tbuckley/cabot-search huggingface dataset:
Abstract P374: Understanding the Mediating Role of Allostatic Load on the Relationship Between Long-Term Financial Strain and Subclinical CVD Among Black Women: The Study of Women's Health Across the Nation (SWAN)
Authors: Brittany Brown-Podgorski, Emma Barinas-Mitchell, Jared W Magnani, Maria M Brooks, Rebecca C Thurston, Imke Janssen, Sherri-Ann M Burnett-Bowie, Carrie Karvonen-Gutierrez, Marian Jarlenski
Journal: Circulation (2024)

Introduction: Black adults are disproportionately burdened by poor cardiovascular health, and Black women bear the brunt of this disparity. Cardiovascular disease (CVD) disparities among Black women have been attributed to chronic exposure to psychosocial stressors and the cumulative “wear and tear” of these stressors on the body (i.e., allostatic load). Financial strain has been linked to both higher allostatic load and CVD risk. We aimed to determine whether allostatic load (AL) mediates the relationship between financial strain and cumulative CVD risk among Black women. Methods: This study utilized longitudinal data from the Black participants in the Study of Women's Health Across the Nation (SWAN). We conducted a causal mediation analysis with fourfold decomposition to determine if the relationship between long-term financial strain and subclinical CVD was mediated by AL. The study outcome was defined as the presence of any indicator of subclinical CVD from carotid ultrasounds conducted in visit 12/13: carotid artery intima-media thickness (cIMT) ≥ 75 th percentile of the study sample, carotid adventitial diameter (cAD) ≥ 75 th percentile of the study sample, or plaque index (a measure of number and size of plaques) &gt;2. Long-term financial strain was defined as reporting “money problems” or “difficulty paying for basics” at &gt;50% of the 6 most recent visits prior to the carotid ultrasound. AL was calculated using a validated summary score method based on 10 component measures from visit 12: systolic and diastolic blood pressure, serum glucose, BMI, triglycerides, C-reactive protein, HDL-C, total cholesterol, waist-to-hip ratio, and dehydroepiandrosterone sulfate. AL was considered “high” if the score was ≥75 th percentile of the study sample. Results: Of the 390 Black women in our sample [Mean (SD) age at subclinical CVD visit = 60.0 (2.7)], 42.3% had subclinical CVD (24.9% with cIMT or cAD, 9.7% with plaque), 56.9% reported long-term financial strain, and 38.0% had high AL. Both long-term financial strain (β=0.132, p &lt;0.01) and high AL (β=0.134, p &lt;0.01) were associated with a significantly higher likelihood of subclinical CVD. However, causal mediation analysis indicated that the effect of long-term financial strain on subclinical CVD was not mediated by AL (β=0.004, p =0.66). Conclusions: Though higher AL is associated with higher CVD risk among Black women, it did not mediate the causal relationship between long-term financial strain and CVD risk in these midlife women. Future research should examine the pathways by which financial strain and AL influence premature cardiovascular weathering among midlife Black women and explore potential large-scale interventions.
Abstract P373: Psychosocial Risk and Resilience Profile in Rural Alabama: A Preliminary Analysis of Risk Underlying Rural Areas Longitudinal (RURAL) Study
Authors: Larissa Benjamin, Stephanie Broyles, Ramachandran S Vasan, Viola Vaccarino, Tene T Lewis, Mahasin S Mujahid
Journal: Circulation (2024)

Background: Given the disproportionate burden of cardiovascular disease risk and outcomes, there is an urgent need to understand the psychosocial drivers of these inequities. We characterized the psychosocial risk and resilience profiles of a cohort of rural-dwelling adults in the southeast U.S. Methods: This preliminary analysis includes 765 participants with complete covariate data (mean age 47.9 (SD=10.9), 70.7% self-reporting as women, 77.9% Black individuals, 41.4% with annual household income below $15,000; 43.7% possessing a high school diploma/GED or lower) residing in two rural counties in Alabama, part of the larger RURAL study. We evaluated participants across six crucial psychosocial domains: financial strain (continuous), financial adjustments (categorized as 0, 1-3, 4+), housing stability (tertiles), childhood adversity (including general, physical, and emotional trauma experienced before 18 years, categorized into tertiles), depression (measured using CES-D 16; yes/no), and resilience (measured using CD-RISC, categorized into tertiles). We examined the distribution of study outcomes and conducted race and sex-based comparisons. Results: Resilience was high overall and did not vary significantly by race or sex. Significant racial disparities were observed, with Black participants experiencing higher financial strain (mean: 2.84 Black vs. 2.34 White), housing instability (30.1% Black vs. 11.9% White), and elevated depressive symptoms (35.2% Black vs. 25.3% White). Conversely, White participants reported greater general trauma and depression (highest tertile: 17.8% Black, 23.8 % White for general trauma; 64.3% Black vs. 73.8% White for depression). Sex-based differences were statistically insignificant across most psychosocial factors, except for financial adjustments (highest tertile: 27.7% men vs. 36.0% women) and physical trauma (38.0% men vs. 22.0% women). When considering the intersection of race and sex, Black men had the highest prevalence of housing instability (highest tertile: 35.2% Black men, 27.8% Black women, 6.8% White men, 15.8% White women), and elevated depressive symptoms (35.8% Black men, 35% Black women, 15.3 % White men, 31.6% White women). White men had the highest prevalence of physical trauma (highest tertile: 35.8% Black men, 21.3% Black women, 44.1% White men, 25.3% White women), and White women had the highest prevalence of financial adjustments (highest tertile: 30.3% Black men, 33.9% Black women, 20.3% White men, 46.3% White women). Conclusion: Our preliminary analysis of the RURAL study underscores substantial psychosocial adversity in these Southern rural communities. Future investigations should explore the relationship between these psychosocial factors and CVD risk to help identify potential intervention targets to improve cardiovascular health in rural communities.
Abstract P376: Comparison of Heart Failure Admission Rates Between Rural-Urban Continuum Code Designations
Authors: William B Burrows, Jimmy Robinson, Mary E Leigh, Meredith S Duncan, Anna Kucharska-Newton
Journal: Circulation (2024)

Introduction: Approximately 6 million adults in the US have heart failure (HF) and, from 2012 to 2030, the prevalence is estimated to increase by 46%. In 2017, the prevalence of HF among rural residents was 40% higher than among residents of small metropolitan and urban areas and this gap has continued to grow. However, only examining differences among metropolitan vs nonmetropolitan statistical areas or urban vs rural areas means it is impossible to understand within rural variation. Hypothesis: We assessed the hypothesis that county-level HF admission rates would differ by Rural-Urban Continuum Code (RUCC). Methods: Using 2017 data from the Healthcare Cost and Utilization Project, this cross-sectional study investigated the association between RUCC designation and county-level HF admission rates (number of admissions with a principal diagnosis of HF per 100,000 population aged 18+). The sample included 826 counties across 13 states. Rural, Urban, and Metro designations were defined through RUCCs. One-way ANOVA was performed to identify overall differences in HF admission rates across RUCC designations, with post-hoc pairwise comparisons performed using Tukey’s HSD. Results: There was a statistically significant difference in HF admission rates between at least two groups ( F (817, 8)=[13.99, p &lt;.001]). Results from 13 of the 36 pairwise comparisons were statistically significant ( Table ). Conclusion: We identified statistically significant differences in county-level HF hospital admission rates by RUCC. Metro counties had significantly higher HF admission rates than urban and rural counties, but differences across rural counties were not observed. HF prevalence is higher among rural Americans than those in urban and metro areas, but HF hospital admission rates in rural counties are much lower. Further research is needed to investigate the drivers of these differences in prevalence and healthcare utilization.
Abstract P377: Association Between Area Deprivation and Premature Cardiovascular Mortality in South Korea
Authors: Hyeon Chang Kim, Eunji Kim, Hokyou Lee, Donald M Lloyd-Jones, Young Gyu Ko, Byoung Gwon Kim
Journal: Circulation (2024)

Background: The underlying factors for regional disparities in cardiovascular disease (CVD) have yet to be fully understood. There is limited research on the effect of regional-level socioeconomic conditions on CVD mortality. This ecological study aims to investigate the association between area deprivation and premature death from CVD. Methods: The deprivation index was formulated with 10 socioeconomic indicators across all the 250 municipalities in Korea. Mortality rates from total CVD, ischemic heart disease, and cerebrovascular disease in adults &lt;65 years were directly standardized for sex and age using the total population structure. Municipalities are stratified by urbanicity, and the number of hospitals and the size of an area were adjusted in log-linear regression models. Results: The most deprived municipalities showed 41.6% excess mortality for total CVD, 30.3% for ischemic heart disease, and 36.9% for cerebrovascular disease, compared to the least deprived ones. Even after adjusting for the number of hospitals per unit area, the association of area deprivation was more significant in metropolitan areas than in other provinces. As one increment of the deprivation index increased, the adjusted rate ratios for total CVD were 1.031 (1.020-1.043) in metropolitans and 1.009 (1.000-1.019) in other provinces. Additional multilevel analyses showed consistent findings of higher risks in deprived areas. Conclusions: This study highlights a higher risk of premature cardiovascular death in socioeconomically disadvantaged areas. The CVD prevention strategies should reflect regional characteristics, with a particular focus on reducing the burden in deprived metropolitan areas.
Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice
Authors: Christopher A. Cottrell, Xiaozhen Hu, Jeong Hyun Lee, Patrick Skog, Sai Luo, Claudia T. Flynn, Katherine R. McKenney, Jonathan Hurtado, Oleksandr Kalyuzhniy, Alessia Liguori, Jordan R. Willis, Elise Landais, Sebastian Raemisch, Xuejun Chen, Sabyasachi Baboo, Sunny Himansu, Jolene K. Diedrich, Hongying Duan, Cheng Cheng, Torben Schiffner, Daniel L. V. Bader, Daniel W. Kulp, Ryan Tingle, Erik Georgeson, Saman Eskandarzadeh, Nushin Alavi, Danny Lu, Troy Sincomb, Michael Kubitz, Tina-Marie Mullen, John R. Yates, James C. Paulson, John R. Mascola, Frederick W. Alt, Bryan Briney, Devin Sok, William R. Schief
Journal: Science Translational Medicine (2024)

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01
Abstract P490: The Oral Microbiome and Prospective Risks of All-Cause and Cardiometabolic Mortality: The National Health and Nutrition Examination Survey
Authors: Hamdi S Adam, Ryan Demmer, Jim S Pankow
Journal: Circulation (2024)

Background: Dysbiosis of the oral microbiome and periodontitis (an inflammatory disease induced by dysbiosis) are plausible risk factors for cardiometabolic (CM) diseases. The relationship between the oral microbiome and CM mortality is less known. Hypothesis: Greater oral microbial diversity is associated with lower risks of all-cause and CM mortality, while poorer periodontal health is associated with greater mortality risk. Methods: We included n=5,255 adults aged 30+ from the National Health and Nutrition Examination Survey (NHANES) who had periodontal examinations and provided saliva samples at baseline. Baseline enrollment occurred in the 2009-2010 (n=2,681) and 2011-2012 (n=2,574) study cycles. Salivary microbiome data were generated in NHANES via 16s gene sequencing. Shannon and Inverse Simpson alpha diversity metrics were used to quantify oral microbial diversity for each participant. Clinical attachment loss (CAL) and probing depths from periodontal exams were included as historic and active measures of periodontitis, respectively. All-cause (non-accident deaths) and CM mortality (due to cardiovascular disease, cerebrovascular disease, diabetes, nephritis) through 2019 were ascertained via National Death Index linkages. We used multivariable Cox regression to compute hazard ratios and 95% confidence intervals (HR [95%CI]) of all-cause and CM mortality among 2 nd and 3 rd tertiles (vs 1 st tertile) of alpha diversity, CAL, and probing depth. We adjusted for study cycle, demographics, CM risk factors. Results: Mean age (SE) of participants was 48.1(0.2) years and 50% were men. Across 8.8 years of median follow-up, 193 all-cause deaths and 85 CM deaths occurred. Higher alpha diversity were associated with lower risks of all-cause and CM mortality, although non-significant. Relative risk of CM mortality in CAL Tertiles 3 vs. 1 is 1.81 (1.05, 3.09) (see Table ). Conclusion: Lower oral microbiome diversity and poorer indicators of periodontitis were not associated with all-cause and CM mortality.
Abstract P497: Saliva, Plasma, and Multi-Fluid Metabolomic Profiles of Excess Adiposity and Their Associations With Diabetes Progression Among Puerto Ricans
Authors: Zicheng Wang, Caleigh M Sawicki, Danielle E Haslam, Liming Liang, David T Wong, Kaumudi J Joshipura, Frank B Hu, Jorge E Chavarro, Shilpa N Bhupathiraju
Journal: Circulation (2024)

Introduction: Plasma metabolomic profiles of BMI are associated with type 2 diabetes (T2D) risk but none have examined saliva or combined information from multiple biofluids. Our aim was to identify plasma, saliva, and plasma-saliva multi-fluid metabolomic profiles of BMI and waist circumference (WC) and examine their associations with diabetes progression. Methods: We included 911 participants from the San Juan Overweight Adult Longitudinal Study, a 3-year prospective cohort of overweight Puerto Ricans. At baseline, using LC-MS, we quantified metabolites from saliva (n=635) and plasma (n=1,051). We used elastic net regression with 10-fold cross-validation to identify metabolomic profiles from plasma, saliva, and plasma and saliva (multi-fluid) that were predictive of BMI and WC. We used Cox-proportional hazard models to evaluate associations between metabolomic profiles and diabetes progression adjusting for age, sex, socioeconomic factors, lifestyle, and medication use. Results: For BMI metabolomic profiles, we identified 207 metabolites in plasma, 118 metabolites in saliva, and 225 in the multi-fluid profile. For WC, we identified 157, 89, and 210 metabolites for plasma, saliva, and multi-fluid profiles, respectively. Highly positively weighted metabolites across all BMI and WC metabolomic profiles included those in pathways of alanine and aspartate metabolism, purine metabolism, and sphingomyelins. BMI and WC metabolomic profiles were highly correlated (r=0.80-0.88). Each SD increase in saliva, but not plasma or multi-fluid, metabolic profile of BMI was significantly associated with diabetes progression (Table). Saliva, but not plasma or multi-fluid, metabolomic profile of WC was significantly associated with progression from pre-diabetes to T2D. All associations became stronger after further adjustment for anthropometric measures of BMI and WC. Conclusion: Saliva is an underexplored and easily accessible biofluid to measure metabolites that associate with diabetes progression.
Abstract P496: Proteomic BMI Signature and Incidence of Type 2 Diabetes
Authors: Xuan Wang, Hao Ma, Xiang Li, Yoriko Heianza, Lu Qi
Journal: Circulation (2024)

Background: Obesity exhibits heterogeneity in physiological states and metabolic phenotypes cross individuals. A recent study identified a proteomics signature of obesity which better captures such heterogeneity than classical Body Mass Index (BMI). Aims: We aimed to create a proteomics-inferred BMI signature and investigate whether the proteomic-inferred BMI was associated with incident Type 2 Diabetes (T2D). Methods: This study included 34,317 adults in the UK Biobank who were free of T2D and had complete data on proteomics metrics assessed by antibody-based Olink assay. Sixty-seven pre-identified proteins were available and used to create the proteomic BMI signature. Cox proportional models were used to estimate the association between proteomic BMI signature and incident T2D. Results: The proteomic BMI signature was strongly correlated with actual BMI (Pearson correlation coefficients=0.75, P &lt;0.001). During a mean follow-up of 13.2 years, a total of 1,651 T2D events were documented. We observed that per standard deviation increase in proteomic BMI signature was significantly associated with a 250% higher risk of T2D (HR, 2.50, 95%CI, 2.37, 2.64). Compared with the lowest Quartile, the HR (95%CI) for the Quartile 2 to the Quartile 4 of proteomic BMI signature were 2.06 (1.61, 2.64), 3.56 (2.83, 4.48), and 10.0 (8.08, 12.4), respectively ( P -trend&lt;0.001). Also, we observed that the associations between proteomic BMI signature and incident T2D were stronger in women than men ( P for interaction &lt; 0.001). Compared with the lowest Quartile, the HR (95%CI) for highest Quartile of proteomic BMI signature were 16.63 (9.75, 28.36) for women and 8.06 (6.37, 10.19) for men. Conclusions: Higher proteomics-inferred BMI was significantly associated with higher risk of incident T2D, and such association was stronger in women than men. Our results suggest that proteomic BMI signature may serve as a surrogate metabolic indicator to better understand the mechanism underlying the association of BMI and T2D.
Targeting micromotion for mimicking natural bone healing by using NIPAM/Nb2C hydrogel
Authors: Qianhao Yang, Mengqiao Xu, Haoyu Fang, Youshui Gao, Daoyu Zhu, Jing Wang, Yixuan Chen
Journal: Bioactive Materials (2024)

Natural fracture healing is most efficient when the fine-tuned mechanical force and proper micromotion are applied. To mimick this micromotion at the fracture gap, a near-infrared-II (NIR-II)-activated hydrogel was fabricated by integrating two-dimensional (2D) monolayer Nb
Evolutionary Dynamics of Chromatin Structure and Duplicate Gene Expression in Diploid and Allopolyploid Cotton
Authors: Guanjing Hu, Corrinne E Grover, Daniel L Vera, Pei-Yau Lung, Senthil B Girimurugan, Emma R Miller, Justin L Conover, Shujun Ou, Xianpeng Xiong, De Zhu, Dongming Li, Joseph P Gallagher, Joshua A Udall, Xin Sui, Jinfeng Zhang, Hank W Bass, Jonathan F Wendel
Journal: Molecular Biology and Evolution (2024)

Abstract Polyploidy is a prominent mechanism of plant speciation and adaptation, yet the mechanistic understandings of duplicated gene regulation remain elusive. Chromatin structure dynamics are suggested to govern gene regulatory control. Here, we characterized genome-wide nucleosome organization and chromatin accessibility in allotetraploid cotton, Gossypium hirsutum (AADD, 2n = 4X = 52), relative to its two diploid parents (AA or DD genome) and their synthetic diploid hybrid (AD), using DNS-seq. The larger A-genome exhibited wider average nucleosome spacing in diploids, and this intergenomic difference diminished in the allopolyploid but not hybrid. Allopolyploidization also exhibited increased accessibility at promoters genome-wide and synchronized cis-regulatory motifs between subgenomes. A prominent cis-acting control was inferred for chromatin dynamics and demonstrated by transposable element removal from promoters. Linking accessibility to gene expression patterns, we found distinct regulatory effects for hybridization and later allopolyploid stages, including nuanced establishment of homoeolog expression bias and expression level dominance. Histone gene expression and nucleosome organization are coordinated through chromatin accessibility. Our study demonstrates the capability to track high-resolution chromatin structure dynamics and reveals their role in the evolution of cis-regulatory landscapes and duplicate gene expression in polyploids, illuminating regulatory ties to subgenomic asymmetry and dominance.
Increased risk of depression and anxiety in individuals with Darier disease
Authors: Philip Curman, William Jebril, Henrik Larsson, Etty Bachar-Wikström, Martin Cederlöf, Jakob D Wikström
Journal: British Journal of Dermatology (2024)

Patients with Darier disease have an increased risk of depression and anxiety, which agrees with patterns of increased prescription of antidepressants and anxiolytics in people with the disease.
Connecting Species-Specific Extents of Genome Reduction in Mitochondria and Plastids
Authors: Konstantinos Giannakis, Luke Richards, Kazeem A Dauda, Iain G Johnston
Journal: Molecular Biology and Evolution (2024)

Mitochondria and plastids have both dramatically reduced their genomes since the endosymbiotic events that created them. The similarities and differences in the evolution of the two organelle genome types have been the target of discussion and investigation for decades. Ongoing work has suggested that similar mechanisms may modulate the reductive evolution of the two organelles in a given species, but quantitative data and statistical analyses exploring this picture remain limited outside of some specific cases like parasitism. Here, we use cross-eukaryote organelle genome data to explore evidence for coevolution of mitochondrial and plastid genome reduction. Controlling for differences between clades and pseudoreplication due to relatedness, we find that extents of mtDNA and ptDNA gene retention are related to each other across taxa, in a generally positive correlation that appears to differ quantitatively across eukaryotes, for example, between algal and nonalgal species. We find limited evidence for coevolution of specific mtDNA and ptDNA gene pairs, suggesting that the similarities between the two organelle types may be due mainly to independent responses to consistent evolutionary drivers.
Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model
Authors: Yuanyuan Jin, Danyang Cai, Lihua Mo, Gaosa Jing, Li Zeng, Hui Cheng, Qi Guo, Mali Dai, Yuqin Wang, Jinrun Chen, Guojun Chen, Xingyi Li, Shuai Shi
Journal: Biomaterials (2024)
ATP Inhibition for Starvation/Mild Photothermal/Photodynamic Synergy Therapy Using Polypeptide Nanoparticles Conjugating 2‐Deoxy‐D‐Glucose and Dye under NIR Phototheranostic Strategy
Authors: Yixuan Xu, Huiping Dang, Changchang Teng, Dalong Yin, Lifeng Yan
Journal: Advanced Healthcare Materials (2024)

Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down-regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2-deoxy-D-glucose (2DG) is an anti-glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low-temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx-BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as-prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR-I/II fluorescence imaging-guided starvation/MPTT/PDT synergy therapy for tumors.