tbuckley/cabot-search huggingface dataset:
Abstract P224: Optimism And Favorable Cardiovascular Health Maintenance Among African Americans: The Jackson Heart Study
Authors: Harold H Lee, Sakurako Okuzono, Claudia Trudel-Fitzgerald, Peter James, Mario Sims, Laura Kubzansky
Journal: Circulation (2022)

Background: Higher optimism is associated with maintaining favorable cardiovascular health (FCH) among White adults, but evidence for this relationship is limited among African American adults, whose cardiovascular disease risk is higher than Whites. We investigated whether higher optimism is associated with more FCH over ~12 years among African American adults. Methods: Data were drawn from African-American women (n=2,730) and men (n=1,479) in the Jackson Heart Study (age=20-93 years). Participants free of CVD at baseline (2000–2004) were included in the analyses. Optimism was measured using the Life Orientation Test-Revised at the baseline period, and examined as a binary variable due to its skewed distribution. FCH was characterized according to whether participants had healthy status on each of five components of cardiovascular functioning (i.e., blood pressure, lipids, body mass index, type 2 diabetes, and smoking status) repeatedly assessed 3 times over ~ 12 years of follow-up; measures were obtained either from a clinical visit or via self-report. Linear mixed-effects models examined whether optimism predicted FCH level over time or FCH change rate, adjusting for covariates such as sociodemographic characteristics, depressive symptoms, and health behaviors. In secondary analyses, we evaluated potential effect modification by sex and income as well as the likelihood of meeting the recommendation for each FCH component separately in relation to optimism using generalized estimating equations with the Poisson distribution. Results: Adjusting for all covariates, higher (vs. lower) optimism was associated with better FCH pooled across time (β=0.10, 95% confidence interval=0.02–0.17) but not with the rate of change in FCH level. We did not find sufficient evidence for effect modification by sex and income (p-interactions&lt;0.05), which may be due to lack of power. In the analyses examining FCH sub-components, optimism was not associated with the rate of change in meeting the guidelines, except smoking; unexpectedly, participants with higher optimism had a slower rate of change towards non-smoking (p-interaction=0.03). However, this is likely driven by large differences at baseline: optimistic participants’ non-smoking proportion changed from 89.3% (baseline) to 93.2 % (visit 3) vs. 84.8% (baseline) to 92.9% (visit 3) in participants with lower optimism. In the analyses examining FCH sub-components without time-interaction, higher vs. lower optimistic participants had a higher likelihood of not being diabetic (RR=1.03, 95% confidence interval=0.99-1.07) in the fully adjusted model. Conclusions: Optimism may contribute to establishing future patterns of FCH in adulthood, but other factors may be more strongly related to how slowly or quickly favorable FCH declines over time.
Abstract P103: Perceived Stress, Social Support, And Blood Pressure In Urban Haiti
Authors: Jean Lookens Pierre, Lily D Yan, Vanessa Rouzier, Jessy G Devieux, Linda M GERBER, Alexandra Apollon, Stephano St-Preux, Miranda Metz, Marie Deschamps, Jean William Pape, Margaret Mcnairy
Journal: Circulation (2022)

Introduction: Stress is associated with multiple adverse health outcomes, including hypertension. The impact of stress on health may be moderated by social support. The distribution of stress, support, and their association with hypertension have not been well described in low-income countries that face severe poverty. Over the past decade, Haiti has suffered massive natural disasters including the 2010 earthquake, cholera outbreak, COVID-19 pandemic, and recurrent civil instability—all of which may act as prolonged stressors. Hypothesis: We assessed the hypotheses that 1) there are high levels of both stress and support in Haiti, and 2) high support would moderate the relationship between high stress and hypertension. Methods: We measured stress and social support using validated instruments in a population-representative cohort of adults living in urban Port-au-Prince, Haiti between March 2019 and April 2021. Stress was measured using the Perceived Stress Scale, while social support was measured using the Multidimensional Scale of Perceived Social Support. For visualization, continuous scores were categorized using equal-width groups (stress: low (1-5), moderate (6-10), high (11-16); support: low (7-21), low-moderate (22-35), moderate (36-49), moderate-high (50-64), high (65-77)). Linear regression models were used to quantify the associations between: 1) stress and support adjusting for age and sex, 2) blood pressure and stress adjusting for age and sex. A formal moderation analysis was conducted to assess if support moderated the relationship between stress and blood pressure. Results: Among 2,817 adults, 59.7% female and the median age was 40 years (IQR 28-55). The majority had an income of less than 1 US dollar a day (69.7%). The median stress score was 8 out of 16 points, and median support score was 61 out of 77 points. Stress was higher with older ages (60+ years versus 18-29 years: +0.79 points, 95% CI 0.51 to 1.08) and in females (+0.85 points, 95% CI +0.65 to +1.06). Support was higher in males (+3.29 points, 95% CI 2.19 to 4.39). Support was inversely associated with stress, adjusting for age and sex (-0.04 points, 95% CI -0.04 to -0.03). Stress was not associated with systolic or diastolic blood pressure after adjustment for age and sex. Support did not moderate the association between stress and blood pressure. Conclusion: In this urban cohort of Haitian adults living with chronic civil instability, stress was moderate and support was high. While support was associated with lower stress, it did not moderate the relationship between stress and blood pressure. Despite the high levels of instability in Haiti, participants displayed resiliency through high levels of support, which may be an underutilized resource in reducing stress and long-term negative health outcomes.
Abstract P182: Large Scale Analyses Of Gene-by-smoking Interaction On Cardiovascular Disease
Authors: Erin Richard, Steven Cao, Rany Salem
Journal: Circulation (2022)

Introduction: Cardiovascular disease risk is determined by both genetic susceptibility and lifestyle factors such as smoking. However, gene-by-smoking interactions have been understudied in this context. The objective of this study was to leverage large-scale individual level data to carry out a genome-wide gene-by-smoking interaction analysis on cardiovascular outcomes including coronary heart disease (CHD), stroke and peripheral artery disease (PAD). Methods: Our study sample included 401,384 unrelated, European-ancestry participants of the UK Biobank study. CHD, stroke, and PAD outcomes were based on data from baseline questionnaires and linked data from inpatient admissions and death registries. Smoking status (ever vs never) was based on self-report at baseline. Gene-environment interaction analyses were carried out using GEM (https://github.com/large-scale-gxe-methods/GEM), a new, computationally efficient software tool developed for biobank scale data. Using generalized linear models, we carried out a test of the genetic main effect adjusted for smoking status, a formal test for gene-by-smoking interaction, and a joint test of the main genetic and interaction effects. Single nucleotide polymorphisms with a minor allele frequency less than 1% were excluded from analyses. Results: The formal interaction test revealed a novel genome-wide significant (GWS) gene-by-smoking signal for PAD within the IREB2 gene (p=2.0x10 -8 ), which has been previously associated with smoking intensity and lung disease. The joint test has been shown to increase power for genetic discovery, which we observed here. The joint test for PAD identified 10 additional loci reaching genome-wide significance (p&lt;5x10 -8 ) that were not revealed in the main effect analyses. Several of these loci are in genes linked with measures of body composition in earlier studies ( PNLIP, CDH4, STAT5A, PRKCE ). We did not detect any GWS gene-by-smoking interactions for CHD or stroke. However, for CHD, two novel loci within the ARSG and SARS1 genes were identified using the joint test but had no GWS main effects. Both genes have been associated with LDL-cholesterol levels in prior genome-wide studies. Although our analyses did not yield any signals that exceeded the GWS threshold for stroke, we did identify 25 and 47 independent loci that reached genome-wide suggestive significance (p&lt;1x10 -5 ) for the formal interaction and joint tests, respectively. We are augmenting the current analyses to include additional data from approximately 120,000 trans-ethnic ancestry individuals. Conclusion: The analysis of gene-by-smoking interactions can provide novel insights into the genetic architecture and pathophysiology of cardiovascular disease.
Three cognitive mechanisms for knowledge tracking
Authors: Dora Kampis, Gergely Csibra
Journal: Behavioral and Brain Sciences (2021)

Abstract We welcome Phillips et al.'s proposal to separate the understanding of “knowledge” from that of “beliefs.” We argue that this distinction is best specified at the level of the cognitive mechanisms. Three distinct mechanisms are discussed: tagging one's own representations with those who share the same reality; representing others' representations (metarepresenting knowledge); and attributing dispositions to provide useful information.
Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
Authors: Olivier Govaere, Sine Kragh Petersen, Nuria Martinez-Lopez, Jasper Wouters, Matthias Van Haele, Rosellina M. Mancina, Oveis Jamialahmadi, Orsolya Bilkei-Gorzo, Pierre Bel Lassen, Rebecca Darlay, Julien Peltier, Jeremy M. Palmer, Ramy Younes, Dina Tiniakos, Guruprasad P. Aithal, Michael Allison, Michele Vacca, Melker Göransson, Rolando Berlinguer-Palmini, James E. Clark, Michael J. Drinnan, Hannele Yki-Järvinen, Jean-Francois Dufour, Mattias Ekstedt, Sven Francque, Salvatore Petta, Elisabetta Bugianesi, Jörn M. Schattenberg, Christopher P. Day, Heather J. Cordell, Baki Topal, Karine Clément, Stefano Romeo, Vlad Ratziu, Tania Roskams, Ann K. Daly, Quentin M. Anstee, Matthias Trost, Anetta Härtlova
Journal: Journal of Hepatology (2021)
Abstract EP17: Associations Between Neighborhood Child Opportunity And Cardiovascular Fitness For New York City Public School Youth
Authors: Amy Zhao, Hiwot Zewdie, S. Scott Ogletree, Sarah Messiah, Sarah Armstrong, Asheley C Skinner, Cody Neshteruk, J. Aaron Hipp, Sophia Day, Kevin Konty, Emily D'Agostino
Journal: Circulation (2022)

Introduction: Fewer than 1/4th of US youth meet physical activity guidelines, leading to physical fitness-related cardiovascular disease disparities tracking into adulthood. Neighborhood opportunity may serve as a critical modifiable factor to reduce youth cardiovascular health-related disparities. The present analysis uses the Child Opportunity Index (COI), a comprehensive measure of children’s neighborhood opportunity, to examine associations between neighborhood context and multiple youth cardiovascular fitness outcomes. Methods: Data were drawn from the NYC FITNESSGRAM (n = 300,000), comprising of fitness data from New York City (NYC) public school youth (grades K-12). Generalized linear mixed models were run to estimate overall and sex-stratified associations between overall COI and individual COI indicators (greenspace, healthy food, walkability, commute time) and youth cardiovascular fitness (body mass index (BMI) percentiles, curl-ups, push-ups, PACER, and sit and reach). Geographically weighted regression (GWR) models explored spatial variation of COI-fitness associations across NYC. Results: Overall COI was associated with improved youth cardiovascular fitness outcomes, with the strongest magnitude of effects across aerobic capacity and muscular strength and endurance measures (PACER: β: 0.15, 95% CI: 0.14, 0.15, curl-ups: β: 0.13, 95% CI: 0.12, 1490.13, and push-ups: β: 0.13, 95% CI: 0.12, 0.13). Greenspace was positively associated with muscular endurance (curl-ups: β: 1.13, 95% CI:0.76, 1.50; push-ups: β: 1.53, 95% CI: 1.21, 1.84), and walkability and commuting time were positively associated with aerobic capacity (PACER: β: 2.11, 95% CI: 1.72, 2.50; β: 2.03, 95% CI: 1.87, 2.19, respectively). Stratified models showed strengthened COI-fitness associations among girls versus boys. GWR models were largely consistent with findings from multilevel models, except for overall COI-BMI associations, which varied in magnitude and direction across regions in NYC. Conclusion: Neighborhood opportunity was associated with multiple measures of youth cardiovascular fitness, though geographic models demonstrate that certain associations vary in magnitude and direction across NYC. Continued research on neighborhood factors and cardiovascular fitness may better inform public health efforts to reduce health disparities modifiable through comprehensive place-based interventions.
Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance
Authors: V. Pellegrinelli, S. Rodriguez-Cuenca, C. Rouault, E. Figueroa-Juarez, H. Schilbert, S. Virtue, J. M. Moreno-Navarrete, G. Bidault, M. C. Vázquez-Borrego, A. R. Dias, B. Pucker, M. Dale, M. Campbell, S. Carobbio, Y. H. Lin, M. Vacca, J. Aron-Wisnewsky, S. Mora, M. M. Masiero, A. Emmanouilidou, S. Mukhopadhyay, G. Dougan, M. den Hoed, R. J. F. Loos, J. M. Fernández-Real, D. Chiarugi, K. Clément, A. Vidal-Puig
Journal: Nature Metabolism (2022)
Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma
Authors: Dongjiang Chen, Son B. Le, Tarun E. Hutchinson, Anda-Alexandra Calinescu, Mathew Sebastian, Dan Jin, Tianyi Liu, Ashley Ghiaseddin, Maryam Rahman, David D. Tran
Journal: Journal of Clinical Investigation (2022)

Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors — cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) — and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.
For Whom the Bell Tolls? A Toll-Like Receptor 9 Agonist's Journey from Vaccine Adjuvant to Promising Agent in Anti–PD-1–Resistant Melanoma
Authors: Ryan J. Sullivan
Journal: Cancer Discovery (2021)

Abstract Summary: Developing effective therapies in anti–PD-1–resistant melanoma is a key unmet need. The combination of pembrolizumab with the intralesional TLR9 agonist vidutolimod showed promise in this patient population with correlative analysis suggesting that patients with a “cold” tumor immune microenvironment may be the best patients to study further. See related article by Ribas et al., p. 2998.
Abstract EP02: Identification Of Genetic Signals For “Diabesity” --- Type 2 Diabetes And Obesity -- Among African American And European American Participants In Four Cohorts Of The TOPMed Consortium
Authors: Kei Hang Katie Chan, Qing Liu, Alex P Reiner, Roberta De Vito, Charles Kooperberg, Jennifer Brody, Leslie Lange, Joann E Manson, Adolfo Correa, L. Adrienne Cupples, Matthew Flickinger, Jie Li, Xiaochen Lin, Tracy Madsen, Kari E North, Laura M Raffield, Alisa Manning, James B Meigs, Simin Liu
Journal: Circulation (2022)

Background: Diabesity defines the concurrent manifestation of type 2 diabetes (T2D) and obesity (BMI≥30 kg/m 2 ) in the development of cardiovascular diseases, although the genetic basis for this joint phenotype remain poorly understood. Objective: This study aimed to identify the overlapping genetic patterns for diabesity incidence in 3,231 self-reported African American (AA) and 8,252 European Americans (EA) participated in four cohorts of the Trans-Omics for Precision Medicine (TOPMed) consortium. Methods: Using marker set enrichment analysis (MSEA) of whole genome sequencing data, specific gene sets (pathways) and key driver (KD) genes (important hub genes overrepresented in a network of pathways) were identified for diabesity incidence. Using multi-tissue and multi-species gene expression signatures as molecular indicators of drug functions, their potential drug signatures were also examined. Results: Testing genome-wide significance (P-value &lt; 10 -8 ) identified seven independent loci, six of which were replicated in the T2D Knowledge Portal (https://t2d.hugeamp.org/ )( NPFFR1, TRIO, G6PD, BCL11A, IGF1, and TCF7L2, P&lt;0.05) for diabetes and/or such obesity-related traits as blood pressure, lipids, glucose and insulin levels. One novel variant for diabesity, rs144540309, is an intronic region of GPAT3 (G&gt;A, AA MAF = 0.004, beta=3.66 and P=1.00e-8) whose enzyme plays important roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, and entero-endocrine hormone production, along with 12 KEGG/Reactome/Biocarta pathways enriched for diabesity in AAs and 11 for EAs. In AAs, the top three pathways (ranked by P-value and false discovery rate [FDR]) were mitotic spindle checkpoint, resolution of sister chromatid cohesion, and rho GTPases activate formins, along with six KD genes ( NCKAP1L, CDCA8 , BUB1 , IRF5 , FYB , and C15orf23 ); in EAs, colorectal cancer, prostate cancer, and beta Catenin independent WNT signaling were the top 3 pathways (FDR≤0.25) including LEF1 . Top repositioned drugs derived from diabesity-related gene sets (FDR≤0.25) included Benzbromarone, Fenofibrate, Interleukin-1β, and antihypertensive. Conclusion: Our study supports the notion that both pathway and network-based analytical approaches may identify novel signals from gene sets for highly clustering clinical phenotypes such as diabetes and obesity and improve their target validation for intervention.
Observed CD4 counts at entry into HIV care and at antiretroviral therapy prescription by age in the USA, 2004–18: a cohort study
Authors: Jennifer S Lee, Elizabeth Humes, Brenna C Hogan, Amy C Justice, Marina Klein, Kelly Gebo, M John Gill, Michael J Silverberg, Peter Rebeiro, Michael Horberg, Maile Karris, Charles Rabkin, Richard D Moore, Keri N Althoff
Journal: The Lancet HIV (2022)
Laparoscopic versus open pancreaticoduodenectomy with major vein resection for pancreatic head cancer: A single surgeon’s experience
Authors: Min Kyu Sung, Ki Byung Song, Sarang Hong, Yejong Park, Bong Jun Kwak, Woohyung Lee, Jae Hoon Lee, Dae Wook Hwang, Song Cheol Kim
Journal: International Journal of Surgery (2022)
Clarification of Conflict of Interest Disclosures
Authors: Beth Darnall
Journal: JAMA Internal Medicine (2022)

to Stanford University; serving on the advisory board for Clinical Pain Advisor, an online pain media outlet, and that compensation for her services was paid to Stanford University; receiving royalties from 2 books on patient self-help for opioid reduction and pain management for chronic pain; and receiving from Tarsus and Neurovations travel reimbursements to present pain research findings at the PainWeek conference and the Kauai Pain Conference, respectively."I regret any confusion this has caused and have requested that these articles be corrected online.
AL AMYLOIDOSIS: MECHANISMS OF DISEASE AND BIOMARKERS
Authors: Giovanni Palladini, Marco Basset
Journal: HemaSphere (2022)

Light chain (AL) amyloidosis is caused by usually small B cell, usually plasma cell, clones that produces a monoclonal light chain (LC) causing organ toxicity, aggregating and forming deposits in tissues. Biomarkers of clonal and organ involvement play a key role in the diagnosis, treatment stratification and in the therapeutic strategy, including response assessment. Serum and urine immunofixation (IFE) and free LC (FLC) measurements are used to detect the amyloid LC. Investigation of chromosomal abnormalities in plasma cells offers precious information for the choice of treatment. Patients with t(11;14) have poorer outcomes with bortezomib and dexamethasone (BDex) with/without cyclophosphamide. These patients can be treated with BDex plus melphalan, daratumumab-bortezomib combinations, and possibly in the future with venetoclax. On the other hand, gain1q21 is associated to a dismal outcome after first-line melphalan and dexamethasone or after lenalidomide or daratumumab-based regimens in relapsed/refractory disease. Patient survival is best predicted by cardiac biomarkers that are also used for stratification in clinical trials and to assess eligibility to stem cell transplant. Proteinuria and estimated glomerular filtration rate are used to assess the risk of dialysis. The replacement of 24h-proteinuria with urinary albumin/creatinine ratio for renal staging has been recently proposed. Hematologic response (HR) is assessed by IFE and FLC measurement and organ response (OR) by changes in NT-proBNP and proteinuria, according to validated response criteria. Organ response can also be graded or combined with HR in a composite HR and OR model. Novel technologies will improve our ability to assess deep HR, as mass spectrometry for identification of amyloid LC and next generation flow cytometry for minimal residual disease identification (MRD). It has been shown that in patients who attain complete response the absence of MRD is associated with a higher probability of also attaining OR. This indicates that very small, undetectable concentrations of the amyloid LC can sustain persistent organ dysfunction. Finally, it is under investigation the possible additional prognostic role of advanced cardiac imaging at diagnosis and after treatment. Clinical observation assisted by biomarkers and advanced imaging will improve our knowledge of the mechanisms of disease in cardiac amyloidosis, giving a better perspective of the role of organ toxicity and amyloid load.
Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy
Authors: Sara Ranjbarvaziri, Kristina B. Kooiker, Mathew Ellenberger, Giovanni Fajardo, Mingming Zhao, Alison Schroer Vander Roest, Rahel A. Woldeyes, Tiffany T. Koyano, Robyn Fong, Ning Ma, Lei Tian, Gavin M. Traber, Frandics Chan, John Perrino, Sushma Reddy, Wah Chiu, Joseph C. Wu, Joseph Y. Woo, Kathleen M. Ruppel, James A. Spudich, Michael P. Snyder, Kévin Contrepois, Daniel Bernstein
Journal: Circulation (2021)

Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM.