Browse Articles

Abstract MP35: Community Prevalence of the Cardiovascular-Kidney-Metabolic (CKM) Syndrome: The Dallas Heart Study

Introduction: The recent AHA presidential advisory on Cardiovascular-Kidney-Metabolic Syndrome (CKM) proposed a novel staging scheme, but limited data exist regarding CKM stage prevalence in the community. Prior population-based studies have lacked subclinical imaging measures, and have not reported variability by age, gender, and race/ethnicity. Methods: We estimated the population prevalence of CKM stages in Dallas County, from among 2,817 participants in the population-sampled Dallas Heart Study who attended study Visit 1 (2000-2002). Participants underwent protocol measurement of body composition, lipids, fasting blood sugar, serum creatinine, NT-proBNP, hs-cTnT, urinary albumin and creatinine, coronary artery calcium by cardiac CT (CAC), and cardiac function and mass by cardiac MRI. These were used to operationalize the following CKM stages: 0 – no CKM risk factors; 1 – excess or dysfunctional adiposity (body mass index, waist circumference, and fasting blood glucose); 2 – metabolic risk factors (hypertriglyceridemia, hypertension, diabetes, metabolic syndrome) and chronic kidney disease; 3 – subclinical cardiovascular diseases (CAC, LV hypertrophy or dysfunction by cardiac MRI, elevated cardiac biomarkers (NT-proBNP or hs-cTnT), high AHA-PREVENT or KDIGO scores); 4 – prevalent cardiovascular diseases (coronary heart disease, heart failure, atrial fibrillation, stroke). We used sampling weights to estimate the prevalence of CKM stages in Dallas County in 2000-2002 overall and by age category (30-44, 45-59, 60-65 years), gender, and race/ethnicity. Results: Among the 2,817 participants with a mean age of 44±10 years, the sample weighted demographics were 50% women, 52% non-Hispanic White, 20% non-Hispanic Black, and 26% Hispanic race/ethnicity. Among Dallas County adults, only 10% were CKM Stage 0 (no risk factors). The weighted prevalence of CKM Stages 1 through 4 was 16%, 46%, 23%, and 5%, respectively ( Figure A) . CKM stage prevalence was similar between men and women, while CKM Stage 4 was more frequent among older individuals and among non-Hispanic Black compared with non-Hispanic White and Hispanic individuals ( Figure B ). Conclusion: The public health burden of CKM is substantial. Ninety percent of Dallas County residents in 2000-2002 had some form of CKM syndrome, nearly half demonstrated metabolic dysfunction (Stage 2), and nearly one-fourth had subclinical cardiovascular disease (Stage 3).

Abstract MP48: Null Causal Associations between Circulating Caffeine Levels and its Metabolites with Cardiac Function and Heart Failure

Introduction: Observational studies have shown that coffee consumption relates to a decreased risk of heart failure (HF). Our recent findings indicate that caffeine metabolism, not caffeine itself, relates to the onset of HF. The causal effect of circulating caffeine levels on HF and cardiac function is largely inconclusive. Hypothesis: We hypothesize that circulating caffeine level is not causally associated with cardiac function and HF. Methods: We extracted the summary results from genome-wide association (GWAS) studies of plasma caffeine, HF, and 15 cardiac structure and function measures for left atrium, left ventricle, and right ventricle from public databases. Genetic instruments of caffeine were selected if the variants were associated with caffeine at p<5×10 -8 . After clumping at r<0.001, two independent lead variants on gene CYP1A2 , rs2472297, and AHR , rs4410790, were included in the analysis. Using the two-sample Mendelian Randomization (MR) approach, we examined the associations between caffeine level, cardiac function measurements, and HF on each selected variant, and pooled estimates were generated using the inverse-variance weighted method. Results: The summary of caffeine, cardiac function, and HF was from GWAS of European descent, consisting of 9,876 participants from six cohorts, up to 29,506 participants from UK Biobank, and 47,309 cases and 93,014 controls from the Heart Failure Molecular Epidemiology for Therapeutic Targets study, respectively. CYP1A2 and AHR were not causally associated with HF individually or jointly (Odds Ratio meta =1.001, 95% CI = 0.999, 1.004). Both genes also yield insignificant results between caffeine levels and measures of the left ventricle, left atrium, and right ventricle, key parameters underlying HF ( Figure ). Conclusion: We observed no causal association between circulating caffeine and the risk of HF, suggesting health-beneficial effects of coffee consumption may relate to the improved molecular pathways instead of circulating caffeine levels.

Significant amplification of electromagnetic waves in disordered dispersive temporal multilayered structures with randomness in plasma frequency or dielectric permittivity

Cas9-mediated gene-editing frequency in microalgae is doubled by harnessing the interaction between importin α and phytopathogenic NLSs

Pathogen-derived nuclear localization signals (NLSs) enable vigorous nuclear invasion in the host by the virulence proteins harboring them. Herein, inspired by the robust nuclear import mechanism, we show that NLSs originating from the plant infection–associated Agrobacterium proteins VirD2 and VirE2 can be incorporated into the Cas9 system as efficient nuclear delivery enhancers, thereby improving the low gene-editing frequency in a model microalga, Chlamydomonas reinhardtii , caused by poor nuclear localization of the bulky nuclease. Prior to evaluation of the NLSs, IPA1 (Cre04.g215850) was first defined in the alga as the nuclear import-related importin alpha (Impα) that serves as a counterpart adaptor protein of the NLSs, based on extensive in silico analyses considering the protein’s sequence, tertiary folding behavior, and structural basis when interacting with a well-studied SV40TAg NLS. Through precursive affinity explorations, we reproducibly found that the NLSs mediated the binding between the Cas9 and Impα with nM affinities and visually confirmed that the fusion of the NLSs strictly localized the peptide-bearing cargoes in the microalgal nucleus without compensating for their cleavage ability. When employed in a real-world application, the VirD2 NLS increases the mutation frequency (~1.12 × 10 −5 ) over 2.4-fold compared to an archetypal SV40TAg NLS (~0.46 × 10 −5 ) when fused with Cas9. We demonstrate the cross-species versatility of the Impα-dependent strategy by successfully applying it to an industrial alga, Chlorella Sp. HS2. This work, focused on affinity augmentation, provides insights into increasing the frequency of gene editing, which can be advantageously used in programmable mutagenesis with broad applicability.

Abstract P2052: Expanding Opportunities for Black and Hispanic Undergraduate Students Pursuing Science, Medical and Health-Related Careers with the American Heart Association’s Scholars Program

Introduction: Black and Hispanic students entering science, medical and health-related careers remain disproportionately low due to systemic inequities in educational support and opportunities. Recognizing the significant role undergraduate (UG) pathway programs play in preparing students for advanced careers, the American Heart Association (AHA) established the AHA Scholars Program. This program expands opportunities for individuals enrolled in Historically Black Colleges and Universities and Hispanic-Serving Institutions to receive mentorship and engage in research and career-enriching experiences, fostering their academic and career growth to empower them to become healthcare professionals and researchers. Objectives: To gather information on the current employment and education status of individuals who participated in the program over the past eight years, and to understand how participation in the program impacted their career and education paths. Methods: A cross-sectional survey was administered to 250 unique alumni in May 2024. Eighty-four individuals completed the survey, representing a response rate of 40%. Descriptive statistics and content analysis were used to analyze quantitative and qualitative questions, respectively. Results: Among respondents who completed their UG degrees, 68% reported pursuing/completing postgraduate (PG) education, with about 59% pursuing/completing a PG degree program in a science or health-related field. Among employed respondents, 65% reported working in a science or health-related industry. Many respondents felt their program experience prepared them very well or more than adequately for PG education (81%) and a career in a health-related field (78%). Almost 76% of respondents indicated their program experience had a substantial positive impact on their overall career progression. Receiving professional skill development, learning how to engage in networking opportunities, gaining research experience, and increasing self-confidence were other ways the program helped respondents prepare for their PG education or career. Conclusion: By creating opportunities for students to engage in skill-building and career-enriching experiences, the AHA Scholars Program has demonstrated its potential to support and promote the advancement of Black and Hispanic students in science, medical and health-related fields, contributing to the development of a more diverse workforce and the advancement of health equity.

Abstract P1015: Human Blood Proteome Profiles Across Middle and Late Adulthood Exhibit Three Life-Stage Waves Differentially Linked to Age-Related Diseases

Introduction: The circulating proteome has emerged as a crucial resource for predicting biological aging. Recent studies identified life-stage specific waves of proteomic expression; however, little is known about the relations between life-stage proteomic waves and age-related disorders. Hypothesis: Life-stage proteomic waves during middle and late adulthood are differentially associated with diseases and mortality. Methods: The study included a total of 53,105 participants (aged 39-70 years) from the UK Biobank study, with the measurements of 2,922 Olink plasma proteins. We used differential expression-sliding window analysis (DE-SWAN) to analyze differential expression of protein levels within a window of 10 years, while sliding the window in increments of 2 year from middle to old. We constructed a coefficient-weighted protein scores for aging waves, and then used the Cox models to assess the associations between protein scores and the risk of 22 leading diseases and mortality. Results: We identified three distinct life-stage proteomic waves peaking at ages 50, 56, and 67, comprising 943, 708, and 1,103 differentially expressed proteins, respectively. Protein scores from all waves showed significant and varying associations with 10 diseases across neurodegenerative, cardiovascular, autoimmune, respiratory, metabolic, and liver categories. The protein scores of age 56 wave demonstrated the strongest associations with most diseases including ischaemic stroke, ischaemic heart disease, rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, lung cancer, and mortality (Hazard ratio [HR] ranges: 1.30-2.10). There were distinct association patterns for specific diseases. For instance, Alzheimer's dementia showed a peak risk at age 56 (HR 1.34), rising from age 50 (HR 1.25) and remaining essentially unchanged at age 67 (HR 1.31). In contrast, vascular dementia displayed consistently higher risk at ages 50 and 56 (HR 1.59), followed by a decline at age 67 (HR 1.48). Liver diseases showed a unique pattern, with the highest risk at age 50 (HR 2.74), followed by a gradual but monotonically decrease through ages 56 (HR 2.38) and 67 (HR 2.00). Conclusions: Our findings indicate life-stage specific association patterns between circulating proteomic profiles and risks of a wide spectrum of diseases, highlighting the essentiality of age-based strategies in prevention and treatment of diseases.

Some new evidence using fractional integration about trends, breaks and persistence in polar amplification

Photoreduction of mercuric bromides in polar ice

In the polar regions, which are vulnerable receptors of mercury pollution, atmospheric mercury depletion events (AMDEs) efficiently convert elemental mercury (Hg(0)) into oxidized mercury (Hg(II)) via bromine oxidation. Hg(II) subsequently deposits onto snow and sea ice. While field observations have shown that a large percentage of deposited mercury is re-emitted from the ice to the atmosphere by a photoinduced process, the fundamental photochemistry that drives the re-emission process remains unknown. Here, using multiconfigurational quantum chemistry, we find that the photoreduction of HgBr 2 , HgBr 3 − , and HgBr 4 2− in ice is more efficient than in the gas phase. This results from the influence of water molecules on the molecular geometry and electronic structure of mercuric bromides in ice, which enhances the absorption intensities at wavelengths relevant in the troposphere (λ > 290 nm), as compared to gas phase. Kinetic modeling shows that ~30 to 60% of deposited mercury in AMDEs can be reemitted due to the photoreduction of mercuric bromides in ice, in agreement with field observations. Our results reveal a photoreduction mechanism of sunlight-induced excited state chemistry of mercuric bromides on ice. These findings strongly suggest that this chemistry should be incorporated into atmospheric models to account for ice-atmosphere mercury cycling in the polar environments, currently not considered.

Abstract P1099: A Daily Diary Examination of the Associations of Adverse Childhood Experiences, Anticipated Discrimination, and Blood Pressure among Sexual and Gender Minority Adults

Background: Chronic psychosocial stressors, such as anticipated discrimination and adverse childhood experiences, have been shown to influence hypertension risk among stigmatized adults. Emerging research suggests that individuals exposed to adverse childhood experiences later report greater discrimination as adults. Researchers theorize that exposure to adverse childhood experiences likely moderate the association between discrimination and blood pressure (BP); however, this remains underexplored. Therefore, we sought to examine whether adverse childhood experiences moderated the associations of anticipated discrimination and BP in a diverse sample of adults. Methods: Data were obtained from a 30-day online diary study of sexual and gender minority (SGM; e.g., gay/lesbian, bisexual, transgender) adults in the United States. Participants completed daily electronic diaries that assessed anticipated discrimination every morning. Home BP was assessed every day at awakening and before bedtime. Adverse childhood experiences, including childhood physical, emotional, and sexual abuse, were assessed at baseline using a validated questionnaire. Mixed-effects linear models, adjusted for demographic factors, estimated the associations between daily anticipated discrimination and BP and the moderating role of adverse childhood experiences. Results: The sample included 31 SGM adults with a mean age of 27.1 years (±7.50). Approximately 83% of participants were Latinx and 49% were multiracial. We found that 39% of the sample reported exposure to 4 or more adverse childhood experiences. Results of mixed-effects linear models suggested that daily anticipated discrimination was not significantly associated with BP. However, we did find evidence that childhood physical abuse significantly strengthened the association between daily anticipated discrimination and morning diastolic BP (β(SE) = 2.36 (0.88), p = 0.01). Childhood emotional and sexual abuse were not significant moderators. Conclusions: Our findings highlight the importance of considering the moderating effects of adverse childhood experiences on the association between daily anticipated discrimination and BP among SGM people. Future research is needed with larger samples to understand the role that adverse childhood experiences (particularly childhood physical abuse) may play in sensitizing individuals to greater exposure to psychosocial stress and subsequent hypertension risk in adulthood.

Abstract P1165: Dietary Quality Among Pregnant People With Overweight/Obesity: Comparison Between Randomized Controlled Trial Participants in Early Pregnancy With Non-Pregnant NHANES Matched Participants

Background: Poor dietary quality is associated with perinatal obesity, including excess gestational weight gain, a risk factor for future cardiometabolic disease. Despite the need to assess and intervene on dietary quality in pregnancy, few studies have identified screeners that are easy to use and have comparable performance in research as well as the general population. We sought to describe the dietary patterns of participants in early pregnancy using the Dietary Screener Questionnaire (DSQ) and compare the results with a matched non-pregnant sample from the 2009-2010 wave of the National Health and Nutrition Examination Survey (NHANES) who also completed the screener to demonstrate the external validity of our DSQ results. Methods: We compared the baseline dietary quality data from an ongoing randomized controlled trial (RCT) to assess the effectiveness of a remote lifestyle intervention targeting dietary quality on gestational weight gain with matched controls from non-pregnant NHANES participants. Baseline DSQ responses were collected from the RCT participants at ≤ 15 weeks of gestation. We selected a non-pregnant NHANES sample matched for age (20-44), sex (female), BMI (≥ 25), and complete DSQ data. We estimated daily intake of added sugar (total and from sweetened beverages), fiber, fruits and vegetables, and dairy using the standard scoring procedures and compared the samples using the Mann-Whitney U test. Results: At baseline, 383 RCT participants completed the DSQ with a mean age of 34.2 years (SD = 5.0). The NHANES sample included 651 people (mean age = 32.9 years, SD = 7.4 years). Pregnant RCT participants had a significantly lower consumption of daily total sugar (median = 13.2 tsp, IQR = [11.6, 15.0]) and sugar from beverages (median = 4.5 tsp, IQR = [3.9, 6.1]) compared to matched NHANES non-pregnant participants (total: median = 15.3 tsp, IQR = [12.9, 19.8]; beverages: median = 6.6 tsp, IQR = [4.4, 11.0]; both p < 0.001). Other dietary quality measures were comparable between samples (Figure 1). Conclusion: Dietary patterns of RCT participants in early pregnancy and matched non-pregnant NHANES 2009-2010 participants were similar, except for sugar intake, indicating that the DSQ results may be generalizable to a broader population like people in NHANES. The lower intake of added sugar, particularly from sweetened beverages, may reflect decreased intake in early pregnancy or secular changes in the last 15 years.

Quantification of extrusion-induced excavation volume in shield tunnelling through squeezing cohesive-frictional ground

Abstract When tunnelling through weak and highly deformable ground, relevant deformations occur ahead of the tunnel face and result in face displacements that are opposite to the advance direction (“extrusion”). In mechanised tunnelling, the cutterhead continuously removes the ground extruding at the tunnel face during advance. Therefore, the total excavation volume is higher than the volume that corresponds to the tunnel cross-section area. Previous investigations by the authors showed that the additional, extrusion-induced excavation volume may be considerable in the case of purely cohesive ground. This paper extends this work for the case of cohesive-frictional ground. Firstly, we quantify the extrusion-induced excavation volume for a wide parameter range by means of a numerical model that uses re-meshing to consider the continuous re-profiling taking place at the tunnel face during advance. The results of the performed parametric study are summarised in a single dimensionless design chart. Secondly, we derive a simple closed-form expression, which, despite the underlying simplifications, allows for an accurate and rapid quantification of the extrusion-induced excavation volume. The results show that face extrusion has an effect on excavation volume in the cohesive-frictional case, although less pronounced than when tunnelling through low-permeability clays with purely cohesive short-term strength. The study suggests that if the additional excavation volume due to face extrusion is not taken into account in the design of the mechanised advance, it may (a) pose logistical and disposal challenges and (b) lead to erroneous conclusions about the stability of the tunnel face, both of which affect the rate of tunnel advance.

TEX38 localizes ZDHHC19 to the plasma membrane and regulates sperm head morphogenesis in mice

Sperm morphogenesis is a tightly regulated differentiation process, disruption of which leads to sperm malfunction and male infertility. Here, we show that Tex38 knockout (KO) male mice are infertile. Tex38 KO spermatids exhibit excess retention of residual cytoplasm around the head, resulting in abnormal sperm morphology with backward head bending. TEX38 interacts and colocalizes with ZDHHC19, a testis-enriched acyltransferase catalyzing protein S-palmitoylation, at the plasma membrane of spermatids. ZDHHC19 and TEX38 are each downregulated in mouse testes lacking the other protein. TEX38 stabilizes and localizes ZDHHC19 to the plasma membrane of cultured cells and vice versa, consolidating their interdependence. Mice deficient in ZDHHC19 or harboring a C142S mutation that disables the palmitoyltransferase activity of ZDHHC19 display phenotypes resembling those of Tex38 KO mice. Strikingly, ZDHHC19 palmitoylates ARRDC5, an arrestin family protein regulating sperm differentiation. Overall, our findings indicate that TEX38 forms a stable complex with ZDHHC19 at the plasma membrane of spermatids, which governs downstream S-palmitoylation of proteins essential for morphological transformation of spermatids.

Abstract P1108: Plasma metabolome of a cholesterol-lowering plant-based diet and cardiometabolic disease risk

Introduction: The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C), however, less is known about its long-term impact on cardiometabolic disease. Objective metabolic response to diet using metabolomics can provide additional insight into how diet affects disease risk. Objective: To investigate whether a metabolomic signature can characterize adherence to the portfolio diet and whether this signature is associated with cardiometabolic disease. Methods and Results: The metabolomic signature discovery cohort included 633 plasma samples from four previously conducted randomized controlled trials (RCTs) on the portfolio diet. The validation cohorts included 11,985 participants from the Nurses’ Health Studies (NHS) I&II and Health Professionals Follow-up Study (HPFS). Adherence to the portfolio diet was assessed using a portfolio diet score, and the plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. Using elastic net regression, a metabolomic signature of 56 metabolites was found, most of which were amino acids and amines (34%), glycerophosphocholines (14%), glycerophosphoethanolamines (7%), and indoles (7%). The signature was highly correlated with portfolio diet adherence in the RCTs (r=0.87, p<0.001). In the NHS/HPFS cohorts, a simplified signature showed an attenuated relationship with the portfolio diet score (r=0.26, p<0.001). In the RCTs, using linear mixed models, the signature was associated with lower total cholesterol, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, triglycerides, and systolic blood pressure. In the NHS/HPFS cohorts, using multivariable linear regression, the signature was associated with lower total cholesterol, LDL-C, non-HDL-C, and HDL-C. In multivariable Cox regressions in the NHS/HPFS cohorts, the signature was inversely associated with total mortality (HR: 0.94 [95% CI: 0.89, 0.99]) and type 2 diabetes (0.92 [0.84, 0.99]), but not cardiovascular disease (0.96 [0.86, 1.08]). Conclusions: A metabolomic signature that reflects adherence and metabolic response to the cholesterol-lowering plant-based portfolio diet was identified, which was then associated with several cardiovascular disease risk factors in both the RCTs and cohorts, and lower risk of mortality and type 2 diabetes in the cohorts. Further research on this dietary pattern and replication in other cohort studies is warranted.

Abstract 055: Gestational Diabetes and Risk of Type 2 Diabetes: Exploring the Role of Gut microbiome and Blood Metabolome in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

Introduction: Women with a history of gestational diabetes mellitus (GDM) have a higher risk of type 2 diabetes (T2D), but the underlying mechanisms, particularly the roles of gut microbiota and blood metabolites, remain unclear. Hypothesis: Women with history of GDM have an altered gut microbiota and blood metabolites, which may lead to a higher T2D risk. Methods: Among parous women from HCHS/SOL, gut microbiome was assessed by shotgun sequencing (visit 2, 2014-17). We identified microbial species associated with presence vs. absence of history of GDM (visit 2, n=1525), and serum metabolites associated with both history of GDM (baseline, 2008-11, n=2968) and GDM-related microbiota (visit 2, n=391). We also examined prospective associations of the GDM-related microbiome (visit 2, n=798) with incident T2D over 6 years follow-up, and of microbial-related metabolites (baseline, n=2341) with incident T2D over 12 years. Results: Seven species showed differential abundance between women with and without history of GDM, including higher abundance of 4 species (e.g., Parabacteroides merdae CAG:48 ), and lower abundance of 3 species (e.g., Dialister sp. CAG:588 ). A GDM-related microbiome score, generated via linear combination of 7 species, was associated with higher T2D risk (RR=1.08 [95% CI: 1.00, 1.18] per SD). Fifteen metabolites (e.g., saturated sphingomyelins) were associated with both history of GDM and the microbiome score in consistent direction, 9 of which were prospectively associated with incident T2D (Fig. 1A). Proxy association analysis based on these metabolites suggested a positive relationship between the GDM-related microbiome and T2D (Fig. 1B). A metabolite score derived from the 9 microbial-related metabolites partially mediated the relationship between GDM and T2D risk (21.8%, 95% CI: 8.1%, 54%). Conclusion: Among U.S. Hispanic/Latino women, history of GDM is associated with an unfavorable gut microbiota and related metabolites, suggesting a potential role of gut microbiota in GDM-T2D relationship.

Respiratory compliance related to prognostic of lung transplant patients with veno‑venous extracorporeal membrane oxygenation support

Archaeology and traversing America’s pre-Columbian fault line

Abstract MP47: Cardiovascular risk factors for dementia: Causal estimates on individual-level data

Background: The 2024 Lancet Commission report highlights 14 modifiable risk factors that if eliminated can prevent nearly half of dementia, of which most are cardiovascular risk factors. The causal aspects remain however unclear, hence we aimed to establish causal estimates for these cardiovascular risk factors. Methods: We used individual-level data from 408,788 European participants from the UK Biobank. We computed polygenetic risk scores of individual risk factors for each participant, exploiting independent instrumental variants from the largest genomic consortia for each risk factor. We conducted univariable and multivariable linear Mendelian randomization analyses and assessed genetic shapes by nonlinear approaches. Findings: Genetically predicted high BMI (OR, 95% CI: 1.04, 1.02-1.07), smoking (1.18, 1.06-1.32), high systolic (1.14, 1.09-1.20) and diastolic (1.10, 1.02-1.19) blood pressure, type 2 diabetes (1.04, 1.00-1.09), high LDL cholesterol (1.12, 1.01-1.23) and high triglycerides (1.19, 1.01-1.41) were associated with increased risk of all-cause dementia. Results for Alzheimer’s disease and vascular dementia were in the same direction. Moreover, genetically predicted high physical activity was associated with reduced risk of Alzheimer’s disease (0.58, 0.33-0.99), and longer education was associated with all-cause dementia (0.72, 0.65-0.79), Alzheimer’s disease (0.71, 0.62-0.81), and vascular dementia (0.64, 0.52-0.77) Sensitivity analyses supported the main results, and no nonlinear shapes were detected. Interpretation: These findings provide causal insights into cardiovascular risk factors for dementia, underscore the importance of more targeted interventions to mitigate these risk factors for dementia prevention, and give hope for maintaining brain health by timely treatment of high cholesterol and triglycerides alongside hypertensive medication, smoking cessation and maintenance of normal weight.

Abstract P1028: Prospective associations of optimism and cynicism with Life’s Essential 8: The Study of Women’s Health Across the Nation (SWAN) Study

Introduction: Hostility and Optimism are traits known to be associated with the risk of cardiovascular disease (CVD). However, important gaps remain in understanding the behavioral and biological mechanisms of these associations among multi-ethnic midlife women transitioning through menopause. We aim to assess the associations of optimism and cynicism with Life’s Essential 8 (LE8) and its components. Methods: Participants were from the SWAN study, a multi-ethnic longitudinal study of the menopause transition. Optimism and cynicism were assessed at baseline and visit 1 via the Life Orientation Test (0[low]-18[high]) and the Cook-Medley Cynicism scale (0 [low] – 13 [high]), respectively. The total and component-specific LE8 scores (0[worst]– 100[best]), including dietary health, physical activity, sleep quality, nicotine exposure, blood pressure, blood glucose, blood lipids and body mass index (BMI), were measured 5 years after baseline. Linear regression models adjusting for demographics and menopause related variables (listed in figure) were used to test the associations of quartiles of optimism or hostility in relation with each LE8 outcome separately. Results: A total of 1,907 women (mean (SD) baseline age: 45.9 (2.7) years; 48% White, 27%% Black, 9% Chinese, 7% Hispanics, 10% Japanese) with available data on main predictors and outcomes were included in the analysis. Compared women with the lowest quartile of the optimism scores, women in the highest quartile had 3.3 (95% CI: 1.1-5.3) points higher total LE8 scores (p-trend= 0.0005). Conversely, women in the highest quartile of hostility had 2.2 (0.4-4.1) points lower total LE8 scores (p-trend= 0.075) than women with the lowest quartile of hostility. Of the 8 components, higher optimism scores were associated with better sleep and physical activity scores, whereas higher hostility scores were associated with lower physical activity and diet scores, Figure 1. An analysis accounted for both traits together showed similar results compared to the analysis of the two traits separately. Conclusion: Optimism was positively associated with total LE8 scores, while cynicism was negatively associated with total LE8 scores. Optimism and cynicism play more important roles in health behavior components than health measures components. Supported by NIH/DHHS {Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720}.

TNMpBC-NeoBCSS model: a breast cancer specific survival prediction model for triple-negative metaplastic breast carcinoma patients with neoadjuvant therapy

Copy number variation contributes to parallel local adaptation in an invasive plant

Adaptation is a critical determinant of the diversification, persistence, and geographic range limits of species. Yet the genetic basis of adaptation is often unknown and potentially underpinned by a wide range of mutational types—from single nucleotide changes to large-scale alterations of chromosome structure. Copy number variation (CNV) is thought to be an important source of adaptive genetic variation, as indicated by decades of candidate gene studies that point to CNVs underlying rapid adaptation to strong selective pressures. Nevertheless, population-genomic studies of CNVs face unique logistical challenges not encountered by other forms of genetic variation. Consequently, few studies have systematically investigated the contributions of CNVs to adaptation at a genome-wide scale. We present a genome-wide analysis of CNV contributing to the adaptation of an invasive weed, Ambrosia artemisiifolia . CNVs show clear signatures of parallel local adaptation between North American (native) and European (invaded) ranges, implying widespread reuse of CNVs during adaptation to shared heterogeneous patterns of selection. We used a local principal component analysis (PCA) to genotype CNV regions in whole-genome sequences of samples collected over the last two centuries. We identified 16 large CNV regions of up to 11.85 megabases in length, eight of which show signals of rapid evolutionary change, with pronounced frequency shifts between historic and modern populations. Our results provide compelling genome-wide evidence that CNV underlies rapid adaptation over contemporary timescales of natural populations.