tbuckley/cabot-search huggingface dataset:
Abstract 6931: Epigenetic Modification of the Von Willebrand Factor Promotor Drives in situ Thrombosis in Chronic Thromboembolic Pulmonary Hypertension
Authors: Xue D Manz, Robert Szulcek, Xiaoke Pan, Petr Symersky, Chris Dickhoff, Jisca Majolée, Veerle Kremer, Elisabetta Michielon, Ekatarina S Jordanova, Teodora Radonic, Irene V Bijnsdorp, Sander R Piersma, Thang V Pham, Connie Jimenez, Frances S De Man, Reinier A Boon, Jan Voorberg, Peter L Hordijk, Jurjan Aman, Harm Bogaard
Journal: Circulation (2021)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thromboembolic obstructions of the pulmonary circulation; disease progression may involve in situ thrombosis. C...
Abstract 11527: A Pilot of Food Insecurity and Its Sequelae on Health (FISH)
Authors: Tiffany W Ardoin, Michael Dreznick
Journal: Circulation (2021)

Introduction: Health outcomes data on community interventions addressing food insecurity is scarce. Hypothesis: The FISH Research study measures the effects of an 8 week Geaux Get Healthy Clinical Program (GGH), a program that provides food insecure community members with access to local resources including cooking classes, nutrition classes and grocery store tours. We proposed that addressing food insecurity with the GGH program can improve food insecurity and metabolic health. Methods: Eligible participants included patients who qualified for the GGH Program ages 18-65, were English-speaking and without audiovisual deficits. Upon enrollment, participants met with the Health Specialist and then at 8-12 weeks, and again at 6 months. Participants completed validated surveys regarding access to healthy foods, knowledge of a healthy diet, and motivation to prepare healthy meals; and the PHQ-9 (Patient Health Questionnaire-9) survey. At each visit, vital signs (including weight, height and waist circumference) and laboratory measurements (Hemoglobin A1C, lipid panel) were obtained. Patient data related to chronic disease and ER/hospital utilization was abstracted from the medical record. Results: At the time of this analysis, a total of 53 participants were enrolled. Participants’ average BMI was 34 ( SD =9.06), 64% had diabetes/pre-diabetes and 55% had hypertension at time of enrollment. In the first 6 months, we had 11 (21%) FISH participants complete all assessments. The mean USDA Food Insecurity Scores were 6.9 (very low food security) at initial visit; 4 (low food security) at 8-12 weeks; and 2.7 (low food security) at 6 months. A non-parametric Friedman test of differences among the repeated measures of food security was conducted and resulted in a significant Chi-square value of 9.69 ( p =0.008). Conclusions: We are encouraged that participating in the GGH program may lead to sustainable improvements in food insecurity, at least among those interested in signing up for the FISH research study. We are eager to see the future results of the GGH program’s effects on metabolic health.
Abstract 12481: Automated Assessment of Video Quality and Ejection Fraction in Emergency Department Point-of-Care Echocardiograms
Authors: Bryan He, Dev Dash, Youyou Duanmu, Ting Xu Tan, David Ouyang, James Zou
Journal: Circulation (2021)

Introduction: Bedside point of care ultrasound (POCUS) has greatly improved bedside emergency medicine through improved cost-effectiveness, prompt availability to augment physical exams, and the ability to evaluate unstable patients at the bedside. While most emergency rooms have ultrasound machines, there is severe underutilization of this bedside imaging modality, in part due to the lack of formalized ultrasound training in most emergency room physicians. Accuracy of bedside assessment of cardiac function remains variable and operator dependent. Methods: To aid with interpreting and improving the quality of emergency room transthoracic echocardiograms (TTEs), we train a deep learning algorithm to take POCUS videos and identify patients with a reduced ejection fraction. Our algorithm also identifies which POCUS videos are low quality and need to be retaken. We curated all patients who received POCUS echocardiograms in the apical 4 chamber view from Stanford ED between July 2020 and November 2020, including 927 videos from 574 patients recorded from three different machines (Phillips, GE venue, and Mindray). Each video is annotated with their ejection fraction (775 normal, 152 reduced) and their quality (768 sufficient, 159 low). Results: Using these videos, we trained and evaluated our model using 10-fold cross-validation over patients, achieving an AUROC of 0.92 (0.89 - 0.94) for predicting ejection fraction on videos of sufficient quality and an AUROC of 0.81 (0.78 - 0.85) for predicting video quality. We use our model to identify videos with qualities ranked in the top quartile and find that on these videos, our model achieves an AUROC of 0.94 (0.91 - 0.97). Conclusions: This algorithm can be run on commodity hardware in real-time, aiding in ultrasound education and significantly decreasing the barrier to entry into ED POCUS for TTEs. the quality predicted by the model can be given as feedback to physicians to aid with improving video quality and image acquisition.
Abstract 14072: Long-Term Mortality Following 59253 Patients Who Underwent Coronary Artery Bypass Surgery in New South Wales, Australia: A Statewide Population-Linkage Study From 2001-2018
Authors: Evan Eldic, Karice Hyun, Farzaneh Boroumand, Austin Ng, David Brieger
Journal: Circulation (2021)

Purpose: To describe changes in long-term mortality following coronary artery bypass graft (CABG) in New South Wales (NSW), Australia, from 2001-2018. Methods: Patients who underwent CABG were identified from the NSW Admission-Patient-Data-Collection registry linked to the NSW death registry and were stratified into six, 3-year groups. Changes in comorbidities and procedural techniques over time were determined. Primary outcome was death (end of follow-up: 31-December-2018). Secondary outcome was time to first percutaneous coronary intervention (PCI) post-CABG, with death as the competing event. Outcomes analyses using Cox regression were adjusted for baseline and procedural differences and geographical clustering. Results: A total 59253 patients underwent CABG during the study period. From 2001-03 to 2016-18, procedural numbers fell (11875 vs 7606); however patient complexity increased (Charlson comorbidity index [CCI]&gt;0: 40% vs 55%) as did male patients (77% vs 83%). During a median (interquartile range) follow-up of 7.7yrs (3.8-12.1yrs), 16,484 (27.8%) patients died. Factors associated with increased long-term mortality included older age (&gt;75 vs ≤60: hazard ratio [HR]=6.69, 95% confidence interval [CI]=6.33-7.08), female sex (HR=1.06, 95%CI=1.02-1.11), acute myocardial infarction (HR=1.86, 95%CI=1.80-1.92), atrial fibrillation (HR=1.38, 95%CI=1.29-1.47), valvular heart disease (HR=1.84, 95%CI=1.56-2.18), and CCI (per-1-score increase: HR=1.31, 95%CI=1.26-1.35). Multivariable survival analysis showed that, compared to 2001-03, the risk of death reduced from 2004-06 to 2016-18: HR=0.96, 95%CI=0.93-1.00 to HR=0.61, 95%CI=0.54-0.70, respectively. Multivariable time-to-PCI analysis with death as the competing event showed no significant difference over the years. Conclusion: Between 2001 and 2018, though CABG volume has decreased, proportionally more males and higher comorbid patients had CABG in recent years. Female sex and other major comorbidities were expectedly related to an increased association with mortality. Overall, mortality has fallen significantly over time, with no significant trend of PCI undertaken over time in these post CABG patients.
NCOG-34. A DESCRIPTIVE ANALYSIS OF GLIOMATOSIS CEREBRI CASES, COMPARED ACCORDING TO IDH STATUS
Authors: Lisa Boris, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Anna Choi, Alexa Christ, Ewa Grajkowska, Varna Jammula, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Eric Burton, Nicole Lollo, Marissa Panzer, Lily Polskin, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Jing Wu, Zied Abdullaev, Kenneth Aldape, Martha Quezado, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2021)

Abstract Gliomatosis cerebri (GC) is a controversial entity no longer recognized as a histopathologic-defined diagnosis, characterized by diffuse, commonly bilateral infiltration of cerebral hemispheres. The purpose of this report is to describe clinical, imaging, patient-reported outcomes (PRO’s) and pathologic characteristics of clinically-defined cases from a large natural history study cohort (N=769). Of 19 patients, 10 male, 16 white, mean age at diagnosis 43 (19-70), seventeen presented as primary GC, while 2 developed GC after treatment. Ten patients were IDH-WT, 7 IDH-M, and 2 IDH undetermined. The majority (7/10) IDH-WT patients presented acutely (5 with seizures), whereas, 3 had a protracted presentation of 2 weeks-3months with 6/10 having enhancing tumors and 8/10 undergoing biopsy only. On histopathologic review, 4 were anaplastic astrocytoma (AA), 3 GBMs, 2 grade II astrocytoma, and 1 histone-mutated glioma. Nearly all (9/10) IDH-WT patients received radiation with concurrent and adjuvant temozolomide. 7/10 IDH-WT patients had a survival of only 1.5yrs or less from diagnosis. Of the 7 IDH-M patients, 4 had protracted presentations of 1 month-5 years. 6/7 had non-enhancing tumors at presentation. 4 had biopsy only and 3 underwent partial resection. 3 were AA, 2 grade II astrocytoma, 1 grade II oligodendroglioma, and 1 grade IV astrocytoma. 3/7 received radiation with concurrent and adjuvant temozolomide, 3/7 chemotherapy alone, and 1 RT alone. All 7 IDH-M patients survived 3+ years from diagnosis (range 3-10+ yrs). Both patients who developed GC later, were IDH-M, with prolonged survival (3.5yrs and the other still alive 10+yrs). PRO's at time of last clinical assessment revealed GC patients to be highly symptomatic with mean overall symptom burden, depression, and anxiety higher than our overall glioma population. GC patients have a varied clinical course mandating further investigation to enable better prognostic definition to refine treatments based on the varying clinical and molecular characteristics.
CSIG-31. MULTI-OMICS TO EDGE INTO PRECISION MEDICINE FOR DIPG
Authors: Nanyun Tang, Kristin Leskoske, Krystine Garcia-Mansfield, Ritin Sharma, Hannah Tolson, Patrick Pirrotte, Michael Berens
Journal: Neuro-Oncology (2021)

Abstract DIPG is an incurable pediatric brain tumor with 80% of patients harboring H3F3A (H3.3) mutation that substitutes methionine for lysine at position 27 (K27M), resulting in global depletion of H3.3K27 me3 (trimethylation). These histone mutations modify the epigenome and alter oncogenic transcription, causing oncogenic insults to progenitor cells in early neurodevelopment (1). To determine the reprogramming pathways in the cell context of H3.3K27M tumors, we conducted LC-MS based proteomic and phosphoproteomic analysis on seven patient-derived DIPG cell lines. Three normal neuronal stem cell lines were included as non-tumor brain cells for comparison. Pathway analysis identified 29 pathways that are significantly altered in DIPG compared to normal brain cells at both the protein abundance and phosphosite level. Notably, AKT and MAPK associated PI3K signaling, VEGF signaling, mTOR signaling, and HIF1a signaling were differentially active in H3.3K27M tumors compared to healthy control cell lines. We saw significantly higher activity of multiple kinases involved in axon guidance and cytoskeletal remodeling in DIPG, such as PTK2B, DYRK2, TTBK2 and MARK2. This is the first time to report an increased abundance and kinase activity of PYK2 protein (coded by PTK2B), a close homologue of FAK and its associated signaling in DIPG. PYK2 has been proposed to act in concert with Src to link Gi- or Gq-coupled receptors with the mitogen-activated protein (MAP) kinase signaling pathway (2). Because of the shared signaling across kinase pathways, targeting activated PYK2 in DIPG may complement inhibitors of other dysregulated signaling networks in DIPG such as MAPK2, VEGFR, PI3K and Src. Our data also found that IL13RA2 was upregulated in DIPG. We conclude that for H3 K27M DIPG tumors, campaigns to target PYK2, MAPK2, VEGFR, PI3K, Src and IL13Ra2 using small molecules that traverse the blood brain barrier loom as promising opportunities for drug development.
Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors
Authors: Wei Hong, Ang Li, Yanhong Liu, Xiangjun Xiao, David C. Christiani, Rayjean J. Hung, James McKay, John Field, Christopher I. Amos, Chao Cheng
Journal: Cancer Research (2021)

Clonal hematopoiesis (CH) is a phenomenon caused by expansion of white blood cells descended from a single hematopoietic stem cell. While CH can be associated with leukemia and some solid tumors, the relationship between CH and lung cancer remains largely unknown. To help clarify this relationship, we analyzed whole-exome sequencing (WES) data from 1,958 lung cancer cases and controls. Potential CH mutations were identified by a set of hierarchical filtering criteria in different exonic regions, and the associations between the number of CH mutations and clinical traits were investigated. Family history of lung cancer (FHLC) may exert diverse influences on the accumulation of CH mutations in different age groups. In younger subjects, FHLC was the strongest risk factor for CH mutations. Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene
Assessment of Immunoglobulin Heavy Chain Variable Region (<i>IGHV</i>) Mutation Status with a Next-Generation Sequencing (NGS) Immunosequencing Assay for Measurable Residual Disease (MRD)
Authors: Lik Wee Lee, Travers Ching, Bryan Howie, Keyur P. Patel, Philip A. Thompson, Nitin Jain, Alessandra Ferrajoli, Zeev E. Estrov, Jan A. Burger, Michael J. Keating, Rashmi Kanagal-Shamanna, William G. Wierda, Lanny R. Kirsch
Journal: Blood (2021)
RADT-13. SPARE TRIAL: SCALP-SPARING RADIATION WITH CONCURRENT TEMOZOLOMIDE AND TUMOR TREATING FIELDS FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Ryan Miller, Andrew Song, Ayesha S Ali, Voichita Bar-Ad, Nina, L Martinez, Jon Glass, Iyad Alnahhas, David Andrews, Kevin Judy, James Evans, Christopher Farrell, Maria Werner-Wasik, Inna Chervoneva, May Ly, Joshua Palmer, Haisong Liu, Wenyin Shi
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Current adjuvant treatment for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). We report our clinical trial evaluating feasibility and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. METHODS Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma with a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of tri-modality treatment within 30 days of completion of chemoradiation treatment. RESULTS Thirty patients were enrolled. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median follow-up was 10.8 months (range 1.6 to 21.3 months). Twenty (66.7%) patients had unmethylated MGMT promotor and ten (33.3%) patients had methylated promoter. Scalp dose constraints were achieved for all patients. Skin adverse events (erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). The median PFS for the entire cohort was 9.1 months (at least 8.5 months, 95% confidence). The median PFS for patients with MGMT promoter methylation status was 11.4 months (at least 9.5 months, 95% confidence). Overall survival was not reached. CONCLUSIONS Concurrent TTFields with scalp-sparing chemoradiation is feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation.
Abstract 8929: Mineralocorticoid Receptor as an Epigenetic Regulator of Vascular Aging
Authors: Jaime Ibarrola Ulzurrun, Seung K Kim, Qing Lu, Jennifer J Dupont, Lauren A Biwer, Joshua J Man, Jacob D Jaffe, Iris Z Jaffe
Journal: Circulation (2021)

Introduction: Vascular stiffness increases with age and independently predicts cardiovascular events but vascular fibrosis mechanisms are unclear. Epigenetic changes accumulate with age and contribute to aging pathology. We showed that aging-associated increase in vascular stiffness/fibrosis are mitigated by treating old mice with mineralocorticoid receptor (MR) antagonist (MRA) or by genetic deletion of MR in smooth muscle cells (SMC-MR-KO). Hypothesis: We hypothesized that SMC-MR regulates vascular fibrosis genes by modulating epigenetic histone modifications in the aging vasculature. Methods and Results: Global histone proteomic profiling revealed increased acetylation (ac) and decreased methylation (me) of histone H3 lysine 27 (H3K27) in old vs young mouse aorta that is attenuated by SMC-MR-KO. Similarly, RNA profiling shows downregulation of fibrotic genes (CTGF, MMP2 and Integrin-α5) with aging in mouse aortas from SMC-MR-KO mice. Mechanism was explored in primary low passage human aortic SMC (HASMC). Comparison of protein levels in HASMCs from old vs young people shows increased MR, decreased H3K27-specific methyltransferase EZH2, increased H3K27ac and increased fibrosis gene expression in aged HASMC. Treatment of young HASMC with H 2 O 2 (aging inductor) increased MR and decreased EZH2 in association with decreased H3K27me. These epigenetic changes were associated with increased H3K27ac and MR enrichment at the promoter of fibrosis genes by ChIP along with increased fibrosis gene expression. Conversely, treatment of aged HASMC with MRA increased EZH2 and H3K27me with decreased fibrosis gene expression. Finally, treatment of 12 month old mice with MR antagonist for 4 months or deletion of MR from SMC prevented aging induction of vascular stiffness by pulse wave velocity in association with decreased H3K27ac at promoters and decreased expression of fibrosis genes in aging aortas. Conclusion: These data support a model in which rising SMC-MR with aging contributes to vascular fibrosis via EZH2 reduction leading to decreased H3K27me and increased H3K27ac and MR recruitment to promote transcription of fibrotic genes. These findings suggest the therapeutic potential for MRAs for aging-associated vascular stiffening/fibrosis.
Hospital-Level Percutaneous Coronary Intervention Performance With Simulated Risk Avoidance
Authors: Ashwin S. Nathan, Pratik Manandhar, Daniel Wojdyla, Adam Nelson, Paul N. Fiorilli, Stephen Waldo, Robert W. Yeh, Sunil V. Rao, Alexander C. Fanaroff, Peter W. Groeneveld, Tracy Y. Wang, Jay Giri
Journal: Journal of the American College of Cardiology (2021)
Abstract 12171: Recruitment and Enrollment of Midlife Latinas in a Multi-Component Intervention to Reduce Cardiovascular Disease Risk: Challenges and Innovations During COVID-19
Authors: Yamnia I Cortes, Mayra Duran, Valentina Marginean, Latesha K Harris, Andrea Cazales, Lymari Santiago, Margarita Diaz Mislan, Krista Perreira
Journal: Circulation (2021)

Introduction: Latinos continue to be underrepresented in clinical research. The novel coronavirus (COVID-19) pandemic has presented additional challenges to conducting clinical research among Latino communities. Menopausia, Salud y Corazón is a two-group pilot intervention designed to reduce cardiovascular disease (CVD) risk in Latinas during the menopause transition. The purpose of this report is to summarize the innovative recruitment methods developed in response to COVID-19, which may enhance future clinical research with Latinas. Methods: This is a two-group, repeated measures experimental study. Eligible participants are Latinas age 40-60 years, who are perimenopausal or early postmenopausal, and free of CVD. In response to COVID-19, the recruitment and enrollment protocol was adjusted to include: remote modalities of recruitment, limited in-person visits, and adhering to COVID-19 safety guidelines (i.e., social distancing, personal protective equipment, sanitizing, temperature and symptom checklists). We recruited at drive-thru health fairs, churches, social media, and word of mouth. A bilingual research team was able to establish rapport and build relations. We developed communication strategies via mailings, infographics, phone calls, video conferencing and text messages that addressed Latino cultural values such as respeto (respect), familismo (loyalty to family), and confianza (trust). Results: After 8 months of recruitment, 79 women were screened for eligibility, with mean age 47.9 ± 5.2 years. All participants completed screening in Spanish and 16.4% (n=13) rated their overall health as “very good/excellent.” Twenty-eight (35.4%) participants screened were recruited through word of mouth and 29.1% were recruited through their parish. Of the individuals screened, 38 (48.1%) were eligible. The most common reason for ineligibility was menopause status (n=21, 26.5%) Conclusions: Despite the challenges presented by COVID-19, we found that midlife Latinas are receptive to research engagement. Researcher flexibility, multiple modalities of recruitment, a bilingual research team, and communication strategies that address cultural values are important elements for the representation of Latinas in research.