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Abstract WE525: Longitudinal changes in visceral adiposity, glycemic traits, and inflammatory proteomic profiles

Circulation Cong Wang, Azam Yazdani, Olga Demler et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we525

Central obesity is related to an elevated risk of type 2 diabetes (T2D) and cardiovascular diseases (CVD), partly through chronic inflammation caused by metabolically active visceral adipose tissue (VAT). However, how changes in VAT modulated secretion of circulating inflammatory proteins and its interplay with glycemic control remain unclear. Our study aims to investigate the associations of concurrent longitudinal changes in VAT, glycemic control, and inflammatory proteomic profiles in a well-phenotyped cohort of middle- to older-aged US adults, to help elucidate mechanisms underlying obesity and risk of T2D and CVD. We analyzed 562 participants (age 63.7±6.1) in the prospective VITamin D and OmegA-3 TriaL (VITAL) study with baseline and 2-year data for DXA-derived VAT mass, plasma proteomics (Olink Explore 384 inflammation panel), and glycemic traits: fasting glucose, hemoglobin A1c (HbA1c), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). We computed within-person 2-year changes (Δ) in VAT and glycemic traits and assessed their associations with individual Δproteins using multivariable linear models adjusting for baseline exposure and protein levels, demographics, lifestyle factors, and VITAL treatment group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. Over 2 years, participants had a non-significant increase in VAT mass (mean=9.1g, p=0.66), glucose (mean=1.26mg/dL, p=0.09), HbA1c (mean=0.03%, p=0.24), and HOMA-IR (mean=1.26, p=0.11). VAT gain was significantly associated with concurrent changes in 34 inflammatory proteins (false discovery rate [FDR]<0.05), including increases in FSTL3, HGF, IL18R1, and decreases in IL17RB, and CD276. Among them, 19 proteins were also related to Δglucose, 11 with ΔHbA1c, and 25 with ΔHOMA-IR; CD22, ENPP7, IL18R1, LGALS9, LILRB4, SERPINB8, SIGLEC1, TLR3, TREM2 were shared across all glycemic traits. Proteins related to ΔVAT were enriched onto the cytokine-cytokine receptor interaction pathway. Longitudinal VAT change and concurrent changes in glycemic control were accompanied by distinct proteomic changes reflective of inflammation, particularly through cytokine signaling. These findings underscore a potential biological link between VAT change, metabolic dysregulation, and inflammation, highlighting VAT as a promising upstream intervention to target in T2D and CVD prevention.

Enhancing tensile strength of 3D-printed wood-PLA composites via a particle swarm optimization framework

PLoS ONE Biplab Bhattacharjee, P. Mathiyalagan, Koushik V. Prasad et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0344945

In the evolving landscape of additive manufacturing, this study pioneers the optimization of FDM (Fused Deposition Modelling) parameters to enhance the tensile performance of eco-friendly Wood-PLA composites. Leveraging the systematic Taguchi L9 orthogonal array, the investigation explored the synergistic effects of three critical printing factors: layer thickness (0.1, 0.2, 0.3 mm), infill density (25%, 50%, 75%), and nozzle temperature (190°C, 200°C, 210°C), across distinct infill patterns such as Triangular, Cubic, and Zig-zag. Unique to this work is the strategic composition of the bio composite filament comprising 80% polylactic acid (PLA) reinforced with 20% wood fibres, reflecting a sustainable material innovation. The mechanical behaviour was characterized through ISO 527 tensile testing, while Scanning Electron Microscopy (SEM) provided microstructural insights into fibre distribution and interlayer bonding. The key optimized parameters layer thickness (0.1 mm), infill density (75%), nozzle temperature (210 °C), and cubic infill pattern are explicitly stated early, along with the corresponding maximum tensile strength of 46.41 MPa, as statistically validated by Analysis of Variance (ANOVA). The reported 28% improvement is now clearly defined as being relative to the average tensile strength of non-optimized printing configurations. This research advances the understanding of process-property relationships in bio composite 3D printing, offering a validated framework for fabricating mechanically robust, environmentally sustainable components. This study directly supports the Sustainable Development Goals (SDG 9: Industry, Innovation and Infrastructure; SDG 12: Responsible Consumption and Production) by promoting sustainable additive manufacturing.

Abstract TU156: A Single Hypertensive Measurement Independent of an Average of Three Measurements is Associated with a Higher Risk of Cardiovascular Disease

Circulation Ashley Berlot, Benjamin Grobman, Hannah Col et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu156

Background: Hypertension (HTN) guidelines recommend averaging up to three blood pressure (BP) measurements. However, it is unclear how to interpret risk for cardiovascular disease (CVD) when only one of the three measurements indicates hypertension. Hypothesis: A single seated HTN reading will be associated with CVD events and mortality, independent of HTN, based on the average of three measurements. Methods: Atherosclerosis Risk in Communities (ARIC) is a prospective cohort of adults 45-64 years old, followed for CVD events and mortality. During Visit 1 (1987-1989), participants underwent three consecutive seated BP measurements (after a five-minute rest; each separated by one minute). Our primary exposure was the number (zero to three) of HTN measurements, defined as systolic BP (SBP) > 130 mmHg. This analysis excluded adults with CVD at baseline. We determined the number of times systolic HTN was observed overall and in strata of HTN treatment. In addition, we examined the association between number of HTN measurements and outcomes using cumulative incidence plots. We also used multivariable-adjusted Cox proportional hazard models to determine the association of number of systolic HTN measurements or HTN based on the average of the three measurements with CVD and all-cause mortality. Results: Participants (N=13095) had a mean (SD) age of 54 (6) years old. The sample was 56.2% female and 25.3% Black, with an average SBP of 121 ± 18 mm Hg across the three measurements. Of those with HTN from the average of three measurements, 79 (7.9%) had only one HTN measurement and 577 (70.2%) had two HTN measurements ( Table 1) . A greater number of HTN measurements was associated with higher risk of CVD or mortality ( Figure) . A single HTN measurement was associated with CVD or mortality risk regardless of HTN based on the mean SBP ( Table 2) . A count of three HTN measurements was more strongly related to CVD than the average when mutually adjusted. Interactions for treatment status were non-significant across outcomes. Conclusion: Among this population of middle-aged, community dwelling adults, a single occurrence of systolic BP > 130 mmHg was associated with higher risk of CVD or mortality independent of HTN based on the mean SBP. Future work should evaluate whether treatment of adults with a single HTN measurement, but no HTN based on a mean SBP, reduces their risk of CVD.

Abstract MPTH58: The Impact of Postpartum Remote Blood Pressure Monitoring on Hospital Readmission

Circulation Sharon Casey, Ema Mujic, Idalis Chestnut et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.mpth58

Introduction: Postpartum hypertension is a leading cause of severe maternal morbidity and mortality. Approximately half of those with hypertensive disorders of pregnancy (chronic hypertension, preeclampsia, gestational hypertension) remain hypertensive after delivery and are at an increased risk of being readmitted to the hospital postpartum. Postpartum remote blood pressure monitoring (RBPM) may be an effective tool to reduce hospital readmission rates. Hypothesis: Postpartum RBPM reduces both short-term (30 day) and long-term (1 year) hospital readmission rates. Methods: We conducted an electronic medical record (EMR) based cohort study. We included patients who delivered between 2021-2023 with hypertensive disorders of pregnancy and were enrolled in an RBPM program (RBPM group). We used a comparison group of patients who delivered at the same hospital between 2016-2018, prior to the RBPM program (pre-implementation group), who would have been eligible to participate had the program been in place. Sociodemographic and pregnancy data were abstracted from the patient EMR. For analyses, we included deliveries ≥20 gestational weeks among patients aged ≥18 years. We evaluated risk of short- and long-term hospital readmission for 1) all-causes and 2) hypertension-related reasons. Log-binomial regression estimated risk ratios (RR) and 95% confidence intervals (CI) for the effect of postpartum RBPM on hospital readmissions. Results: Among 4,948 patients (pre-implementation: n=2,807, RBPM: n=2,141), baseline characteristics were similar (non-Hispanic Black: 46% vs 46.3%, mean maternal age: 31 (SD 6.1) vs 30 (SD 6.1) years, respectively). The RBPM group had lower short-term readmission rates for all-causes (4.9% vs 5.7%) and hypertension-related reasons (4% vs 4.3%). The RBPM group also had lower long-term readmission rates for all-causes (6.9% vs 7.5%). In models adjusted for type of hypertensive disorder in pregnancy and age, the RBPM group had a lower risk of short-term readmission compared to the pre-implementation group (all-causes: RR 0.69 (95% CI 0.55, 0.89); hypertension-related: RR 0.70 (95% CI 0.53, 0.93)). The RBPM group was also less likely to be readmitted long-term compared to the pre-implementation group (all-causes: RR 0.76 (95% CI 0.62, 0.94); hypertension-related: RR 0.77 (95% CI 0.59, 0.98)). Conclusions: In a diverse, safety-net population, postpartum RBPM reduced hospital readmissions within 30 days and 1 year following hypertensive disorders of pregnancy.

Structural insight into the CUB2 domain’s role in enteropeptidase-mediated trypsinogen activation

Proceedings of the National Academy of Sciences Qiuyue Song, Lisi Peng, Xiaoli Yang et al. Mar 24, 2026 DOI: 10.1073/pnas.2521394123

Elucidating the structure and function of enteropeptidase (EP) is essential for advancing our understanding of its biological significance, particularly in regulating trypsinogen activation. Using cryo-EM and enzymatic activity, we uncovered the significance of the CUB2 domain in mediating the cleavage of macromolecular substrates. We identified crucial binding loops and key residues for EP’s proteolytic function. The mutation E574A enhanced the proteolytic activity of EP, whereas the mutation N619A diminished its cleavage efficiency, highlighting the importance of surface-charged interactions in modulating EP’s activity. A proteolytic cycle was proposed to deepen our understanding of the trypsinogen activation by EP. This work offers valuable insights into the molecular mechanisms underlying EP’s interaction with its substrate, and opens up avenues for therapeutically modulating EP-mediated proteolysis.

Association between diabetes mellitus and impaired single-leg stance in patients with chronic liver disease: A cross-sectional study

PLoS ONE Kenichi Fudeyasu, Makoto Asaeda, Toshihiro Kawae et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345407

Diabetes mellitus (DM) is highly prevalent among patients with chronic liver disease (CLD) and is associated with disease progression and complications. However, the impact of DM on physical function, particularly balance, in patients with CLD remains unclear. The aim of this study was to investigate the association between DM and physical function in patients with CLD, with a specific focus on impaired single-leg stance test (SLST). This retrospective study analyzed the medical records of patients with CLD at Hiroshima University Hospital between 2014 and 2017. Logistic regression analysis was performed to identify factors associated with impaired SLST. Receiver operating characteristic curve analysis was conducted to determine cutoff values for predictive factors. The analysis included 152 patients with CLD, of whom 78% had comorbid DM. Patients with DM had a significantly higher prevalence of impaired SLST than those without DM (20% vs. 0%, p = 0.002, Cramer’s V 0.23). In 118 patients with CLD who had comorbid DM, age (odds ratio [OR] 1.089, 95% confidence interval [CI] 1.020–1.177, p = 0.009), body mass index (OR 1.176, 95% CI 1.045–1.343, p = 0.006), and extracellular water-to-total body water ratio (ECW/TBW) (OR 1.065, 95% CI 1.003–1.138, p = 0.039) were significant independent factors associated with impaired SLST (Nagelkerke pseudo- R² 0.31, p < 0.001). The ECW/TBW had the highest predictive accuracy, with a cutoff value of 0.393 (area under the curve = 0.733, sensitivity = 73.9%, specificity = 68.8%). DM was associated with impaired SLST in patients with CLD, suggesting a decline in balance. Age, body mass index, and ECW/TBW are significant predictors of impaired SLST. An ECW/TBW ratio of 0.393 indicates “subclinical” edema in patients with CLD and DM and should be considered in the assessment of fall risk.

Abstract TH844: Beyond the heart: neuropsychiatric factors as leading risk markers for sudden cardiac arrest in the young

Circulation Thomas Laurenceau, Richard Chocron, Pierre Cezard et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th844

Background: Sudden cardiac arrest (SCA) in young adults, with survival rates below 15%, represents a major public health concern. Most cases occur in individuals without identifiable cardiac disease. Current prevention strategies, focused on cardiovascular risk factors, may therefore overlook key non-cardiac contributors. Methods: We conducted a population-based case–control study linking the exhaustive Paris Cardiac Arrest Center registry (2011–2020) to national electronic health records, including 1,061 SCA cases and 3,183 matched controls aged ≤40 years, and 21,199 cases with 63,597 controls aged >40 years. All prospectively collected medical diagnoses and prescriptions from the preceding five years were analyzed using an interpretable machine learning model (Explainable Boosting Machine). Age-specific risk markers were ranked by their relative contribution to model performance, and findings were externally validated in the Seattle–King County registry (2013–2021). Results: In young adults, neuropsychiatric drugs accounted for three of the top five predictors of SCA (antiepileptics, antipsychotics, and anxiolytics), while beta-blockers were the only cardiovascular marker among the top ten. In older adults, cardiovascular diseases and related treatments predominated. Model performance was robust (AUC = 0.74 [95% CI 0.70–0.78] in ≤40 years; 0.80 [0.79–0.81] in >40 years). The overrepresentation of neuropsychiatric factors in the young was confirmed in the U.S. validation cohort. Conclusion: Neuropsychiatric disorders and treatments emerged as major risk markers for SCA in adults under 40, underscoring the need to integrate them with cardiovascular factors and to promote interdisciplinary prevention strategies.

Abstract TU270: Sleep Disturbance and Risk of Cardiovascular Disease Hospitalization in Over Two Million Adults: Evidence From a Japanese Health Insurance Claims Database

Circulation Koki Ono, Aya Hirata, Takumi Hirata et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu270

Introduction: There is increasing evidence that sleep disturbances may lead to adverse cardiovascular disease (CVD) outcomes. Therefore, documenting sleep disturbances at health check-ups may improve CVD risk assessments. However, nationwide evidence in Asian populations remains limited. Objective: To investigate the association between sleep disturbances and incident CVD among individuals who underwent health check-ups using a nationwide Japanese medical claims database. Methods: A retrospective cohort study was conducted using the DeSC database (DeSC Healthcare, Inc), containing medical claims and check-up data from April 2014 to June 2024. Adults aged 40-74 years old who underwent a health check-up between April 2014 and May 2023 were enrolled and followed via linked insurance claims ensuring at least one year of follow-up data. Sleep disturbance was defined as those with regular use of sleep medication at baseline, serving as an indicator for serious insomnia symptoms. The primary outcome was a first CVD hospitalization event due to a CVD diagnosis (I00-I99) via the ICD-10. A multivariable Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD events associated with baseline sleep disturbances, adjusting for age, sex, diabetes, hypertension, dyslipidemia, obesity, smoking status, and alcohol intake. Subanalyses excluding those with baseline sleep apnea/narcolepsy, known independent risk factors of CVD, were also conducted. Model discrimination was evaluated using Harrell’s C-index. Results: A total of 2,014,700 individuals (mean age 59.4±10.0 years; 56.0% female) were included for analysis. At baseline, 99,514 (4.9%) participants had evidence of sleep disturbance. Mean follow-up was 45.6±30.7 months, during which 77,952 participants had a CVD event. Cox models displayed that baseline sleep disturbances were associated with an elevated risk of CVD compared to those without (HR: 1.71, 95% CI: 1.67-1.76). Results excluding those with sleep apnea/narcolepsy also produced consistent findings. The model had an acceptable C-index of 0.705. Conclusion: Individuals with sleep disturbances at baseline had a higher risk of developing CVD during follow-up. Sleep disturbances severe enough to require sleep medication may indicate underlying conditions associated with an elevated risk of CVD. These findings suggest that assessing sleep disturbances at health check-ups may be useful for future CVD risk stratification.

On the optimal integration of intelligent agents into network systems to steer cooperation

Proceedings of the National Academy of Sciences Feng Fu, Xingru Chen, Nicholas A. Christakis Mar 24, 2026 DOI: 10.1073/pnas.2537939123

Sociotechnical networks, in which humans and technologies act as interacting entities (also known as “hybrid systems”), increasingly face perturbations by automated agents. What this implies for immersive steering of collective behavior, and how this shapes the stability and resilience of cooperation, remain unclear. Here, we extend evolutionary graph theory by incorporating a distinct type of node representing embedded intelligent agents, namely, algorithmic nodes that autonomously implement prescribed behavioral responses during interactions. These agents are randomly placed within a social network and exert local influence in their neighborhood in social dilemma games. Individual behavior changes are driven by evolutionary dynamics. We derive closed-form analytical results characterizing evolutionary stability and long-run cooperation levels, and show that there exists an optimal, intermediate prevalence of intelligent agents that best promotes cooperation. Our work offers insights into the optimal alignment of human populations with respect to the social good using intelligent agents.

Formulation and in-vitro functional evaluation of a Bacillus-based multi-strain probiotic consortium relevant to protein-energy malnutrition

PLoS ONE Priya Mori, Ishita Modasiya, Mehul Chauhan et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345821

Protein-energy malnutrition (PEM) remains a critical global health challenge, characterized by impaired nutrient absorption and chronic gut inflammation. While probiotics offer a potential therapeutic avenue, the efficacy of single-strain interventions is often limited. This study aimed to formulate and evaluate a Bacillus -based multi-strain probiotic consortium (MSPC) specifically tailored for PEM. Three strains— Bacillus spizizenii BAB 7915, Bacillus tequilensis , and Bacillus rugosus -were selected based on their non-antagonistic, synergistic growth profiles. The MSPC demonstrated superior functional attributes compared to individual strains, exhibiting significant proteolytic activity (0.52 ± 0.03 U/mL) and robust anti-inflammatory potential (5.33 ± 0.06 U/mL). Additionally, the consortium showed high tolerance to gastrointestinal conditions and strong antioxidant properties. These results suggest that the MSPC can effectively enhance protein hydrolysis and mitigate gut inflammation, providing a scientifically validated, low-cost formulation for the nutritional rehabilitation of PEM patients.

Abstract 46: Daily Step Count Is Lower Across Perceived Physical Fatigability Severity Strata in Older Caribbean Men

Circulation Namhyun Kim, Iva Miljkovic, Reagan Garcia et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.46

Background: Perceived physical fatigability (i.e., fatigue experienced in response to activities of standardized intensity and duration) is a sensitive, person-reported outcome measure and strong prognostic indicator of age-related functional decline and cardiometabolic health. Modifiable lifestyle behaviors such as physical activity and sleep may influence fatigability. Evidence linking these lifestyle behaviors to fatigability in diverse older populations is limited. We examined accelerometer-measured daily activity and sleep by perceived physical fatigability severity among 205 African Caribbean men from the population-based Tobago Health Study. Methods: Men wore an ActiGraph CentrePoint Insight Watch for 7-days on their non-dominant wrist to measure activity and sleep. Daily step count was derived using the modified Verisense algorithm from the GGIR R package. Sleep measures were estimated with the HDCZA sleep detection algorithm during the nocturnal sleep period. Perceived physical fatigability was assessed using the Pittsburgh Fatigability Scale, modified for the Caribbean (PFS; range 0-50; higher PFS score=greater fatigability). PFS Physical scores were classified into 6 established severity strata. Results: Men were mean±SD 68.0±4.3 years old, overweight (BMI=27.7±5.1 kg/m 2 ), and had 1.03±0.23 m/s 4-meter gait speed. Mean PFS score was 20.0±8.1; prevalence of more severe fatigability (PFS≥15) was 71%. Daily step counts were lower by 51% across fatigability severity strata ranging from 11,586±4,376 (least severe) to 5,640±3,461 (most severe, PFS≥25) steps/d, p trend <0.001 (Table 1). Mean sleep duration (5.3±1.1 hours/d) and wake after sleep onset (1.4±0.6 hours/d) did not differ across fatigability severity strata, both p>0.15. Sleep regularity (i.e., day-to-day consistency of sleep-wake timing) differed across severity strata, p trend =0.02. Conclusion: Our novel data reveal an approximately two-fold higher burden of perceived physical fatigability in our Caribbean population, substantially greater than reported in age-comparable Caucasian men, despite high activity levels. Both lower daily activity and less regular sleep patterns were associated with fatigability severity, suggesting fatigability, a predictor of functional decline, may represent a multidimensional phenotype of lifestyle behaviors. Future work will extend to women and explore additional modifiable factors associated with perceived physical fatigability in African Caribbean populations.

Abstract TU144: The Rising Toll of Environmental Toxins: An Age-, Sex-, and Region-Stratified Analysis of Cardiovascular Disease Attributable to Lead Exposure Across 204 Countries (1990–2023)

Circulation Anusha Parisapogu, Asmita Gera, SHAHZAD AHMED SAMI et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu144

Background: Lead exposure (LE) remains a widespread environmental toxin with no known safe threshold and has been increasingly recognized as a modifiable risk factor for cardiovascular disease (CVD). Understanding its global burden is critical for informing prevention strategies and public health policy. Methods: We estimated the global CVD burden attributable to LE (1990–2023, 204 locations) using the GBD 2023 comparative risk assessment. Population Attributable Fractions (PAFs) were calculated by integrating blood lead levels and relative risks, then applied to estimate attributable deaths, YLDs, YLLs, and DALYs, stratified by standard demographics. Result: Between 1990 and 2023, total deaths due to CVD attributable to LE increased from 1.8 million (95% UI: 1.3–2.3) in 1990 to 3.4 million (2.5–4.2) in 2023. YLDs nearly doubled, rising from 1.8 million (1.1–2.6) to 3.7 million (2.2–5.5), while YLLs increased from 39.2 million (29.1–51.4) to 66.3 million (50.5–82.1). Regionally, age-standardized DALY rates declined across most areas, with the greatest annual reductions observed in High-income regions (AAPC: –3.41%) and Central Europe, Eastern Europe, and Central Asia (AAPC: –1.45%). In contrast, Low SDI regions showed an increasing trend (AAPC: +0.63%), indicating rising burden. The steepest increases in age-standardized DALY rates were observed in South Asia among those aged 95+ years (AAPC: +1.68%) and 90–94 years (+1.66%), while the most significant declines occurred in High-income regions, particularly among individuals aged 25–29 years (AAPC: –4.26%) and 30–34 years (–4.01%). Sex-stratified analysis demonstrated that females experienced a slightly larger decline in age-standardized death rates (AAPC: –1.12%) and YLLs (–1.23%) compared to males (–0.99% and –1.16%, respectively). However, YLDs declined marginally for both sexes (females: –0.42%; males: –0.48%). Conclusion: Despite global efforts to reduce environmental LE, the burden of CVD attributable to lead has continued to rise in absolute terms, with widening disparities across regions and demographic groups. While high-income regions have achieved notable reductions, older adults in low-income and South Asian settings are increasingly affected. These findings underscore the urgent need for equitable, targeted policies to eliminate LE and mitigate its long-term cardiovascular impacts, particularly in aging populations of low-resource settings.

Influence of extracellular magnesium ions on the functional state and biophysical and structural properties of connexin36 hemichannels

Proceedings of the National Academy of Sciences Aníbal García, Valeria Márquez-Miranda, Nicolás Bravo-Acuña et al. Mar 24, 2026 DOI: 10.1073/pnas.2538150123

Connexin36 (Cx36) is highly expressed in inhibitory and excitatory neurons as well as pancreatic β-cells, where it forms gap junction channels that coordinate metabolic and electrical responses. In addition, Cx36 forms hemichannels in pancreatic β-cells, where it may play a critical role in endocrine cell signaling. Despite this, the regulatory mechanisms and biophysical properties of Cx36 HCs remain poorly understood. Using HeLa cells lacking endogenous expression of large-pore channels and transfected with mouse Cx36-EGFP, we evaluated hemichannel activity through dye uptake assays and membrane current recordings. We found that Cx36 hemichannel activity is strongly inhibited by extracellular Mg 2+ , rather than Ca 2+ , in contrast to hemichannels formed by other connexins. Under reduced extracellular Mg 2+ , or under alkaline extracellular pH conditions, Cx36 hemichannels exhibited increased activity and allowed Ca 2+ influx, as detected by ratiometric dye FURA-2. Under low extracellular Mg 2+ conditions, Cx36 hemichannels exhibited increased permeability to small molecules and were blocked by La 3+ and quinine, but not by high glucose concentration. In-silico studies revealed interactions between Mg 2+ and two amino acid residues within a pore constriction (D47–E49), which alter the electrostatic potential of the hemichannel pore. Consistent with these observations, mutation of either amino acid residue to alanine (D47A or E49A) markedly reduced the inhibitory effect of extracellular Mg 2+ . Together, these findings offer critical insights into the regulation of Cx36 hemichannels and suggest that alterations in Mg 2+ homeostasis may have significant consequences for Cx36-mediated signaling.

Improving the composition of donor milk using machine learning and optimisation techniques

PLoS ONE Jacqueline Muts, Danée Knevel, Dick den Hertog et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345653

Background and aims The macronutrient composition of donor human milk (DHM) can vary substantially due to several factors such as maternal age, diet, and lactation duration. However, consistent macronutrient levels in DHM facilitate the administration of the required amounts to preterm infants. The current pooling strategy at most human milk banks combines milk from different batches from a single donor. This study aims to stabilize the macronutrient quality of DHM by pooling milk from different donors by utilizing machine learning prediction and optimisation techniques. Methods The current pooling strategy is compared with a new theoretical approach that pools milk batches from up to 5 donors. To predict the crude protein and energy content, we used the following variables: body mass index, the donor’s diet (vegetarian or non-vegetarian), maternal age, full-term or preterm delivery, lactation stage, and volume pumped. These predictions are then used within an optimisation model to create milk pools that minimize the deviations from the target macronutrient levels (1.0 g protein/100 mL and 70 kcal/100 mL). Results The prediction model is based on 2236 created single-donor pools from 480 donors. Random forest regression models provided the most accurate predictions of macronutrient content. The new pooling strategy using multiple donors shows reduced deviations from target values compared to the current single-donor approach (average total absolute deviation 0.402 versus 0.664). Conclusion This study proves the potential of data-driven methods to improve operational efficiency in human milk banks, and improving the consistency of donor human milk.

Abstract WE568: Place of Death for Cerebrovascular Mortality, 2018–2023: Hospice–Forward U.S. Trends From CDC WONDER

Circulation Tam Tran, Wei Jun Lee, Dang Nguyen et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we568

Background: Where cerebrovascular deaths occur reflects emergency access, end-of-life preferences, and palliative capacity. Whether hospice’s role changed during and after the pandemic is unclear. Hypothesis: Out-of-hospital (OOH) deaths rose in 2020 and stabilized thereafter; hospice’s share within OOH would not expand meaningfully post-2020. Methods: CDC WONDER Multiple Cause of Death (final, 2018–2023; I60–I69). Place of death was grouped as hospital (inpatient, emergency/outpatient, dead-on-arrival [DOA]) vs OOH (home, hospice facility, nursing/long-term care [LTC], other/unspecified). We computed annual counts, OOH share, and OOH composition (hospice, home, LTC). For adjustment, a binomial GLM (logit link) modeled OOH/(total) by Year, Sex, Race (Single-Race-6), Education with frequency weights; marginal year predictions were averaged by observed stratum totals. We explored small-cell instability with Beta–Binomial empirical-Bayes (EB) for Race×Year; subgroup cross-tabs were suppression-limited in U.S. totals. Results: There were 1,775,960 cerebrovascular deaths (2018–2023). OOH share was 80.0% (2018) , 81.7% (2020 peak) , 80.1% (2023) ; adjusted estimates closely matched crude ( 2018–2023 adj. range: 79.9%–81.7%), indicating trends were not explained by demographic shifts . Within OOH , hospice’s share was stable: 7.7% (2018) , 6.8% (2020) , 7.8% (2023) ; era means pre 2018–2019 vs post 2021–2023 were 7.7% vs 7.5% of OOH and 6.2% vs 6.0% of all deaths. By contrast, home deaths comprised a rising fraction of OOH ( 12.5% → 16.0% ; era means 12.6% → 16.7% ), while LTC was flat to slightly lower ( 15.8% → 15.4% ; era means 15.7% → 14.6% ). In hospitals, the mix shifted toward inpatient (92.9%→94.1%) and away from ER/outpatient (7.0%→5.9%); DOA ~0–0.1%. EB did not alter national conclusions given suppression in subgroup cross-tabs. Conclusions: Cerebrovascular deaths remain predominantly out-of-hospital (~80%) with a 2020 peak and stabilization thereafter. Hospice’s proportional role did not expand post-pandemic , while home deaths grew within the OOH mix. These findings suggest sustained reliance on community/residential settings without compensatory growth in facility-based hospice. Strengthening early palliative engagement , equitable hospice referral pathways , and community stroke preparedness —paired with monitoring of place-of-death indicators—may better align preferences, capacity, and system performance in the post-COVID era.

Abstract TH807: A Community Health Worker-led Nutrition-Enhanced Hypertension Management Intervention: Randomized Pilot Feasibility Trial

Circulation Jessica Cheng, Emily Gelsomin, Kristine Gu et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th807

Background: Diet modification is an AHA/ACC Class 1 recommendation for hypertension management. Few clinical dietary interventions for hypertension exist, particularly in low-income settings. Community health workers (CHWs) could fill this gap. This pilot trial assessed the feasibility and acceptability of a nutrition-enhanced CHW intervention embedded within an existing hypertension management program. Methods: Health center patients who enrolled in a CHW hypertension (Basic) program at a Boston, MA health system were eligible for this randomized pilot study if they were ≥21 years old and spoke English or Spanish. The Basic program included home blood pressure (BP) monitoring, hypertension education, and CHW communication with PCP about uncontrolled BP. Participants were randomized to the Basic program (Control) or the nutrition-enhanced Basic program, which included 4 modules on label reading, simplified nutrition guidance (e.g., traffic light categories, green=healthy), healthy eating on a budget, and meal planning, and accompanying worksheets/activities. Participants were followed for 4 months. Participants completed surveys at baseline and 4 months; BP measures were obtained from the electronic health record. Primary outcomes were feasibility and acceptability. Secondary outcomes, assessed with mixed models, compared intervention vs. control groups in 4-month changes in BP, diet quality (rapid Prime Diet Quality Score), and nutrition knowledge (General Nutrition Knowledge). Results: Of 108 adults potentially eligible, 60 (56%) enrolled in the study. Study participants were mostly female (66%) and Hispanic (68%) and had mean age of 57.7 (sd=12.6) years. At baseline, 90% were taking BP medications daily, and 38% had food insecurity. In the intervention group (N=31), 74% completed ≥3 of 4 nutrition modules, 81% completed ≥3 of 6 worksheets/activities, and 100% completed the home food/cooking assessment. All intervention components were acceptable (rated ≥7.5 of 10 points). At follow-up, systolic and diastolic BP decreased, and diet quality and nutrition knowledge increased in both groups; however, there were no between-group differences (Table). Conclusion: A CHW nutrition education and support intervention within a hypertension management program was feasible and acceptable but did not demonstrate short-term differences in diet or health. A larger trial with longer follow-up is needed to assess intervention effectiveness.

Partner preferences for resources adapt to income and gender economic inequality

Proceedings of the National Academy of Sciences Macken Murphy, Sylvia K. Harmon-Jones, Auguste G. Harrington et al. Mar 24, 2026 DOI: 10.1073/pnas.2527295123

For over three decades, scholars have contested whether sex differences in ideal partner preferences for age, resources, and physical attractiveness result chiefly from evolution or cultural gender inequality. Here, we test a perspective compatible with each of these competing views: partner preferences for resources adapt strategically, such that they become stronger for the sex that is poorer and individuals who are poorer, as such preferences are more useful to these individuals. Our preregistered experiment placed 602 people from five countries in one of 45 virtual ecologies, varying participants’ personal income and their local gender economic inequality. Results show that people exhibit stronger ideal partner preferences for resources when they are poorer and when their sex is poorer. This pattern was evident in three different measures of stated partner preferences for resources, namely, ranked preferences and rated preferences for resource-relevant traits (e.g., whether a potential partner has a good job), and importance placed on dating or marrying up, financially. Preferences regarding age gaps were, surprisingly, unaffected, even though older age is associated with access to resources in naturally varying populations. Consistent with our theoretical perspective, which expects ideal partner preferences will adapt primarily to environmental variables that alter the fitness of those preferences, sex differences in stated preferences for physical attractiveness in romantic partners were largely unaffected. These results are discussed in the context of behavioral ecology, which offers a framework to interpret both our results and the mixed findings of past literature.

Wild mushroom consumption susceptibility among Chinese university students: A machine learning study

PLoS ONE Yu Chen, Xinjie Zhao, Ying Yue et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345659

Objectives To investigate factors associated with susceptibility to wild mushroom consumption using machine learning approaches and identify key predictors for targeted intervention development. Methods A cross-sectional survey of 216 Chinese university students employed three machine learning algorithms (Logistic Regression, Random Forest, Extremely Randomized Trees [ExtraTrees]) to predict consumption susceptibility based on demographics, media usage, and cognitive factors. Susceptibility was assessed through scenario-based questions following established frameworks from tobacco research. Model performance was evaluated using AUC with 95% confidence intervals calculated via bootstrap resampling (1,000 iterations). Sensitivity analyses were conducted using alternative susceptibility thresholds. Results 65.3% were classified as susceptible to consumption. Logistic Regression achieved highest performance (AUC = 0.776, 95% CI: 0.679–0.862). Risk perception emerged as the strongest predictor (importance = 0.133 ± 0.044), followed by mushroom picking experience (0.101 ± 0.017) and content impression (0.089 ± 0.018). Among the 63 participants (29.2%) who reported using AI models, 75.93% indicated trust levels of ‘fairly trust’ or above. Conclusions In this exploratory study of Chinese university students from a single institution, cognitive factors, particularly risk perception and identification ability, showed the strongest associations with consumption susceptibility. These preliminary findings suggest that targeted interventions enhancing risk awareness may be relevant for this population, though replication across diverse samples is needed before broader conclusions can be drawn.

Abstract WE556: Digital Media Exposure and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

Circulation Manthar Ali Mallah, Shaista Shareef, Naila Bohio et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we556

Background: social media, screen time, online gaming, and digital work settings are just a few examples of the rapidly expanding digital media use that has sparked worries about its possible effects on physical health. Recent data indicates that extended use of digital media may affect the physiological, behavioral, and psychological processes linked to cardiovascular disease (CVD). Methods: From the beginning until June 2025, we performed a thorough literature search in PubMed, Scopus, Web of Science, and EMBASE. Studies that reported correlations between different types of digital media exposure (such as screen time, social media use, and internet usage) and cardiovascular outcomes (such as hypertension, coronary artery disease, myocardial infarction, and stroke) were eligible. Results: A total of 42 studies (n = 1,240,378 participants) met inclusion criteria. A substantially higher risk of cardiovascular events was linked to high digital media exposure (≥6 hours/day) (pooled OR = 1.27; 95% CI: 1.12–1.44). Stronger correlations were found by subgroup analyses between younger persons (18–35 years old) and those who reported passive screen time or other forms of sedentary media usage. The risk of CVD mortality was higher for individuals in the highest category (median duration, 10.2 h/d) than for those in the lowest category (median duration, 2.98 h/d) (pooled HR, 1.29; 95% CI, 1.13–1.47). Screen time was linked to a comparable risk of CVD as total sedentary time, with a cut-off point of 5–6 hours per day. Conclusions: Existing systematic reviews and meta-analyses demonstrate significant association between high digital media exposure and increased cardiovascular disease risk.

Abstract TH934: Real-World Comparison of Crizanlizumab With or Without Hydroxyurea Versus Usual Care on Vaso-Occlusive Crisis Frequency in Sickle Cell Disease

Circulation Jingjing Sun, G Caleb Alexander, Lydia Pecker et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th934

Introduction: Sickle cell disease causes recurrent vaso-occlusive crises (VOCs) that drive morbidity and healthcare use. Hydroxyurea (HU) is standard therapy, yet many still experience VOCs. Crizanlizumab offers a new option to prevent VOCs. The phase 2 SUSTAIN trial showed reduced VOC rates versus placebo, whereas the phase 3 STAND trial found no significant benefit, leaving uncertainty about its effectiveness in practice. We hypothesized that crizanlizumab (±HU) would have similar annualized VOC rates compared with usual care in real-world practice. Methods: We conducted a new-user cohort study using electronic health record data from TriNetX (2018–2025). Eligible patients were aged ≥16 years with ≥3 claims for sickle cell disease and ≥12 months of clinical activities. The exposure group included patients initiating crizanlizumab (±HU); the comparator group included those receiving usual care (HU users or HU non-users). The outcome was the annualized rate of VOCs requiring healthcare visits, identified using ICD-10 codes and IV pain medication use. We assigned a pseudo-index date for HU non-users by matching them to the crizanlizumab cohort on demographics. We used stabilized inverse probability of treatment weighting and negative binomial regression to estimate adjusted incidence rate ratios (IRRs). Results: The study included 891 crizanlizumab users (234 with HU, 657 without HU) and 12,196 usual-care patients (3,255 HU users, 8,941 HU non-users). The mean age was 31 vs. 32 years; 61% were female, and 93% vs. 97% were Black. After weighting, covariates were well balanced. For the primary comparison of crizanlizumab (±HU) vs. usual care, unadjusted VOC rates were 1.62 vs. 0.37 per year; weighted VOC rates were 1.62 vs. 1.52 per year, and the IRR for VOCs was 1.08 (95% CI, 0.82–1.41). For the subgroup comparison of crizanlizumab plus HU vs. HU users, unadjusted VOC rates were 2.20 vs. 0.76 per year; weighted VOC rates were 2.20 vs. 1.60 per year, and the IRR for VOCs was 1.36 (95% CI, 0.89–2.08). For the subgroup comparison of crizanlizumab without HU vs. HU non-users, unadjusted VOC rates were 1.41 vs. 0.23 per year; weighted VOC rates were 1.41 vs. 2.45 per year, and the IRR for VOCs was 0.58 (95% CI, 0.41–0.82). Conclusions: In this real-world study, crizanlizumab (±HU) showed similar VOC rates to usual care overall. Crizanlizumab with HU showed no added benefit over HU users, while crizanlizumab without HU reduced VOCs compared with HU non-users.