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Abstract TU273: Early Life Exposures and Age at Menopause in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation Nekayla Anderson, Megan McCabe, Rachel Sinkey et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu273

Background: Younger age at menopause (premature and early menopause) occurs more often in Black women than in White women and is associated with an increased cardiovascular disease risk. Traditional risk factors for early onset are well studied, but the role of adverse childhood experiences (ACEs) is unclear. This study examined the association between ACEs and age at menopause. We hypothesized that women reporting ACEs are more likely to experience menopause at younger ages compared to those reporting no ACEs. Methods: A cross-sectional analysis was conducted in 4,491 Black and White women aged 45 years from the REasons for Geographic and Racial Differences in Stroke Study. ACEs were assessed in the Childhood and Family Life Factors ancillary study using the Childhood SES Factors questionnaire and categorized into groups (0, 1, 2-3, and 4+ ACEs) for analyses. Age at menopause was measured as the self-reported age at last menstrual period, and categorized as premature (<40), early (40- 45), normal (45- 55), and late menopause (>55). Multinomial logistic regression was used to estimate separate odds ratios (OR) and 95% confidence intervals (CI) for early, premature, and late versus normal menopause. A crude (model 1) and four sequentially adjusted models, for demographic (model 2), socioeconomic (model 3), behavioral (model 4), and reproductive (model 5) covariates, were fit. Results: Women were primarily White (70%), with a mean age at menopause of 45.6 years (± 8.1). Most women (58%) experienced a normal age at menopause, whereas 22% experienced premature, 14% experienced early, and 6% experienced late menopause. Approximately 22% reported 1 ACE, 24% reported 2-3 ACEs, and 7% reported 4+ ACEs. Reporting 2–3 ACEs (versus no ACEs) was associated with higher odds of premature menopause (fully adjusted OR [95% CI] = 1.33 [1.09–1.63]) and early menopause (fully adjusted OR [95% CI] = 1.32 [1.03–1.69]). Reporting ≥4 ACEs (versus no ACEs) was associated with higher odds of premature menopause in models 1-4 (model 4 OR [95% CI] = 1.65 [1.22–2.22], but this effect was attenuated in the fully adjusted model. No associations were observed for late menopause. Conclusion: Women with 2–3 ACEs were more likely to experience premature and early menopause, while associations for ≥4 ACEs with premature were inconsistent. Further research is needed to understand how ACEs contribute to differences in reproductive aging and menopause timing.

The <i>Arabidopsis</i> FRIENDLY (FMT) protein interacts with NAC and determines where nuclear-encoded mitochondrial proteins are translated

Proceedings of the National Academy of Sciences Valentina Montoya-Brach, Jeanne Roignant, Grégory Renard et al. Mar 24, 2026 DOI: 10.1073/pnas.2521483123

Mitochondria are not only the powerhouses of the cell. They are also dynamic signaling hubs, playing a key role in cellular metabolism and adaptation. Proper mitochondrial function depends largely on the import of proteins encoded by the nucleus. Using proximity labeling (TurboID), we show that Arabidopsis thaliana FRIENDLY (FMT) protein is in close proximity to several organellar-destined proteins, mostly mitochondrial, during their translation. Many of the corresponding mRNAs are immunoprecipitated with FMT. Remarkably, when FMT is absent, its target mRNAs lose their correct cellular localization. Our TurboID approach, associated with immunoprecipitations and confocal microscopy, also demonstrates the interaction between FMT and the Nascent polypeptide Associated Complex (NAC), a ribosome-associated platform involved in the maturation and sorting of nascent peptides. Taken together, these results suggest that FMT, through its interaction with NAC and the ribosome, is involved in the spatial regulation of translation in the cell.

Utilizing large language models to construct a dataset of Württemberg’s 19th-century fauna from historical records

PLoS ONE Maximilian C. Teich, Belen Escobari, Malte Rehbein Mar 24, 2026 DOI: 10.1371/journal.pone.0344181

Constructing datasets on past biodiversity from historical sources is crucial for understanding long-term ecological changes. Typically, compiling such datasets relies on prior knowledge of the sources’ composition and requires considerable manual effort. To overcome these challenges, we implement an automated approach based on prompted large language models (LLMs) to detect mentions of species in texts from 19th-century Württemberg and link these mentions to identifiers in the GBIF database. Based on our evaluation, we find that LLMs can reliably identify species in the texts with high recall (92.6%) and precision (95.3%), while providing estimates of the correct species identifier with considerable accuracy (83.0%). As our approach is easily scalable and adaptable to other contexts and languages, it offers a promising way to advance dataset generation from historical material using limited resources.

Abstract TU258: Height Loss Predicts All-Cause and Cardiovascular Disease Mortality among Residents of Evacuation Zones Following the Great East Japan Earthquake: The Fukushima Health Management Survey

Circulation Fumikazu Hayashi, Hiroshi Kobayashi, Kanako Okazaki et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu258

Introduction: Major disasters such as the Great East Japan Earthquake and prolonged displacement can exacerbate undernutrition, psychological stress, and limited medical access. These factors increase the risk of lifestyle-related disorders and functional decline, thereby accelerating long-term height loss. Height loss has been associated with increased all-cause and cardiovascular disease (CVD) mortality. However, the predictive value of height loss in postdisaster settings remain unclear. Using data from the Comprehensive Health Check (CHC) of the Fukushima Health Management Survey, we aimed to examine annual height loss among residents of evacuation zones in Fukushima Prefecture and its association with postdisaster all-cause and CVD mortality. Hypothesis: Pronounced long-term height loss after a disaster predicts increased all-cause and CVD mortality. Methods: We analyzed 36,856 residents of evacuation zones (15,427 men and 21,429 women) aged 40–90 years who participated in at least one CHC in both fiscal years (FY) 2011–2013 and FY 2014–2016. All-cause and CVD deaths were identified from the date of the last CHC through December 31, 2020. Annual height loss (mm/year) was calculated as: [(height at last CHC [mm] – height at baseline CHC [mm]) / follow-up years]. Participants were divided into sex-specific quintiles, with the highest quintile defined as the stature-decline group. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between height loss and mortality outcomes. Models were adjusted for age, sex, body mass index, anemia, number of comorbid lifestyle-related diseases, smoking status, alcohol consumption, exercise habits, and evacuation experience at the final CHC. Results: Over a mean follow-up of 4.5 years, 1,974 all-cause and 441 CVD deaths occurred. The height loss group included a higher proportion of evacuees (55.0%) than the no-height loss group (52.4%). Pronounced height loss was significantly associated with increased all-cause (multivariate HR: 1.50; 95% CI: 1.37–1.65), CVD (1.63; 1.34–1.98), heart disease mortality (1.70; 1.35–2.14), and stroke mortality (1.47; 1.01–2.13) (Table 1). Conclusions: Height loss is a simple predictor of both all-cause and CVD mortality in disaster-affected populations.

Abstract TH961: Beyond Traditional Risk Factors: A Data-Driven Approach to Coronary Artery Disease (CAD) Prediction

Circulation Isheeta Gupta, Mallikarjun Verma Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th961

Background: Coronary artery disease (CAD) remains the leading cause of death worldwide, accounting for over 370,000 deaths in the United States in 2022. Traditional tools such as the Framingham Risk Score (c-statistics 0.65–0.75) have limited predictive accuracy and often fail to capture nonlinear interactions among risk factors. Improved early risk stratification could reduce mortality by up to 30%. Advances in machine learning (ML) offer new opportunities to integrate demographic, behavioral, and physiological variables for more precise prediction. This study aims to enhance CAD risk detection using feature engineering, synthetic data balancing, and optimized ML models. Methods: We analyzed a publicly available cardiovascular dataset of 70,000 adults containing 11 predictors (age, height, weight, systolic and diastolic blood pressure, cholesterol, glucose, smoking, alcohol, and physical activity). Age was converted from days to years, and implausible outliers were excluded. New features such as body mass index (BMI), pulse pressure (sbp_hi – dbp_lo), and categorical age bins were engineered to improve clinical interpretability. To address class imbalance, we applied Synthetic Minority Over-Sampling with Nominal and Continuous features (SMOTENC), generating a balanced dataset of 1 million records. Two ML models, XGBoost and HistGradientBoostingClassifier, were trained using RandomizedSearchCV with stratified k-fold cross-validation. Model performance was evaluated via accuracy, F1-score, and confusion matrices. Results: XGBoost achieved the highest overall accuracy (90.94%) and F1-score (0.91) across both classes, outperforming HistGradientBoostingClassifier (accuracy 80.68%). Incorporating engineered variables improved interpretability, while synthetic oversampling effectively mitigated class imbalance. The optimized XGBoost model demonstrated a 6% performance improvement over baseline implementations, underscoring the importance of robust preprocessing and hyperparameter tuning. Conclusions: Feature-engineered and balanced ML models significantly improve CAD prediction accuracy compared with traditional methods. These data-driven approaches can support clinical decision-making by identifying high-risk individuals earlier and more precisely. Future work will integrate genetic, socioeconomic, and wearable device data to refine personalized prevention strategies and expand this framework to other chronic disease domains.

Gustatory sensing by ovipositor drives maternal avoidance of hesperidin to benefit the offspring in a major agricultural fly pest

Proceedings of the National Academy of Sciences Bao Dong, Yuanyuan Peng, Ruohan Kou et al. Mar 24, 2026 DOI: 10.1073/pnas.2526937123

Females of the oriental fruit fly ( Bactrocera dorsalis ) disproportionately oviposit in unripe fruits, despite their lower nutritional value compared to ripe fruits, but the sensory cues driving such counterintuitive site selection have not been determined. Here, using an oriental fruit fly–mango interaction system, we identified a specific flavonoid compound, hesperidin, as a major avoidance cue driving oviposition site selection in this species. Hesperidin accumulates as mango fruits ripen, and high concentrations suppress both larval growth and adult emergence. This indicates that higher levels of hesperidin exert a direct harmful effect on B. dorsalis larvae within ripe fruits. Interestingly, we found that B. dorsalis females perceive hesperidin via gustatory sensors on the ovipositor. The BdorGr28b gene is strongly expressed in the ovipositor, and we showed that the corresponding protein is the major hesperidin receptor. These results demonstrate that gustatory sensing via the ovipositor drives maternal avoidance of hesperidin to benefit the offspring in B. dorsalis . Our study provides insight into oviposition site selection in this species and the broader functional repertoire of insect gustation.

An interdisciplinary rehabilitation program for adults with dementia—A randomized controlled pilot trial evaluating social participation, loneliness and mental health

PLoS ONE Josefine Lampinen, Håkan Littbrand, Ingeborg Nilsson et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345518

Background To meet the complex needs of adults with dementia, a team-based, individualized rehabilitation approach may be required. This randomized controlled pilot trial evaluated the feasibility of a person-centred multidimensional interdisciplinary rehabilitation program for older adults with dementia, in terms of follow-up and response rates, and potential short- and long-term effects in adults with dementia on social participation, loneliness, and mental health. Methods Participants (mean age (SD) 78.7 (±6.6) years), were randomized to an intervention group (n = 31) or usual care (n = 30). The rehabilitation program consisted of a 20-week rehabilitation period and two follow-ups after 5 and 14 months. An interdisciplinary team performed assessments and interventions based on the individual’s goals. Assessors blinded to group allocation performed structured assessments at baseline and after 5, 12, 24, and 36 months. Results Initially, response rates in participants with dementia were high for all assessments in the areas of social participation, loneliness, and mental health. Response rates after 12 months decreased, particularly for cognitively demanding questions with multiple-choice options in the area of social participation. Overall, there were few statistically significant differences between the groups in the outcomes over 36 months, but some of the findings seemed potentially clinically meaningful in favor of the intervention group: increased frequency of active recreation and organized social activities outside the home, as reported by both participants with dementia and caregivers or staff; as well as experienced more frequent visits to family and friends; and short-term reduction in depressive symptoms. Conclusions Assessments made of loneliness and mental health in this study over three years seemed feasible. It seemed cognitively demanding for participants with dementia to answer questions regarding social participation over time; therefore it seemed worthwhile to also ask informal caregivers or staff to avoid data loss. The positive findings noted during assessments and potential effects indicate that it is relevant to proceed further to an adequately powered RCT and conducted in additional geographical regions. Trial registration ISRCTN – The UK’s Clinical Study Registry: http://www.isrctn.com/ISRCTN59155421

PAM-VT 2 Study: Long-Term Scar Evolution and Ablation Lesion Assessment by Late Gadolinium Enhancement Cardiac Magnetic Resonance After Ventricular Tachycardia Ablation

Circulation Ivo Roca-Luque, Paz Garre, Sara Vázquez-Calvo et al. Mar 24, 2026 DOI: 10.1161/circulationaha.125.074748

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is useful for identifying ventricular tachycardia (VT) substrate in patients with structural heart disease. While preprocedural LGE-CMR is widely used for planning, the role of postprocedural LGE-CMR in evaluating VT ablation success and long-term scar evolution has been less explored. This study aimed to prospectively and systematically assess the long-term evolution of scar and ablation lesions using serial postablation LGE-CMR with long-term follow-up. METHODS: This prospective study included 51 patients (mean age, 65.2±9.8 years; men, 95.8%; ischemic heart disease, 83%; left ventricular ejection fraction, 34.5±10.4%) undergoing their first substrate-based VT ablation between March 2019 and July 2020. Preprocedural LGE-CMR and 2 postprocedural scans at 3 to 6 months (CMR-1) and 18 to 24 months (CMR-2) were performed. Scar characteristics, including core scar, border zone, and conducting channels, were analyzed. VT recurrence was monitored, and factors associated with recurrence were evaluated using a Cox proportional hazards model. A Kaplan-Meier curve was used to represent the VT-free survival function. RESULTS: Core scar mass increased significantly from baseline to CMR-1 (12.2±1.5 to 19.8±1.6 g, P &lt;0.01) and remained stable at CMR-2. In contrast, the border zone decreased significantly over time (pre, 25.3±1.8 g; CMR-1, 20.8±2.0 g; CMR-2, 16.7±2.1 g; P &lt;0.01). A significant decrease in conducting channels was noted after ablation and persisted at CMR-2 (pre, mean 2.4±0.2/median 2 [interquartile range, 1–3]; CMR-1, mean 1.4±0.2/median 1 [interquartile range, 0–1]; CMR-2, mean 1.6±1.0/median 1 [interquartile range, 0–1]; P &lt;0.001). VT recurrence occurred in 29.4% of patients during a median follow-up of 3.1 years. The number of conducting channels at CMR-1 and their relative reduction from baseline were related to VT recurrence. The persistence of 2 or more conducting channels at CMR-1 was associated with a higher recurrence rate: 75.6 versus 19.5% (hazard ratio [HR]; 4.1; 95% CI, 2.4–12.1; P =0.012). Evidence of favorable left ventricular remodeling was observed, with a significant reduction in left ventricular volume at CMR-2 (131.8±8.6 mL; CMR-1, 156.7±8.1 mL and 160.8±7.6 mL at baseline &lt;0.01). CONCLUSIONS: Postablation LGE-CMR reveals durable changes in scar characteristics, with early scar evaluation at 3 to 6 months strongly associated with long-term VT recurrence. The reduction in scar heterogeneity and conducting channels is sustained over time, underscoring the usefulness of LGE-CMR for assessing ablation success. Additionally, VT ablation appeared to be associated with favorable reverse remodeling, highlighting potential benefits beyond arrhythmia control. These findings support the use of LGE-CMR for personalized management following VT ablation.

Abstract 61: Association of Cumulative Blood Pressure Elevation During Young Adulthood With Cardiovascular and Kidney Outcomes in Midlife.

Circulation Dasom Son, Kyoung Hwa Ha, Hyeok-Hee Lee et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.61

Introduction: While non-optimal blood pressure (BP) is the most common modifiable risk factor preceding cardiovascular disease (CVD), the cumulative impact of early-life elevated BP on premature CVD and particularly kidney outcomes remains less understood. We hypothesized that higher cumulative BP through young adulthood was associated with higher risks of CVD and kidney events in midlife. Methods: From the Korean National Health Insurance Service database, we included adults aged 40 years without prior CVD or CKD who had ≥3 health examination records with BP measurement: at age 30 (2002–2004), age 40 (2012–2014), and ≥1 in between (median, 8 visits total). For each participant, cumulative BP was calculated as the area under the serial BP-time curve from age 30 to 40 (mm Hg × years) and analyzed in quintiles or as a continuous variable using linear or restricted cubic spline terms. Outcomes were incident CVD (myocardial infarction, ischemic stroke, heart failure, or cardiovascular death) events, kidney events (incident CKD, kidney replacement therapy, or kidney-related death), and the composite of CVD or kidney events after age 40. Results: Among the 291,887 participants included, 3,894 CVD events, 2,902 kidney events, and 6,698 composite CVD or kidney events occurred over a median follow-up of 10.2 years after age 40. Cumulative incidence and multivariable-adjusted HRs of all outcomes increased monotonically toward higher quintiles of cumulative SBP and DBP from age 30 to 40 (Figure 1). Each 100 mm Hg × year higher cumulative SBP (e.g., 10 mm Hg higher × 10 years) was associated with 27% (HR, 1.27; 95% CI, 1.23–1.32) higher hazard of CVD events and 22% (HR, 1.22; 95% CI, 1.17-1.28) higher hazard of kidney events. Each 50 mm Hg × year higher cumulative DBP (e.g., 5 mm Hg higher × 10 years) was associated with 20% (HR, 1.20; 95% CI, 1.17–1.23) higher hazard of CVD events and 16% (HR, 1.16; 95% CI, 1.13-1.20) higher hazard of kidney events. All associations showed a log-linear, dose-dependent pattern (Figure 2). The associations were similar by sex and for composite CVD or kidney events and subtypes and remained significant after adjustment for single-visit BP at age 40. Conclusions: Higher cumulative BP in young adulthood was associated with increased risks of CVD and kidney events in midlife, highlighting the importance of maintaining optimal BP throughout early life.

Wolves fear humans but learn quickly about us

Proceedings of the National Academy of Sciences Daniel T. Blumstein Mar 24, 2026 DOI: 10.1073/pnas.2602695123

Nickel price forecasting based onempirical mode decomposition and deep learning model with expansion mechanism

PLoS ONE Jiaolong Li, Zhaoji Yu, Jichen Zhang et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0341559

As a critical material for stainless steel production, electric vehicle (EV) batteries, and advanced technology alloys, nickel plays a pivotal role in the global energy transition, with its strategic value becoming increasingly evident. This study presents a novel hybrid forecasting framework that combines Ensemble Empirical Mode Decomposition (EEMD) with a Dilated Long Short-Term Memory (Dilated LSTM) network to address the high uncertainty and complexity of nickel price fluctuations. By leveraging EEMD for multi-scale decomposition and Dilated LSTM for advanced temporal feature extraction, the proposed EEMD-DilatedLSTM model is designed to enhance predictive precision across different time horizons.Empirical results demonstrate that the proposed model outperforms benchmark algorithms in both short-term and medium-to-long-term prediction of nickel futures prices. Ablation studies validate the effectiveness of the hybrid architecture, and interpretability analyses highlight the decisive influence of low-frequency components in medium-to-long-term forecasting. Additionally, the Shapley value of copper price fluctuations is identified as a key driver, emphasizing its transmission effect on nickel prices.This study provides a robust methodological framework for strategic metal price forecasting, offering valuable insights for risk management in resource-driven enterprises and informing evidence-based industrial policy design by governments.

Abstract TU112: SGLT2 inhibitors Improve Cardiovascular Outcomes in Patients with Transthyretin Amyloid Cardiomyopathy

Circulation Muhammad Sohaib Asghar, Sana Murtaza, Muhammad Maaz Bin Rehan et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu112

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in cardiovascular-kidney-metabolic diseases, but the high-risk population of patients with transthyretin amyloid cardiomyopathy has been traditionally excluded from its trials (ATTR-CM). Tafamidis remains the only approved treatment, but its limited availability and high residual mortality demand alternative therapies. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the outcomes of patients with ATTR-CM. Hypothesis: SGLT2i might improve cardiovascular outcomes in patients with transthyretin amyloid cardiomyopathy. Methods: A comprehensive search of Medline, Google Scholar, Clinical trial registries, and the Cochrane Library was conducted up to October 2025. Study selection and data extraction were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses. Results: A total of eight studies (8451 participants, six propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.34-0.7], cardiovascular mortality (HR 0.39, 95% CI 0.23-0.65), and heart failure hospitalizations (HFHs) (HR 0.64, 95% CI 0.54- 0.76) compared to non-use. SGLT2i preserved renal function by significant attenuation of decline in estimated GFR (MD: 3.34 ml/min/1.73 mm2, 95% CI: 0.75, 5.94). SGLT2i also reduced cardiac wall stress with attenuation of the increase in pro B BNP levels (MD: -424.48 from baseline compared to control, 05% CI: -803.54, -45.41). Conclusions: The use of SGLT2 may confer cardiorenal protection in patients with ATTR-CM with significant potential to reduce morbidity and healthcare utilization. These findings highlight SGLT2i as a viable adjunct to existing therapies like tafamidis and warrant further investigation through adequately powered, long-term RCTs randomized trials.

Abstract WE548: Greater Cardiovascular Risk Is Associated with Higher Liver Dysfunction: An NHANES Analysis Using FIB-4 and PREVENT Equations

Circulation Raymond Truong, Angel Gutierrez, Adrian Bacong et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we548

Background: Cardiovascular disease (CVD) and liver dysfunction share metabolic pathways involving systemic inflammation and dysregulation. While evidence suggests liver dysfunction contributes to increased CVD risk, it is unclear whether individuals with higher predicted CVD risk also have poorer liver function. Hypothesis: We hypothesized that individuals with higher predicted CVD risk, assessed by the PREVENT equation, would also have poorer liver function, measured by the non-invasive Fibrosis-4 (FIB-4) index. Methods: We conducted a cross-sectional analysis of pooled NHANES 2011–Pre-pandemic 2020 data. Eligible participants (n=12,733) with complete data for both PREVENT and FIB-4 scores were included. PREVENT scores estimated 10-year CVD risk; FIB-4 was calculated using age, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Platelet counts. Associations were examined using weighted linear regression, with PREVENT and FIB-4 modeled bidirectionally. Results: Higher PREVENT risk was significantly associated with elevated FIB-4 scores (β = 0.07; 95% CI: 0.06, 0.08; p &lt; 0.001), and higher FIB-4 was associated with increased PREVENT risk (β = 2.17; 95% CI: 1.16, 3.19; p &lt; 0.001). Risk increased progressively across categories of both scores (all p&lt;0.001). Conclusions: Higher predicted CVD risk is linked with poorer liver function, and higher FIB-4 scores independently predict increased CVD risk. Integrating liver function into CVD risk prediction models may improve long-term risk stratification and patient outcomes.

The α-synuclein proteostasis network and its translational applications in Parkinson’s disease

Proceedings of the National Academy of Sciences Christine M. Lim, Michele Vendruscolo Mar 24, 2026 DOI: 10.1073/pnas.2513317123

Parkinson’s disease (PD) is a debilitating neurodegenerative condition that results in a loss of mobility and muscle control. A neuropathological hallmark of PD is the presence of aberrant inclusions, known as Lewy pathology, of which α-synuclein (α-Syn) is a major component. The accumulation of α-Syn may be due to an imbalance in the proteostasis system regulating α-Syn. To investigate this hypothesis, we delineated the proteostasis network (PN) of α-Syn in the human substantia nigra at the proteomic and transcriptomic level. We then defined an α-Syn proteostasis activity score (PAS) that quantifiably describes the relative activity of the α-Syn PN in promoting or inhibiting α-Syn aggregation. We report a corresponding PAS signature indicative of disease state, age-of-death in PD patients, and brain regional vulnerability to α-Syn aggregation in PD and healthy brains. After establishing the relevance of our network to PD, we developed a transcriptome-derived network model as an operational digital twin of the α-Syn PN in human substantia nigra cells from single-cell data and used it to prioritize candidate targets for PD. We then further showed the application of the α-Syn PN toward facilitating drug repurposing. Overall, this proof-of-concept study illustrates how our computational framework can identify and prioritize putative therapeutic targets and repurposing candidates for PD, providing testable hypotheses for experimental validation.

Integrating natural gradients and controlled assays to reveal bacterial responses to cadmium in Theobroma cacao L., soils

PLoS ONE Claudia Jaramillo-Mazo, Daniel Bravo, Diego Fernando Villanueva-Mejía et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345645

Cadmium (Cd), a toxic heavy metal found in agricultural landscapes worldwide, has been pointed out in cropped soils with Theobroma cacao L., as one of the main contaminants that translocate into plant tissues. Among the factors linked to cadmium translocation into plants, the role of soil bacterial communities in chemical transformation in soils has been poorly investigated. Overall, soil bacterial communities are shaped by diverse environmental and anthropogenic factors that influence crop yield and health. Cadmium alters soil microbial communities and increases the risk to human health through plant uptake. Although the impacts of cadmium on soil bacteria have been studied in other crops, there is limited information on cacao. Thus, this study aimed to assess the responses of soil bacterial communities in cacao farms to cadmium exposure, both natural and spiked. A total of 225 rhizosphere soil samples were collected from 16 plots across five cacao farms in two Colombian departments. The complementary approaches used were: (i) 16S rDNA amplicon sequencing to assess the composition of the bacterial community in soils with natural Cd concentrations, and (ii) isothermal microcalorimetry (IMC) to measure the temporal metabolic responses of bacteria to Cd in closed systems for 80 hours at 25 °C. The findings suggest that nearly 28% of the bacterial community responds to high cadmium concentrations in soils, both in natural and experimental conditions. Field-based observations revealed that Cd-responsive taxa detected under natural soil conditions included several unculturable bacterial groups, whereas laboratory experiments with Cd spiking predominantly selected for previously characterized cadmium-tolerant bacteria (CdtB). Significant variation in natural Cd-bacterial community composition and Cd-related metabolic activity was observed across the farms. Moreover, Cd-responsive bacterial taxa exhibited increased abundance during Cd spikes. As expected, contrasting patterns were revealed by the activity-response measured by IMC and taxonomic analyses of 16S rRNA gene sequences.

Abstract TU121: Life’s Essential-8 Cardiovascular Health Metrics, Carotid Intima-Media Thickness, and Carotid Plaque: A Cross-Sectional Study among Japanese Men

Circulation Rajib Mondal, Aya Kadota, Sayuki Torii et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu121

Introduction: The American Heart Association’s new Life’s Essential-8 (LE8) metrics is considered a comprehensive framework for pursuing optimal cardiovascular health (CVH). However, its relationship with carotid atherosclerotic plaque is inadequately studied globally and not clarified in Asians. Hypothesis: We assessed the hypothesis that LE8 CVH is associated with carotid intima-media thickness (CIMT) and carotid plaque among Japanese men. Methods: We cross-sectionally analyzed data from 938 randomly selected asymptomatic men aged 40-79 years participating in the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), Kusatsu, Shiga, during 2006-2008. Utilizing diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure metrics, we quantified and categorized LE8 CVH (high, 80-100 points; moderate, 50-79 points; and low, 0-49 points) as the exposure. Ultrasonography-derived intima-media thickness (IMT) and plaque numbers were quantified from the right and left common carotid artery (CCA) to the internal carotid artery via the carotid bifurcation. The average of these segment-specific IMT values was calculated and defined as the mean CIMT. The prevalence of increased CIMT (mean IMT &gt;1 mm), increased IMT in CCA (mean IMT in CCA &gt;1 mm), and carotid plaque (plaque count ≥1), and the plaque burden (total count) were evaluated as the outcomes. Multivariable (adjusted for age and family history of cardiovascular disease) modified Poisson regression and negative binomial regression analyses were used. Results: Participants (mean [SD] age, 63.7 [10.0] years) had a prevalence of high, moderate, and low CVH of 16.7%, 77.6% and 5.6%, respectively. The prevalences of increased CIMT, increased IMT in CCA, and carotid plaque were 15.0%, 12.6%, and 77.5%, respectively. Compared to individuals with high CVH, those with moderate and low CVH had a higher risk (risk ratio [95% confidence interval]) of increased CIMT (2.06 [1.23-3.43] and 3.04 [1.53-6.05], respectively), increased IMT in CCA (2.01 [1.14-3.56] and 2.87 [1.28-6.46], respectively), and carotid plaque (1.09 [0.99-1.20] and 1.17 [1.01-1.36], respectively), and had a relative increase in the expected plaque counts (1.34 [1.14-1.59] and 1.65 [1.24-2.18], respectively). Conclusions: Lower LE8 CVH is associated with a higher risk of CIMT and carotid plaque in Japanese men. Healthy lifestyle practices may reduce the risk of subclinical carotid atherosclerosis.

Abstract TH940: Enhancing Patient Safety Through Health Literacy: A Quantitative Outcomes Study of the P.L.A.N. Counseling Tool in People Experiencing Homelessness

Circulation Esha Kanna, Shreyas Saride, Avaneesh Rade et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th940

Introduction: Low health literacy is a significant barrier to chronic disease management and patient safety, leading to poor medication adherence and increased adverse events. These issues are particularly pronounced among people experiencing homelessness, who face disproportionate challenges with uncontrolled hypertension. This study evaluates whether a structured, low-resource counseling tool can improve hypertension health literacy and self-efficacy in this high-risk population. Methods: A pre-test and post-test design was used with twelve adult male residents of the Union Gospel Mission (UGM) Calvert men's shelter in Dallas. Each participant received a one-on-one session using the P.L.A.N. (Problem, Life Impact, Actions, Need for Help) framework, designed to facilitate simple, patient-centered dialogue. Surveys assessing objective hypertension knowledge and subjective self-confidence were completed directly before and after the intervention. The post-survey also measured satisfaction with the tool through dichotomous and open-ended questions. Paired t-tests were used to analyze changes in scores. Results: Use of the P.L.A.N. tool led to significant gains in both domains. Mean knowledge scores increased from 66% to 89.3% (p = 0.0001). Mean confidence scores improved from 65% to 83% (p = 0.0047). Qualitative feedback was unanimously positive with 100% of participants indicating they would reuse the worksheet and that it enhanced their understanding and empowerment. All data was collected at the Dallas UGM Calvert shelter and the sample size was twelve. Conclusions: In conclusion, the P.L.A.N. tool is a promising, resource-efficient intervention for improving health literacy and patient-centered outcomes in underserved populations, directly addressing safety risks linked to low literacy rates. Despite limitations of sample size and single-site design, these results support further research in larger, diverse settings and with longitudinal tracking of clinical outcomes, including sustained medication adherence and blood pressure control. This framework offers a replicable, practical method for empowering vulnerable patients and enhancing patient safety.

The potential for onshore wind repowering to hasten the energy transition in the United States

Proceedings of the National Academy of Sciences Andreas Mühlbauer, Yuanbei F. Fan, Daniel J. Sambor et al. Mar 24, 2026 DOI: 10.1073/pnas.2521050123

This study explores whether repowering onshore wind farms will help the United States (US) meet a much larger share of its current electricity demand with wind. Repowering upgrades existing wind farms with new turbines, increasing wind-farm capacity and electricity generation, with less new land requirements than greenfield projects. We analyze the US Wind Turbine Database and project the potential of US wind repowering under different scenarios. Results show that repowering alone could more than double the current US onshore wind nameplate capacity, from 153 GW to ~314 GW, at existing farms. The resulting annual onshore wind electricity generation could increase from 453 TWh in 2024 to ~911 TWh for the same weather year after repowering the fleet. Repowering could allow onshore wind to meet 21%, instead of 10.5%, of 2024 US electricity demand. Repowering is a potential multi-billion-dollar industry in the United States.

Voiding symptoms aggravate with decreasing stromal/epithelial ratio and increasing glandular-epithelial content in patients undergoing laser enucleation for benign prostatic hyperplasia, independently from prostate size

PLoS ONE Patrick Keller, Sheng Hu, Wenbin Zhu et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345306

Introduction Benign prostatic hyperplasia (BPH) includes epithelial, stromal and mixed hyperplasia, but their specific contributions to voiding symptoms and prostate volume (PV) are unknown. Here, we examined relationships of symptoms and PV with stromal and epithelial markers in patients undergoing laser enucleation for BPH. Methods Tissues were obtained from holmium or thulium laser enucleation of the prostate (n = 146 patients). Expressions of the smooth muscle marker calponin-1 (CNN1) and the glandular-epithelial cell marker keratin-19 (KRT19) were assessed by RT-PCR and Western blot, and analyzed for correlation with international prostate symptom score (IPSS), maximum urinary flow rate (Q max ), and PV. Results The ratio of CNN1/KRT19 mRNA correlated positively with Q max (r = 0.3809, p = 0.0263), and by trend negatively with IPSS (r = −0.2161, p = 0.0944). Accordingly, the IPSS increased with keratin protein expression (r = 0.4244, p = 0.0307), while the Q max tended to correlate negatively with keratin expression (r = −0.2058, p = 0.4999). PV correlated negatively with CNN1 mRNA expression (r = −0.205, p = 0.0405). The inverse correlation of CNN1 with PV persisted in patients without catheterization (r = −0.2568, p = 0.0457), but was lacking in catheterized patients after separated analyses. Conclusions Voiding symptoms in patients undergoing laser enucleation for BPH aggravate with increasing keratin content. Symptoms in patients needing surgery for BPH depend rather on glandular-epithelial hyperplasia, but not on stromal hyperplasia, what might explain why these patients are refractory to treatment with α 1 -blockers.

Abstract WE493: Intersections of Social Determinants, Food Insecurity, Diet Quality, and Mental Health in Mortality Risk: Joint and Mediating Effects

Circulation Shuyue Deng, Lu Wang, Caroline Owens et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we493

Background: Poor nutrition is a major contributor to disease and mortality, and intersects with food insecurity, broader social determinants of health (SDOH), and mental health. However, few studies have examined how these factors jointly shape mortality risk or mediate each other. Objective: To evaluate independent and mediating relationships among diet quality, food insecurity, SDOH, and mental health in relation to mortality among U.S. adults. Methods: Ten cycles of the National Health and Nutrition Examination Survey (1999–2018) were linked to the National Death Index. Diet quality was assessed using the Alternative Healthy Eating Index–2010 (AHEI-2010). Food insecurity was defined from the U.S. Household Food Security Survey Module. SDOH were summarized in a composite score (range: 0-8), including income, education, employment, insurance, SNAP participation, marital status, and homeownership. Mental health was represented using depressive symptoms and sleep indicators, each evaluated separately as sensitivity analyses. Demographic-adjusted Cox models evaluated the independent associations of diet quality, food insecurity, SDOH, and mental health with all-cause mortality, and their mediating effects. Additional analyses examined the extent to which prevalent cardiometabolic conditions mediated the diet–mortality association. Results: In multivariable models, each higher SDOH unit was associated with 14% higher mortality. Food insecurity mediated 20% of this association; diet quality, 12%; and depressive symptoms, 5%. Adjusting for SDOH, food insecurity was associated with 77% higher mortality, mediated by diet quality (1%) and depressive symptoms (7%). Evaluating all factors jointly, each higher SDOH unit was associated with 19% higher mortality; each 10 units of AHEI-2010, 9% lower; food insecurity, 79% higher; depressive symptoms, 36% higher; and sleep trouble, 34% higher. Conclusions: Diet-related metrics mediate a relatively small proportion of mortality risk related to SDOH but are themselves independently associated with mortality. Diet quality and depressive symptoms are not major downstream mediators of the food insecurity-mortality relationship but rather reflect independent risks. These new findings suggest a need to address each of these important risks to poor health, without assuming that policies to address one will address the others.