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Abstract TU191: Urinary sodium and potassium excretions, gut microbiome, circulating metabolites, and cardiometabolic risk

Circulation Xinxiu Liang, Jun Li, Yanping Li et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu191

Background: A high-sodium, low-potassium diet promotes hypertension and cardiovascular disease (CVD). Intricate interactions between the gut microbiota and minerals, encompassing absorption, transformation, and signaling, point to an underexplored role of gut bacteria in this diet-cardiometabolic disease association. Aim: To characterize microbial features in response to sodium and potassium, map related shifts in circulating metabolites, and evaluate associations between the identified metabolites and incident cardiometabolic events. Design: In 264 men from the Men's Lifestyle Validation Study, we examined the gut taxonomic and functional compositions in response to 24-hour urinary sodium and potassium excretion. We further assessed plasma metabolomic profiles responsive to the identified gut microbial features and their associations with coronary heart disease (CHD), CVD, and type 2 diabetes (T2D) among 12,225 participants from Nurses' Health Study (NHS), NHSII, and the Health Professionals Follow-up Study. Results: We identified 25 sodium-responsive species, including Collinsella , Desulfovibrio , and Roseburia species, along with 4 potassium- and 4 sodium-to-potassium ratio-responsive species. Microbial scores correlated strongly with urinary sodium, potassium, and their ratio (Pearson r = 0.37–0.57). High-sodium and low-potassium microbiome scores were linked to a favorable plasma metabolomic profile, characterized by higher imidazole propionate, and lower hippuric acid and 3-indolepropionic acid levels. These metabolomic alterations were associated with an increased risk of developing CHD (Quintile5 vs. Quintile1: HR=2.14 [95%CI: 1.53, 2.99]; p-trend < 0.0001), CVD (HR=1.56 [1.34, 1.83]; p-trend < 0.0001), and T2D (HR=3.03 [2.56, 3.60]; p-trend < 0.0001). Conclusions: Our findings linked high sodium and low potassium intake to a specific gut microbial pattern that predicted an adverse metabolomic profile precipitating an elevated risk of developing cardiometabolic conditions. Overall, these data suggest that the human gut microbiome can actively participate in the etiological processes linking high salt intake with adverse health outcomes.

All pure multipartite entangled states of qubits can be self-tested

Nature Communications Maria Balanzó-Juandó, Andrea Coladangelo, Remigiusz Augusiak et al. Mar 24, 2026 DOI: 10.1038/s41467-026-70829-x

28-day cement strength prediction via transformer-based feature extraction and XGBoost

PLoS ONE Dianyuan Ju, Xiaoyu Ma, Rongfeng Zhang et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345378

The 28-day compressive strength of cement is a key indicator for assessing cement quality. To overcome the time delays inherent in manual testing, this paper proposed a 28-day cement strength fusion prediction method based on a Transformer feature extractor and an XGBoost meta-learner. This method first encoded the physicochemical multi-source strength variables through the Transformer embedding layer, then calculated the attention scores using the multi-head attention mechanism to allocate weights dynamically. Next, XGBoost’s gradient boosting tree structure and regularization techniques were employed to enhance the robustness of the cement strength prediction model in small-sample scenarios. Finally, the method was validated using real-world 28-day strength testing data from cement plants. The results indicated that, compared to the model without feature extraction, the regression model’s R 2 increased by 5.62%, and its RMSE decreased by 22.33% after applying Transformer feature extraction. Furthermore, when compared with other small-sample models, XGBoost achieved the highest average R 2 of 0.93 in 5-fold cross-validation (CV). Its training efficiency, robustness to noise, and ability to handle feature missingness outperformed other meta-learners. Compared to other methods, TF-XGBoost achieved the highest average R 2 of 0.94 in 25 Monte Carlo (MC) CVs, providing the best fit. The method proposed in this paper demonstrates higher accuracy, better generalization, and greater stability, offering a new approach for the prediction of cement 28-day strength with small sample sizes.

Abstract WE427: Percent Black Residents Modifies the Association between Neighborhood Private Well Use and CVD Mortality

Circulation Matthew Loop, Helen Moylan, Jieun Park et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we427

Introduction: More magnesium in drinking water is associated with lower CVD risk, while more lead is associated with higher CVD risk. Rural US residents often rely on private well water, which has more variable concentrations of these substances than municipal water. Our previous work in Alabama demonstrated that more households reliant on private wells was associated with less hypertensive heart and stroke/cerebrovascular disease mortality. Although self-reported Black race is associated with higher CVD mortality, it is not a confounder for private well use, which depends on rurality of residence. However, it is unknown whether self-reported Black race may be an effect modifier for the protective associations with private well use. Hypothesis: In Alabama, the neighborhood-level relationship between high private well use and lower CVD mortality depends on percentage of self-reported Black residents. Methods: We used mortality data for Alabama Census block groups (CBGs) from 2016 to 2019 for 3 types of CVD: hypertensive heart disease, ischemic heart disease, and stroke/cerebrovascular disease. We estimated the rate ratio (RR) and 95% CIs for a 1 SD higher percentage of households reliant on private wells, adjusted for age group (45 - 54, 55 - 64, 65 - 74, and 75+ years) and rurality. We tested for interactions between the percentage of households reliant on private wells and the percentage of residents who reported Black only race on the 2020 Census. A p-value of 0.05 was considered statistically significant. Data were provided by the Alabama Department of Public Health, the EPA, and the US Census. Results: Median (1 st quartile, 3 rd quartile) percentage of households reliant on private wells in a CBG (n = 3,919) was 7% (0%, 38%). The percentage of Black residents was 18% (5%, 48%). The adjusted RRs for a higher percentage of households reliant on private wells differed by percentage of Black residents for hypertensive death and ischemic death. The protective association for higher percentages of households reliant on private wells was more protective in CBGs with higher percentages of Black residents (see Figure 1). Conclusions: The association between more private well use and hypertensive heart and ischemic heart disease mortality depended upon the percentage of Black residents. Further research is needed to understand whether some groundwater quality parameters, such as water hardness, may be more beneficial for Blacks than for Whites.

Abstract TH935: Glucagon-Like Peptide-1 Receptor Agonists Are More Frequently Prescribed to Individuals at Lower Predicted Cardiovascular Risk Than Those at Higher Risk Among People Without Diabetes

Circulation Shuhan Yang, Lucas Mavromatis, Michael Fang et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th935

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1s) are effective for weight loss. Moreover, the SELECT trial showed that semaglutide reduced cardiovascular disease (CVD) events in adults without diabetes and with established CVD. However, it is unknown whether GLP-1s are preferentially prescribed to those with higher CVD risk in real-world practice. We aimed to describe GLP-1 use by CVD status and by CVD risk, estimated using the American Heart Association’s PREVENT equation, among adults without diabetes. Methods: We analyzed electronic health record data from Geisinger, a large regional health system in Pennsylvania, USA, and identified GLP-1 users and non-users between June 2021 and February 2025. We included adults aged 30-79 years (the PREVENT equation age range) without diabetes and body mass index (BMI) ≥27 kg/m^2 at GLP-1 initiation or a randomly selected clinic visit (for non-users). Distributions of BMI and 10-year total CVD (atherosclerotic CVD and heart failure) risk from the PREVENT primary equation were compared by GLP-1 use. We employed multivariable logistic regression to assess associations between CVD risk categories (low [<5%], borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%], prevalent CVD, and unknown risk) and GLP-1 use, adjusting for age, sex, BMI, and use of antihypertensive agent and statin. Results: Of 204,786 adults without diabetes and with BMI ≥27 kg/m^2, there were 16,248 (7.9%) GLP-1 users, and 15% had prevalent CVD. Compared with non-users, GLP-1 users were younger (mean 52 vs. 57 years), more often female (71 vs. 55%), and had higher BMI (mean 39 vs. 34 kg/m^2, p<0.001; Figure 1 ). Among people without CVD, GLP-1 users had lower 10-year PREVENT total CVD risk than non-users (mean 5.3 vs. 7.7%, p <0.001; Figure 2 ). Higher CVD risk was associated with lower GLP-1 use (low risk: 11.4%; borderline: 8.6%; intermediate: 5.6%; high: 3.2%; prevalent CVD: 7.1%), with adjusted odds ratios of 0.41 (95% CI, 0.36-0.48) and 0.65 (0.61-0.69) for high risk and prevalent CVD, respectively, compared with low risk ( Table 1 ). Conclusions: Among patients without diabetes, GLP-1s were more often prescribed to those at lower CVD risk in clinical practice, despite evidence of cardiovascular benefits primarily in patients with established CVD. Weight loss may have been prioritized in treatment decisions. This risk–treatment paradox underscores the need for risk-based prescribing to better reach patients most likely to benefit.

Hh and EGFR-Ras signaling promote distinct steps of tumor progression in the Drosophila follicle epithelium

Nature Communications Sari Anschütz, Hannah Müller, Andrea Schubert et al. Mar 24, 2026 DOI: 10.1038/s41467-026-70844-y

Abstract Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here, we combine single-cell transcriptomics with in-depth genetic and imaging analysis to investigate the role of the EGFR-Ras and Hedgehog signaling pathways in homeostasis of the Drosophila follicle stem cell lineage. We find that Hedgehog signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of the epithelial-mesenchymal-transition associated transcription factor Zfh1. Overactivation of Hedgehog signaling generates a mixed transcriptional state comparable to partial epithelial-mesenchymal-transition. EGFR-Ras overactivation induces cell cycle defects by activating the transcription factors Pointed and E2f1 and impedes differentiation. Overactivation of both pathways blocks differentiation and induces tumor-like growth where follicle cells exhibit a loss of tissue architecture, sustained proliferation and a reduced lifespan of the host. These findings provide new insight into how signaling pathways converge at the transcriptional level to prevent malignant cell behavior.

Correction: mHealth intervention to improve quality of life in patients with chronic diseases during the COVID-19 crisis in Paraguay: A study protocol for a randomized controlled trial

PLoS ONE Tamara Escrivá-Martínez, Mª Dolores Vara, Nadia Czeraniuk et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345669

Abstract TU241: Psychosocial Assets Promote Cardiovascular Health Across Adulthood: A Mixed Methods Investigation

Circulation Julia Boehm, Farah Qureshi, Laura Kubzansky Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu241

Introduction: There is growing recognition that psychosocial factors contribute to cardiovascular outcomes. A large body of research consistently finds that risk factors like depression increase risk for cardiovascular disease. In contrast, psychosocial assets like purpose in life promote healthy functioning but are less well-understood. This study used a mixed methods approach to assess a variety of psychosocial assets and compare the strength of associations between each asset and a composite measure of cardiovascular health (CVH) assessed 12 years later. We hypothesized adults with higher levels of psychosocial assets at midlife would have better CVH in older adulthood. Methods: Data came from 1,980 participants in the United Kingdom’s National Child Development Study. At age 50, participants wrote an open-ended response to the prompt “Imagine that you are now 60 years old… please write a few lines about the life you are leading.” Two judges rated each response (1=not at all; 7=very) for eight psychosocial assets: optimism, purpose, social connections, life satisfaction, personal growth, agency, enjoyment, and overall positivity. Interrater agreement for each asset was excellent (Finn’s r = .84-.90). CVH at age 62 was defined using the American Heart Association’s Life’s Essential 8 metric (although diet data were not available). CVH components were self-reported (physical activity, sleep, nicotine exposure) or clinically assessed (systolic and diastolic blood pressure, lipids, glucose, body mass index) and combined into an overall CVH score with higher scores indicating better CVH (range=27-100). Separate linear regression analyses examined the association between each psychosocial asset at age 50 and CVH at age 62, adjusting for confounders at age 50 (sociodemographic characteristics, response word counts, depressive symptoms, and health status). Results: All psychosocial assets were positively associated with better CVH scores in fully adjusted models ( p s≦.05), except for social connections. Purpose (b=1.60, 95% confidence interval [CI]=.56-2.64), personal growth (b=1.36, 95% CI=.50-2.22), and agency (b=1.21, 95% CI=.34-2.09) showed the strongest associations with CVH. Conclusions: Higher levels of most midlife psychosocial assets were linked with better CVH over time, suggesting there are multiple paths to protection. These findings highlight specific psychosocial assets that could be intervention targets in future cardiovascular prevention efforts.

Abstract WE435: Metabolomic Signatures Linking Continuous Glucose Monitoring–Derived Fasting Glucose Variability to Increased Type 2 Diabetes Risk

Circulation Jin Dai, Wen Dai, Yoriko Heianza et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we435

Introduction: Fasting plasma glucose is a cornerstone for diagnosing prediabetes and diabetes. However, a single measurement overlooks substantial intraindividual variability, as revealed by continuous glucose monitoring (CGM). A recent study showed that two-week CGM-based fasting glucose assessments reclassified ~40% of individuals previously deemed normoglycemic as having prediabetes. Yet, the systemic metabolic features underlying short-term fasting glucose variability, and its prospective association with type 2 diabetes risk, remain unknown. Methods: We analyzed 1059 Israeli adults from the Human Phenotype Project (HPP) who wore a CGM device for two weeks between 2018-2020 and had available Nightingale metabolomics and real-time dietary logging. Fasting glucose was defined as CGM readings between 6-9 AM with prior fasting duration 8 hours. Short-term fasting glucose variability was quantified as the standard deviation (SD) of fasting glucose. Associations between individual metabolites and fasting glucose SD were assessed using linear regression, adjusting for age, sex, education, body mass index (BMI), smoking, alcohol intake, physical activity, diet, CGM-derived mean glucose, and mean fasting glucose. Elastic-net regression with ten-fold cross-validation (100 repeats) identified metabolites jointly associated with fasting glucose SD, with those selected 70 times were included in the metabolomic signature. The signature was then evaluated for incident type 2 diabetes among 6246 diabetes-free adults in the UK Biobank (2006–2010 baseline; follow-up through 2022) using Cox models. Results: In the HPP, 81 metabolites were associated with fasting glucose SD (FDR<0.05), with 67 having inverse associations (e.g., average diameter for HDL particles and phospholipids in Large LDL) and 14 having positive associations (e.g., concentration of medium and small LDL particles). A 24-metabolite panel was jointly associated with fasting glucose SD. In the UK Biobank, each 1-SD increase in the metabolomic signature corresponded to an 18% higher risk of type 2 diabetes (HR, 1.18, [95% CI, 1.07–1.31]; P <0.001) independent of BMI, HbA1c, and fasting plasma glucose. Conclusions: Short-term fasting glucose variability signals systemic metabolic dysregulation and predicts type 2 diabetes risk beyond HbA1c and fasting glucose, suggesting that it may capture unique aspects of glycemic dysregulation beyond traditional metrics.

Acid-tolerant injectable bioadhesive for sutureless repair of large gastric perforation

Nature Communications Ze Wang, Bo Cao, Longsong Li et al. Mar 24, 2026 DOI: 10.1038/s41467-026-71031-9

Abstract Bioadhesives represent promising alternatives to sutures towards gastric perforation management, however, significant challenges persist concerning instant wet adhesion and durable stability in gastric perforation sealing, particularly in direct contacting with acidic gastric fluids on large perforation injuries. Here we report an injectable acid-tolerant hydrogel composed of FDA-approved components for sutureless repair of large gastric defects. The hydrogel displays rapid in situ gelation, instant wet adhesion, and high burst pressure for efficient sealing despite excessive mechanical challenges, tissue irregularities and gastric juices. The enhanced hydrogen bonding interactions among amide-linked skeleton enable robust acid-tolerant interfaces to accommodate durable adhesion under the fluidically, chemically and mechanically dynamic in-vivo environments. A larger-scale porcine gastric perforation is applied to validate the sealing efficacy via a combined laparoscopic-endoscopic technique. The negligible postoperative adhesion, suppressed inflammation and interference-free transcriptome and microbiome verify the therapeutic outcomes. The proposed bioadhesives hold great promise for clinical treatment of digestive diseases.

‘Fend for yourself’: Nurses’ experiences transitioning to Family Care Team practice settings in Newfoundland and Labrador

PLoS ONE Robin Devey-Burry, Julia Lukewich, Dana Ryan et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345818

Background Family Care Teams were introduced in Newfoundland and Labrador (NL) as a strategy to strengthen primary care through team-based models that optimize interprofessional collaboration. Nurses, including nurse practitioners (NPs), registered nurses (RNs), and licensed practical nurses (LPNs), play critical roles in these models; however, little is known about nurses’ transition to these settings or the supports shaping their integration and effectiveness. To address this gap, we explored nurses’ experiences transitioning into Family Care Teams, including supports for integration and the barriers and facilitators influencing this process. Methods As part of a qualitative descriptive study, we conducted semi-structured interviews with 25 nurses (6 NPs, 13 RNs, 6 LPNs) employed in Family Care Teams across five NL health zones. During the interviews, nurses described their experiences working in Family Care Teams, available practice supports, current roles, and barriers and facilitators to maximizing scope of practice. Interviews were transcribed and analyzed using qualitative content analysis and constant comparison. Results Participants described their transition to Family Care Teams in two stages: 1) orientation and 2) supportive learning relationships. Orientation was highly variable, ranging in length and structure. Learning in this area was often self-directed, technology-focused, and asynchronous, with limited emphasis on clinical preparation or role expectations. Mentorship and shadowing opportunities were inconsistently available, with many nurses lacking access to experienced role models within the newly established teams. These gaps contributed to role ambiguity, underutilization of nursing scope of practice, and prolonged adjustment periods. Conclusions Our findings reveal gaps in orientation and mentorship during nurses’ transition into Family Care Teams in NL. A common yet adaptable transition framework, expanded student placements, and structured mentorship are critical to optimizing nursing roles in team-based care. Strengthening practice supports and clarifying nursing contributions can improve access and care quality while informing broader initiatives to support nurses’ transition into primary care.

Abstract TH871: High Lipoprotein (a) Associated with Decreased Bone Mineral Density in Post-Menopausal Women

Circulation Rayan Mamoon, Radiah Khandokar, Janet Rosenbaum Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th871

Introduction: Cardiovascular markers, including lipoprotein(a) (Lp(a)), are hypothesized to be associated with skeletal bone health because of an association between oxidative stress and bone marrow adiposity, but the US does not routinely test Lp(a) levels. This study evaluates whether high Lp(a) levels are linked to lower bone mineral density among post-menopausal women. Methods: This hypothesis was tested using data from the Study of Women' s Health Across the Nation (SWAN), a longitudinal study of women who were initially pre-menopausal or early perimenopausal and who reached menopause at visit 7, within 7 years of baseline (n=1357). High Lp(a) was defined as greater than or equal to 100 mg/dl. Spine bone mineral density was assessed at visit 10 utilizing Dual-energy X-ray absorptiometry (DEXA) scan, and coded as decreased if BMD decreased by 10% or more between visits 7 and 10. We analyzed the data using chi-square tests of association and Poisson multivariate regression adjusting for confounding variables measured at baseline: age, race, smoking status, BMI, LDL cholesterol, calcium and vitamin D supplements, HDL cholesterol, and physical activity. Results: Women with high Lp(a) were 35.4% more likely to have decreased bone mineral density than women with low Lp(a). Individuals with high Lp(a) levels were more likely to smoke, have higher BMI, LDL levels, and total cholesterol; they were also less likely to regularly exercise, take calcium supplements, and have high HDL. Women with high Lp(a) were 84.3% more likely to have decreased bone mineral density than women with low Lp(a), controlling for confounders. Conclusion: Our study provides suggests benefits to assessing Lp(a) levels in individuals at risk for cardiovascular mortality and declining bone health including women prior to the menopausal transition. Early detection of elevated Lp(a) levels could allow the possibility to offset the effects of elevated Lp(a) through management of more easily modifiable cardiovascular markers such as low-density lipoproteins. Novel Lp(a) lowering medications may also help protect skeletal bone health in individuals who are at risk of declining bone health.

Abstract WE428: Climate-Related Exposures During Pregnancy Influence Maternal Cardiometabolic Risk: Findings from the GROWell Trial

Circulation Jennifer Phipps, Clare Cannon, Paige Smith et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.we428

Background: Pregnancy-related complications increase risk for long-term cardiovascular (CV) disease. Environmental exposures such as fine particulate matter (PM 2.5 ) and extreme heat may exacerbate these risks through oxidative stress and inflammation, yet their relationships with perinatal health remain poorly understood. We examined how environmental and psychosocial factors jointly influenced gestational weight gain (GWG), postpartum weight retention (PPWR), and adverse pregnancy outcomes (APOs), including gestational diabetes, preeclampsia, and preterm birth, among a California cohort. Methods: Data were drawn from 303 participants in the GROWell trial, a mobile lifestyle intervention for pregnant and postpartum women with overweight or obesity. Structural equation models (SEMs) tested hypothesized pathways between environmental exposures (latent factors for PM 2.5 and extreme heat over 7-, 30-, and 90-day periods), behavioral and psychosocial variables (diet, physical activity, anxiety), sociodemographics, and maternal outcomes (GWG, PPWR, APOs). Results: Model fit was excellent for both GWG (CFI = 0.88, RMSEA = 0.047) and PPWR (CFI = 0.87, RMSEA = 0.049). Higher PM 2.5 exposure predicted lower GWG (β = –0.19, p = 0.01), while greater physical activity (β = –0.11, p = 0.048) and older age (β = –0.16, p = 0.005) also predicted less gain. Extreme heat was not directly related to GWG but increased odds of APOs (β = 0.22, p = 0.04). In the PPWR model, neither PM 2.5 nor heat predicted weight retention. Anxiety symptoms showed a borderline association with lower PPWR (β = –0.13, p = 0.05). Non-White participants experienced higher PM 2.5 exposure (β = –0.18, p = 0.03), reflecting environmental inequities. Conclusions: Extreme heat increased risk for APOs, whereas higher PM 2.5 exposure was inversely related to GWG. Neither environmental exposure directly predicted PPWR, suggesting complex, time-specific pathways may link environmental stressors to maternal CV risk. Results highlight the need for interventions that address both lifestyle and structural drivers of CV risk across the perinatal continuum. Mobile lifestyle applications could be adapted to provide alerts to users when they are in high heat and high pollution environments to improve maternal outcomes.

Tuft cells shape airway remodeling by eliciting OXGR1- and SOX9-dependent stem cell programs

Nature Communications Minkyu Lee, Xin Wang, Qihua Ye et al. Mar 24, 2026 DOI: 10.1038/s41467-026-70763-y

Efficacy of heparin in respiratory support of near-term rabbits with meconium-induced acute lung injury: Linear regression model analyses

PLoS ONE Siyu Xie, Qiang Gu, Guiyin Zhuang et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0345718

Objectives To explore the pharmacotherapeutic efficacy of heparin in the management of meconium-induced acute lung injury (ALI) in near-term newborn rabbits subjected to mechanical ventilation (MV) and ancillary respiratory medications. Methods Newborn rabbits at 30-day gestation (term 31 days) were anesthetized, intratracheally intubated and received human meconium-saline suspension, followed by parallel MV with individually adjusted tidal volume in a multi-plethysmograph-ventilator system. When ALI was induced after initial 3-h MV, therapeutic effects of single or combined subcutaneous heparin (100 U/kg), surfactant (200 mg/kg), and inhaled nitric oxide (iNO, 10 ppm), were compared for lung protective ventilation and survival as outcome, analyzed with linear regression models. Results Significantly reduced respiratory compliance by meconium was reinstalled during ensuing 7-h MV, with improved survival, among the treatment groups. The impact was verified by lung injury severity, surfactant phospholipid pools, and multiple mRNA expressions of surfactant proteins, lung fluid clearance-related factors, inflammatory mediators, growth factors, endothelial cell injury and coagulation-related factors as subphenotyping biomarkers. The overall benefits of heparin alone, or exerted with the dual and triple regimens, were discernible by both generalized linear model and Cox proportional hazard ratio regression for survival and other major variables as outcome. Its adverse effects were intangible. Conclusion The comparable efficacy of heparin, alongside the PS and NO, was corroborated in attenuating meconium-mediated, ventilator-induced ALI, which should warrant clinical investigation to validate.

Abstract TH875: Assessing Calibration and Recalibration of Clinical Prediction Models Using Pseudo-Values Regression

Circulation Andrea Bellavia, Aurora Gaeta, Sabina Murphy Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th875

Introduction: Clinical risk scores are evaluated in terms of discrimination (correctly classifying patients) and calibration (accurately predicting individualized risks). When comparing new and existing models, however, the impact of additional variables is generally limited to measures of discrimination and reclassification, with no consensus on how to test calibration improvements. This study introduces the application of pseudo-values (PV) methods to evaluate calibration and recalibration. Hypothesis: We hypothesize this approach to be particularly valuable when additional variables enhance risk prediction without necessarily improving discrimination, and for assessing model calibration at different time points without assuming proportional hazards. Methods: Individuals PVs are estimated by comparing the full sample estimate to those when that individual is excluded (leave-one-out estimator). In survival analysis PVs are used to retrieve information on censored individuals, enabling linear modeling of time-specific event risks - the measure of interest for calibration assessment - and straightforward derivation of calibration plots. The deviance of a PV model summarizes model fit, with lower values indicating better agreement between observed and predicted risks, and statistical tests are available for comparing the fit of nested models. Moreover, PV models allow estimating time-specific risks without proportionality assumptions, providing a flexible tool for assessing calibration at different time points. As an illustration, we applied the PV approach to compare alternative versions of the TIMI Risk Score for Atherothrombosis in diabetes, evaluating clinical and biomarker data in 36,632 individuals. Results: Figure 1 compares the PV implementation of the original risk score (left panel) and a second model with selected biomarker data (right panel). In this example, the expanded model provided similar overall performances (Brier score: 0.039 vs 0.040) and a moderate increase in discrimination (C-statistic: 0.735 vs 0.698). Calibration plots indicate better accuracy, confirmed by a significant improvement in model fit (p<0.001). Calibration was remarkably similar when predicting event risks at different times (Figure 2) with poorer performances only at the extremes of the risk distribution. Conclusions: The PV approach complements existing methods for clinical prediction with survival data, offering advantages for the assessment of model calibration and recalibration.

Abstract TU262: Sleep Duration Associated with Social, Structural, and Emotional Determinants of Health

Circulation Michael Grandner Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.tu262

Introduction: Few studies have examined population-level sleep health relative to salient but less well-studied structural / social / emotional determinants of health. Methods: Data were used from the 2002 BRFSS (N=193,225). Sleep duration was typical sleep within a 24-hour period and was categorized as <=4h, 5h, 6h, 7h (reference group), 8h, 9h, and 10+h. Participants were asked how often they experienced stress (mind is "troubled all the time"), emotional support ("the social and emotional support you need"), social isolation ("feel socially isolated from others"), food insecurity ("[did] not last, and you didn’t have money to get more"), employment insecurity ("lost employment or had hours reduced"), housing insecurity ("not able to pay your mortgage, rent or utility bills"), transportation insecurity ("lack of reliable transportation"), use of food stamps, and inability to pay utility bills. Weighted models were adjusted for age, sex, race/ethnicity, education, income, and employment. Results: The experience of stress "Sometimes," "Usually," or "Always" were associated with a greater likelihood of <=4h, 5h, and 6h ("Always" was associated with 10+h only), and a lower likelihood of 8h and 9h (all p<0.0005). Emotional support "Sometimes," "Rarely" and "Never" were associated with elevated likelihood of <=4h, 5h, and 6h (all p<0.0005). Social isolation "Sometimes," "Usually," and "Always" were associated with an increased likelihood of <=4h, 5h, 6h, and 10+h (all p<0.0005). Food insecurity "Rarely," "Sometimes," "Usually," and "Always" were associated with <4h, 5h, and 6h (all p<0.0005), and 10+h (all p<0.014). Employment insecurity was associated with <=4h, 5, and 6h (all p<0.001). Housing insecurity was associated with <=4, 5, and 6h (all p<0.0005) and 10+h (p=0.003). Transportation insecurity was associated with <=4h, 5h, 6h, and 10+h (all p<0.0005). Food stamps use was associated with <=4h, 5h, and 6h (all p<0.003). Inability to pay bills was associated with <=4h, 5h, and 6h (all p<0.0005) and 10+h (p=0.005). In a forward stepwise model, unique variance was contributed by (in order) social isolation, emotional support, food insecurity, inability to pay bills, transportation insecurity, housing insecurity, and food stamps. Conclusions: Structural, social, and emotional determinants of health are strongly related to insufficient sleep. Sleep health may partially mediate adverse health outcomes and should be a target for improving social/emotional health.

CD8+ T cells sustain vaccination-induced immunity against dissemination of contained tuberculosis in immunosuppressed hosts

Nature Communications Socorro Miranda-Hernandez, Manoharan Kumar, Alec Henderson et al. Mar 24, 2026 DOI: 10.1038/s41467-026-70911-4

The characteristics of patients’ medical care, living will, and signs of death by age and the place of death: A cross-sectional study using a questionnaire survey targeting physicians with expertise in end-of-life care

PLoS ONE Mitsutaka Yakabe, Tatsuya Hosoi, Shoya Matsumoto et al. Mar 24, 2026 DOI: 10.1371/journal.pone.0343868

Objectives Few studies have examined how age and place of death among end-of-life patients are associated with the medical care they receive and the signs of death. Therefore, we aimed to clarify the characteristics of medical care, the implementation of living wills, and the signs of death in end-of-life patients by administering a self-developed questionnaire to physicians with expertise in end-of-life care. Methods Data were obtained through a web-based questionnaire administered to physicians registered with the Japan Society For Dying With Dignity. Each physician was asked to share data on a patient they had cared for, such as age, sex, place of death, presence of medical procedures and a living will, and signs of death. Results In total, 437 patients, aged 79.4 ± 15.3 years, were analyzed. Pain control and palliative care were provided to 225 and 278 patients, respectively. Moreover, 172 patients possessed a living will. After adjusting for factors using logistic regression analysis, the odds ratios (ORs) for pain control and palliative care were significantly lower in the older age groups. The OR for pain control in nursing homes, compared with home, was 0.305 [95% confidence interval (CI), 0.081–0.920], and the OR for palliative care was 0.212 [95% CI, 0.073–0.544]. The ORs of living wills were significantly lower in patients aged ≥90 years (0.401 [95% CI, 0.199–0.800]) than in those aged 20–64 and in hospitals (0.494 [95% CI, 0.294–0.815]) than at home. Factor analysis of 18 signs of death identified three factors. Factor 1 reflected global terminal decline, and receipt of palliative care was significantly associated with the signs loading on factor 1. Conclusion Provision of pain control, palliative care, and living wills differed by age group and place of death. Our findings suggest priorities for end-of-life care across settings and for representative studies.

Abstract TH932: National Trends in Oral Anticoagulant Use Among U.S. Adults and Different Subgroups: Analysis of NHANES 2009–2020

Circulation Trang Nguyen, Trang Dang, Thu Nguyen et al. Mar 24, 2026 DOI: 10.1161/cir.153.suppl_1.th932

Background: Over the past decade, direct oral anticoagulants (DOACs) have increasingly replaced warfarin as the preferred agents for multiple indications, with specific agents favored for different patient groups based on evidence of efficacy, safety, and convenience. However, the extent to which DOACs and warfarin are used among patients with chronic diseases such as atrial fibrillation, cancer, chronic kidney disease (CKD), and obesity remains insufficiently characterized. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to March 2020 (n = 55,999) to estimate national trends in the use of oral anticoagulant (OAC) among U.S. adults (≥18 years). All estimates were generated using survey-weighted methods accounting for NHANES’s complex, multistage, stratified cluster design. Results: Over the past decade, the prevalence of DOAC use in the US adult population increased from 0.03% (95% CI: 0.01–0.11%; dabigatran used only) in 2009–2012 to 1.3 % (95% CI:1.1–1.6%) in 2017–March 2020, with apixaban (44.6%) and rivaroxaban (43.1%) being the predominant agents. During the same period, warfarin use decreased from 1.6% (95% CI:1.3–1.9%) to 0.9% (95% CI:0.7–1.2%) ( Figure 1A). Similar increasing trends in overall OAC and DOAC use, accompanied by corresponding declines in warfarin use, were observed across subgroups. Among adults with atrial fibrillation and a CHA2DS2-VA score ≥2, the prevalence of DOAC use increased from 27.6% (95% CI:18.7–36.6%) in 2013–2016 to 53.4% (95% CI:41.3–65.5%) in 2017–March 2020 (Figure 1B). From 2009 to 2020, the prevalence of OAC use among adults with cancer was over threefold higher than among those without cancer (5.7% vs 1.5%; p < 0.001) (Figure 1C). In adults with CKD stages 3–5, DOAC use increased from 0.2% to 11.6%, with apixaban comprising 77.4% of OAC use in stage 4 CKD in 2017–March 2020 (Figure 1D). Across body mass index (BMI) categories, OAC use increased among overweight and obese adults but declined among those with normal or low body weight. In 2017–March 2020, apixaban (0.8%; 95% CI:0.2–3.6%) and rivaroxaban (0.4%; 95% CI:0.1–3.1%) were the most commonly used OACs in underweight individuals (Figure 1E). Conclusions: DOAC use increased between 2009 and March 2020 in the U.S. general adult population and across different subgroups. Apixaban emerged as the predominant DOAC used among individuals with atrial fibrillation, advanced CKD, cancer, and low body weight.