Browse Articles

Abstract P3029: Phenotypic and Genetic Correlations of Imaging Traits in the Abdomen-Heart-Brain Axis: Insights into Multimorbidity of Cardiometabolic Diseases and Depression

Objective: The development of multimorbidity of cardiometabolic diseases (CMDs) and depression likely involves pathophysiological processes across multiple organs. This study aimed to investigate imaging traits in the abdomen-heart-brain axis linked to the CMDs-depression multimorbidity and assess their phenotypic and genetic connections using magnetic resonance imaging (MRI) data. Methods: This study analyzed multi-organ MRI data including 7 abdominal, 82 cardiac, and 676 brain traits from 31,839 UK Biobank participants. CMDs included coronary artery disease, stroke, heart failure, type 2 diabetes, hypertension and hyperlipidemia. First, multivariable logistic regressions estimated associations of imaging traits with the CMDs-depression multimorbidity. Second, multivariable linear regressions quantified pairwise correlations among significant cross-organ traits. Third, transcriptome-wide association study (TWAS) identified shared genes of traits significantly correlated with each other across all 3 regions (i.e., triads). Fourth, LASSO regressions constructed genomics scores using single nucleotide polymorphisms from the shared genes. Fifth, the prediction performance of imaging traits and genomics scores for the CMDs-depression multimorbidity was evaluated by AUCs. FDR correction was used to adjust for multiple testing. Results: Seven abdominal, 27 cardiac, and 340 brain traits were significantly associated with the CMDs-depression multimorbidity. Among 11,749 pairs of significant cross-organ imaging traits, 6385 abdomen-heart-brain triads were identified, with liver volume as the most connected node. The directions of associations among imaging traits in these cross-organ triads aligned with directions of their biological functions, suggesting multiple organs acting as a coordinated system. TWAS revealed TNFSF12 from whole blood as the shared gene underlying the significant liver-heart-brain connection associated with the CMDs-depression multimorbidity. The integration of imaging traits with genomics score (AUC = 0.84) improved prediction performance for the CMDs-depression multimorbidity, outperforming demographic and lifestyle models (AUC = 0.78) (P = 0.014). Conclusions: This study identified highly correlated cross-organ imaging traits that were associated with the CMDs-depression multimorbidity. A shared gene was found for a liver-heart-brain triad. Imaging traits and genomic score significantly enhanced prediction performance on top of traditional factors.

Effects of binding partners on thermal reversion rates of photoswitchable molecules

The binding of photoswitchable molecules to partners forms the basis of many naturally occurring light-dependent signaling pathways and various photopharmacological and optogenetic tools. A critical parameter affecting the function of these molecules is the thermal half-life of the light state. Reports in the literature indicate that, in some cases, a binding partner can significantly influence the thermal half-life, while in other cases it has no effect. Here, we present a unifying framework for quantitatively analyzing the effects of binding partners on thermal reversion rates. We focus on photoswitchable protein/binder interactions involving LOV domains, photoactive yellow protein, and CBCR GAF domains with partners that bind either the light or the dark state of the photoswitchable domain. We show that the effect of a binding partner depends on the extent to which the transition state for reversion resembles the dark state or the light state. We quantify this resemblance with a ϕ switching value, where ϕ switching = 1 if the conformation of the part of the photoswitchable molecule that interacts with the binding partner closely resembles its dark state conformation and ϕ switching = 0 if it resembles its light state. In addition to providing information on the transition state for switching, this analysis can guide the design of photoswitchable systems that retain useful thermal half-lives in practice. The analysis also provides a basis for the use of simple kinetic measurements to determine effective changes in affinity even in complex milieu.

Abstract MP30: Estimated Health Benefits, Costs, and Cost-Effectiveness of Eliminating Dietary Industrial Trans-fatty Acids in China

Objectives: To estimate the potential health benefits, costs, and cost-effectiveness of mandating a limit on industrial trans-fatty acids (iTFA) in all foods, fats, and oils in China. Methods: A multiple cohort proportional multistate life table model was used to project the impact of eliminating dietary iTFA on ischemic heart disease (IHD) burden and costs over different time horizons (5 years, 10 years, and population lifetime). Nationally representative data on iTFA intake were derived from the 2015-2018 China Total Diet Study and China National Health and Nutrition Survey 2011. The health benefits were modelled as averted IHD deaths, events, and health-adjusted life years (HALYs) gained. Net costs were estimated by combining healthcare costs and policy implementation costs, which included government monitoring and industry reformulation costs. Cost-effectiveness was assessed through incremental cost-effectiveness ratios, with both costs and HALYs discounted at 3%. Results: Over 10 years, the mandatory iTFA limit was estimated to prevent approximately 111K IHD deaths (95% uncertainty interval [UI]: 101K-120K), 744K IHD events (95% UI: 678K-807K), 330K HALYs (95% UI: 301K-357K), resulting in a healthcare cost saving of around 2.8 billion USD (95% UI: 2.5-3.0). Over the population lifetime, the intervention was projected to avert 1.9 million (95% UI: 1.7-2.0) IHD deaths, 3.4 million (95% UI: 3.0-3.7) IHD events, and 5.9 million (95% UI: 5.4-6.4) HALYs, saving approximately 5.1 billion USD (95% UI: 4.6-5.7) Policy implementation costs were estimated at 165 million USD (95% UI: 132-198) over the first 10 years and 295 million USD (95% UI: 261-329) over the population lifetime ( Figures 1-2 ). The intervention was estimated to be cost-saving regardless of the time horizon, with robust findings across sensitivity analyses. Conclusions These findings suggest that legislating a mandatory limit on iTFAs could be a cost-saving strategy to prevent a substantial number of IHD events and deaths in China.

Abstract P3004: Plasma and Serum Water T ₂ are Strong Predictors of Cardiometabolic Health: Implications for Point-Of-Care Screening

Introduction: Plasma and serum water T 2 are global biosensors of metabolism. They detect changes in the average rotational diffusion time of water induced by shifts in metabolic balance (Fig. 1). Water T 2 can be measured using a miniaturized magnetic resonance device (Fig. 2). However, the performance of T 2 parameters in combination with other readily available measures of cardiometabolic health is unknown. Hypothesis: The accuracy of water T 2 for predicting cardiometabolic health can be enhanced by including age, body mass index, and pulse rate. Specific Aim: Quantify the predictive accuracy of plasma or serum water T 2 with and without other measures. Methods: This is a secondary analysis of FWT2, an observational cross-sectional study of 72 disease-free adults. Other study exclusions were pregnancy and fasting <10 h. Hydrogen T 2 relaxation decay curves were recorded for plasma or serum at 37°C using a Bruker mq20 magnetic resonance relaxometer. Water T 2 was resolved using a discrete component analysis (XPFit, Alango Ltd.). Statistical analyses utilized JMP Pro v17.2 (SAS Institute): factor analysis, machine-learning predictor screening, and multi-variable linear regression. Goodness-of-fit and predictive accuracy were measured using adjusted R-squared (R 2 adj), root mean square error, corrected Akaike’s information criterion (AICc), Bayesian information criterion (BIC), and k-fold cross-validation R 2 (R 2 k-fold). Results: Table 1 shows the parameters for each regression model. Cardiometabolic health, the outcome or Y variable, was one of two latent variables generated by factor analysis: CMH1 for Phase 1&2 and CMH2 for Phase 2 only (Table 1). By itself, plasma water T 2 was a good predictor of cardiometabolic health (models 1A and 3A). The addition of age, BMI, and pulse rate improved the R 2 adj from 0.631 (3A) to 0.796 (3B). Improvements (decreases) were observed for RMS error, AICc, and BIC, with an improvement (increase) in R 2 k-fold. Models with serum water T 2 showed similar trends. Conclusions: Plasma and serum water T 2 are strong predictors of cardiometabolic health, especially when combined with age, BMI, and pulse rate. Water T 2, along with other predictors, explained up to 84% of the variance in cardiometabolic health. The predictive value of T 2 is independent of adiposity. Buoyed by predictive accuracy, measurement simplicity, and device portability, plasma and serum water T 2 show promise for metabolic health screening at the point of care.

Environmental justice beyond race: Skin tone and exposure to air pollution

Recent research, focused mostly on the United States and Western Europe, shows that marginalized communities often face greater environmental degradation. However, the ethnoracial categories used in these studies may not fully capture environmental inequality in the Global South. Moving beyond conventional ethnoracial variables, this study presents findings exploring the link between skin tone and fine particulate matter (PM 2.5 ) exposure in Colombia. By matching household geolocations from a large-scale longitudinal survey with satellite-based PM 2.5 estimates, we find that skin tone predicts both initial pollution exposure levels and their changes over time. Although average exposure levels remained stable during our study period, the environmental justice (EJ) landscape in Colombia contemporaneously underwent a complete transformation. In 2010, lighter-skinned individuals faced higher PM 2.5 exposure, but darker-skinned individuals experienced steeper increases in the following years. By 2016, the EJ gap had reversed, with people with the darkest skin tones exposed to PM 2.5 levels nearly one SD higher than those faced by people with the lightest skin tones. These patterns remain robust when controlling for a comprehensive set of theoretically relevant covariates, including ethnoracial self-identification and income. Disproportionate exposure to pollution from fires partially explains the observed disparities. Decomposition analysis shows that this variable, local collective action, and economic marginalization account for a sizeable share of the EJ gap. However, one-third of the gap remains unexplained by observable characteristics. With climate change intensifying fire incidence, the disproportionate disease burdens that vulnerable groups face might deepen unless policy measures are taken to reverse this trend.

Abstract P1104: The Association Between Subjective Social Status and Dietary Quality Within Occupational Groups of African Americans: The Jackson Heart Study

What people eat is a major contributor to health outcomes, including development of metabolic, cardiovascular, and other chronic diseases. Dietary quality varies widely is influenced by factors including sex, race, geographic location, socioeconomic status, self-perception of community standing, and occupation. These factors potentially interact, making an understanding of dietary quality difficult to fully disaggregate and therefore challenging to modify from a population health perspective. This study sought to analyze the interaction between subjective social status (SSS) and occupation on dietary quality among African Americans in the Deep South, as well as assess their marginal effects. Hypotheses Dietary quality will vary by occupational groups and levels of SSS. There will be an interaction between occupational groups and (SSS) on dietary quality. Methods: A cross-sectional analysis of data from participants of the Jackson Heart Study was completed. Participants ( n = 4,727) who had complete data for occupation, the alternative healthy eating index (AHEI, a measure of diet quality) score, and SSS (as measured by the Community MacArthur Scale) at exam 1 were included in the analysis. A general linear model with main and interaction effects for SSS and occupation group was fit to AHEI. Results: Type III F -tests from ANOVA showed no significant interaction between SSS and occupational groups with respect to mean AHEI scores ( p = 0.7635). Significant main effects were found for both the occupational groups and SSS level ( p < 0.0001). Pairwise comparisons of occupational groups revealed significantly different mean AHEI scores among several groups. Most notably, those in the management/professional occupation appeared to have higher mean AHEI compared to all the other groups. Mean AHEI was estimated to increase by 0.3723 units (SE = 0.0781) for every one-unit increase in SSS. Residual diagnostics and goodness-of-fit methods verified model adequacy. Conclusions In conclusion, occupation and SSS each contribute significantly to dietary quality as measured by AHEI; some occupational groups show significant differences in dietary quality; and there is no evidence of an interaction between occupation groups and SSS, indicating that the positive association between subjective social status and dietary quality is the same for each occupational group.

Abstract P3017: <i>Helicobacter pylori</i> Seroprevalence and its Association with Blood Pressure and Hemoglobin A1c in the National Longitudinal Study of Adolescent to Adult Health (Add Health)

Introduction: Chronic Helicobacter pylori ( H. pylori ) infection, a ubiquitous enteric bacterium, may lead to systemic inflammation, possibly increasing the risk of hypertension (HTN) and type 2 diabetes mellitus (T2D). Studies linking H. pylori infection with HTN and T2D have produced mixed results. Objective: To determine if H. pylori seropositivity is associated with elevated blood pressure (BP), hemoglobin A1c (HbA1c), and annual change in SBP, DBP, and HbA1c over a median of 10 years using Add Health. Methods: Wave IV (2008-2009) Add Health participants were tested for immunoglobulin antibodies to H. pylori with a binary cutoff for seropositivity of 13.217 U/mL. Systolic BP (SBP), diastolic BP (DBP), and HbA1c were measured at Waves IV and V (2016-2018). Annual rates of change in SBP, DBP, and HbA1c were calculated by dividing the difference in value between Waves IV and V by the number of years elapsed for each participant. Prevalence differences (PD), differences in point estimates, and 95% confidence intervals (CI) were determined using multivariable linear regression models accounting for Add Health's complex sampling design and adjusting for age, sex, race/ethnicity, education, income, childhood socioeconomic status, body mass index, smoking, alcohol use, and medication use. Results: The median ages in Wave IV and V were 28 and 37 years, respectively, with 54% being female. In the final analytic sample (N=4,600), 958 (21%) participants were seropositive for H. pylori . Seropositive participants were more likely to be non-Hispanic Black (24% vs 9.3%) and less likely to be college graduates (12% vs 19%) than seronegative individuals. In adjusted models, there were no differences in SBP (PD -0.79 mmHg (CI -2.79, 1.22)), DBP (PD -0.65 mmHg (CI -2.79, 1.22)), and HbA1c (PD -0.01% (CI -0.08, 0.05)) by H. pylori seroprevalence. The adjusted annual mean (standard deviation) change in SBP (-0.12 (0.81) vs 0.03 (0.85)), DBP (0.23 (0.60) vs 0.22 (0.59)), and HbA1c (-0.02 (0.05) vs -0.02 (0.04)) from Wave IV to V was not different between seropositive and seronegative participants. Conclusions: In a cohort of younger adults, H. pylori seropositivity was not associated with higher BP or HbA1c or differences in annual rate of change in SBP, DBP, and HbA1c over a median of 10 years. Further research is needed to understand the relationship between H. pylori infection and cardiometabolic disorders over a longer period of time as individuals age into mid to late life.

Decoding planetary surfaces by counting cracks

Planets are often covered with thin cracked shells. From mud films to lithospheres of rock or ice, fracture networks form two-dimensional (2D) tessellations of convex polygons whose geometry encodes their genesis. Here, we chart the geometry of 2D fracture mosaics across the solar system, and decode their formative conditions using a new dynamical crack model. We show that mosaics can be projected onto a Symbolic Ternary Diagram, where the relative proportions of “T,” “X,” and “Y” junctions are uniquely related to contributions from distinct modes of fracture. Most planetary mosaics cluster in a region associated with hierarchical fracture networks, where sequential cracking favors formation of T junctions. Exceptions to this rule may betray the presence of water. Europa’s fracture networks stand apart due to the predominance of X junctions; this is a special feature of ice, where healing of cracks by refreezing of water allows new fractures to overprint older ones. Several fracture networks on Mars appear as outliers due to the high proportion of Y junctions. These patterns—previously interpreted as ancient mudcracks and frozen polar terrain, based on geological evidence—are consistent with the twisting of crack junctions by cyclic volume change. Our findings suggest that counting cracks could aid in the identification of other water-influenced planetary environments.

Abstract P1150: Self-Efficacy is Associated with Health Behaviors Related to Cardiovascular Risk among Hispanic/Latinx and Somali Immigrants to the United States

Introduction: Despite being healthier than the general population on arrival, immigrants to the US often face systemic barriers to healthy lifestyle behaviors and increased risk of cardiovascular disease (CVD). Self-efficacy has been associated with healthy diet and physical activity behaviors, but associations and construct validity have not been well studied in large samples of immigrant populations. Hypothesis: Self-efficacy for a healthy diet and physical activity will be associated with better dietary quality and intake and more physical activity, respectively. We also assessed the construct validity of measurement scales in this population. Methods: Set in southeast Minnesota and embedded with the Rochester Healthy Community Partnership, a 20-year community-based participatory research partnership, the Healthy Immigrant Community study enrolled Hispanic/Latinx and Somali immigrants into a randomized intervention to reduce obesity and CVD risks. Baseline assessments included biometric measures and self-reports of dietary intake, physical activity, and quality of life in English, Spanish, or Somali. Two self-efficacy items (“How confident are you that you can eat a healthy diet?”; “How confident are you that you can participate in regular exercise or physical activity?”) were rated as a percentage interval (0%=not at all confident; 25%; 50%=somewhat confident; 75%; 100%=very confident). Results: In total, 451 participants, 268 (59%) Hispanic/Latinx and 183 (41%) Somali, completed baseline assessments for this analysis. The mean age was 45 years (range=18-87), 59% were female, and 37% lacked health insurance over ≤12 months. Participants reporting more confidence to eat a healthy diet were more likely to eat fruits and vegetables as snacks ( p =&lt;0.001), and less likely to drink fruit drinks or sports drinks ( p =0.02) or regular soda ( p =&lt;0.001). Those reporting more confidence to be physically active were also reported higher levels of physical activity ( p =0.001). Validated self-efficacy scales had a wide distribution of scores, suggesting that the measures can be appropriately used among these immigrant communities. Conclusion: Higher self-efficacy for a healthy diet and physical activity were significantly associated with healthier eating and physical activity behaviors. Lifestyle interventions to reduce CVD risk may benefit from incorporating culturally tailored strategies to enhance self-confidence and support health equity in immigrant communities.

Abstract P3090: 3-Minute Heart Health App: A Feasibility Study

Background: Cardiovascular (CV) health can be estimated using CV risk factors or can be evaluated more precisely by investigating individual fitness and subclinical disease. Current options involve expensive procedures requiring specialist monitoring and interpretation or radiation exposure and have inequitable access. In contrast, the change in heart rate in one minute after maximum exercise, or heart rate recovery (HRR) is a significant predictor of mortality that does not require specialized equipment and can be done in many settings. In this feasibility study, we aim to assess max heart rate achieved by adults after two minutes of exercise and determine HRR using a Bluetooth heart rate monitor. Methods: We developed the 3-Minute Heart Health App to facilitate this accessible approach to evaluating heart health. We partnered with a primary care clinic to enroll healthy, asymptomatic patients after their visit and listed the study on the University StudyFinder website. For this ongoing pilot study, the app is being paired with a chest band heart rate monitor. When exercise begins, the app provides a countdown timer and displays the patient’s percent of age-adjusted max heart rate (MHR) achieved. After 2 minutes of exercise, the app signals participants to stop and heart rate is monitored for 1 minute. The app then displays the age-adjusted Heart Fitness Grade and HRR (Figure 1). Results: Pilot testing has allowed us to strategically design and optimize the user experience while exploring feasibility of this approach. Of eight patients approached in clinic, seven consented and enrolled. An additional four participants were recruited via StudyFinder. Age ranged from 23 to 73 years; 10/11 were able to achieve &gt;70% of MHR and 7/11 reached &gt;85% of MHR in 2 minutes. Average HRR was 39 bpm; all but 1 had HRR &gt;25bpm. Participant feedback included desiring different exercises to increase heart rate and alternative heart rate monitor devices. There was overall enthusiasm about a routine evaluation of cardiovascular health that participants can monitor over time. Conclusion: Our preliminary findings suggest that the 3-Minute Heart Health test is acceptable and can be implemented in an outpatient setting This study is ongoing and more data are being collected to further determine acceptability and to evaluate characteristics of participants who reach a target MHR with normal/abnormal HRR.

Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH)

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al. , Sci. Rep. 7 , 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple lipophilic ester prodrugs. Surprisingly, this enzyme is taken up by the malaria parasite, Plasmodium falciparum , where it localizes to the parasite cytoplasm and retains enzymatic activity. Using a fluorogenic ester library, we characterize the structure–activity relationship of APEH and compare it to that of P. falciparum esterases. We show that parasite-internalized APEH plays an important role in the activation of substrates with branching at the alpha carbon, in keeping with its exopeptidase activity. Our findings highlight a mechanism for antimicrobial prodrug activation, relying on a host-derived enzyme to yield activation at a microbial target. Mutations in prodrug-activating enzymes are a common mechanism for antimicrobial drug resistance [E. S. Istvan et al. , Nat. Commun. 8 , 14240 (2017); K. M. V. Sindhe et al. , mBio 11 , e02640-19 (2020); J. H. Butler et al. , Acs Infect Dis. 6 , 2994–3003 (2020)]. Leveraging an internalized host enzyme would circumvent this, enabling the design of prodrugs with higher barriers to drug resistance.

Abstract P1157: Changes in Artificial Intelligence-Enabled Electrocardiogram-Derived Age During Mental Stress Testing and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Heart Disease

Background: The gap between artificial intelligence-derived age (ECG-Age) and chronological age has been validated as a strong predictor of increased cardiovascular morbidity and mortality, independent of age, and is a potential biomarker of biological aging. Acute stress may cause real-time, transient changes in autonomic function via electrophysiological signals that, when repeated over time, may contribute to biological aging and represent mechanisms linking stress and Major Adverse Cardiovascular Events (MACE). We hypothesized that acute mental stress induced in a laboratory is associated with increased ECG and that this increase is associated with a higher risk of MACE among individuals with stable coronary heart disease (CHD). Methods: We pooled two prospective cohorts of participants with stable CHD from a university-based hospital network in Atlanta. Stress was induced using a standardized mental stress test (public speaking task) and measured 12-lead ECGs during rest, mental stress, and recovery periods. To measure ECG-age, we utilized a published algorithm using a neural network on &gt;500,000 independent patients. The study endpoint was MACE including nonfatal myocardial infarction, hospitalization for heart failure, or cardiovascular death. The difference in ECG-Age between resting and acute mental stress was used to define the stress Age-Gap. Cox proportional hazard regression modeled the association of stress Age-Gap operationalized as tertiles adjusting for chronological age, sex, race, cardiovascular risk factors, and baseline Cohen perceived stress scale. Results: 442 participants in the total sample pool (38% women). Over a 5-year median follow-up, 95 participants (21%) experienced MACE. At rest, the mean chronologic age was 55.7±9.9 years, and ECG-Age was 57.1 ±10.7 years, with rest Age-Gap of 0. 9±9.6 (p=0.16). During stress, the stress Age-Gap of 1.95±9.8 (p&lt;0.0001), while recovery Age-Gap was 1.1±10.3 (p=0.13). Those that demonstrated the largest ECG-Age positive change between rest and stress by ECG (top tertile) had a higher risk for MACE when compared to those with the lowest or negative ECG age change (bottom tertile), see Figure. Conclusion: Among patients with stable CHD, acute mental stress caused changes in biological age as measured by AI-ECG consistent with accelerated biological aging. Such changes were associated with MACE. These results uncover accelerated biological aging as a mechanism linking acute stress to CVD outcomes.

Abstract P1145: Feasibility of a Culturally-tailored Diet and Physical Activity Intervention for Zimbabwean Immigrants in the US

Background: CVD risk factors are a significant health concern among African immigrants in the US. Zimbabwean immigrants in the US have high rates of hypertension, obesity, hyperlipidemia, and diabetes. Culturally tailored interventions are effective in reducing CVD risk in African Americans but given the unique cultural differences between African immigrants and other African Americans, r interventions tailored specifically for African immigrants are needed. Objective: We assessed the feasibility of a culturally targeted lifestyle intervention (LIFESTYLE) for Zimbabwean immigrants in the US. LIFESTYLE is based on CDC dietary and physical activity guidelines for Americans, customized with input from a community advisory board comprised of members from the same community, a nutritionist, and an exercise scientist to include foods and physical activities preferred by the Zimbabwe immigrants. Methods: A 12-week community-based intervention study was conducted in the New England region. LIFESTYLE utilized a pre&amp;post-intervention design, followed by focus group interviews. Feasibility was assessed by the ability to recruit and retain participants, their engagement in prescribed intervention activities, and their feedback in post-intervention focus group interviews. Day 1 activities included consent, demonstration of recommended food portions, physical activity, educational modules on nutrition and physical activity and completion of research questionnaires. A research coordinator conducted weekly check-ins. Weight, waist-circumference, BP, HbA1C, and physical activity were recorded. Focus group interviews were conducted on the last day of the study. Results: Of the 35 participants who initially agreed to participate, 25(71%) came. Of these, 23(92%) enrolled, 1 dropped out at week 2 and another at week 11. Overall, 21(91%) completed the study. Findings from post-intervention focus group interviews include: portion control was manageable; check-in reminders were helpful; activities enhanced family time; the food questionnaire was cumbersome; and achieving 150 minutes weekly of physical activity was challenging. Conclusion: LIFESTYLE intervention for Zimbabwean immigrants was feasible as indicated by high participation and adherence to the intervention. Areas of improvement identified include recruitment as nearly 30% (10/35) who initially agreed to participate were no-shows; decreasing questionnaire burden, and enhancing support for engagement and adherence.

A simple, statistically robust test of discrimination

In observational studies of discrimination, the most common statistical approaches consider either the rate at which decisions are made (benchmark tests) or the success rate of those decisions (outcome tests). Both tests, however, have well-known statistical limitations, sometimes suggesting discrimination even when there is none. Despite the fallibility of the benchmark and outcome tests individually, here we prove a surprisingly strong statistical guarantee: Under a common nonparametric assumption, at least one of the two tests must be correct; consequently, when both tests agree, they are guaranteed to yield correct conclusions. We present empirical evidence that the underlying assumption holds approximately in several important domains, including lending, education, and criminal justice—and that our hybrid test is robust to the moderate violations of the assumption that we observe in practice. Applying this approach to 2.8 million police stops across California, we find evidence of widespread racial discrimination.

Abstract 035: Time-restricted eating for weight loss maintenance: a pilot feasibility and acceptability, randomized controlled trial.

Background: Time-restricted eating (TRE) interventions demonstrate heterogeneity in the eating window duration. The purpose of this study was to examine the feasibility, acceptability, and adherence of two TRE strategies (10-hr vs 6-hr). Methods: Eligible participants had ≥5% non-surgical weight loss (self-reported) within the last 3 months and BMI: 20.5-45 kg/m 2 ; were 25-65 y; had an eating window &gt;12 h/day and completed a 4-week (wk) run-in to determine weight stability and eating window length. Participants were randomized to a self-selected 10 h (TRE10) or 6 h (TRE6) eating window for 12 weeks. Both arms received 8 educational and behavioral counseling sessions via videoconferencing (WebEx). Participants in both arms were asked to enter all eating occasions (foods and caloric beverages) into a smartphone application (MyCircadianClock) to assess eating window adherence. Feasibility and acceptability were determined based on retention and participant experience using an investigator-developed questionnaire (TRE Experience Questionnaire [TRE-EQ]). Mann-Whitney U test was used to compare data between the two arms. Baseline data are reported as means and standard deviations. Results: Participants were 46±10 y, 55% White, 36% African American, 27% Hispanic, and mostly female (73%) with a BMI of 30.1±6.2 kg/m 2 . The average self-reported weight loss before randomization was 9.2%±4.3%. A total of 29 participants were enrolled and 22 (n=11/arm) were randomized. Retention was 90%, with only two participants dropping out during the study, one from each arm. Additionally, TRE-EQ data indicates the participants in the TRE10 agreed to more statements around less hunger (p=0.09), their assigned program was easy to follow (p=0.02), their assigned program fits their daily routine (p=0.08) and they were adherent to their eating window (p=0.03) compared to participants in the TRE6 arm. Data from the mCC app suggests no difference between TRE10 and TRE6 regarding eating window adherence (p=0.41). There was a trend for the TRE10 arm to log fewer days with at least one eating occasion outside the designated eating window than the TRE6 arm (p=0.06). Conclusions: A 12-week 10-hr TRE intervention is more feasible and acceptable for adults with recent weight loss compared to a 6-hr TRE intervention.

Abstract P1168: The Association Between Self-Perceived Risk of Heart Disease and Barriers and Motivators to Research Participation

Purpose: Prior studies have investigated how barriers and motivators (B&amp;M) impact women’s participation in heart health-related research, but there is limited understanding of how women’s perceptions of their own heart health risk impact such B&amp;M. This study aimed to investigate the association between self-perceived risk of heart disease and B&amp;M to heart health-related research participation. We hypothesize that self-perceived risk of heart disease will be associated with encountering increased barriers or motivators to research participation on average. Methods: Data from the Barriers and Motivators to Research survey from the American Heart Association’s Millennial Women’s Health Study (MWHS) were used to conduct this analysis. B&amp;M were measured using the established B&amp;M research scale employed in prior health research. B&amp;M were tallied among each participant and the number of total B&amp;M were counted. We performed descriptive statistics and the association between B&amp;M and perceived risk of heart disease was assessed by performing one-way ANOVA Kruskal-Wallis tests for nonparametric data. Results: A total of 200 women participated in the study. Of these, 39% were Black and 21% were Hispanic, with an average age of 44 (10.9). Sixty-five percent of women within the study population perceived themselves to be at risk of heart disease and 60% of the population reported that they did not experience barriers, instead reporting that they felt motivated to participate in research. We found that there was no significant difference in average total amount of barriers or motivators between any groups that perceived themselves to be at risk of heart disease ( = 8.5, = 4, p = 0.07, = 7.6, = 4, p = 0.11). Additionally, women who reported a single barrier to participation in research were more likely to report encountering at least 3 motivators to research participation. Conclusion: Women who perceived themselves to be at risk for heart disease reported strong motivation to participate in heart-related research. Although most women in our sample did not report encountering barriers to participation, those who did identified barriers such as difficulty finding time to participate and lack of interest in learning about the information research may provide about their health. Further research is necessary to gain a deeper understanding of the specific motivators and barriers experienced by women from minoritized backgrounds when invited to participate in heart research.

Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways

Identifying conserved mechanisms used by viruses to delay host innate responses can reveal potential targets for antiviral therapeutics. Here, we investigated coronavirus nonstructural protein 15 (nsp15), which encodes a highly conserved endoribonuclease (EndoU). EndoU functions as an immune antagonist by limiting the accumulation of viral replication intermediates that would otherwise be sensed by the host. Despite being a promising antiviral target, it has been difficult to develop small-molecule inhibitors that target the EndoU active site. We generated nsp15 mutants of the coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mouse hepatitis virus (MHV)-A59 and identified conserved residues within the amino-terminal domain that are required for EndoU activity. Loss of EndoU activity caused the activation of host sensors, which limited viral replication in interferon-responsive cells and attenuated disease in MHV-infected mice. Using transcriptional profiling, we found that MHV EndoU mutant viruses upregulate multiple host sensors, including Z-form nucleic acid-binding protein 1 (ZBP1). We found that nsp15 mutants induced early, robust ZBP1-mediated necroptosis. EndoU mutant viruses also induced ZBP1-independent apoptosis and pyroptosis pathways, causing early, robust cell death that limits virus replication and pathogenesis. Overall, we document the importance of the amino-terminal domain for EndoU function. We also highlight the importance of nsp15/EndoU activity for evading host sensors, delaying cell death, and promoting pathogenesis.

Letter by Dai et al Regarding Article, “Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction”

Abstract P1010: Prediction Algorithms of Sarcopenia in US Older Adults

Sarcopenia is a significant risk factor for falls, disability, and mortality in US older adults. Currently, simple screening tools identifying sarcopenia in US older adults remain less clear. PURPOSE: The study developed simple prediction algorithms for sarcopenia using several anthropometric variables from the National and Nutrition Health Examination Survey (NHANES). Methods: The study participants included 3,377 men and women aged 60 to 80. All participants completed baseline anthropometric measurements, clinical evaluations, gait speed, 5 times sit-to-stand test (SST), and body composition assessment. Sarcopenia was defined as the combination of low muscle mass and SST or slow gait speed following the guidelines of the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH). Low muscle mass was classified using the appendicular skeletal muscle mass (ASM) divided by height in meters squared as &lt;7.0 kg/m 2 in men and &lt;5.5 kg/m 2 in women or ASM divided by body mass index (BMI) as &lt;0.789 in men and &lt;0.512 in women. Slow gait speed was classified as &lt;0.8 m/s in both men and women. Low muscle strength was classified as greater than 15 seconds of SST. Multivariate stepwise logistic regression models were used to develop prediction algorithms for sarcopenia. Harrel’s c-statistics were used to measure the discrimination, and the Hosmer-Lemeshow Chi-square statistics were used for calibration measures. The bootstrap procedures were used to cross-validate the developed prediction model’s accuracy. Results: The prediction algorithms for sarcopenia included age, sex, BMI, and waist girth using EWGSOP criteria (cases = 74), indicating the c-statistics of 0.94 with bootstrap cross-validation c-statistics of 0.9416. The P-value of the Hosmer-Lemeshow statistics was 0.92. Using FNIH criteria to define sarcopenia (cases = 224), age, sex, height, BMI, and waist girth maximized the discrimination index (c-statistics = 0.95) with the bootstrap cross-validation of 0.949. There was a valid calibration measure (P-value for the Hosmer-Lemeshow statistics = 0.18). Conclusion: There was good discrimination and calibration measures to predict sarcopenia using EWGSOP criteria (age, sex, BMI, and waist girth) and FNIH criteria (age, sex, height, BMI, and waist girth). Public health agencies should consider recommending these simple prediction algorithms for screening sarcopenia across community-based US older adults.

RNA-targeted proteomics identifies YBX1 as critical for efficient HCMV mRNA translation

Viruses have evolved unique strategies to circumvent host control of protein synthesis and enable viral protein synthesis in the face of the host response. Defining the factors that regulate viral messenger RNA (mRNA) translation is thus critical to understand how viruses replicate and cause disease. To identify factors that might regulate viral mRNA translation, we developed a technique for identifying proteins associated with a native RNA expressed from its endogenous promoter and genomic locus. This approach uses a guide RNA to target dCas13b fused to a biotin ligase domain to a specific RNA, where it covalently labels proteins in close proximity. Using this approach, we identified multiple proteins associated with transcripts encoding the human cytomegalovirus (HCMV) IE1 and IE2 proteins and found that several associated proteins positively or negatively regulate HCMV replication. We confirmed that one such protein, the cellular Y-box binding protein 1 (YBX1), binds to HCMV immediate early mRNAs and is required for efficient viral protein expression and virus replication. Ablating YBX1 expression reduced the association of HCMV immediate early mRNAs with polysomes, demonstrating a role for YBX1 as a positive regulator of viral RNA translation. These results provide a powerful tool for unraveling RNA–protein interactions that can be used in a wide range of biological processes and reveal a role for YBX1 as a critical regulator of HCMV immediate early gene expression.