing larger holes. Using the Ni@C catalyst, together with evidence-informed experimental protocols to avoid oxidation before, during, and after membrane electrode assembly fabrication and testing, we achieved a milestone PGM-free AEMFC peak power density performance of 1.0 W/cm 2 . This is a demonstration of a Watt-scale performance for a PGM-free AEMFC.
Abstract TU174: UPF Intake Patterns in the Context of Overall Diet are Differently Associated with Self-Reported Health Status
Introduction: Excess ultra-processed food (UPF) intake has been consistently associated with adverse health. Yet, UPFs are heterogeneous ranging from possibly beneficial (e.g., whole-grain bread) to harmful (e.g., sugary drinks). Dietary guidance should consider UPF subgroups’ contribution to diet, as their convenience, affordability, and shelf stability may support healthy eating, especially in low income households. Objectives: To evaluate how patterns of UPF subgroups intake relate to diet quality and self-reported health status. Methods: We conducted a secondary cross-sectional analysis of 1,118 Supplemental Nutrition Assistance-participating adults in New England in Summer 2023. Using a 155-item FFQ, we calculated Healthy Eating Index (HEI) 2015 total and component scores and categorized foods into 4 NOVA groups and 19 mutually exclusive UPF subgroups. We used k-means cluster analysis to group UPF subgroups and 12 Dietary Guidelines-based food groups, selecting 4 clusters based on relevant metrics. We compared UPF subgroups, food groups, diet quality, and health status across clusters using chi-square and Kruskal-Wallis tests; logistic regressions assessed associations between clusters and self-reported health status. Results: Across 4 clusters, participants in healthier clusters were older, but food insecurity was highest in the Sweet Tooth cluster (Tbl 1). HEI-2015 scores (57-73) and UPF intake (40-70% of calories) varied. The Sweet Tooth and Convenience-Seeking Carnivores clusters had the lowest HEI-2015 scores and highest UPF intake, characterized either by high intake of sugary UPFs (e.g. sugary drinks/dairy based desserts) or ready-to-eat UPFs, processed meats/cheeses, and lean meat, respectively. Despite differing UPF intake, Mindful UPF Moderates and Traditional Healthy clusters had higher HEI-2015 scores, with the former reporting the highest dairy and whole grain sub-scores (Fig 1). Compared to the Sweet Tooth cluster, the 3 other clusters had 1.7-2.0 greater odds of very good/excellent health (Tbl 2). Conclusion: We identified 4 clusters with varied intake of UPF subgroups. Despite high UPF intake in 3 clusters, only the Sweet Tooth cluster was associated with worse health compared to the healthiest cluster, indicating that the pairing of UPF subtypes and less processed foods may be important to consider for UPF dietary guidance. Our findings suggest not all UPF patterns carry equal health risks and that UPF subgroup intake may modify health effects.
Abstract TH941: Cardiovascular Health of First-Time Fathers During Pregnancy: Findings from the Dad Bod Observational Cohort Study
Introduction: Promoting optimal cardiovascular health (CVH) earlier in life is essential for preventing future cardiovascular disease. The transition to fatherhood represents a major life stage for young adult men, characterized by biological, psychological, and social changes that may influence cardiovascular health behaviors and risk factors. Identifying and characterizing CVH profiles of first-time fathers provides a foundation for targeted lifestyle and behavioral interventions that may improve not only paternal health but also family well-being. This study characterized baseline CVH, as assessed by the American Heart Association’s Life’s Essential 8 (LE8), among first-time fathers during their partner’s pregnancy. Methods: The Dad Bod Study is a prospective, longitudinal cohort of first-time fathers aged 19–39 years. Participants completed baseline assessments remotely during their partner’s second trimester. Metrics for the AHA LE8, including diet quality (Healthy Eating Index 2020), physical activity (International Physical Activity Questionnaire), nicotine exposure, sleep duration (Pittsburgh Sleep Quality Index), body mass index, blood lipids and fasting glucose (via dried blood spot), and blood pressure, were collected and scored using standardized AHA algorithms. Results: Among 117 participants, mean age was 32.2 years (SD=4.5). The sample was predominantly White (82.9%), married (93.2%), employed for wages (94.0%), and high-income, with 67.5% reporting annual household income ≥$150,000. The mean LE8 score indicated good overall cardiovascular health (M=81.6, SD=11.8, range=43.1-100.0). Individual LE8 components revealed excellent scores for were highest for nicotine exposure (M=95.7, SD=12.4), sleep (M=90.8, SD=16.4), and fasting glucose (M=90.2, SD=18.7), while diet showed the lowest mean score (M=60.7, SD=26.1). Conclusion: Findings highlight generally favorable cardiovascular health among expectant first-time fathers, though diet quality emerged as a key area for improvement. The prenatal period may represent an opportune window to engage fathers in lifestyle interventions that promote heart-healthy behaviors. The Dad Bod Study will further examine how psychosocial and behavioral factors influence CVH and assess changes in LE8 scores through one year postpartum to better understand trajectories across the transition to fatherhood.
Abstract TH911: Association of Stroke with Social Determinants of Health and Race-Gender Demographics
Introduction: Social determinants of health (SDoH) are recognized as key contributors to adverse cardiovascular outcomes. However, the magnitude of the association between stroke and race-gender demographics has not been well characterized. This study aimed to evaluate the association between SDoH and stroke across different races and age groups. Methods: We conducted a retrospective cross-sectional analysis of the 2001-2018 NHANES, applying 18-year sampling weights across 9 survey cycles restricted to the fasting subsample. Variables with >10% missingness were imputed using fully efficient fractional imputation. Eight SDoH indicators, as shown in Table 1, were assessed. A cumulative SDoH score (0-8) was calculated and categorized into quartiles based on the unweighted distribution of the score. Continuous variables were summarized as weighted mean ± SE, and categorical variables as weighted percentages [95% CI]. Associations between stroke and quartiles of SDoH score were evaluated using survey-weighted logistic regression, adjusting for demographics, laboratory, lifestyle factors, and comorbidities. Results: A total of 21,712 adults were included (mean age 46.6±0.2 years; 48.1%[47.5-48.8] male; stroke prevalence 2.7%[2.4-3.0]). The mean SDoH score was 2.3±0.0, with median [IQR] of 3[1-4]. Stroke prevalence by each SDoH indicator is shown in Table 1. In fully adjusted models, higher SDoH quartiles were associated with greater odds of stroke compared with Q1 (aOR Q2 1.63(1.21-2.20), p=0.002; aOR Q3 1.76(1.27-2.44), p=0.001; aOR Q4 2.35(1.82-3.03), p<0.001). Black participants had a higher risk of stroke than White (aOR Black 1.31(1.04-1.68), p=0.025). In sex-stratified analyses, associations were pronounced in men (aOR Q2 1.91(1.27-2.89), p=0.002; aOR Q3 1.83(1.13-2.97), p=0.015; aOR Q4 2.76(1.78-4.28), p<0.001). Among men, Black race was associated with higher odds compared to White (aOR Black 1.77(1.20-2.63), p=0.005). In women, higher SDoH quartiles remained associated with stroke (aOR Q3 1.81(1.15-2.85), p=0.010; aOR Q4 2.38(1.64-3.46), p<0.001), though no racial disparity was observed (aOR Black 1.04(0.77-1.40), p=0.811). Conclusion: Cumulative social disadvantage was independently associated with a higher risk of stroke, with especially strong effects observed among men and Black participants. Beyond optimizing control of traditional comorbidities, addressing adverse SDoH, particularly among Black men should be one of the prioritized strategies for stroke prevention.