tbuckley/cabot-search huggingface dataset:
Computational Psychiatry Across Species to Study the Biology of Hallucinations
Authors: Katharina Schmack, Torben Ott, Adam Kepecs
Journal: JAMA Psychiatry (2021)

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Abstract 10935: Identification of Small-Molecule ERBB4 Agonists to Treat Heart Failure
Authors: Eline Feyen, Julie Cools, Jens Van fraeyenhove, Michiel Tubeeckx, Tine Bruyns, Hans De Winter, Dominique Audenaert, Gilles W De Keulenaer, Vincent F Segers
Journal: Circulation (2021)

Introduction: Heart failure is a complex syndrome with a poor prognosis. The neuregulin-1 (NRG1)/ERBB4 axis has been shown to be cardioprotective and is a possible target for heart failure therapy. Clinical trials with NRG1 are ongoing, but require intravenous administration. Our aim is to develop a small-molecule ERBB4 agonist with cardioprotective properties. Methods: A high-throughput diversity screening (HTS) of 10,240 compounds was performed on a cellular ERBB4/ERBB4 dimerization assay. Ligand binding of hit compounds was tested in co-administration studies with NRG1 (0.1 μM) and competition binding assays with fluorescently labeled NRG1 (0.03 μM). Selectivity, post-receptor phosphorylation, and cell toxicity of hit compounds were determined using Luminex® RTK phosphoprotein, U2OS ERBB2/ERBB3 dimerization and adenylate kinase assays. Biological effects were studied in vitro in different doses (4-32 μM) on TGF-β-induced collagen synthesis by human dermal and atrial fibroblasts, and on angiotensin II (AngII, 1000 ng/kg/min)-induced left ventricular (LV) remodeling in mice with 2 selected hit compounds (83 μg/kg/h), administrated through osmotic pumps (N=4-5/group). After 28 days, left ventricular myocardial fibrosis and cardiomyocyte cross sectional area (CSA) were analyzed. Results: The HTS resulted in 8 similar pyrimidine derivatives inducing ERBB4/ERBB4 but not ERBB2/ERBB3 dimerization (Emax 9 to 33% relative to NRG1, and EC50 6x10 -6 M to 2x10 -7 M). Two compounds were excluded due to in vitro toxicity. The other 6 compounds were non-toxic and induced ERBB4, but not ERBB1, ERBB2 or ERBB3 phosphorylation in EFO-21 cells. Competition assays showed allosteric binding, and co-administration studies with NRG1 revealed that compounds potentiated NRG1-induced ERBB4 receptor dimerization up to 2.5 fold. Selected compounds showed significant dose-dependent antifibrotic effects in cultured human atrial and dermal fibroblasts and significantly attenuated AngII-induced LV myocardial fibrosis by 76%±26%, whereas cardiomyocyte CSA was not affected. Conclusions: We identified novel pyrimidine derivative small-molecule ERBB4 agonists with antifibrotic properties, both in vitro and in a mouse model of AngII-induced LV fibrosis.
Abstract 11322: Role of Centhaquine (lyfaquin®) in the Protection of Renal Tissues After Acute Kidney Injury
Authors: Amaresh Ranjan, Seema Briyal, Zhong Zhang, Anil Gulati
Journal: Circulation (2021)

Background: Acute Kidney Injury (AKI) is frequently associated with an in-hospital complication of sepsis, heart conditions, hemorrhagic shock, and surgery. However, at present, no specific drug to...
Abstract 8870: Hemodynamic Impact of Atrial Pacing in Patients with Fontan Physiology and Junctional Rhythm: A Cardiac Catheterization Study
Authors: Mohammad Alnoor, Grant Burch, Laurie Armsby, Seshadri Balaji
Journal: Circulation (2021)

Introduction: Sinus node dysfunction is a common problem and can adversely impact patients who have undergone the Fontan operation (FO). In FO patients with an adequate junctional escape rhythm (JR), the benefit of atrial pacing to restore atrioventricular synchrony remains unclear. We studied the impact of atrial pacing on hemodynamics in patients with FO and JR undergoing cardiac catheterization. Methods: Data was collected retrospectively on all FO patients with JR who underwent atrial pacing during cardiac catheterization. Hemodynamics (pulmonary artery pressure, left atrial pressure, and cardiac index) were obtained at baseline and after atrial pacing for 5-10 minutes. Results: Six patients, with a mean age of 11 years (range 3-21) met inclusion criteria. The type of FO was extracardiac in 5 and a lateral tunnel in one. A pacing catheter was placed through the Fontan fenestration in 4, via the IVC recess behind the right atrium in 1, and via the left pulmonary artery in 1. Patients were paced 10 bpm faster than their JR rate (100 bpm in 3, 88 bpm in 1 and 70 bpm in 2. With pacing, there was a significant decrease in left atrial pressure from (mean ±SEM) 9.4 ± 1.1 mmHg to 5.8 ± 1.4 mmHg (p=0.02), a significant increase in cardiac index from 2.7 ± 0.4 L/min/m 2 to 3.5 ± 0.5 L/min/m 2 (p=0.03) and no significant change in pulmonary artery pressure, from 13mmHg ± 1.4 to 12.2mmHg ± 2.2 (p=0.1) Conclusion: In FO patients with JR, atrial pacing acutely decreased the left atrial pressure, increased the cardiac output and did not result in a significant change in the pulmonary artery pressure. Our study supports further investigation into the utility of prophylactic atrial pacemaker implantation in Fontan patients with significant durations of JR on ambulatory monitoring.
Abstract 9923: Global Circumferential Strain and Cardiovascular Events in Patients with Myocarditis Related to Immune Checkpoint Inhibitors
Authors: Thiago Q Silva, Magid Awadalla, Malek Hassan, Amna Zafar, Zsofia Drobni, Carlos Gongora, Syed S Mahmood, Lili Zhang, Carol Chen, Stephane EDERHY, Ana Barac, Maeve Jones-O'Connor, Sean Murphy, Otavio R Coelho-filho, Muhammad A Rizvi, GAGAN SAHNI, Anant Mandawat, Tocchetti G Carlo Gabriele, Sarah Hartmann, Hannah Gilman, Eduardo Zatarain-Nicolás, Michael Mahmoudi, Dipti Gupta, Caroline Michel, Ana Gonzalez Mansilla, Antonio Calles, Marcella Cabral, Francisco Fernandez-Aviles, Juan Jose Gavira, Nahikari S Gonzalez, Manuel Garcia Y Castro, Jonathan Afilalo, Ryan Sullivan, Sarju Ganatra, Daniel Zlotoff, Eric Yang, lucie heinzerling, Franck Thuny, Leyre Zubiri, Kerry Reynolds, Alexander Lyon, Anju Nohria, Michael Fradley, Paaladinesh Thavendiranathan, Tomas Neilan
Journal: Circulation (2021)

Introduction: Myocarditis is a rare but highly morbid complication of immune-checkpoint inhibitors (ICI) use. Improved methods for detection and risk stratification are needed. Cytotoxic chemotherapy associates with reduced global circumferential strain (GCS) but no data is available on the utility of GCS in ICI myocarditis. Hypothesis: We hypothesized that GCS by echocardiography would be reduced in ICI myocarditis and the magnitude of reduction would have prognostic implications. Methods: In this retrospective cohort, GCS from 75 patients with ICI myocarditis (cases) and 49 ICI treated patients without myocarditis (controls) was compared. Pre-ICI GCS values were available for 10 cases and 39 controls. Measurements were performed by a reader blinded to group and time (TomTec, Germany). Major adverse cardiac event was defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death. Results: Cases and controls had similar age (66±15 vs. 63±12 years; p=0.19), sex (male: 55% vs. 66%; p=0.22) and cancer type (p=0.08). Pre-ICI GCS values were lower in cases (n=10) than in controls (n=39) (-21.7±2.0 vs. -23.5±2.9, p=0.04), but within normal range. Overall, 56% (n=42) of cases had left ventricular ejection fraction (LVEF) &gt;50% at presentation. The GCS was lower in cases than in controls (-17.5±4.2 vs. -23.5±3.0, p&lt;0.001) in the entire cohort and in both preserved (-19.7±3.8 vs. -23.6±3.0, p&lt;0.001) and reduced EF (-14.6±2.7 vs. -20.9±2.3, p&lt;0.001) strata. Over a median follow-up of 30 days, 28 events occurred. An absolute GCS value &lt; the median (17.1%) was associated with an increased rate of events (HR: 4.9, 95% CI: 1.6-15.0, p=0.005, Figure), adjusted for age and LVEF. The association was also noted when GCS is treated as continuous (HR: 1.18, 95% CI: 1.03-1.35, p=0.02). Conclusions: Global circumferential strain is lower in patients with ICI-myocarditis and the magnitude of the reduction in GCS has prognostic significance.
Abstract 11313: Pericarditis Recurrence After Initial Uncomplicated Clinical Course
Authors: Antonio Abbate, Alessandra Vecchie, Juan Ignacio Damonte, juan guido chiabrando, MEGAN S DELL, Aldo Bonaventura, Benjamin W VAN TASSELL, Daniel Berrocal, Tamas S Gal, Antonio Abbate
Journal: Circulation (2021)

Introduction: Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. The exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is, however, unknown. Objectives: We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the USA. Methods: We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis (according to ESC criteria) and then selected only those with uncomplicated course (without in-hospital death, large pericardial effusion [&gt;20 mm] or tamponade, constriction, or failure of treatment) at the VCU Medical Center (Richmond, VA) between 2009 and 2018. Results: A total of 240 patients met acute pericarditis criteria: 174 (72%) patients had an uncomplicated course (median age was 50 [interquartile range 34 to 62] years, 45% females, 51% Black). Pericarditis was considered idiopathic in 89 patients (51%). During a median follow-up time of 184 [17- 434] days, 23 (13%) patients experienced at least one episode of recurrent pericarditis. When compared with those without recurrence, patients with recurrent pericarditis were more frequently females (15 [65%] vs 63 [42%], p=0.035) and had a higher prevalence of subacute/delayed presentation (defined as symptoms over several days without a clear-cut acute onset) (3 [13%] vs 1 [0.7%], p=0.008). There were no other clinical (including the use of anti-inflammatory therapies and pericarditis etiology) or laboratory differences between those with and without pericarditis recurrence at follow-up. At multivariate logistic regression analysis only subacute presentation remained predictor of recurrence at follow-up (odds ratio 20, 95% confidence interval [1.81-198.11], p=0.014). Conclusions: Approximately one every six patients with an acute pericarditis experience a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Subjects with subacute presentation were at significantly higher risk of recurrence.
Abstract 107: Selective Igf-1 Production By Resident Cardiac Macrophages Orchestrates Adaptive Cardiomyocyte Growth During Hypertensive Stress
Authors: Rysa Zaman, Homaira Hamidzada, Slava Epelman
Journal: Circulation Research (2021)

Objective: Adaptive cardiomyocyte growth is an essential compensatory response to hypertension. While hypertension activates cardiac immune cells, their role in adaptation is unclear. Here, we define the transcriptional heterogeneity and functional role of cardiac resident macrophages (RMs) in vivo in hypertensive heart disease. Methods: We performed flow cytometry, immunofluorescence, and single-cell transcriptomics on fate-mapped cardiac RMs isolated from mice with angiotensin II infusion in acute (day 4) and chronic hypertensive stress (day 28). Following inducible depletion of RMs or specific genetic deletion of Igf1 in RMs during hypertension in mice, functional outcomes were tested with echocardiography and immunohistochemistry. Lastly, we also performed single-cell RNA sequencing on human cardiac macrophages from healthy and diseased samples. Results: Cardiac RMs possess numerous transcriptionally diverse cell states with a core repertoire of reparative gene programs that includes high expression of Igf1 in normotensive animals. Individual cell states were differentially responsive during hypertension while all maintained their original transcriptional identity. Hypertension drove selective in situ proliferation and numerical expansion of some cardiac RMs, directly correlating with increased cardiomyocyte size. Inducible ablation of RMs, or selective deletion of RM-derived IGF-1 caused complete absence of adaptive cardiomyocyte growth and development of cardiac dysfunction. Single-cell transcriptomics further identified a conserved IGF1 -expressing macrophage subpopulation in human cardiomyopathy. Conclusions: Here, we defined the absolute requirement of cardiac RM-produced IGF-1 in adaptive cardiomyocyte growth during hypertension, identifying a novel and essential pathway of RM-directed cardiac adaptation to disease.
Abstract 12197: Rural Caregivers With Low Health Literacy Show Greater Improvements in Diet Quality From a Cardiovascular Disease Risk Reduction Intervention Designed to Address Low Health Literacy Than Those With High Health Literacy
Authors: Junghee Kang, Misook L Chung, Martha J Biddle, Terry A Lennie, Jennifer Miller, Debra K Moser
Journal: Circulation (2021)

Introduction: Rural caregivers of those with chronic illnesses have higher cardiovascular disease (CVD) risk than urban caregivers. Diet is a major lifestyle factor that contributes to CVD risk. We conducted a randomized controlled trial of a CVD risk reduction intervention called Rural Intervention for Caregivers’ Heart Health (RICHH), that was designed to promote CVD risk reduction, including healthy eating and that was designed to be accessible to those with low health literacy (HL). We tested the moderating effect of HL on the impact of the intervention on diet quality. Hypothesis: Rural caregivers with low HL would gain equal or greater benefits from the RICHH intervention on diet quality compared to those with high HL. Methods: The newest vital sign (NVS), rural-urban commuting area (RUCA) code ≥4 or living in Appalachian counties, and Healthy Eating Index-2015 (HEI-2015) were used to determine HL, rurality, and diet quality, respectively. The HEI-2015 was computed based on a food frequency questionnaire at baseline and post-intervention. The RICHH intervention was delivered using videoconference technology by nurse interventionists once a week for 12 weeks. A linear mixed effect model was used to evaluate the moderation effect of HL (NVS ≥ 4) on the impact of the intervention on diet quality. Results: A total of 296 rural caregivers (54.5 ± 13.7 years old, 76% female) completed the study. The improvement in HEI-2015 scores was greater in the low HL group than in the high HL group controlling for age and sex (beta estimate = 9.21, SE = 3.31, P = 0.0058). Conclusions: The RICHH intervention was effective in improving diet quality of rural caregivers compared to the control group. In particular, rural caregivers with low HL benefited more from the intervention aimed at increasing diet quality. Thus, addressing low HL could play an important role to improve diet quality and to reduce CVD risk among caregivers residing in rural environment.
Abstract 9788: Advanced Atrio-Ventricular Block in Patients with Active Covid-19 Infection
Authors: ivan mendoza, Karina Gonzalez, Heliodoro Rodriguez, Igor Morr, Susana Blanco, Hildelia Hernandez, Elias Urbaez, Elio Rodriguez, Yolimar Meza, Elirub Rojas, Francesca Misticcio, Jose Torres-Viera, Ivan Mendoza
Journal: Circulation (2021)

Introduction: Cardiac arrhythmia is a frequent complication of COVID-19, However, there are currently only a few case reports of advanced atrioventricular block (AVB). Hypothesis: We sought to describe a case series of AVB as a complication of COVID-19. Methods: We included a series of ten (10) consecutive patients with confirmed COVID-19, who developed advanced AVB in a prospective observational multi-center study. Patients underwent clinical, laboratory evaluation, Holter, telemetry, Echocardiogram, Chest X-Ray, chest CT scan and cardiac MRI. Results: Of the ten (10) patients, 5 were female (50%) with a mean age of 62,7 +- 11,5 years. Eight (8) developed complete AVB, one a 3:1 AVB and one 2:1 AVB. None of the patients had a history of cardiac arrhythmia AVB was not related to medication or intubation. Six patients developed AVB during their hospitalization for COVID-19 and 4 after the first month as a late sequela. Four patients were asymptomatic, one presented syncope, two dyspnea and two dizziness. Six patients presented reverse AVB early by a high dose of corticosteroid in six and colchicine in 3 cases, with no recurrent episodes.Four patients required a permanent pacemaker for persistent conduction defect. Conclusions: Advanced AVB could be a complication of COVID-19. The conduction disturbance was reversed by corticosteroids with or without colchicine in six of ten cases The resolution with corticosteroids of the advanced AVB in these patients could reflect the transient nature of the viral infection and the inflammatory response associated with it in some patients. Four patients required a pacemaker. Physicians should be aware of this complication.
Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme
Authors: Line Elmerdahl Frederiksen, Friederike Erdmann, Luzius Mader, Hanna Mogensen, Camilla Pedersen, Line Kenborg, Andrea Bautz, Mats Talbäck, Elli Hirvonen, Thomas Tjørnelund Nielsen, Elisabeth Anne Wreford Andersen, Anna Sällfors Holmqvist, Ole Sylvester Jørgensen, Jens Richardt Møllegaard Jepsen, Nea Malila, Henrik Hasle, Laura Madanat-Harjuoja, Maria Feychting, Jeanette Falck Winther
Journal: The Lancet Psychiatry (2021)
Abstract 11238: Impact of Baseline Heart Failure and Heart Failure Subtype on Brain Natriuretic Peptide Levels in Patients with Acute Pulmonary Embolism
Authors: Ayla Cash, Matthew Niedoba, Konrad Katterle, Vanessa Pasadyn, Pamela Brewster, Alexandria Mann, Rajesh Gupta
Journal: Circulation (2021)

Introduction: Among patients with acute pulmonary embolism (PE), elevated levels of brain natriuretic peptide (BNP) correlate with right ventricular dysfunction and increased morbidity and mortality. Suggested BNP cut-offs for PE risk stratification in the general population range from 90-100 pg/mL. It is unclear whether this BNP cut-off should be used for PE risk stratification among patients with heart failure (HF), who may have elevated BNP at baseline. Methods: Patients diagnosed with acute PE between 2010 and 2015 at the University of Toledo Medical Center were identified. Patients were categorized as: no HF, heart failure with reduced ejection fraction (HFrEF), or heart failure with preserved ejection fraction (HFpEF). No HF was defined as having no prior history of HF and an ejection fraction (EF) ≥ 50%. HFrEF was defined as history of HF and an EF &lt; 50%. HFpEF was defined as history of HF and an EF ≥ 50%. HF was defined as subjects with HFrEF or HFpEF. Results: One hundred and eighty-three patients with acute PE were identified for this study. One hundred and forty-two patients were classified as no HF (median BNP 112 [interquartile range (IQR) 49-355] pg/mL), while 41 were classified as HF (median BNP 422 [IQR 179-940] pg/mL) (p&lt;0.0001). When HF was further sub-categorized, we found significant differences in BNP levels between subjects with HFrEF (median BNP 923 [IQR 464-2296] pg/mL) vs. subjects with HFpEF (median BNP 247 [IQR 88-726] pg/mL) (p=0.002). Median BNP among patients with HFrEF was significantly higher compared to patients with no HF (p&lt;0.0001). Median BNP among patients with HFpEF was not significantly different compared to patients with no HF (p=0.416). Conclusions: Patients with HFrEF who present to the hospital with acute PE have significantly higher median BNP compared to patients with HFpEF or no HF. These results suggest that risk stratification for PE using current BNP cut-off guidelines may not be optimal for patients with HFrEF.
Leading Causes of Death Among Adults Aged 25 to 44 Years by Race and Ethnicity in Texas During the COVID-19 Pandemic, March to December 2020
Authors: Jeremy Samuel Faust, Alexander Junxiang Chen, Max Jordan Nguemeni Tiako, Chengan Du, Shu-Xia Li, Harlan M. Krumholz, Michael L. Barnett
Journal: JAMA Internal Medicine (2021)

This cohort study examines mortality data from Texas, a racially and ethnically diverse state, to better understand excess mortality among adults aged 25 to 44 years during early months of the COVID-19 pandemic.
Treatment of Diabetes — To Pump or Not to Pump
Authors: James O’Connell, David M. Nathan, Timothy O’Brien, Derek T. O’Keeffe
Journal: New England Journal of Medicine (2021)

This interactive feature about a person with type 1 diabetes mellitus and impaired awareness of hypoglycemia offers a case vignette accompanied by two essays supporting the use of a continuous glucose monitor paired with an insulin pump or a continuous glucose monitor with alerts.