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Abstract P3104: Assessment of Dietary Recall Plausibility Using an Updated Formula that Considers Energy Intake Measured by Doubly-Labeled Water

Circulation Leinys Santos Baez, Michele N. Ravelli, Diana A. Diaz-Rizzolo et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3104

Background: Self-reported, free-living energy intake (rEI) by dietary recalls are notoriously inaccurate. Assessment of rEI plausibility have been limited to arbitrary assumptions or validation against measured energy expenditure (mEE) by doubly-labeled water (DLW). We aimed to identify plausible dietary recalls using an updated formula that considers measured energy intake calculated by DLW (mEI) instead. Methods: In a two-week cross-sectional study, up to six rEI by repeated Automated Self-Administered 24-Hour (ASA24®) Dietary Assessment Tool, with body energy store changes (ΔBES) measured by quantitative magnetic resonance (QMR) on days 1 and 14, mEE assessed by DLW, and mEI computed by energy balance equation (mEE + ΔBES). Participants were asked to maintain an eucaloric diet. A rEI:mEI ratio was calculated for each participant, and a group cut-off was calculated using the formula: ±1SD = √(CVrEI 2 )/d)+(CVmEI 2 ). Dietary recall entries within ±1SD of the cutoffs were categorized as plausible (PR), <1SD categorized as under-reported (UR), >1SD categorized as over-reported (OR). Spearman correlations and linear regression performed to evaluate the linear relationships for continuous variables. Results are mean±SD. Significance set at p<0.05. Results: In our cohort (n=39, age: 60.6±6.9 years, BMI: 33.1±6.4 kg/m 2 , 33.3% men), 50%, 26.3%, 23.7% of the dietary recalls were UR, PR and OR, respectively. The rEI:mEI ratio showed a significant negative correlation with body weight (ß=-0.38, p =0.02). Greater mEI predicted higher body weight (ß=26.6, p<0.01) and BMI (ß=51.4, p=0.02). In contrast, no relationships were observed between rEI and body weight (ß=9.3, p=0.09) or BMI (ß=22.5, p=0.28). However, in PR entries alone, rEI predicted greater body weight (ß=19.5, p<0.01) and BMI (ß=44.8, p=0.04). Conclusion: These preliminary results align with past studies supporting higher implausible energy intake in adults with greater body weight, based on self-reported dietary recalls. In contrast to rEI, we found a consistent and significant association between mEI and PR, with body weight and BMI. This supports the notion that higher energy requirements are needed to maintain energy balance in individuals with greater body mass. These findings support this method for identifying plausible reporting (PR) when assessing dietary intake.

Abstract P1143: Not So Invincible: Young Adults with Prediabetes Report Fear of Future Diabetes Motivates Behavior Change

Circulation Abigail Arons, Mai Baalbaki, Amy Beck Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1143

Introduction: Young adulthood is an unmet opportunity for cardiovascular prevention. While prediabetes is often assessed in young adult primary care visits, the “young invincibles” assumption presumes youth are unmotivated by long term health. No qualitative study has garnered young adults’ perspectives on what prediabetes means to them. Methods: Semi-structured interviews in English and Spanish with outpatients ages 18-26 with prediabetes (HgbA1c or chart diagnosis) January to September 2024, at one safety net hospital and one academic medical center. We excluded patients with diabetes, or who were unaware of their diabetes risk. Interviewees were asked about diabetes risk perceptions and experiences discussing prediabetes with providers. We used thematic analysis to determine themes. Results: We interviewed 24 participants (63% female, 71% Latino/a/x, 29% Black, 61% food insecure, 39% any college). Several key themes emerged (Table 1). Participants understood prediabetes accurately and had mixed perceptions of whether diabetes was avoidable for themselves. Learning of prediabetes had a strong emotional impact, often grounded in family experiences with diabetes. Fear of diabetes prompted behavior changes, which youth largely made on their own, with short duration. Youth preferred honest, encouraging communication from providers. Conclusions Fear of future diabetes motivates behavior change for young adults. Health care providers’ conversations with young adults about prediabetes have lasting emotional impact. Providers should use honest, clear language that emphasizes the possibility of change. Strengthening connections to supportive programs could continue momentum after these conversations to facilitate lasting behavior change.

Widely accessible prognostication using medical history for fetal growth restriction and small for gestational age in nationwide insured women

Scientific Reports Herdiantri Sufriyana, Fariska Zata Amani, Aufar Zimamuz Zaman Al Hajiri et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92986-7

Abstract P3098: Differences in Diet Quality Across US Census 2020 Regions: A Secondary Analysis in the Women’s Health Initiative

Circulation Matthew Landry, Jaylen Lee, Lesley Tinker et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3098

Diet quality is a key modifiable risk factor for cardiovascular health. Racial and ethnic disparities in diet quality have been well-documented. However, few studies test how geographical context affects these associations in older women. Furthermore, these inequities have been reported to be unevenly distributed across different geographic regions in the United States (US). This analysis aimed to examine differences in diet quality across the four US Census 2020 regions (i.e., Northeast, Midwest, South, West) using data from the Women's Health Initiative (WHI) study. Informed by prior studies, we hypothesized that diet quality would differ across the four US Census regions, with the Northeast having the highest diet quality and the South having the lowest diet quality. In a secondary analysis of baseline data from the WHI, a large-scale longitudinal study of postmenopausal women, participants' dietary intake was assessed using a food frequency questionnaire. A Healthy Eating Index (HEI-2020) score was calculated as a measure of overall diet quality. Linear regression models were used to compare HEI-2020 scores across the four US Census regions adjusting for relevant sociodemographic covariates (age, education, income, employment, marital status, and race and ethnicity). In 161,299 women (M age = 63.2 ±7.2) with dietary intake data, mean HEI-2015 scores differed across regions, with the highest score in the West (63.7 ±0.1) and the lowest score in the Northeast (62.1 ±0.1). These regional differences persisted even after adjusting for sociodemographic covariates (p<0.001). Statistically significant interactions between race/ethnicity and census region on HEI-2020 total score were observed. Non-Hispanic White women living in the West region had the highest diet quality (64.9 ±0.2), while Hispanic women of any race in the Northeast had the lowest diet quality (61.1 ±0.1). This analysis reveals significant regional differences in diet quality among postmenopausal women across the US. Contrary to our hypothesis, WHI participants in the West region exhibited the healthiest diets and women in the Northeast region exhibited the least healthy diets. Findings highlight a need for targeted dietary assessments and public health initiatives to assess for regional differences in dietary intake. Given the disparities in diet observed in this analysis, other population-wide cohort studies should further account for potential geographic differences involving diet analyses.

Abstract MP68: Mosaic Chromosomal Alterations, Frailty and Cardiovascular Disease Mortality: A Population-based Cohort Study Among Chinese Adults

Circulation Mingyu Song, Yuxuan Zhao, Yuting Han et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.mp68

Background: Mosaic chromosomal alterations (mCAs), representing a group of large-scale structural alterations detected in a fraction of peripheral leukocytes, serve as an indicator of genomic aging. We aim to investigate the association between expanded mCAs (cell fraction ≥10%) and cardiovascular disease (CVD) mortality, and examine whether combining mCAs with frailty index (FI), an indicator of phenotipic aging, contribute to the prediction of CVD mortality. Methods: A total of 100,297 genotyped participants aged 30-79 years from China Kadoorie Biobank were included, whose baseline information were collected from 2004-2008 and followed till Dec 31, 2023. MoChA pipeline was used to detect expanded mCAs events, including mCAs on autosomes, and the loss of X and Y chromosomes. FI was calculated using a previously validated equation using 28 health-related variables, which categorized participants into three groups: robust (FI≤0.1), prefrail (0.1<FI≤0.25), and frail (FI≥0.25). We used Cox proportional hazards models to estimate the associations of the expanded mCAs, FI, as well as joint categories of expanded mCAs and FI with CVD mortality. Results: After a median follow-up of 17.2 years (IQR: 15.7-18.2), 13,655 deaths from CVD diseases were recorded. Expanded mCAs were associated with an increased risk of CVD mortality independent of FI (hazard ratio [HR] and 95% confidence interval [CI]=1.24 [1.13, 1.36]), including deaths from ischaemic heart diseases (IHD, 1.24 [1.08, 1.42]), from strokes (1.20 [1.03, 1.39]) and from pulmonary heart diseases (PHD, 2.20 [1.03, 4.68]). Compared with robust participants without expanded mCAs, frail participants with expanded mCAs had around three-times increased risks of CVD mortality (2.98 [2.17, 4.07]), deaths from IHD (3.18 [2.03, 4.96]), and death from strokes (2.79 [1.64, 4.74]), and had sixteen-times increased risks of PHD mortality (16.51 [3.63, 75.01]). Conclusion: Combining expanded mCAs, a novel pre-symptomatic marker, with frailty index might increase the prediction of death from multiple CVD diseases.

Novel 5-HT6R modulators as mTOR-dependent neuronal autophagy inductors

Scientific Reports José Miguel Alcaíno, Gonzalo Vera, Gonzalo Almarza et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92755-6

Early evidence of avocado domestication from El Gigante Rockshelter, Honduras

Proceedings of the National Academy of Sciences Amber M. VanDerwarker, Heather B. Thakar, Kenneth Hirth et al. Mar 11, 2025 DOI: 10.1073/pnas.2417072122

Molecular research suggests that avocados ( Persea americana Mill.) were domesticated multiple times in the Americas. Seed exchange, hybridization, and cloning have played an essential role across their wild distribution from Mexico to South America to create the modern varieties of today. Archaeological sites with well-preserved and directly radiocarbon-dated botanical assemblages are rare, however, so we know very little about the complexities of the domestication process. Here, we define an early locus of avocado domestication using well-dated desiccated and carbonized avocado remains from El Gigante rockshelter in western Honduras spanning the last 11,000 y. Measurements of avocado seeds and rinds show evidence for long-term management resulting in selection for larger, more robust fruits through time that culminated by 2,250 to 2,080 calendar B.P. (cal. B.P.). However, human-directed selection for larger fruits with thicker rinds is evident as early as 7,565 to 7,265 cal. B.P. Seed morphology is similar to P. americana var. guatemalensis and is congruent with genetic data for the development of this variety in both the highlands of Guatemala and Honduras. Increases in seed size and rind thickness through time are consistent with genetic evidence for the enrichment of putative candidate genes for fruit development and ripening in this variety.

Abstract P3086: Future Heart Motion Measurements in Deep Learning-based Predictive Imaging

Circulation Lucy Lu, Viswanathan Rajagopalan, Richard Segall Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3086

Introduction: Predicting the motion of heartbeats and the progression of cardiovascular diseases offers potential opportunities to provide early warnings and timely prevention, diagnosis, and/or treatment. However, quantitative measurement for predicting subsequent heart motion in medical imaging is unclear. We hypothesized that amplitude measurement in the frequency domain can be used to detect subsequent heart motion in a recurrent neural network architecture. Methods: We performed image annotations on two-dimensional echocardiographic videos from the public domain and defined the Regions of Interest from diseased/control left ventricular (LV) areas of beating human hearts (20 videos with 1500 frames each). Pathologies included myocardial infarction and aortic aneurysms. Following the reduction of video frames into one-dimensional sequences, we converted the sequences into the frequency domain using Fast Fourier Transform. We also used a deep learning-based recurrent neural network architecture, especially Long Short-Term Memory model to perform both one-class and two-class Time-Series Analyses. We subsequently performed quantitative evaluation of the analyses. Results: The Time-Series Analysis of amplitude measurements was able to successfully predict subsequent frames. For one-class Time-Series Analysis, the average accuracy for high-quality videos was 0.82 for both control and diseased regions. For all videos, the accuracy was 0.81 for control regions and 0.82 for diseased regions. For two-class abnormality detection, the average precision was 0.9996 for high-quality videos and 0.9353 for all videos, the average recall was 0.98116 for high-quality videos and 0.9215 for all videos, the average specificity was 0.9995 for high-quality videos and 0.9353 for all videos, the average sensitivity was 0.9996 for high-quality videos and 0.9353 for all videos, and the average accuracy was 0.8918 for high-quality videos and 0.8378 for all videos. We also generated the Area Under the Receiver Operating Characteristic curve (AUROC), and its average was 0.95. Conclusions: Using Fast-Fourier Transform and Long Short-Term Memory model, we successfully measured future heartbeats in both diseased and control LV walls. The results showed high precision, recall, sensitivity, specificity, and Receiver Operating Characteristics. These suggest that the progression of regional wall motion abnormalities may be predicted in cardiovascular diseases.

Abstract P1042: Effects of urban greenspace on time to major adverse cardiovascular events among women with breast cancer: Insights from the Greater Milwaukee Area

Circulation Jean Bikomeye, Sergey Tarima, Yuhong Zhou et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p1042

Background: Cardiovascular disease (CVD) remains a significant concern among breast cancer (BC) survivors, particularly following potentially cardiotoxic treatments, such as anthracyclines and anti-HER2 drugs, which increase the risk of major adverse cardiovascular events (MACE). Social determinants of health (SDOH) and environmental factors influence health outcomes, including those related to CVD. Greenspace has been associated with cardiovascular and cancer-related health benefits, yet its specific impact on MACE among BC survivors remains unknown. Objective: This study aims to investigate the association between urban greenspace and time to first MACE incidence among individuals with BC after being treated with cardiotoxic therapies in the greater Milwaukee, WI area. Methods: A retrospective cohort study was conducted using electronic medical records from the Froedtert Health System, linked to the National Death Index. Cox proportional hazards regression models were used to assess the association between percent tree canopy cover and MACE-specific hazards, adjusting for sociodemographic, clinical, and neighborhood-level factors. Results: Among the 849 women included, 44.6% experienced a MACE. Non-Hispanic Black (NHB) women had a higher proportion of MACE incidence. Adjusted models indicated a 18% and 20% lower MACE-specific hazard for women in the second and third quartiles of percent tree canopy cover, as compared to the women in the first (lowest) quartile, respectively. Racial/ethnic disparities in MACE incidence were evident, with the NHB group having a higher proportion of MACE (61.9%) compared to NHW women (41.6%). Discussion: Our findings suggest a protective effect of urban tree canopy on time to incident MACE among BC survivors receiving cardiotoxic treatments. These results underscore the importance of considering environmental factors in Cardio-Oncology care and highlight the benefits of greenspace in mitigating cardiovascular complications among individuals with BC. Future research should delve into environmental factors, behavioral factors, and biological mechanisms that underlie these associations. Additionally, longitudinal studies should be conducted to evaluate greenspace-based interventions for BC survivors, aiming to advance precision Cardio-Oncology interventions. Observed racial/ethnic disparities in MACE incidence underscore the urgent need for equity-focused interventions addressing greenspace access and MACE-related disparities.

Tick-borne encephalitis virus seroprevalence and infection incidence in Switzerland, 2020–2021

Scientific Reports Arthur Brêchet, Philipp Köhler, Tamara Dörr et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92560-1

EGFR-induced lncRNA <i>TRIDENT</i> promotes drug resistance in non–small cell lung cancer via phospho-TRIM28-mediated DNA damage repair

Proceedings of the National Academy of Sciences Tanvi Saxena, Anan Quan, Erica Chan et al. Mar 11, 2025 DOI: 10.1073/pnas.2415389122

Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript ( TRIDENT ), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non–small cell lung cancer. Knocking down TRIDENT leads to decreased tumor-cell proliferation in both in vitro and in vivo model systems and induces sensitization to chemotherapeutic drugs. Using ChIRP-MS analysis we identified TRIM28 as a protein interactor of TRIDENT . TRIDENT promotes phosphorylation of TRIM28 and knocking down TRIDENT leads to accumulation of DNA damage in cancer cells via decreased TRIM28 phosphorylation. Altogether, our results reveal a molecular pathway in which TRIDENT regulates TRIM28 phosphorylation to promote tumor cell growth and drug resistance. Our findings suggest that TRIDENT can be developed as a biomarker or therapeutic target for EGFR mutant non–small cell lung cancer.

Abstract P3150: Age-standardized trends in Incidence Rates of Noncommunicable diseases among Adults Aged 30 to 79 in Senegal from 2000 to 2019

Circulation Ngone GAYE, Mame Ka, Damaris Kyem et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p3150

Introduction: Noncommunicable diseases (NCD) represent a significant global health burden in Sub-Saharan Africa (SSA). However, most SSA countries lack reliable data despite the need for surveillance of NCD trends to inform targeted preventive strategies. Objective: To analyze trends over two decades in the incidence of NCD (cancers, cardiovascular diseases, chronic respiratory diseases, diabetes, and chronic kidney diseases) among adults in Senegal Methods: Data were sourced from the WHO Health Inequality Data Repository data. Using the Cox-Stuart test for trend, we compared trends of age-standardized incidence of NCD (cancers, cardiovascular diseases, chronic respiratory diseases, diabetes, and chronic kidney diseases) among adults aged 30-79 in Senegal from 2000 to 2019. Results: From 2000 to 2019, there was a non-significant increase in NCD incidence among adults in Senegal (p-value 0.08). The age-standardized incidence rate per 100,000 population increased steadily from 351,478 cases to 358,419 cases per 100,000 population from 2000 to 2019 (Figure 1). Incidence rates in females were consistently higher than in males. Rates in females increased from 190,856 cases to 194,619 cases per 100,000 population between 2000 and 2019 (p-value 0.33) as compared to 160,622 cases to 163,799 cases per 100,000 population in males (p-value 0.33). There were differences in the trends by sex among NCD subtypes (Figure 2). Incidence rates were higher in females for neoplasm (p-value 0.08), chronic respiratory diseases (p-value 0.08), and diabetes and chronic kidney diseases (p-value 0.08), while cardiovascular disease incidence was higher in males (p-value 0.08). Conclusion: There was a non-significant increase in age-standardized NCD incidence among adults in Senegal. Reliable epidemiological data, as well as targeted interventions focusing on risk factors, early detection, and access to quality health care, are crucial to improving health outcomes in Senegal.

Abstract P2119: MESA Heart Failure Risk Score: Trajectory and LE8 Healthy Behavior Impact in Brazilian Adults

Circulation Marcus Vinicius Nascimento-Ferreira, Augusto Cesar De Moraes Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2119

Background: Heart failure (HF) is a leading cause of mortality, particularly among older adults. HF risk scores developed in high-income Western countries are being incorporated into national guidelines in low- and middle-income countries (LMICs) without a systematic evaluation of their performance in these populations. Existing HF risk scores, including those recalibrated for LMICs, fail to accurately capture risk in Brazilian population. Objective: To evaluate the trajectory of the Multi-Ethnic Study of Atherosclerosis (MESA) heart failure (HF) risk score in a representative Brazilian sample over 10 years and its association with the Life’s Essential 8 health behaviors (LE8HB). Methods: We analyzed 13,664 Brazilian adults (54.4% women) from six cities, followed from 2008-2010 (W1), 2012-2014 (W2), and 2017-2019 (W3) from the ELSA-Brasil study. The primary outcome was the 10-year MESA HF risk score trajectory, composed of age, sex, smoking status, BMI categories, systolic blood pressure, heart rate, and diabetes status. LE8HB was evaluated based on diet, physical activity, nicotine exposure, and sleep, with scores categorized as high (80-100), moderate (50-79), and low (0-49). Multivariate regression models adjusted for alcohol intake, waist circumference, creatinine, income, and city assessed LE8HB's association with HF risk. Results: At W1, the mean age was 52.1 years, increasing to 59.6 years at W3. Over this period, the mean heart failure (HF) risk score significantly increased from 4.2 at W1 to 5.0 at W3. Concurrently, the proportion of participants with high adherence to LE8HB increased from 16.0% to 20.3%. We identified three distinct HF risk trajectory groups: low HF risk (W1 mean = 2.1, W2 = 2.3, W3 = 3.0), moderate HF risk (W1 = 4.6, W2 = 4.7, W3 = 5.4), and High HF risk (W1 = 7.7, W2 = 7.8, W3 = 8.6). Participants with higher LE8HB adherence had a significantly lower HF risk score (mean = 5.6, 95% CI: 5.4–5.8) compared to those with low LE8HB adherence (mean = 4.1, 95% CI: 3.9–4.3). Conclusion: The Multi-Ethnic Study of Atherosclerosis effectively stratified heart failure risk trajectories in Brazilian adults. Although heart failure risk increased across all groups, individuals with healthier behaviors consistently showed lower risk trajectories. The MESA score is a promising tool for recalibration, accounting for lifestyle patterns in the Brazilian population.

The virome investigation of the globally endangered Eld’s deer (Rucervus eldii) on Hainan Island, China

Scientific Reports Haoxiang Su, Dandan Zheng, Zihan Li et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92781-4

The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8 <sup>+</sup> T cells

Proceedings of the National Academy of Sciences Jiacheng Jin, Ruohan Zhang, Jianying Li et al. Mar 11, 2025 DOI: 10.1073/pnas.2424061122

Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction of cancer, requiring a substantial amount of proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role of transcriptional regulation in this process, paired transcriptomic and proteomic analyses reveal that the RNA profile is poorly correlated with protein levels. This discrepancy underscores the importance of post-translational modifications (PTMs) in controlling protein abundance during activation. However, the impact of PTMs on the CD8+ T cell protein dynamic remains underexplored. We identify that neddylation, a recently discovered PTM, is activated in response to T cell receptor (TCR) stimulation and enriched in effector CD8+ T cells from colon cancer patients. Mechanistically, we found the rate-limiting enzyme of neddylation, neural precursor cell expressed developmentally down-regulated protein 8 activating enzyme E1 (NAE1), is induced by the NFATc1, a critical transcription factor downstream of TCR signaling. Our observation revealed that genetic ablation of NAE1 significantly disturbed the proteomic landscape related to activation and mitochondrial function. As a result, CD8+ T cells lacking NAE1 exhibited severely compromised activation, proliferation, and survival, which was accompanied by impaired mitochondrial function. Consistently, deletion of NAE1 in CD8+ T cells abolished their antitumor function and promoted tumor progression. By contrast, the overexpression of NAE1 significantly improved the function of tumor-infiltrating CD8+ T cells. Overall, we uncovered neddylation, a previously underappreciated PTM, as a proteomic checkpoint for CD8+ T cell activation. Enforced expression of NAE1 offers promising therapeutic potential for boosting the antitumor CD8+ T cell responses.

Abstract P2091: Relations Between Plasma and Digitally-Obtained Neuropsychological Biomarkers: Data from the Disparities and Equity in Childhood Cardiovascular Exposures and Alzheimer’s Dementia (DECADE) Study

Circulation Ileana De Anda-Duran, Jessica Woo, Elaine Urbina et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2091

Background: Plasma proteins associated with Alzheimer’s disease (AD) include β-amyloid-42 (Aβ 42 ), phosphorylated -tau at threonine-181 (p-tau 181 ), and neurofilament light chain (NfL). This study assessed the relationship between these biomarkers and digital neuropsychological test performance. Methods: Middle-aged participants in the DECADE study had blood drawn and completed the Rowan Digital Cancellation Test (RDCT) consisting of 64 targets embedded among foils. Within 90 seconds, participants circled as many targets as possible, alternating between letters and symbols. RDCT outcomes included correct targets; ‘think’ time between correct targets; ‘ink’ time to circle correct targets; total pen strokes; commission errors; and total pen stroke distance and were summarized using factor analysis. Their association with AD biomarkers was done using linear regression. Results: The first 77 participants (age=55.3±8.7; 81.6% female) were included, with serum Aβ 42 (mean±SD: 7.8 + 2.7 pg/ml), p-Tau 181 (17.2 + 11.1 pg/ml), and NfL (10.5 + 13.8 pg/ml) assessed. Factor analysis identified 2 factors (Table). Higher scores on Factor 1 (49.2% variance) correspond to fewer correct responses, more think time, commission errors, and pen strokes. Higher scores on Factor 2 (27.9% variance) correspond to more correct responses, fewer commission errors, ink time, and pen strokes. Adjusting for age, sex, education, and both RDCT factor scores, NfL was negatively associated with Factor 2 (R 2 = 0.176, β= -0.445[JW1] , SE=2.57; p&lt; 0.01 ) suggesting worse RDCT test performance with increasing biomarker level. In contrast, Aβ42 was positively associated with Factor 1 (R 2 =0.268, β= 0.503, SE= p&lt; 0.003. Analyses involving p-Tau 181 were not significant. Conclusion: In this community-dwelling, middle-aged sample, plasma levels of AD-related proteins are associated with digital measures of neurocognitive performance. Middle-age assessment of serum AD-related proteins and digital neuropsychological performance have the potential to help identify emergent neurodegenerative illness.

Abstract P2108: Longitudinal Changes of Chemical Exposome on Blood Pressure after Bariatric Surgery among Adolescents

Circulation Shudi Pan, Zhenjiang Li, Qiran Jia et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2108

Background: The heterogeneous response in cardiometabolic outcomes following obesity treatment, such as bariatric surgery, is well documented, yet the underlying environmental contributors remain unclear. One potential factor is the chemical exposome which can have an obesogenic effect. To date, no prior studies have examined the longitudinal changes in chemical exposures after obesity treatment and their influence on cardiometabolic outcomes. This study aimed to assess the associations between chemical exposome trajectories and blood pressure after bariatric surgery among adolescents. Methods: We quantified the plasma chemical exposome in 5 classes (polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFAS), phthalates, pyrethroid pesticides and other pesticides) in plasma collected prior to surgery and post-surgery at 6-months, 1 year and 3 years using gas and liquid chromatography with high-resolution mass spectrometry. The cohort included 149 adolescents from the prospective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Outcomes were systolic and diastolic blood pressure measurements (SBP, DBP), mean arterial pressure (MAP) and pulse pressure at 3 years and 5 years following surgery. We used linear mixed models with random intercepts and slopes to estimate exposure trajectories, and model-based clustering based on each chemical exposure trajectories to generate aggregate exposure trajectory profiles. Linear regression was used to assess the associations of these profiles with blood pressure, adjusting for baseline age, race, sex, parents’ annual income, BMI and blood pressure medications. Results: Two distinct exposure trajectory profiles were generated based on longitudinal changes in individual chemicals. Profile 1 (100 participants) showed a decrease in pesticides and an increase in phthalates. Profile 2 (49 participants) showed the opposite trend. Compared with profile 1, profile 2 was statistically significantly lower for the association in MAP (b = -3.91 mmHg, 95%CI: -7.41, -0.41) and DBP (b = -3.41 mmHg, 95%CI: -6.68, -0.14) three years after bariatric surgery. The associations with blood pressure at five years were weaker. Conclusion: This study identified chemical exposome trajectory profiles after bariatric surgery and highlighted how longitudinal changes in these exposures may play an important role in explaining the heterogeneity in cardiometabolic outcomes after bariatric surgery.

Experimental study on gas permeability and radon control performance of red clay covering layer on uranium mill tailings pond

Scientific Reports Guokai Xiong, Jianyong Dai, Hong Wang et al. Mar 11, 2025 DOI: 10.1038/s41598-025-92362-5

Dynamic investigation of hypoxia-induced L-lactylation

Proceedings of the National Academy of Sciences Jinjun Gao, Ruilong Liu, Kevin Huang et al. Mar 11, 2025 DOI: 10.1073/pnas.2404899122

The recently identified histone modification lysine lactylation can be stimulated by L-lactate and glycolysis. Although the chemical group added upon lysine lactylation was originally proposed to be the L-enantiomer of lactate (K L-la ), two isomeric modifications, lysine D-lactylation (K D-la ) and N-ε-(carboxyethyl) lysine (K ce ), also exist in cells, with their precursors being metabolites of glycolysis. The dynamic regulation and differences among these three modifications in response to hypoxia remain poorly understood. In this study, we demonstrate that intracellular K L-la , but not K D-la or K ce , is up-regulated in response to hypoxia. Depletion of glyoxalase enzymes, GLO1 and GLO2, had minimal impact on K D-la , K ce , or hypoxia-induced K L-la . Conversely, blocking glycolytic flux to L-lactate under hypoxic conditions by knocking out lactate dehydrogenase A/B completely abolished the induction of K L-la but increased K D-la and K ce . We further observed a correlation between the level of K L-la and hypoxia-inducible factor 1 alpha (HIF-1α) expression under hypoxic conditions and when small molecules were used to stabilize HIF-1α in the normoxia condition. Our result demonstrated that there is a strong correlation between HIF-1α and K L-la in lung cancer tissues and that patient samples with higher grade tend to have higher K L-la levels. Using a proteomics approach, we quantified 66 K L-la sites that were up-regulated by hypoxia and demonstrated that p300/CBP contributes to hypoxia-induced K L-la . Collectively, our study demonstrates that K L-la , rather than K D-la or K ce , is the prevailing lysine lactylation in response to hypoxia. Our results therefore demonstrate a link between K L-la and the hypoxia-induced adaptation of tumor cells.

Abstract P2138: Childhood Parental Incarceration and Adverse Pregnancy Outcomes

Circulation Nicole Fields, Jaclyn Borrowman, Natalie Cameron et al. Mar 11, 2025 DOI: 10.1161/cir.151.suppl_1.p2138

Background: Adverse childhood experiences (ACEs) are associated with adverse pregnancy outcomes (APOs). However, the association between specific ACEs, such as parental incarceration, with APOs is not well understood. We examined whether: (1) childhood parental incarceration and its duration are associated with APOs and (2) if the association differed by race and ethnicity. Methods: Parous participants ≥ 18 years without: (1) history of CVD or diabetes and (2) did not have a pregnancy prior to age 18 in Wave V (2016-2018) of the US National Longitudinal Survey of Adolescent to Adult Health were analyzed. Childhood parental incarceration was defined as incarceration of the respondent’s parent/parental figure before age 18. Duration of parental incarceration was calculated by taking the difference of the age of respondents when the parent started and ended incarceration. Our outcome was defined as the self-reported occurrence of any APO (gestational diabetes, hypertensive disorder of pregnancy, small for gestational age, and pre-term birth). Multivariable logistic regression models assessed associations between parental incarceration and APOs. Covariates included age, difficulty paying bills, marital status, and smoking status during pregnancy. Models were stratified to assess interaction by race and ethnicity. Results: Among 2,088 participants, 234 (11.2%) reported a history of parental incarceration. Women with a history of parental incarceration were younger at first pregnancy, disproportionately Black, more likely to struggle paying bills, and had a higher prevalence of APOs. In unadjusted models, women who experienced childhood parental incarceration had 45% increased odds of experiencing an APO (OR 1.45; 95% CI: 1.10-1.92) but was nonsignificant after adjustment (OR 1.16; 95% CI: 0.83-1.62). Duration of incarceration was not associated with occurrence of APOs though the association differed by race such that a one-year increase in duration of parental incarceration was associated with 6% increased odds of having an APO among Black women (OR 1.06; 95% CI: 1.001-1.12). Conclusions: Longer duration of childhood parental incarceration was associated with higher odds of APOs for Black women. Future research should examine biological pathways by which parental incarceration contributes to deleterious health outcomes, particularly in minoritized communities.