tbuckley/cabot-search huggingface dataset:
Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial
Authors: Simon J Bowman, Robert Fox, Thomas Dörner, Xavier Mariette, Athena Papas, Thomas Grader-Beck, Benjamin A Fisher, Filipe Barcelos, Salvatore De Vita, Hendrik Schulze-Koops, Robert J Moots, Guido Junge, Janice N Woznicki, Monika A Sopala, Wen-Lin Luo, Wolfgang Hueber
Journal: The Lancet (2021)
Abstract 13103: Increased Mitochondrial Oxidative Stress and Decreased Mitochondrial Respiration in an in vitro Model of Ischemia Reperfusion Injury
Authors: Ahmed Ismaeel, Evlampia Papoutsi, Dimitrios Miserlis, William Bohannon, Robert Smith, Gleb Haynatzki, Panagiotis Koutakis
Journal: Circulation (2021)

Introduction: Peripheral artery disease (PAD) patients experience ischemia during activity and reperfusion of ischemic skeletal muscle during rest. Cycles of ischemia and reperfusion (I/R) result i...
EPCO-24. MACHINE LEARNING ALGORITHMS UTILIZING TRANSCRIPTIONAL SIGNATURES PREDICT SURVIVAL OUTCOMES IN GLIOMA
Authors: zhaoming Zhou, Mingyao Lai, Juan Li, Qingjun Hu, Changguo Shan, Cheng Zhou, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastomas (GBM) is a common primary malignant brain tumor. This study performed RNA-seq with 227 glioma samples with the aim to identify the immune-related gene markers for glioma prognosis prediction. METHODS Differentially expressed genes (DEGs) were identified between glioma and healthy samples in the TCGA dataset. Differentially expressed immune-related genes (DE-IRGs) were determined by intersecting DEGs to the immune-related genes in the ImmProt database. Independent survival associated DE-IRGs were selected by univariate and multivariate cox-regression analysis in TCGA dataset and validated in the CGGA databases and our RNA-seq data. Further enrichment analysis demonstrated the hub-genes among those prognosis-associated DE-IRGs. After the expression of hub-genes were confirmed by immunohistochemistry (IHC), the hub-genes protein levels on slides were further utilized to establishing the prognosis prediction models by several machine learning methods, including least absolute shrinkage and selection operator (LASSO), generalized linear model (GLM) and linear discriminant analysis (LDA). RESULTS There were 404 DE-IRGs determined in glioma in comparison with healthy tissue samples in TCGA. After evaluated by univariate and multivariate cox-regression, 55 DE-IRGs remaining significant. Thirty-four DE-IRGs were verified to be survival associated in both CGGA and our sequencing cohort, among which, 4 hub-genes (LIF and MDK, LAMB1, and CALU) were determined by enrichment analysis. All of the 4 hub-genes were expression confirmed on the protein level by IHC staining. Based on the staining results, a survival risk score (SRS) was established by machine learning methods (GLM, LDA, and LASSO). Based on SRS, glioma patients were divided into high- and low-risk groups, the overall survivals were significantly different between those two groups, regardless of the tumor grades or pathology types. CONCLUSIONS This study identified a potential immune prognostic signature (LIF and MDK, LAMB1, and CALU) of glioma that would be helpful for OS predicting and for potential therapeutics development.
Abstract 9995: Predictors of Functional Mitral Regurgitation Severity in Non-Ischemic Cardiomyopathy
Authors: Tom Wang, Duygu Kocyigit, Nicholas Chan, Wai Hong W Tang, Brian P Griffin, Scott D Flamm, Deborah H Kwon
Journal: Circulation (2021)

Background: Functional mitral regurgitation is a result of left ventricular and/or atrial remodeling and dysfunction leading to the leaflet malcoaptation, and associated with adverse prognosis. This study assesses the associations between clinical and chamber quantification parameters by cardiac magnetic resonance (CMR) imaging with FMR severity. Methods: This study includes a retrospective cohort of adult NICM patients undergoing CMR during 2002-2017. Quantitative left ventricle, left atrial and right ventricle parameters measured by CMR and clinical factors were assessed for their associations with mitral regurgitant fraction using multivariable linear regression analyses. Results: In 633 NICM patients, mean age was 52.6 years, 256 (40.4%) were female and mitral regurgitant volume and fraction were 11±11 mL and 14±13% respectively. Mitral regurgitant fraction was greater than 20%, 30% and 40% in 26.5%, 11.8% and 6.5% of the cohort respectively. In multivariable linear regression analyses(Table), female sex, higher left-ventricular end-diastolic volume indexed, left ventricular ejection fraction and left atrial volume indexed, and reduced right ventricular ejection were all independently associated with higher mitral regurgitation fraction. Conclusion: FMR is prevalent in NICM patients, and interestingly, female sex and higher left ventricular ejection fraction were independently associated with mitral regurgitation severity, while other predictors include adverse left ventricular and left atrial remodeling, and right ventricular dysfunction.
Abstract 11194: Reducing Arm Muscle Activation by Using an Ablation Catheter Torque Tool: Electromyographic Analysis and User Perception
Authors: Paige Mass, Rohan Kumthekar, Justin Opfermann, Elizabeth D Sherwin, Charles I Berul
Journal: Circulation (2021)

Background: Cardiac ablation catheters are small in diameter and require significant finger dexterity and grip strength to maintain stability and maneuver safely. We designed a catheter torque tool to reduce the muscle activation required to manipulate cardiac ablation catheters and improve user perception of task workload. Objective: The purpose of this study was to evaluate muscle usage and user perception when completing a simulated ablation task with and without the use of a novel ablation catheter torque tool. Methods: Participants, comprised of cardiology attendings and fellows, were fitted with surface electromyographic (EMG) sensors on 6 key muscle groups in the left hand and forearm. Maximum voluntary contraction (MVC) was collected for equal comparison among participants. A standard ablation catheter was inserted into a pediatric cardiac ablation simulator and subjects navigated the catheter tip to 6 specific electrophysiologic targets including a 1-minute simulated radiofrequency lesion. EMG activity normalized to percentage of MVC was collected throughout the task. The task was repeated 4 times, twice with and twice without the torque tool, in randomized order. A NASA Task Load Index (TLX) survey was completed by the participant at the conclusion each task. Results: Thirteen participants completed the study. Using Wilcoxon’s test, there was a significant difference (P &lt; 0.01) in mean percent of MVC in 4 of the 6 muscle groups when comparing bare catheter versus catheter with torque tool: abductor pollicis, brachioradialis, flexor carpi ulnaris, and extensor carpi radialis. The total expended energy for the abductor pollicis (P &lt; 0.01) and extensor carpi radialis (P = 0.02) were significantly reduced. Perceived physical demand, effort, and frustration were also significantly reduced when using the torque tool (P &lt; 0.01). Conclusions: Use of our novel catheter torque tool reduced the amount of muscle activation necessary to manipulate an ablation catheter during a simulated ablation task. Users’ perceived physical demand, effort, and frustration were less when the tool was used. This tool may improve catheter stability, increase procedure safety, and reduce operator stress and muscle fatigue when performing catheter ablation procedures.
Abstract 11070: Antihypertensive Medication Challenges, Adherence, and Blood Pressure in African Americans with a History of Uncontrolled Hypertension
Authors: Doyle M Cummings, Alyssa Adams, Jacquie Halladay, Erica Richman, Andrea Cherrington, Muna Anabtawi, joanna Ringel, Orysya Soroka, Monika M Safford
Journal: Circulation (2021)

Introduction: African American adults with uncontrolled hypertension may have structural inequities in access to, intensity of, as well as greater challenges using antihypertensive medications, all of which may contribute to inadequate blood pressure (BP) control. Traditional self-reported measures of adherence suffer from social desirability bias and are not consistently correlated with BP control. Hypothesis: African Americans with higher systolic BP (SBP) experience more medication challenges (access, med taking) that are correlated with BP. Methods: Data at baseline are from a cluster randomized trial of patient-level coaching vs. practice level facilitation and the combination of the two interventions in 1596 adult African American patients (39% male; mean age 57 ± 12 yrs.) seen in rural primary care practices with a history of uncontrolled hypertension (average over the last year ≥ 140/90 mmHg). In bivariate and correlation analyses, we examined the cross-sectional association of self-reported medication adherence vs. self-reported medication challenges with SBP level at baseline. These relationships were further examined in a linear regression model with SBP as the outcome while controlling for age, gender, and annual income. Results: Patients were taking a mean of 2.4 antihypertensive medications. SBP level was significantly correlated with the number of antihypertensive medication challenges reported (p &lt; 0.01). While those reporting lower medication adherence also reported significantly more medication challenges, mean SBP was not significantly different by self-reported medication adherence level. However, mean SBP was significantly higher in patients reporting 4 or more medication challenges (158 vs. 155mmHg, p=0.004). In linear regression analysis, age, income, and self-reported medication challenges (β = 0.3; .95% CI: 0.03 - 0.6; p = 0.028) were independently associated with SBP level while gender and self-reported medication adherence were not. Conclusion: African Americans with uncontrolled BP often require more intensive antihypertensive regimens. However, such regimens may be associated with more medication challenges that may adversely impact adherence and BP control.
Utilization of a Targeted Next Generation Sequencing Assay to Identify Copy Number Alterations in Chronic Lymphocytic Leukemia and Monoclonal B-Cell Lymphocytosis
Authors: Julia E. Wiedmeier, Chantal McCabe, Daniel R. O'Brien, Nicholas J. Boddicker, Rosalie Griffin Waller, Cecilia Bonolo De Campos, James R. Cerhan, Sameer A. Parikh, Neil E. Kay, Huihuang Yan, Daniel L. Van Dyke, Susan L. Slager, Esteban Braggio
Journal: Blood (2021)
Abstract 13544: Inflammasome Activation In Kawasaki Disease And Multisystem Inflammatory Syndrome In Children
Authors: Wei-ting Wang, Ming He, Chisato Shimizu, Ben A Croker, Hal Hoffman, Adriana H Tremoulet, John Shyy, Jane Burns
Journal: Circulation (2021)

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly identified syndrome elicited by infection of acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although MIS-C shares several clinical features with Kawasaki disease (KD), a greater magnitude of systemic inflammation is usually associated with MIS-C. Inflammasome activation induces the secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the inflammatory form of cell death, pyroptosis. To provide mechanistic insights into MIS-C and KD, we compared the expression and activation of the inflammasome in blood samples from MIS-C and KD patients. Methods: Expression levels of canonical and non-canonical inflammasome components, including NLRP3 , CASP1 , CASP4 , CASP5 , IL1B , and the inflammatory mediator, TIFA in whole blood from KD and convalescent patients were analyzed from microarray datasets. The expression of these inflammasome-related genes was further examined in whole blood samples from MIS-C, KD, KD shock syndrome (KDSS) and convalescent patients using RT-qPCR. Inflammasome activation and TIFA expression were validated in granulocytes of febrile control, KD and MIS-C patients by Western blotting. Results: TIFA , NLRP3 , CASP1 , CASP4 , CASP5 , IL1B were upregulated in whole blood from MIS-C, KD, and KDSS patients as compared to convalescent patients. However, the differences were not significant among diseases. Although gene expression profiles were similar in KD, KDSS and MIS-C whole blood RNA, the processing of canonical and non-canonical inflammasome caspases, caspase-1, and caspase-4 were only observed in granulocytes isolated from MIS-C patients, but not KD and febrile controls. Moreover, TIFA was upregulated along with the activation of the inflammasome in granulocytes of MIS-C patients. Conclusions: Our results suggest that activation of inflammasomes, especially non-canonical inflammasome induction in granulocytes, is a hallmark of MIS-C, and differentiates it from KD.
From dichotomisation towards intersectionality in addressing covid-19
Authors: Anne-Sophie Jung, Victoria Haldane, Rachel Neill, Melisa Mei Jin Tan, Salma M Abdalla, Michael Bartos, Pami Shresha, Alvin Qijia Chua, Anders Nordström, Helena Legido-Quigley
Journal: BMJ (2021)

<b>Anne-Sophie Jung and colleagues</b> argue that understanding mechanisms of response to the covid-19 pandemic as trade-offs reinforces false dichotomies and hamstrings attempts to create stronger and more equitable health systems
Abstract 10143: Rising Burden Of Cardiovascular Disease Risk Factors And Acute Cardiac Events In Young Adults With Comorbid Depression: A Comparison Of Two Nationwide US Cohorts Hospitalized 10-years Apart
Authors: Ankit Vyas, Krupa Patel, Khizran Agha, Nayana Sasidharan, Waleed Sultan, Umarani Badarabandi, Prerna Bansal, NFN Hiba Ambreen, Zeeshan Mansuri, Rupak Desai
Journal: Circulation (2021)

Background: Previous literature suggests an association between depression and cardiovascular diseases. Due to the paucity of data in the young, we aimed to investigate the prevalence of cardiovascular disease (CVD) risk factors and associated major adverse cardiac and cerebrovascular events (MACCE) in young adults hospitalized with comorbid depression a decade apart. Methods: We conducted a retrospective analysis of the National Inpatient Sample database for the years 2007 and 2017. Young adults (18-44 years) hospitalized with comorbid depression were identified using ICD-9 CM/ICD-10 codes. Frequency and trends in demographics and comorbidities including cardiovascular disease risk factors and MACCE were compared between the 2017 vs. 2007 cohort. Results: A total of 1,274,118 (median age 34 [27-40] yrs, 68.7% females) young admissions were recorded with comorbid depression. When the 2007 cohort was compared with the 2017 cohort, a rising trend in depression was observed (5.5% vs. 8.2%) (p &lt;0.001). The 2017 cohort of young adults with depression more often consisted of male, non-white patients . Burden of CVD risk factors (hypertension, diabetes with chronic complications, smoking and obesity) was also greater in the 2017 cohort.. Although the all-cause mortality remained comparable (0.3%) in both cohorts, there was a significantly higher rate and risk of MACCE including acute myocardial infarction (aOR 1.18, 95%CI:1.10-1.26), atrial fibrillation/ flutter (aOR 1.47, 95%CI:1.40-1.54) and stroke (aOR 1.33, 95%CI: 1.26-1.40) (p &lt;0.001) in the 2017 cohort (Table 1) . Conclusion: This nationwide study reveals alarmingly increased prevalence of CVD risk factors and increase in the rate and risk of MACCE in two cohorts of young adults with comorbid depression studied a decade apart. Burden of mental disorders in young adults has been rising in the last decade and warrants extra vigilance by clinicians to curtail CVD risk and improve MACE-associated outcomes.
Abstract 13287: Sex Differences in the Impact of Parental Obesity on Offspring Cardiac SIRT3 Expression, Mitochondrial Efficiency and Diastolic Function Early in Life
Authors: Alexandre A da Silva, Ana C Omoto, Xuemei Dai, Sydney P Moak, Xuan Li, Zhen Wang, Alan J Mouton, John E Hall, Jussara M Docarmo
Journal: Circulation (2021)

Introduction: Previous studies suggest that the perinatal environment can profoundly impact long-term metabolic health of the offspring. Hypothesis: We tested the hypothesis that parental (paternal + maternal) obesity impairs cardiac function in the offspring early in life. Methods: Within 1-3 days after weaning, offspring from obese rats fed a high fat diet (HFD-Offs) and age-matched offspring from lean rats (ND-Offs) were submitted to echocardiography and cardiac catheterization for assessment of pressure-volume relationships. Then, hearts were digested and isolated cardiomyocytes were used to determine contractile function, calcium transients, proteins related to calcium signaling, and mitochondrial bioenergetics. Results: Female and male HFD-Offs were heavier (72±2 and 61±4 vs 57±2 and 49 ±1 g), hyperglycemic (112±8 and 115±12 vs 92±10 and 96±8 mg/dL), with higher plasma insulin and leptin concentrations compared to female and male ND-Offs respectively. Compared to male ND-Offs controls, male HFD-Offs exhibited similar systolic function but impaired diastolic function as indicated by increased isovolumetric relaxation time (IVRT, 22±1 vs. 17±1 ms), the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E’) (E/E’ ratio, 29±2 vs. 23±1) and Tau (5.7±0.2 vs. 4.8±0.2 ms). The impaired diastolic function was associated with reduced resting free Ca 2+ levels and phospholamban protein expression, increased activated matrix metalloproteinase 2 and reduced sirtuin 3 (SIRT3) protein expression, mitochondrial ATP reserve and ATP-linked respiration. We found no differences in diastolic function or SIRT3 expression levels in female HFD-Offs and ND-Offs. Conclusions: These results indicate that male and female offspring from obese parents have metabolic abnormalities early in life (1-3 days after weaning) and that male, but not female, Offs from obese parents have impaired diastolic dysfunction and reductions in cardiac SIRT3, resting free Ca +2 levels and mitochondrial bioenergetics. (R01 DK121411, NHLBI-PO1HL51971, NIGMS P20GM104357 and U54GM115428)
Abstract 13538: Impact of Autophagy Modulation on Apoptosis in Chemotherapy-Induced Cardiac Toxicity
Authors: Asma Boukhalfa, Meola M Dawn, Joey LaMastro, Sally Robinson, Lin Meng, Sydney Weng, Nicholas Robinson, Greg Martin, David E Sosnovik, Robert M Blanton, Vicky Yang, Howard H Chen
Journal: Circulation (2021)

Background: Cardiotoxicity due to chemotherapy remains a challenge. Cardioprotective interventions have not slowed the progression to heart failure. Cardiomyocyte (CM) death can be attributed to autophagy impairment during chemotherapy-induced toxicity. We hypothesize that autophagy activation can be a viable cardioprotective strategy. Methods: H9C2 rat cardiac myoblasts and cardiac slices generated from euthanized dog hearts were treated with 5-50μM doxorubicin (Dox) +/- autophagy activators for 24 hours. Annexin V (Anx) and TUNEL detection of apoptosis, MTT assay of cell viability, and western blots were performed. C57Bl6 mice were challenged with either single Dox (15 mg/kg i.p.), or repeated doses (4 mg/kg i.p., weekly, 5x) +/- 24-hour pre-starvation. Cardiac function was assessed by echo. Results: Dox significantly increased H9C2 apoptosis, rescued by rapamycin (Fig. A). Autophagy induction by phosphatidylinositol-3-phosphate (Pi3P) restored autophagic flux via downregulating autophagy-inhibitory Rubicon (Fig. B). Autophagy stimulation by Pi3P, statins, or starvation significantly reduced H9C2 apoptosis and improved viability (Fig. C-E), but not in human cancer cells. Single high Dox dose in mice markedly increased CM apoptosis by 24 hours, attenuated by pre-starvation without perturbing Dox retention in the heart (Fig. F). In chronically treated Dox mice, starvation before each Dox dose improved cardiac function and survival (Fig. G-H). Viable dog cardiac slices generated (Fig. I-J) exhibited preserved autophagic flux (Fig. K). Dox (5μM, 30-min exposure) induces autophagy blockade at 24 hours leading to apoptosis (Fig. L). Autophagy restoration by rapamycin reduced apoptosis in cardiac slices but not primary canine cancer cells (Fig. M). Conclusions: Autophagy restoration via modulating Rubicon exerts anti-apoptotic effects in murine and canine CMs, but not in cancer cells, potentially translatable to impact cardio-oncology treatment.
Early Postoperative Mortality Among US Veterans With a Robust Physiologic Reserve Undergoing Open or Endovascular Abdominal Aortic Aneurysm Repair
Authors: Katherine M. Reitz, Daniel E. Hall, Michel S. Makaroun, Edith Tzeng, Nathan L. Liang
Journal: JAMA Network Open (2021)

OSR. 6 Our findings are limited by the inclusion of only patients undergoing AAA repairs and by the lack of data on AAA anatomy, patient preferences, and other outcomes.Among patients with robust physiologic reserve, OSR and EVAR were both associated with equivalently low rates of early postoperative mortality.Therefore, the repair choice for these patients should focus on eligible aortic anatomy and patient preferences for long-term follow-up.
“If It’s Ethical During a Pandemic…”: Lessons from COVID-19 for Post-Pandemic Biobanking
Authors: Kyle B. Brothers, Aaron J. Goldenberg, R. Jean Cadigan
Journal: The American Journal of Bioethics (2021)

This article refers to:Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?
Abstract 12480: Establishing Safety and Risk Profile of Right Heart Catheterization
Authors: Jocelyn V Hull, Mitchell Padkins, Stephanie C El Hajj, Mohammed A Al-hijji, Ryan Lennon, Daniel Crusan, Atta Behfar, Rajiv Gulati, Amrit Kanwar, Salman Farhat, Vaibhav Jain, Abdallah El Sabbagh, Mandeep Singh
Journal: Circulation (2021)

Introduction: We aim to elucidate the incidence of major complications related to right heart catheterization (RHC) and ascertain if there are unique risks with right ventricular biopsy. Methods: Diagnostic RHC procedures from 1/1/2002 through 12/31/2013 were identified using the clinical scheduling system at Mayo Clinic, Rochester. Major complications were identified through electronic records using International Classification of Diseases, Ninth Revision billing codes. All events were recorded and adjudicated. Analysis was performed on four separate patient categories (RHC/RV angiography alone, RV biopsy alone, multiple RHC procedures, and concurrent RHC/LHC procedures) and the overall group. Primary outcomes are described in Table 1. Outcomes were measured within 7 days of the procedure, except for death (same day events) and tricuspid regurgitation (variable time endpoints). Results: There were 17,696 RHC procedures (5,556 RHC/RV angiography, 3,846 RV biopsy alone, 776 multiple RHC procedures, and 7,518 combined RHC/LHC). Patient population had a mean age of 56.5 years (15.3) and was predominantly male (58.5%). Same-day death related to RHC procedure occurred in 1 procedure or 0.6 of 10,000 RHCs. There was no significant difference in the risk of complications across RHC procedure categories except for worsening tricuspid regurgitation, which was significantly (p&lt;0.001) more prevalent with RV biopsy (392 cases, 6.0%) than without (136 cases, 1.2%). Conclusion: The incidence of major complications related to right heart catheterization is rare. Worsening tricuspid regurgitation is the most frequently identified change with a significantly higher prevalence with biopsies.
<i>SOCS1</i> Haploinsufficiency Presenting As Incidental Refractory Thrombocytopenia in a Pediatric Patient with Inflammatory Symptoms and History of Sars Cov-2 Infection
Authors: Jillian Lapinski, Sandra Hoang Ngo, Pui Y Lee, Kelly J. Walkovich, Mark Hannibal, Lauren DeMeyer, Smriti Mohan, Thomas F. Michniacki
Journal: Blood (2021)