tbuckley/cabot-search huggingface dataset:
Abstract 16555: The Relationship of Preeclampsia and Maternal Region of Birth and Duration of Residence in Non-US Born Black Women
Authors: Garima Sharma, Ellen Boakye, Andreea A Creanga, Arthur J Vaught, Sammy Zakaria, Laxmi S Mehta, Roger S Blumenthal, Xiumei Hong, Serena M Ogunwole, Yuelong Ji, Xiaobin Wang
Journal: Circulation (2020)

Introduction: Preeclampsia is a risk factor for cardiovascular disease (CVD) and disproportionately effects black women. Few studies have explored the prevalence of CVD risk factors and preeclampsia risk in non-US-born black women. We investigated the differential risk of preeclampsia by maternal birth country and duration of stay in US-born vs non-US-born black women residing in US. Methods: We analyzed data from 2967 black women (US-born and non-US-born) in the Boston Birth Cohort (1998 - 2016). Maternal sociodemographic characteristics and key CVD risk factors (hypertension, obesity, diabetes, smoking) were characterized in the two groups. We performed multivariate logistic regression to investigate the prevalence of preeclampsia by maternal birth country and the duration of stay in the US (&lt;10 years and ≥ 10 years) after controlling for explanatory variables. In all analyses, US-born black women were used as the reference group. Results: Of the study group, 40.5% were non-US-born (42% Caribbean, 36% from Sub-Saharan Africa and 21% from other regions). US-born black women were younger and had higher baseline prevalence of obesity (BMI≥ 30Kg/m2), multiparity, pregestational diabetes, smoking, maternal stress, lower educational level, and single marital status. As compared to US-born black women, non-US-born women had a 26% lower risk of preeclampsia. When further categorized by their duration of residence in the US, the prevalence of preeclampsia in non-US-born women with duration of stay &lt;10 years was 8.5%, compared to 9.3% in those with duration of stay beyond 10 years (Figure). Conclusions: As compared to US-born blacks, the prevalence of CVD risk factors and preeclampsia is lower in non-US-born blacks. The "healthy immigrant effect” which typically results in health advantages for foreign born women, tends to wane with increasing duration of US residence (≥ 10 years). Further research on the impact of CVD risk factors on preeclampsia is needed.
The EAACI task force on chronic urticaria in children - research and clinical network (CU-kids)
Authors: S. Tsabouri, M. Alvaro-Lozano, S. Arasi, B. Beken, C. Caffarelli, M. K. Church, C. Flohr, S. R. Janmohamed, G. N. Konstantinou, S. Lau, S. Lefevre, T. A. Leslie, C. G. Mortz, G. B. Pajno, C. A. Rutkowski, H. Pite, L. Van der Poel, P. Staubach, T. Zuberbier
Journal: Allergy (2020)
Abstract 017: Meal Intervals And Weight Trajectories In Adults Using The Daily24 Mobile Application: A Prospective Cohort Study
Authors: Di Zhao, Thomas Woolf, Lindsay Martin, Eliseo Guallar, Harold Lehmann, Janelle Coughlin, Shanshan Song, Katherine Holzhauer, Jeanne Clark, Kathleen M McTigue, Michelle Lent, Wendy L Bennett
Journal: Circulation (2021)

Background: Small pilot and randomized controlled studies suggest that time-restricted feeding may decrease body weight. However, the role of meal timing and intervals, measured using mobile applications, has not been examined in larger population-based studies. The objective of this study is to evaluate the association between meal intervals and weight trajectories among adults from a population-based clinical cohort. Methods: Multi-site prospective cohort study of adults recruited from three health systems. Over the 6-month study period, 547 participants downloaded and used the Daily24 mobile application to record the timing of meals and sleep for at least one day. Intervals were calculated as the average of all available daily entries for each participant. We obtained information on weight and comorbidities at each outpatient visit from electronic health records available for up to 10 years prior to until 10 months after baseline. We used mixed linear regression to model weight trajectories. Results: The mean (SD) baseline (at consent) age was 51.1 (15.0) years and body mass index (BMI) 30.8 (7.8) kg/m 2 ; 77.9% were women and 77.5% were White. Average time in the cohort was 5.9 years prior to and 0.3 years after baseline. The mean interval from first to last meal was 11.5 (2.3) hours. The associations between meal intervals and weight trajectories are shown in the Table . The number of meals per day was positively associated with weight change before baseline, and number of snacks and drinks per day was inversely associated with weight change after baseline. Each additional occasion of snacks and drinks was associated with a 3.20 kg weight decrease (95% CI 1.41 to 4.99). None of the other associations were statistically significant. Conclusions: Number of daily meals was positively associated with weight change in previous periods, while the number of daily snacks and drinks was inversely associated with weight trajectory. The intervals from first to last meal was not associated with weight change.
Abstract P218: The Association Of Mid-life Cumulative Exposure To Systolic Blood Pressure, Myocardial Oxygen Demand, And Hypertension With Later-life Central Arterial Stiffness And Its 5-year Change: The Atherosclerosis Risk In Communities Study - Neurocognitive Study (ARIC-NCS)
Authors: Michelle L Meyer, Veeral Saraiya, Hirofumi Tanaka, Priya Palta, Timothy M Hughes, Anna Kucharska-newton, Jingkai Wei, Kunihiro Matsushita, Aaron R Folsom, Ron C Hoogeveen, Gerardo M Heiss
Journal: Circulation (2021)

Background: Greater central artery stiffness predicts cardiovascular disease and all-cause mortality, thus understanding arterial stiffness determinants has prevention implications. Reports of the temporal association of blood pressure with arterial stiffness are conflicting and the association with myocardial oxygen demand has not been evaluated. Objective: Characterize the association of mid- to later-life cumulative exposure to systolic blood pressure (SBP), myocardial oxygen demand, and hypertension (HTN) with arterial stiffness and its 5-year change in older adults. Methods: We included 1,975 adults (1151 women; 359 Black; visit 5 mean age 74 years) examined in visits 5 (2011-13) and 6 or 7 (2016-19) of the population-based ARIC-NCS with measures of arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)). Higher cfPWV indicates greater arterial stiffness. We calculated cumulative exposures as the sum of averages from four consecutive visits from 1987-89 to 1996-98 divided by total time. Myocardial oxygen demand was calculated as the rate pressure product (RPP): (SBP x heart rate)/1,000. We derived HTN duration as the time since first HTN detection. Associations of cumulative exposures with visit 5 cfPWV and the 5-year cfPWV change were evaluated by multivariable linear regression adjusted for demographics and cardiometabolic factors. Results: Over the mean 5.7 years between visits 5 and 6 or 7, cfPWV increased by 144.9 cm/s (SD: 276.0; range -680.0, 961.5 cm/s). HTN at any visit, duration, and the time-weighted cumulative measures were associated with higher visit 5 cfPWV (Table). Prevalent HTN was inversely associated with cfPWV change. No statistically significant associations were observed for the other exposures and cfPWV change. Conclusion: Cumulative exposure to SBP, RPP, and HTN are modifiable traits associated with higher cfPWV at later-life, but not with rate of cfPWV change in older adulthood. HTN at visit 5 was associated with lower cfPWV change, albeit the change is of small magnitude.
Discovery of Candidate DNA Methylation Cancer Driver Genes
Authors: Heng Pan, Loïc Renaud, Ronan Chaligne, Johannes Bloehdorn, Eugen Tausch, Daniel Mertens, Anna Maria Fink, Kirsten Fischer, Chao Zhang, Doron Betel, Andreas Gnirke, Marcin Imielinski, Jérôme Moreaux, Michael Hallek, Alexander Meissner, Stephan Stilgenbauer, Catherine J. Wu, Olivier Elemento, Dan A. Landau
Journal: Cancer Discovery (2021)

Abstract Epigenetic alterations, such as promoter hypermethylation, may drive cancer through tumor suppressor gene inactivation. However, we have limited ability to differentiate driver DNA methylation (DNAme) changes from passenger events. We developed DNAme driver inference–MethSig–accounting for the varying stochastic hypermethylation rate across the genome and between samples. We applied MethSig to bisulfite sequencing data of chronic lymphocytic leukemia (CLL), multiple myeloma, ductal carcinoma in situ, glioblastoma, and to methylation array data across 18 tumor types in TCGA. MethSig resulted in well-calibrated quantile–quantile plots and reproducible inference of likely DNAme drivers with increased sensitivity/specificity compared with benchmarked methods. CRISPR/Cas9 knockout of selected candidate CLL DNAme drivers provided a fitness advantage with and without therapeutic intervention. Notably, DNAme driver risk score was closely associated with adverse outcome in independent CLL cohorts. Collectively, MethSig represents a novel inference framework for DNAme driver discovery to chart the role of aberrant DNAme in cancer. Significance: MethSig provides a novel statistical framework for the analysis of DNA methylation changes in cancer, to specifically identify candidate DNA methylation driver genes of cancer progression and relapse, empowering the discovery of epigenetic mechanisms that enhance cancer cell fitness. This article is highlighted in the In This Issue feature, p. 2113
Multiple-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage
Authors: Grier P. Page, Tamir Kanias, Yuelong J. Guo, Marion C. Lanteri, Xu Zhang, Alan E. Mast, Ritchard G. Cable, Bryan R. Spencer, Joseph E. Kiss, Fang Fang, Stacy M. Endres-Dighe, Donald Brambilla, Mehdi Nouraie, Victor R. Gordeuk, Steve Kleinman, Michael P. Busch, Mark T. Gladwin
Journal: Journal of Clinical Investigation (2021)

Background. The evolutionary pressure of endemic malaria and other erythrocytic pathogens has shaped variation in genes encoding erythrocyte structural and functional proteins, influencing responses to hemolytic stress during transfusion and disease.
Abstract P034: Family Lifestyles And Home Environments Associated With Youth Cardiovascular Health: The Multidimensional Assessment Of Preschoolers Study
Authors: Liliana Aguayo, Lindsay Pool, Matthew M Davis, Lifang Hou, Bradley S Marino, Linda Van Horn, Lauren S Wakschlag, Darwin R Labarthe, Donald M Lloyd-Jones, Norrina B Allen
Journal: Circulation (2021)

Introduction: The importance of healthy family lifestyles and home environments (e.g. environments that support healthy choices for food, physical activity, and sleep) on health behaviors and obesity risks are well-recognized. Less is known about the association of family factors with cardiovascular health (CVH) in youth. We examined the cross-sectional association of family factors (reported by youth and their parents) with youths’ CVH. Methods: Analyses included data from the Multidimensional Assessment of Preschoolers Study. Parents and youth (11.3± 0.7 years old) reported the frequency of ten family factors (e.g. breakfast intake, monitoring of screen time, etc.). The outcome was a 10-point score of youths’ CVH that included 5 CVH metrics (diet, physical activity, smoking, BMI, and blood pressure) summed using the AHA criteria. Pearson correlations were used to compare youth and parents’ reports of family factors and adjusted multivariable linear regression models to examine the association of both reports with youths’ CVH scores. Results: Study included 177 parent-youth dyads, and 22% of youth had ideal, 74% intermediate, and 5% poor CVH. Correlations between parents and youths’ reports of family factors were moderate. Based on parents’ reports, support of healthy beverage choices (i.e. limit sweet and soda beverages and support low fat dairy intake) associated with youths’ CVH scores (β= -0.10, p&lt;0.01). The association of family’ support of youths’ physical activity (i.e. encourage youth's physical activity during leisure time and support enrollment in organized sports/activities) with youths’ CVH scores was nearly significant based on parents’ reports (β= 0.04, p=0.055) and significant based on youths’ reports (β= 0.05, p=0.04). Youths’ CVH scores were not associated with other family factors. Conclusion: Youths’ CVH scores were associated with healthy beverage choices and family support of youths’ physical activity, but not other family factors. These important family factors require further research.
Abstract 874: MLN1202, a Novel CCR2 Antagonist, Decreases C-reactive protein in Patients at Risk for Atherosclerotic Cardiovascular Disease in a Double Blind Placebo Controlled study
Authors: M. Davidson, J. Lekstrom-Himes, J. Gilbert, D. Donaldson, Y. Lee, M. Hu, J. Xu
Journal: Circulation (2007)

Background: Macrophages play a central role in atherosclerotic plaque formation. The CC chemokine receptor 2 (CCR2), expressed on the surface of circulating monocytes, and its ligand MCP-1 (CCL2), are present in atherosclerotic plaques and may play a critical part in endothelial monocyte recruitment and activation. MLN1202 is a humanized monoclonal antibody with high specificity to CCR2, which interrupts MCP-1 binding to CCR2. MLN1202 is being developed for the treatment of immune mediated diseases. Hypothesis: We tested the hypothesis that MLN1202 significantly influences disease activity in patients at risk for ASCVD as measured by a reduction in circulating levels of high sensitivity C-reactive protein (hsCRP), an established biomarker of inflammation. Trial Design: In this double-blind placebo controlled study patients with at least 2 or more risk factors for ASCVD, no history or symptoms of ASCVD disease, and circulating levels of hsCRP &gt; 3mg/L, were randomized 1:1 to receive a single infusion of 10 mg/kg MLN1202 (n 56) or placebo (n = 56). Subjects with hypercholesterolemia on stable doses of lipid-lowering agents were included. Circulating levels of hsCRP were determined every 2 weeks, and clinical examination performed every 4 weeks for 16 weeks following treatment. Results and Conclusion: Patients were recruited from nine centers in the US. The study population had a mean age of 60.9 years and included subjects with hypertension (59%), hypercholesterolemia (70%), significant smoking history (28%), and type 2 diabetes (16%). At screening the median value CRP was 6.8 mg/L with interquartile range from 4.7–9.3 mg/L. PK/PD results showed that the plasma level of MLN1202 required for &gt; 90% receptor saturation was maintained for 6 to 8 weeks. A between-group difference in reduction of hsCRP was statistically significant from week 4 through week 8 following dosing. The maximum difference in absolute median reduction was observed at week 8 and it was 1.6 mg/L (p = 0.0275; Wilcoxon); the observed median percent reduction of hsCRP was 24.2% for MLN1202 group versus 2.5% increase for placebo group at 8 weeks (p = 0.0089; Wilcoxon). These data indicate that blockade of CCR2 reduces a biomarker related to inflammation in patients at risk for ASCVD.
Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines
Authors: Zehua Liu, Shiqi Wang, Christos Tapeinos, Giulia Torrieri, Voitto Känkänen, Nesma El-Sayed, Andre Python, Jouni T. Hirvonen, Hélder A. Santos
Journal: Advanced Drug Delivery Reviews (2021)

Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.
Abstract 16455: Family Support for Physical Activity Predicts Engagement in Leisure Time Physical Activity Among Hispanic Adults at Risk for Cardiovascular Disease or Type 2 Diabetes
Authors: Salman Alreshidi, Kaitlin V Key, Gia Mudd-martin
Journal: Circulation (2020)

Background: Hispanics in the U.S. are less likely to engage in leisure time physical activity than non-Hispanics. Among Hispanics, families influence health behaviors and family support may motivate adults at risk for cardiovascular disease (CVD) or type 2 diabetes (T2D) to participate in physical activity. Objective: The purpose of this study was to examine whether family support predicts engagement in leisure time physical activity among Hispanic adults at risk for CVD or T2D. Methods: Baseline data from Hispanic adults at risk for CVD or T2D were analyzed. Family support for leisure time physical activity was measured using the Family Support subscale of the Social Support for Physical Activity instrument. This consists of 7 items with response options ranging from never (0) to always (4). Sum scores range from 0 to 28 and higher scores indicate greater family support for engagement in physical activity. Leisure time physical activity was measured using the Health-Promoting Lifestyle Profile II (HPLP-II) physical activity subscale. This consists of eight items with response options ranging from never (1) to routinely (4) with higher mean scores indicating higher levels of engagement in leisure time physical activity. Linear regression was used to examine the association between family support and leisure time physical activity, controlling for age, sex, race, financial comfort, education, acculturation, years living in the U.S, marital status, and employment. Results: Participants (N=182) were 40±9 years old; 82.7% were female. The mean HPLP-II score was 1.7±0.5, reflecting low engagement in leisure time physical activity. Results of the regression analysis indicated that greater family support predicted higher levels of engagement in leisure time physical activity (F(10,171)=2.717, p&lt;.004; R 2 =.137). Conclusions: Family support for physical activity may increase engagement in leisure time physical activity in Hispanic adults at risk for CVD or T2D. Interventions that promote family support for physical activity could be an important avenue for reducing CVD and T2D risk in this population group.
The intersection of COVID-19 and cancer: signaling pathways and treatment implications
Authors: Zhi Zong, Yujun Wei, Jiang Ren, Long Zhang, Fangfang Zhou
Journal: Molecular Cancer (2021)

The outbreak of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious public health concern. Patients with cancer have been disproportionately affected by this pandemic. Increasing evidence has documented that patients with malignancies are highly susceptible to severe infections and mortality from COVID-19. Recent studies have also elucidated the molecular relationship between the two diseases, which may not only help optimize cancer care during the pandemic but also expand the treatment for COVID-19. In this review, we highlight the clinical and molecular similarities between cancer and COVID-19 and summarize the four major signaling pathways at the intersection of COVID-19 and cancer, namely, cytokine, type I interferon (IFN-I), androgen receptor (AR), and immune checkpoint signaling. In addition, we discuss the advantages and disadvantages of repurposing anticancer treatment for the treatment of COVID-19.
Abstract 13199: Home Blood Pressure Monitoring Among Us Adults Without Hypertension: How Do Existing Patient and Physician Behaviors Correspond to Current Recommendations?
Authors: Kelsey B Bryant, Matthew B Green, Ian M Kronish, Yiyi Zhang, James Sheppard, Richard McManus, Andrew E Moran, Brandon K Bellows
Journal: Circulation (2020)

Introduction: Home blood pressure monitoring (HBPM) is an option recommended by the 2017 ACC/AHA guidelines to confirm a hypertension diagnosis or identify masked hypertension. Using clinic BP and patient characteristics, the Predicting Out-of-Office BP in the Clinic (PROOF-BP) algorithm can be used to guide HBPM decisions. It is unknown how existing patient use and physician recommendations for HBPM align with current screening recommendations. Methods: We used the 2009-2014 National Health and Nutrition Examination Survey (NHANES) to identify US adults aged ≥20 years without hypertension or antihypertensive medication use. We identified those who would have been recommended to undergo HBPM by ACC/AHA guidelines as those with a mean BP 120-159/&lt;100 mm Hg and by the PROOF-BP algorithm as those with a predicted out-of-office BP 125-134/75-84 mm Hg. We required individuals to have complete data needed for the PROOF-BP algorithm (demographics, BP, smoking, alcohol use, kidney disease) and reported HBPM actual/recommended use. All analyses were weighted to be representative of the US population. Results: We included 7,185 NHANES adults without hypertension; weighted mean (SE) age was 41.5 (0.3) years, 48% female, and mean BP 117.0 (0.3)/70.4 (0.3) mm Hg. Overall, 50.3% of adults without hypertension would have been recommended to undergo HBPM by ACC/AHA guidelines and 29.7% by PROOF-BP ( Table ). Only 13.3% of those recommended HBPM by ACC/AHA guidelines used or were told to use HBPM, compared to 11.5% of those not recommended screening. Similar results were seen among those recommended HBPM by PROOF-BP ( Table ). Conclusions: Our analysis shows that prior to 2017 guidelines, a substantial proportion of US adults may have had their hypertensive status misclassified due to a lack of HBPM or undergo unnecessary monitoring. These findings suggest an opportunity for clinicians and health systems to more clearly target HBPM to those who need it given guidelines currently in use.