tbuckley/cabot-search huggingface dataset:
Abstract 13836: Long Noncoding Rna Meg3 Protects Against Hepatic Endothelial Senescence in Obesity by Regulating Mitochondrial Function
Authors: Xiao CHENG, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Jaydeep Kolape, Sarah L Schlichte, Matthew C Zimmerman, Oleh Khalimonchuk, Mark W Feinberg, Xinghui Sun
Journal: Circulation (2020)

Introduction: Long noncoding RNAs (lncRNAs) contribute to the pathogenesis of obesity, a risk factor for cardiovascular disease. The underlying mechanisms are not completely understood, in part, due to that the functions of the majority of them remain unknown in many processes such as mitochondrial homeostasis and cellular senescence. Here, we set out to test the hypothesis that lncRNAs play key roles in obesity by regulating mitochondrial function and cellular senescence in the endothelium. Methods and Results: In this study, transcriptome analysis revealed that lncRNA maternally expressed gene 3 (Meg3) is one of the top induced lncRNAs in the endothelium from adipose tissue in diet-induced obese mice. Meg3 knockdown potentiated obesity-induced insulin resistance revealed by intraperitoneal glucose and insulin tolerance tests and an increase in fasting plasma insulin levels (1.67-fold increase; p&lt;0.05); diminished insulin signaling revealed by 43% reduction (p=0.038) in Akt phosphorylation on serine 473 in liver and, to a lesser extent, in skeletal muscle (32%; p&lt;0.05), but not in visceral fat; and increased hepatic endothelial senescence in obese mice (e.g., 2.74- and 3.40-fold increase in p21 and p16 expression, respectively; p&lt;0.001). Endothelial cell-specific p53 knockout partially attenuated Meg3 knockdown-induced cellular senescence and completely restored hepatic insulin signaling in obese mice. Meg3 knockdown inhibited mitochondrial bioenergetics, increased mitochondrial superoxide production, and caused fragmentation of mitochondrial network; also impaired autophagy, induced a type 1 interferon response, and triggered cellular senescence in HUVECs. Finally, the expression of Meg3 is induced in fatty livers of obese patients and strongly correlates with the cellular senescence marker p16 (r=0.50; p=0.0007). Conclusions: Deficiency of lncRNA Meg3 contributes to mitochondrial dysfunction, hepatic endothelial senescence, and accelerated obesity-induced insulin resistance. Meg3 induction is important in limiting obesity-induced endothelial senescence and insulin resistance, suggesting that manipulation of Meg3 expression may represent a novel approach to manage obesity-associated cardiometabolic disease.
Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis
Authors: Harsha Kabra, Tanaya Walimbe, Kate Stuart, Camille Indey, Swati Jalgaonkar, Elvis Ikwa, Taylor Skurnac, Julia Chen, Andrew Woolley, Nicholas M. Snead, Nathan Bachtell, Diana J. Leeming, Morten Karsdal, Glenn Prestwich, Alyssa Panitch, John Paderi
Journal: Biomaterials (2020)
Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes
Authors: Gerasimos Filippatos, Stefan D. Anker, Rajiv Agarwal, Bertram Pitt, Luis M. Ruilope, Peter Rossing, Peter Kolkhof, Patrick Schloemer, Ingo Tornus, Amer Joseph, George L. Bakris
Journal: Circulation (2020)

The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD). This randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to <75 mL per min per 1.73 m2, treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite cardiovascular outcome included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Between September 2015 and June 2018, 13 911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite cardiovascular outcome compared with placebo (hazard ratio, 0.86 [95% CI, 0.75-0.99]; P=0.034), with no significant interaction between patients with and without CVD (hazard ratio, 0.85 [95% CI, 0.71-1.01] in patients with a history of CVD; hazard ratio, 0.86 [95% CI, 0.68-1.08] in patients without a history of CVD; P value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone versus 0.8% with placebo in patients with CVD and 2.2% with finerenone versus 1.0% with placebo in patients without CVD). Among patients with chronic kidney disease and type 2 diabetes, finerenone reduced incidence of the composite cardiovascular outcome, with no evidence of differences in treatment effect based on preexisting CVD status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02540993.
The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer
Authors: Berna İmge Aydoğan, Adile Begüm Bahçecioğlu Mutlu, Seher Yüksel, Sevim Güllü, Rıfat Emral, Özgür Demir, Mustafa Şahin, Vedia Tonyukuk Gedik, Demet Çorapçıoğlu, Serpil Dizbay Sak, Murat Faik Erdoğan
Journal: Endocrine Pathology (2020)
Abstract 16550: Community Perception and Treatment of Sore Throat Among Children in a Rheumatic Heart Disease Endemic Setting
Authors: Hadija Nalubwama, JENIFER ATALA, ROSEMARY KANSIIME, Rachel Sarnacki, Emma Ndagire, Emmy Okello, David Watkins
Journal: Circulation (2020)

Introduction: Although Group A Streptococcal (GAS) pharyngitis (sore throat) can be treated, its complications -- acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain significant public health problems in low- and middle -income countries. Examining community perceptions and health seeking behavior for sore throat in these settings could translate into effective ARF/RHD prevention strategies. Objective: To develop a local explanatory model of sore throat health seeking behavior that can be used in designing ARF/RHD preventive interventions Methods: This focus group discussions-based qualitative study was conducted in 3 districts of Uganda (Lira in the north, Wakiso in central and Mbarara in the west). Overall, 50 participants were included in these discussions about sore throat in children. Thematic analysis was done on transcribed and translated audio recordings. Results: Perception of sore throat, treatment practices and challenges/barriers to seeking proper care for sore throat were major topics discussed during the focus group discussions. Across the 3 districts, sore throat was perceived to be a common and serious problem within the community. Although the majority of participants could not tell the exact cause of sore throat, they believed that poor hygiene could be a related factor. Variable methods of treatment were used across all districts. However, traditional medicine use and practices were more common in Lira and Wakiso districts while there was more trust in modern medicine in Mbarara district. Improvement in a child’s symptoms was the most common reason for stopping treatment. Individual, societal and health system factors such as distance to health facility, long waiting time and lack of medicines influenced care givers’ decisions to seek proper care for sore throat. Conclusions: Our findings show interplay between care givers’ knowledge, beliefs and preferences and the health care system as major determinants of caregivers’ behavior to seek proper care for pharyngitis. Community ARF/RHD educational programs in Uganda should emphasize the consequences of untreated or poorly treated pharyngitis and the importance of seeking proper care and treatment.
Trends in Imaging for Suspected Pulmonary Embolism Across US Health Care Systems, 2004 to 2016
Authors: Ralph C. Wang, Diana L. Miglioretti, Emily C. Marlow, Marilyn L. Kwan, May K. Theis, Erin J. A. Bowles, Robert T. Greenlee, Alanna K. Rahm, Natasha K. Stout, Sheila Weinmann, Rebecca Smith-Bindman
Journal: JAMA Network Open (2020)

<h3>Importance</h3> In response to calls to reduce unnecessary diagnostic testing with computed tomographic pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), there have been growing efforts to create and implement decision rules for PE testing. It is unclear if the use of advanced imaging tests for PE has diminished over time. <h3>Objective</h3> To assess the use of advanced imaging tests, including chest computed tomography (CT) (ie, all chest CT except for CTPA), CTPA, and ventilation-perfusion (V/Q) scan, for PE from 2004 to 2016. <h3>Design, Setting, and Participants</h3> Cohort study of adults by age group (18-64 years and ≥65 years) enrolled in 7 US integrated and mixed-model health care systems. Joinpoint regression analysis was used to identify years with statistically significant changes in imaging rates and to calculate average annual percentage change (growth) from 2004 to 2007, 2008 to 2011, and 2012 to 2016. Analyses were conducted between June 11, 2019, and March 18, 2020. <h3>Main Outcomes and Measures</h3> Rates of chest CT, CTPA, and V/Q scan by year and age, as well as annual change in rates over time. <h3>Results</h3> Overall, 3.6 to 4.8 million enrollees were included each year of the study, for a total of 52 343 517 person-years of follow-up data. Adults aged 18 to 64 years accounted for 42 223 712 person-years (80.7%) and those 65 years or older accounted for 10 119 805 person-years (19.3%). Female enrollees accounted for 27 712 571 person-years (52.9%). From 2004 and 2016, chest CT use increased by 66.3% (average annual growth, 4.4% per year), CTPA use increased by 450.0% (average annual growth, 16.3% per year), and V/Q scan use decreased by 47.1% (decreasing by 4.9% per year). The use of CTPA increased most rapidly from 2004 to 2006 (44.6% in those aged 18-64 years and 43.9% in those ≥65 years), with ongoing rapid growth from 2006 to 2010 (annual growth, 19.8% in those aged 18-64 years and 18.3% in those ≥65 years) and persistent but slower growth in the most recent years (annual growth, 4.3% in those aged 18-64 years and 3.0% in those ≥65 years from 2010 to 2016). The use of V/Q scanning decreased steadily since 2004. <h3>Conclusions and Relevance</h3> From 2004 to 2016, rates of chest CT and CTPA for suspected PE continued to increase among adults but at a slower pace in more contemporary years. Efforts to combat overuse have not been completely successful as reflected by ongoing growth, rather than decline, of chest CT use. Whether the observed imaging use was appropriate or was associated with improved patient outcomes is unknown.
Abstract 14442: Tuberculosis-Specific Cell-Mediated Immune Responses Are Associated With Coronary Artery Atherosclerosis Among Persons With and Without HIV in Uganda
Authors: Moises A Huaman, Marcio S Bittencourt, Cissy M Kityo, Sophie Nalukwago, Rashidah Nazzinda, Carl J Fichtenbaum, Chris T Longenecker
Journal: Circulation (2020)

Introduction: Latent tuberculosis infection (LTBI) has been associated with increased odds of acute myocardial infarction. Here we assessed the relationship between subclinical coronary atherosclerosis, LTBI status, and Mycobacterium tuberculosis ( Mtb )-specific cell-mediated responses. Hypothesis: LTBI and the magnitude of Mtb -specific cell-mediated responses are associated with increased rates of subclinical coronary artery disease (CAD). Methods: Cross-sectional study within a cohort of HIV-infected and -uninfected participants enrolled at the Joint Clinical Research Centre in Kampala, Uganda. Participants were ≥45 years with at least one risk factor for cardiovascular disease. Persons living with HIV (PLWH) were on stable antiretroviral therapy with HIV viral load ≤1,000 copies/mL within the 6 months prior to study entry. Participants underwent QuantiFERON®-TB Gold (QFT) testing to define LTBI status. Interferon-γ (IFN-γ) cell-mediated responses to Mtb antigens contained in the QFT TB tube were extracted. Participants underwent coronary computed tomography angiography (CCTA) utilizing a 128-slice Siemen’s scanner. Obstructive CAD was defined as having at least one coronary segment with plaque causing ≥ 50% luminal stenosis (CAD-RADS ≥3). Results: Of 138 participants, 66 (48%) had LTBI (17 PLWH and 49 HIV-uninfected), and 72 (52%) were non-LTBI (38 PLWH and 34 HIV-uninfected). Median age was 57 years; 91 (66%) were female; 120 (87%) had hypertension, 45 (33%) had diabetes mellitus, 24 (17%) had dyslipidemia, and 7 (5%) used tobacco. Median CD4 count was 569 cells/uL in PLWH. Prevalence of obstructive CAD was 9% in LTBI vs. 3% in non-LTBI; p =0.152. Mtb -specific responses were higher in persons with obstructive CAD compared to those without it (IFN-γ IU/mL median [IQR]; 5 [0.4 - 9.6] vs. 0.3 [0.1 - 2.9]; p =0.04). Mtb -specific responses remained associated with obstructive CAD after adjusting for age, sex, HIV status, cholesterol, hypertension, tobacco use, and diabetes mellitus (adjusted OR, 1.33; 95% CI; 1.04 - 1.7). Conclusions: Higher Mtb -specific cell-mediated responses were associated with obstructive CAD. Our findings suggest that Mtb contributes to coronary plaque burden independently of HIV and cardiovascular risk factors.
Abstract 14283: Coronary Microvascular Function is Correlated With Peak Exercise Capacity in Patients With Unexplained Cardiac Exertion Symptoms and Non-obstructive Coronary Artery Disease
Authors: Ali Ahmad, Michel Corban, Takumi Toya, Frederik H Verbrugge, Jaskanwal D Sara, Ilke Ozcan, Lilach O Lerman, Barry A Borlaug, Amir LERMAN
Journal: Circulation (2020)

Introduction: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic patients with no obstructive coronary artery disease. We postulated that exercise capacity and cardiac output augmentation in response to exercise are linked to coronary microvascular function in this patient population. Methods: Fifty-one consecutive patients with unexplained cardiac exertion symptoms, non-obstructive coronary artery disease on angiography (&lt;50% stenosis), and normal left ventricular ejection fraction (&gt;50%) who underwent concurrent clinically indicated coronary reactivity testing and invasive cardiopulmonary exercise testing (CPEX) were included. Microvascular function was assessed by coronary flow reserve (CFR; hyperemic/resting flow) in response to intracoronary adenosine injection. Cardiac output (CO) was calculated at rest and peak exercise using Fick’s formula. CO limitation was defined as a measured (peak CO - resting CO) &lt;80% than the expected [6*absolute ΔVO 2 (Peak VO 2 -Rest VO 2 ) increase in CO in L/min]. The relationship between CFR, maximal exercise capacity, and CO augmentation at peak exercise was explored. Results: Patients were 56.6±10.5 years old and 73% were females. CFR had a modest positive correlation with measured increase in CO (r=0.42; P=0.003) ( Fig 1A ), and with maximal ergometric exercise capacity [in Watts/Kg] (Pearson’s r=0.33, P=0.02) ( Fig 1B ). Patients with, vs. without impaired cardiac limitations during exercise, had significantly lower CFR levels (2.6±0.5 vs 3.1±0.7; P=0.01) ( Fig 2 ). Conclusion: Impaired coronary microvascular function is associated with lower peak exercise capacity and reduced cardiac output augmentation in response to exercise, underscoring the functional ramification of CMD in symptomatic patients.
Abstract 15480: Twiddler’s Syndrome in a Subcutaneous Implantable Cardioverter-Defibrillator
Authors: Chengyue Jin, Jason Jacobson, Sei Iwai, Aileen M Ferrick
Journal: Circulation (2020)

Introduction: Twiddler’s syndrome refers to deliberate or unintentional twisting of pulse generator in device pocket resulting in lead migration, which can present as malfunction of pacemaker or implantable cardioverter-defibrillator (ICD). In the past 50 years, twiddler’s syndrome with transvenous ICD and pacemaker has been well-described and thoroughly studied. However, there are very little data on twiddler’s syndrome with subcutaneous ICD (S-ICD). Case presentation: The patient is a 50-year-old male with a past medical history of hypertrophic cardiomyopathy, cardiac MRI showing left ventricular hypertrophy with a wall thickness of 24 mm, non-sustained ventricular tachycardia and evidence of late gadolinium enhancement scar, who underwent implantation of S-ICD for primary prevention. First follow-up 2 weeks post-implant showed appropriate device function. Two weeks later, remote monitor documented atrial fibrillation and ICD shocks. Surface ECG showed reduced R wave and delivered shock impedance was 7 ohms. Patient reported no symptoms and was clapping hands to music when it occurred. Chest X-Ray revealed S-ICD lead dislodged and retracted with coiling around the generator in the left lateral chest wall (Figure 1). Subsequently patient underwent lead revision and device replacement. To reduce the risk of future dislodgement, during re-implantation, the tip of the ICD lead was secured with 0-Silk. Conclusion: Twiddler’s syndrome is a rare complication after ICD implantation, not only with transvenous-ICDs but also involving S-ICDs. Risk factors include advanced and younger ages, redundant skin, obesity, oversized pocket, and psychiatric disorder. It can be a potentially dangerous and even fatal due to undetected or unsuccessful therapy for ventricular tachyarrythmias. Therefore, it is of paramount importance to diagnose and intervene early to avoid morbidity and mortality in these patients.
The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis
Authors: Xin Hong, Whijae Roh, Ryan J. Sullivan, Keith H.K. Wong, Ben S. Wittner, Hongshan Guo, Taronish D. Dubash, Moshe Sade-Feldman, Benjamin Wesley, Elad Horwitz, Genevieve M. Boland, Dieuwke L. Marvin, Todd Bonesteel, Chenyue Lu, François Aguet, Risa Burr, Samuel S. Freeman, Laxmi Parida, Katherine Calhoun, Michelle K. Jewett, Linda T. Nieman, Nir Hacohen, Anders M. Näär, David T. Ting, Mehmet Toner, Shannon L. Stott, Gad Getz, Shyamala Maheswaran, Daniel A. Haber
Journal: Cancer Discovery (2020)

Abstract Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These are correlated with both intrinsic and acquired resistance to BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The lipogenesis regulator SREBP2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby conferring resistance to inducers of ferroptosis. Knockdown of endogenous TF impairs tumor formation by melanoma CTCs, and their tumorigenic defects are partially rescued by the lipophilic antioxidants ferrostatin-1 and vitamin E. In a prospective melanoma cohort, presence of CTCs with high lipogenic and iron metabolic RNA signatures is correlated with adverse clinical outcome, irrespective of treatment regimen. Thus, SREBP2-driven iron homeostatic pathways contribute to cancer progression, drug resistance, and metastasis. Significance: Through single-cell analysis of primary and cultured melanoma CTCs, we have uncovered intrinsic cancer cell heterogeneity within lipogenic and iron homeostatic pathways that modulates resistance to BRAF inhibitors and to ferroptosis inducers. Activation of these pathways within CTCs is correlated with adverse clinical outcome, pointing to therapeutic opportunities. This article is highlighted in the In This Issue feature, p. 521
Culprit Plaque in Myocardial Infarction: Going Beyond Angiography⁎⁎Editorials published in the Journal of American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Aloke V. Finn, Gaku Nakazawa, Jagat Narula, Renu Virmani
Journal: Journal of the American College of Cardiology (2007)
Abstract 15895: Machine Learning Algorithms to Predict Major Adverse Cardiovascular Events in Patients Undergoing Orthotopic Liver Transplantation: A Retrospective Cohort Study
Authors: vardhmaan jain, Vikram Sharma, Agam Bansal, Cerise Kleb, Chirag Sheth, Cristiano Quintini, Jacek Cywinski, Maan Fares
Journal: Circulation (2020)

Background: Post-transplant major adverse cardiovascular events (MACE) are amongst the leading cause of death amongst orthotopic liver transplant(OLT) recipients. Despite years of guideline directed therapy, there are limited data on predictors of post-OLT MACE. We assessed if machine learning algorithms (MLA) can predict MACE and all-cause mortality in patients undergoing OLT. Methods: We tested three MLA: support vector machine, extreme gradient boosting(XG-Boost) and random forest with traditional logistic regression for prediction of MACE and all-cause mortality on a cohort of consecutive patients undergoing OLT at our center between 2008-2019. The cohort was randomly split into a training (80%) and testing (20%) cohort. Model performance was assessed using c-statistic or AUC. Results: We included 1,459 consecutive patients with mean ± SD age 54.2 ± 13.8 years, 32% female who underwent OLT. There were 199 (13.6%) MACE and 289 (20%) deaths at a mean follow up of 4.56 ± 3.3 years. The random forest MLA was the best performing model for predicting MACE [AUC:0.78, 95% CI: 0.70-0.85] as well as mortality [AUC:0.69, 95% CI: 0.61-0.76], with all models performing better when predicting MACE vs mortality. See Table and Figure. Conclusion: Random forest machine learning algorithms were more predictive and discriminative than traditional regression models for predicting major adverse cardiovascular events and all-cause mortality in patients undergoing OLT. Validation and subsequent incorporation of MLA in clinical decision making for OLT candidacy could help risk stratify patients for post-transplant adverse cardiovascular events.
Fluoroquinolone Resistance in Neisseria gonorrhoeae, Hawaii, 1999, and Decreased Susceptibility to Azithromycin in N. gonorrhoeae, Missouri, 1999
Authors: R. Ohye, V. Lee, P. Whiticar, P. Effler, H. Domen, G. Hoff, J. Joyce, R. Archer, M. Hayes, J. Hale, K. Holmes, L. Doyle, G. Procop
Journal: JAMA (2000)