tbuckley/cabot-search huggingface dataset:
Abstract P468: Correlation Among A1c Improvement, Weight Reduction, and Decreased ASCVD Risk in Participants Enrolled for Type 2 Diabetes Remission: Outcomes at 1 Year From an RCCT Using Whole-Body Digital Twin Technology
Authors: Paramesh Shamanna, Mala Dharmalingam, Arun Vadavi, Mohamed Thajudeen, Ashok Keshavamurthy, Suchitra Bhonsley, Shashank Joshi
Journal: Circulation (2024)

Background and Aims: The effects of digital twin (DT) technology for remission of T2D on cardiovascular risk reduction is unknown. We evaluated the effectiveness of the DT to improve A1c and body weight and ASCVD risk, in patients enrolled to achieve remission of T2DM. DT platform uses AI and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the mobile app and by coaches. Materials and Methods: Data from 208 participants who had been on DT for 1 year were analyzed. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Outcomes included the change in HbA1c, body weight and change in ASCVD risk scores. The DT uses a machine learning algorithm to integrate clinical and sensor data to predict personal glucose response. Patients were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using the mobile app. Results: The study participants had a mean diabetes duration of 3.7±2.7 years and a mean age of 44±8.5 years. Based on the ADA criteria, at 1 year, 72.6% (n=151/208) continued to be under remission. The mean 10-year ASCVD risk (%) at baseline was 7.9 (±7.8, 95% CI 6.8 to 8.9) which reduced to 3.6 (±4, 95% CI 3.1 to 4.2) at 360 days, p&lt;0.0001. A1c (%) at baseline was 8.9 (±1.8, 95% CI 8.7 to 9.2, minimum 5.5, maximum 16.2) which reduced to 6 (±0.6, 95% CI 5.9 to 6.1, minimum 4.7, maximum 9.2), p&lt;0.0001. Body weight (kg) at baseline was 78 (±14.3, 95% CI 76.1 to 79.9) which reduced to 70.4 (±12.9, 95% CI 68.7 to 72.1), p&lt;0.0001. There was a significant correlation between the reduction in A1c and ASCVD (Pearson r 0.41, 95% CI 0.31 to 0.5, p&lt;0.0001). Similarly, there was a significant correlation between the reduction in body weight and ASCVD (Pearson r 0.25, 95% CI 0.12 to 0.3, &lt;0.0001). At baseline, there were 49% of participants who had low risk score (&lt;5%), 16% as borderline risk (5-7.5%), 27% as intermediate risk (7.5-19.9), 8% as high risk (&gt;20%) that at 1 year shifted to 77% as low risk, 11% as borderline, 11% as intermediate risk and 1% as high-risk scores. Conclusion: The implementation of digital twin (DT) technology, utilizing AI and Internet of Things, demonstrated significant potential in T2DM management in participants enrolled to achieve remission. In our study with 208 participants, DT effectively reduced A1c levels, body weight, and ASCVD risk scores over 360 days. The correlations between reductions in A1c, body weight, and ASCVD underscore the potential of DT as a transformative tool in diabetes and cardiovascular risk management.
Abstract P331: Diet and Probiotic Administration Significantly Influence Behavior and Forebrain Inflammation in Male Mice
Authors: Nathan Lichti, Brian Kagel, Jonathan D Westlake, Shreya Singh, Jeffrey Houghton, Joseph Gigliotti
Journal: Circulation (2024)

There is a high degree of comorbidity between psychological and gastrointestinal disease, which implies a functional relationship exists between the two systems. Collectively, research suggests that the gut-brain axis is bidirectional, and involves complex relationships between immune, neural, endocrine, and metabolic pathways. In this pilot study, we seek to further investigate the microbiome’s role in a bottom-up model by studying the short-term effects of different diets and probiotic supplementation on behavior and the expression of inflammatory biomarkers in the forebrain. Weanling, male C57Bl/6 mice were purchased from a commercial vendor and acclimated to a solid diet for one-week. Mice were randomly assigned to receive one of three diets for eight weeks: chow, the American Institute of Nutrition 1993 formulation (AIN), or our novel Americanized diet (AD). After six-weeks of diet, mice were then administered a commercially available probiotic, or water control, for the final two weeks of the study. Aggressive tendencies were measured during the probiotic administration period and dietary intake was recorded during the final week of the study. Animals were then euthanized and the forebrain was dissected and processed for the quantification of mRNA for Bdnf (BDNF), Nfkb1 (Nf-κb), Gfap (GFAP), Ptgs2 (PTGS2), and Nr3c1 (NR3C1) by real-time RT-PCR. Data were analyzed using General Linear Model Procedures in SPSS with significance determined at P&lt;0.05. There was a significant decline (P&lt;0.001) in aggressive behavior over the testing period, and mice administered the probiotic tended (P=0.15) to display less signs of aggression regardless of the diet. For dietary intake, there was a numerical increase in daily caloric intake in mice consuming the AD (~13 kcal/day), while mice consuming chow and AIN were similar (9 and 10 kcal/day, respectively). Additionally, there were numerical differences between probiotic and control groups for two of the diets. Quantification of gene expression in the forebrain revealed that diet significantly (P=0.002) affected GFAP expression, with mice consuming chow having significantly lower values than mice fed AIN or AD. Probiotic treatment significantly (P=0.02) affected NF-κB expression, with mice administered the probiotic having greater forebrain NF-kb as compared to control mice. This was most obvious in mice fed the chow and AIN diets, but not the AD. Collectively, our pilot study’s findings suggest that short term probiotic supplementation and dietary variation have potential effects on neuroinflammation, brain function, and satiety. Furthermore, our data indicates that the efficacy of probiotic administration is dependent upon the quality of diet consumed.
Abstract P141: T2D-DNA Methylation Score and Changes in Glycemic Traits in Response to Weight-Loss Dietary Interventions: The MACRO Trial
Authors: Xiang Li, Minghao Kou, Hao Ma, Xuan Wang, Lydia A Bazzano, Lu Qi
Journal: Circulation (2024)

Introduction: Epigenome-wide association studies (EWAS) have identified several CpGs associated with type 2 diabetes (T2D). A previous study has shown that a DNA methylation score provided more comprehensive information related to T2D risk than individual CpGs. However, whether such T2D-DNA methylation score is associated with changes in glycemic traits in response to weight loss dietary interventions remains unknown. Hypothesis: We hypothesized that a T2D-related DNA methylation score was associated with changes in glycemic traits in response to weight-loss dietary interventions; and may modify the effect of the interventions. Method: The current study included 147 participants from the MACRO trial, who were randomly assigned to a low-fat diet or a low-carbohydrate diet. A weighted DNA methylation score was created by 5 CpGs (cg19693031 at TXNIP , cg11024682 at SREBF1 , cg02650017 at PHOSPHO1 , cg18181703 and SOCS3 , and cg06500161 at ABCG1 ) from a previous EWAS at baseline. One-year changes in glycemic traits were calculated. Results: We found that a higher DNA methylation score was significantly associated with greater reductions in glucose (β: -3.20, SE: 1.08, p=0.003), insulin (β: -2.29, SE: 0.86, p=0.009), and homeostasis model assessments of insulin resistance (HOMA-IR, β: -0.86, SE: 0.30, p=0.005). The DNA methylation score was more strongly associated with changes in glycemic traits than any individual CpG sites ( Figure ). In addition, DNA methylation score significantly interacted with dietary interventions (low-fat vs. low-carbohydrate). The beneficial associations appeared to be stronger among participants with the low-carbohydrate diet (p-interaction=0.009 for glucose, 0.003 for insulin, and 0.004 for HOMA-IR). Conclusions: Our data indicate that a higher DNA methylation score was significantly associated with greater reductions in glycemic traits in response to weight-loss dietary interventions; such beneficial associations were stronger among those who consumed a low-carbohydrate diet.
Abstract P229: Cross-Sectional Relationship Between Posttraumatic Stress Disorder and Atherosclerotic Disease Assessed by Coronary Calcium Score: A Counterfactual Model of Older Male Twins
Authors: Luis C Correia, Amit J Shah, Valeria M Moncayo, Yi-An Ko, Nicholas L Smith, Jeffery Osei, Louis Li, Arshed A Quyyumi, J. Douglas Bremmer, Viola Vaccarino
Journal: Circulation (2024)

Background: Posttraumatic stress disorder (PTSD) is a risk factor for cardiovascular disease. However, the causal relationship between PTSD and atherosclerotic burden is controversial, leaving uncertain whether atherosclerosis is implicated in the association between PTSD and cardiovascular events. Objective: To test the cross-sectional relationship between lifetime PTSD and coronary atherosclerotic burden assessed by calcium score by comparing PTSD-discordant twin pairs, a design that inherently controls for familial and early environmental factors. Methods: We examined 218 male twins from the Vietnam Era Twin Registry, who underwent coronary calcium score assessment with computed tomography as part of the Emory Twin Study Follow-Up study. Lifetime history of PTSD was obtained with the Structured Clinical Interview and PTSD symptom severity with the Clinician-Administered PSTD Scale (CAPS) for DSM-IV diagnostic criteria. Coronary calcium scoring was performed by the Agatston Method as a measure of atherosclerotic burden. The relationship between PTSD and calcium score was tested across individuals and within PTSD-discordant twin pairs as a counterfactual model for genetic and early environmental factors. Initially, 2 linear mixed models were built according to the exposure variable (PTSD clinical diagnosis or symptoms scale), with log-transformed coronary calcium score as the dependent variable. We defined a priori that the model with the lowest Akaike Information Criteria (AIC) would be the primary analysis to drive the conclusion. Based on a priori direct acyclic graph decision process, we defined the need to adjust for income and education as potential confounders and not to adjust for traditional risk factors, considering their potential roles as mediators. Results: Of the 218 twins analyzed, the median age was 68 (IQR 67-70) years, and the calcium score had a median of 114 (IQR 5.2-347). There were 88 twin pairs (30 monozygotic), 26 discordant for the binary diagnosis of PTSD, and 40 discordant for the ordinal PTSD symptom score (within-pair differences in scale points ranged from zero to 48.5). The model with the best AIC was the one with the PTSD score, and showed no increment of log-calcium score as the PTSD symptoms increased, both between individuals (Beta coefficient = - 0.005; 95% CI = -0.02 to + 0.03) and within twin pairs (Beta coefficient = - 0.010; 95% CI = -0.03 to + 0.01). Conclusion: The present analysis does not support a relationship between PTSD and coronary atherosclerotic burden. The link between PTSD and cardiovascular events may occur through other pathways, such as microvascular disease.
Abstract P447: Heart Disease Health Disparities Among Native Hawaiian and Pacific Islander Communities in the United States: A Systematic Review
Authors: Lan N Doan, Michelle Murata, Raynald A Samoa, Erinn Hade, Stella S Yi
Journal: Circulation (2024)

Background: Heart disease is a leading cause of death among Native Hawaiian and Pacific Islander (NH/PI) communities. However, the nature of disease development and risk factors is not well characterized due to poor availability of disaggregated data, hampering efforts towards the design and implementation of culturally-relevant interventions. The purpose of our review is examine known gaps in heart disease prevention measures and programs for NH/PI populations to identify opportunities to mitigate health disparities through structural- and provider-level factors. Methods: We conducted a systematic search of PubMed, Embase, and CINAHL databases to identify peer-reviewed articles focused on heart disease (coronary artery disease, heart attack, heart failure) in NH/PI populations. Eligible studies were assessed for their relevance to NH/PI populations living in the US, US territories and Freely Associated States and their coverage of topics such as prevalence, risk factors, cultural determinants, prevention, and management. Results: Of the 1,440 articles initially identified (3 duplicates removed), 1,437 article titles and abstracts were screened, 585 full-text articles were screened for eligibility and 68 articles were included for analysis. The main reasons for exclusion were the absence of NH/PI individuals, lack of focus on heart disease, grouping NH/PI people with Asian American and other racial groups, and studies conducted outside the US (e.g., Australia, New Zealand). Many of the included articles examined prevalence, risk factors, health behaviors, knowledge, and healthcare utilization, from sources such as the Multiethnic Cohort Study, Behavioral Risk Factor Surveillance Systems, National and Hawaii Vital Statistics and claims data. Culturally-grounded interventions, community-based programs, and initiatives (e.g., Native Hawaiian Health Research Project, Ohana Heart Project, Pacific Islander Health Care Project, Wahine Heart Wellness Program), which incorporate traditional practices, were identified as showing promise in reducing risk and improving heart health among NH/PI adults. Conclusion: The review unveiled a disproportionate burden of heart disease and high prevalence of obesity, diabetes, and hypertension among NH/PI communities, often attributable to lifestyle behaviors, socioeconomic factors, and limited access to healthcare. These disparities are compounded by the underrepresentation of NH/PI populations in national health surveys and the scarcity of comprehensive epidemiological studies featuring robust NH/PI samples. It is evident that further research and policy initiatives are crucial to increase research investments and promote data equity and disaggregation for this population.
Abstract MP62: Adherence to Guideline-Recommended Physical Activity Nullifies Mortality Risks of Extended Sitting in Adults With Diabetes
Authors: Wen Dai, Sandra S Albrecht
Journal: Circulation (2024)

Introduction: Sedentary lifestyles have been associated with increased mortality for people with diabetes. While most governments and health organizations advocate for adults with diabetes to engage in at least 150 min/week of moderate-to-vigorous physical activity (MVPA), it is unclear whether meeting these guidelines can mitigate the heightened mortality risks associated with prolonged sedentary time in this population. Hypothesis: We hypothesized that adhering to the guideline-recommended 150 min/week of MVPA could mitigate the mortality risk from prolonged sedentary time in U.S. adults with diabetes. Methods: This study included 3,533 nonpregnant adults aged 20 years diagnosed with diabetes from the U.S. National Health and Nutrition Examination Survey (2007-2018). Sitting time and MVPA were assessed using the Global Physical Activity Questionnaire. We analyzed sitting time as both a continuous variable (h/d) and as a categorical variable (&lt;4, 4-&lt;6, 6-8, &gt;8 h/d). The mortality status of the participants were ascertained via linkage to the National Death Index by December 31, 2019. Hazard ratios (HRs) and 95% CIs for associations between sitting time and mortality were estimated using Cox models, adjusted for sociodemographic characteristics, lifestyle factors, and Carlson comorbidity index, stratified by MVPA (inactive [&lt;10 min/week], insufficiently active [10-&lt;150 min/week], active [150 min/week]). The presence of multiplicative effect measure modification was evaluated by contrasting the model incorporating continuous sitting time, categorical MVPA, and their interaction term, and the model excluding the interaction. We accounted for the NHANES complex survey design (sampling weights, clustering, and stratification) in all analyses. Results: Among 3,533 adults diagnosed with diabetes (mean [SE] age: 60.3 [0.3] years; 48.7% females; 60.6% non-Hispanic White), 695 deaths were documented over a median (interquartile range) follow-up of 5.6 (3.1-8.7) years. In the fully adjusted models, sitting time was positively associated with mortality risk among adults with diabetes who were physically inactive or insufficiently active but not among active adults ( P for interaction=0.04). Specifically, the HRs (95% CIs) of mortality for 1h/d increment in sitting time across MVPA levels were 1.08 (1.04, 1.12) in inactive adults, 1.09 (1.01, 1.18) in insufficiently active adults, and 1.01 (0.96, 1.06) in active adults. Results remained unaltered when comparing the most sedentary (&gt;8 h/d) to the least sedentary (&lt;4 h/d) categories: across MVPA levels (from low to high), the HRs (95% CIs) of mortality were 1.83 (1.23, 2.72), 1.84 (0.81, 4.17), and 1.11 (0.73, 1.69), respectively. Conclusions: Our findings show that achieving 150 min/week of MVPA can substantially mitigate the elevated mortality risks associated with extended sitting time among U.S. adults with diabetes.
Abstract P520: Sleep Duration and Quality Associated With Behavioral Cardiometabolic Health in Israel: Jewish / Arab Ethnic Differences
Authors: Michael A Grandner, Suzanne Gorovoy, Kathryn Kennedy, Dora Valencia, Elizabeth Rasmussen, Elliot Rosenberg
Journal: Circulation (2024)

Introduction: The role of sleep health in global cardiometabolic disparities has not been sufficiently explored as a modifiable factor. Israeli Jews and Arabs share national and cultural experiences, but differ with respect to important historical, socio-economic, and cultural aspects. Hypothesis: Jewish/Arab Israeli disparities in cardiometabolic health may be partially explained by differences in sleep. Methods: 7,230 Israeli individuals (N=5880 Jews and N=1350 Arabs) responded to the 2017 Israeli Bureau of Statistics population-based survey of households. Behavioral risk factors included poor diet (&lt;4 servings/day of vegetables), sedentary lifestyle (no exercise within the past 3 months), smoking, and obesity (based on self-reported height and weight). Sleep variables included sleep duration (&lt;=5, 6, 7, 8 [reference], or &gt;=9 hours) and sleep difficulty in the past month (none [reference], mild, moderate, or severe). Covariates included age and sex. Results: Israeli Arabs were more likely to be smokers (OR=1.41), sedentary (OR=1.44), obese (OR=1.73), and consume &lt;4 vegetable servings (OR=3.23). In adjusted analyses of sleep duration, smoking was associated with &lt;=5h (OR=1.49, 95%CI [1.23,1.80], p&lt;0.0005) and &gt;=9h (OR=1.33, 95% CI [1.02,1.72], p=0.035), and it was associated with moderate (OR=1.45, 95%CI [1.21,1.75], p&lt;0.0005) and severe (OR=1.57, 95%CI [1.33,1.86], p&lt;0.0005) sleep difficulties. A significant duration-by-ethnicity interaction was observed (p=0.003). Stratified analyses showed that smoking was associated with &lt;=5h and 6h and relationships were stronger in Israeli Arabs. Insufficient vegetable consumption was associated with moderate (OR=1.25, 95%CI [1.04,1.52], p=0.02) and severe (OR=1.32, 95%CI [1.12,1.57], p=0.001) sleep difficulties. A significant duration-by-ethnicity interaction was observed (p=0.02). In stratified analyses, no relationships were seen among Israeli Jews, but among Israeli Arabs, insufficient vegetable consumption was negatively associated with shorter sleep. Sedentary lifestyle was associated with severe sleep difficulties (OR=1.31, 95%CI [1.04,1.65], p=0.02). No interactions were found. Obesity was associated with &lt;=5h (OR=1.36, 95%CI [1.10,1.68], p=0.004) and severe sleep difficulties (OR=1.40, 95%CI [1.17,1.67], p&lt;0.0005). A significant duration-by-ethnicity interaction was found. In stratified analyses, among Israeli Jews, obesity was associated with 7h sleep duration, but among Israeli Arabs, obesity was associated with &lt;=5h, 6h, and &gt;=9h. Conclusions: Behavioral cardiometabolic health factors were associated with poor sleep health, but these relationships were generally stronger among Israeli Arabs. Sleep health may be a fruitful intervention target to reduce disparities.
Abstract MP66: Accelerometer Measured Diurnal Movement Patterns Associated With Frailty in Older Adults: UK Biobank
Authors: Lingsong Kong, Chi Hyun Lee, Susan R Sturgeon, Cassandra N Spracklen, Amanda E Paluch
Journal: Circulation (2024)

Introduction: Frailty is a significant health challenge for the aging population. Older adults with cardiovascular diseases (CVD) tend to be physically inactive and have a high risk of frailty. Little is known about the relationship between diurnal movement patterns and frailty and whether this association differs in older adults with and without CVD. Hypothesis: Less morning, afternoon, and evening movements but more night movements are associated with frailty, especially among those with CVD. Methods: This cross-sectional study included 10,082 participants ≥ 65 years (66.8±1.5 years; 49% female) from UK Biobank. CVD status was identified using ICD-9&amp;10 diagnosis and self-reported CVD. Participants wore Axivity AX3 on the dominant wrist for 7 days, 24 hours/day. Mean accelerations during night (12-6 am), morning (6 am-12 pm), afternoon (12-6 pm) and evening (6 pm-12 am) were calculated. Frailty was determined using Modified Fried Frailty Phenotype. Multivariate logistic regression models were used to examine associations between total movement and diurnal movement patterns with frailty, stratified by CVD status. Results: The diurnal movement patterns showed lower movements during night, increasing during morning, peaking at noon, and decreasing in afternoon and evening, with frail CVD adults having the lowest accelerations during all daytime hours (6 am-midnight). In both CVD and non-CVD older adults, each 5 mg higher overall mean acceleration was associated with 11-18% lower odds of frailty ( Table ). Each 5 mg higher mean acceleration during morning, afternoon and evening was associated with 5-10% lower odds of frailty ( Table ). Every 5 mg higher mean acceleration during night was associated with 14% higher odds of frailty only in non-CVD older adults ( Table ). Conclusions: More activity during any daytime period was associated with lower odds of frailty among older adults in both with and without CVD. Greater night activity was associated with higher odds of frailty, primarily observed in older adults without CVD.
On‐Demand Activatable and Integrated Bioorthogonal Nanocatalyst against Biofilm‐Associated Infections
Authors: Yue Sun, Huisi Zhao, Fang Pu, Hao Liu, Li Chen, Jinsong Ren, Xiaogang Qu
Journal: Advanced Healthcare Materials (2024)

Bioorthogonal chemistry has emerged as a powerful tool for manipulating biological processes. However, difficulties in controlling the exact location and on-demand catalytic synthesis limit its application in biological systems. Herein, this work constructs an activatable bioorthogonal system integrating a shielded catalyst and prodrug molecules to combat biofilm-associated infections. The catalytic species is activated in response to the hyaluronidase (HAase) secreted by the bacteria and the acidic pH of the biofilm, which is accompanied by the release of prodrugs, to achieve the bioorthogonal catalytic synthesis of antibacterial molecules in situ. Moreover, the system can produce reactive oxygen species (ROS) to disperse bacterial biofilms, enabling the antibacterial molecules to penetrate the biofilm and eliminate the bacteria within it. This study promotes the design of efficient and safe bioorthogonal catalysts and the development of bioorthogonal chemistry-mediated antibacterial strategies.