tbuckley/cabot-search huggingface dataset:
Abstract 17085: The Modified US Heart Allocation System Improves Waitlist Mortality for Patients With Hypertrophic Cardiomyopathy
Authors: Mark R Helmers, Cody Fowler, Peter Altshuler, Amit Iyengar, Jason J Han, William Patrick, Edo Birati, Pavan Atluri
Journal: Circulation (2020)

Introduction: On October 18, 2018, the US donor heart allocation policy was restructured to better stratify patients, decrease status exemptions, and improve inequities. Previously, HCM patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system. Methods: Retrospective analysis was performed of the UNOS Transplant Database for all isolated adult single-organ heart transplant patients listed between April 20, 2008 and December 6, 2019. Redo heart transplants were excluded. Patients were grouped by diagnosis (HCM or ICM &amp; NICM) and divided into eras based on allocation system. Era 1 spanned April 20 th , 2008 to October 17 th , 2018 and Era 2 spanned October 18 th , 2018 to December 6 th , 2019. Results: During the study period, 28,930 patients were listed, with 26,354 in Era 1 (750 HCM, 2.8%) and 2,576 in Era 2 (107 HCM, 4.2%). Across eras, no differences in age, ethnicity, gender, dialysis, and mechanical ventilation were noted among HCM patients (p&gt;0.05). ECMO usage for HCM at listing was 1.3% in Era 1 vs 2.8% in Era 2 (p=0.557). Use of bridge-to-transplant LVADs remained low in HCM patients (Era 1: 4.3% vs Era 2: 1.9%, p=0.505). Status upgrades for HCM patients decreased from 49% to 39% (p=0.06). Waitlist survival was improved in Era 2 for HCM patients (Figure 1, p=0.001). Transplant rates trended higher in Era 2 for HCM (Figure 1, p=0.344). Thirty-day mortality post-transplant in HCM patients was 2.36% in Era 1 and 1.47% in Era 2 (p=0.643). Conclusions: The new allocation system has led to significantly increased one-year waitlist survival and a near-significant decrease in status upgrades for HCM patients. Moreover, HCM patients trended towards higher transplant rates and shorter waitlist times in the new system. Continued investigation of listing practices and outcomes of HCM patients is warranted.
Abstract 13940: Using an Angiotensin Converting Enzyme Inhibitor to Treat Cardiovascular and Cognitive Decline in a Rat Model of Vascular Dementia
Authors: JENNIFER SHEARON, Rachel Fenner, Yulia Grigorova, Ross McDevitt, Samuel Ajamu, Valentina Zernetkina, Wen Wei, Jeffrey Long, Peter R Rapp, Edward G LAKATTA, Olga V Fedorova
Journal: Circulation (2020)

Background: Aged Dahl salt sensitive rats (DSS) rats represent a model of vascular dementia, i.e., they develop central arterial stiffness (CAS), hypertension, and cognitive decline. DSS rats have compromised renin-angiotensin system (RAS) which is activated with age and contributes to hypertension. This study examined whether angiotensin converting enzyme (ACE) inhibitor, lisinopril, affects CAS and cognitive functions in aged male DSS (n=26). Methods &amp; Results: Following initial measurements at 16-mo of age (baseline; BL), DSS were administered lisinopril through their water (LISI; 15mg/kg/day, n=11) or control treatment (n=15) for 2-mo. Pulse wave velocity (PWV), a marker of CAS, and systolic blood pressure (SBP) were measured at BL and at 18-mo of age. Open field test (OFT) to assess anxiety-like behavior and Morris water maze (MWM) to assess spatial memory were performed at 18-mo, then aortae and hearts were collected and weighed. Aortic wall collagen abundance was estimated by histochemistry. Statistical analyses were performed by 2-way ANOVA mixed effects model and t-test. The data are presented as mean ± SEM. At 18-mo of age, control animals had high SBP similar to BL (187±4 vs. 184±7 mmHg), while LISI-treated DSS had lower SBP by 39±4 mmHg vs. BL (p&lt;0.01). PWV in control rats increased from 16 to 18-mo (7.0±0.6 vs. 10.8±1.0 m/s; p&lt;0.05), while PWV in LISI-treated DSS decreased after 2-mo of treatment (7.1±0.3 vs. 5.4±0.3 m/s; p&lt;0.01). Lower heart weights (2.9±0.1 vs. 3.7±0.3 g/kg BW; p&lt;0.01), aortic weights (4.4±0.1 vs. 5.0±0.2 mg/mm/kg BW; p&lt;0.01), and aortic medial collagen abundance (14.0±0.3 vs. 19.6±1.0 % of total; p&lt;0.01) were observed in the LISI-treated rats vs. control rats. No differences between LISI-treated and control groups at 18-mo (38±10 vs. 25±6 cm traveled in center) were found in OFT. MWM results indicated that neither group at 18-mo of age was able to learn the task and therefore could not be accurately assessed for differences in spatial memory. Conclusion: Initiation of anti-hypertensive treatment in old age was effective in reducing aortic fibrosis and lowering SBP and PWV in DSS rats. Longer treatment may be needed to improve cognitive function in this model of vascular dementia. Supported by the NIH/NIA Intramural Research Program
Abstract 312: A Multi-view Echocardiography Video Deep Learning Model Outperforms the Seattle Heart Failure Model in Predicting Mortality
Authors: Alvaro Ulloa, Linyuan Jing, Brendan Carry, Christopher Good, David vanMaanen, Dustin Hartzel, Joseph Leader, Christopher M Haggerty, Brandon Fornwalt
Journal: Circulation (2020)

Introduction: Managing heart failure patients relies on mortality prediction models such as the Seattle Heart Failure (SHF) model. We hypothesized that a deep learning model that leverages echocardiography video data could improve prediction performance. Methods: We trained deep neural networks (DNN) to predict 1-year all-cause mortality using echocardiography videos and 158 additional clinical variables (labs, vitals, diagnoses, etc.) acquired from 34,362 patients (812,278 videos). We tested both the DNN and the SHF model on a separate cohort of 2,404 patients with heart failure who underwent 3,384 echocardiograms. We computed the area under the receiver operating characteristic curve (AUC) and its bootstrapped 95% confidence interval (CI) in the test set. Results: The DNN model (AUC of 0.76, 95% CI [0.74, 0.77]) outperformed the SHF model (AUC of 0.70, 95% CI [0.68, 0.71]). This superior performance was observed for patients with both reduced (n=2,026, AUC of 0.76 [0.74, 0.78] vs 0.70 [0.67, 0.72]) and preserved left ventricular ejection fraction (n=1,356, AUC of 0.75 [0.72, 0.78] vs 0.69 [0.66, 0.72]). A Cox Proportional Hazard survival analysis showed that, despite the prediction being for 1-year all-cause mortality, the result held long-term predictive power over the next 9 years with a superior hazard ratio of 2.9 [2.6, 3.2] for the DNN model compared to 2.2 [2, 2.4] for the SHF model. At mid-range operating points, the DNN model also maintained a higher negative predictive value, predicting survival, compared to the SHF model (89% vs 83%, respectively), while maintaining the same positive predictive value of 40%. Conclusion: A deep neural network that automatically analyzes echocardiography videos can outperform traditional risk modeling approaches such as the Seattle Heart Failure Model. This provides additional evidence that deep learning can help improve our ability to make clinically relevant predictions by leveraging complex datasets.
Reprogramming Cell-Signaling By Delivering the Catalytic Domain of Ptpgr Ameliorates Anemia of β-Thalassemia
Authors: Alessandro Mattè, Elisabetta Beneduce, Michela Mirenda, Roberta Russo, Achille Iolascon, Antonella Pantaleo, Francesco Turrini, Angela Siciliano, Enrica Federti, Serge Cedrick, Anne Janin, Christophe Leboeuf, Carlo Laudanna, Lucia De Franceschi
Journal: Blood (2017)
Infographic. Managing a confirmed or suspected COVID-19 case: a guide for sports
Authors: Alan Rankin, Neil Heron
Journal: British Journal of Sports Medicine (2020)

COVID-19 had, and continues to have, a significant impact on the 2020 sporting calendar, with the summer Tokyo Olympics postponed until 2021 and cancellation of a number of other sporting events and tournaments.1 Athletes and their sports are now slowly returning to a ‘new normal’ during this COVID-19 pandemic,2 and as athletes return to their sport in the coming months, we are expecting to see a number of athletes who develop suspected COVID-19 symptoms or indeed test positive for COVID-19. In our roles at sporting facilities/sports organisations, what is our responsibility to both the athlete with suspected COVID-19 symptoms and/or who test positive for COVID-19 as well as the other athletes and staff working within this environment?

First, to minimise the spread of COVID-19, athletes and their support staff need to ensure appropriate physical distancing, hand hygiene, use of face masks, limiting social contacts and considering modified forms of the sport. …
To drain or not to drain? Abscess or empyema?
Authors: Helen McDill, Maged Hassan, Graham Dack, Lindsey Taylor, David Waine, John P Corcoran, Cyrus Daneshvar
Journal: Thorax (2020)

We present a case posing the clinical dilemma of differentiating a large peripheral lung abscess from an empyema, discussing the imaging and management and the clinical issues posed.
Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages
Authors: Anthony J. Covarrubias, Abhijit Kale, Rosalba Perrone, Jose Alberto Lopez-Dominguez, Angela Oliveira Pisco, Herbert G. Kasler, Mark S. Schmidt, Indra Heckenbach, Ryan Kwok, Christopher D. Wiley, Hoi-Shan Wong, Eddy Gibbs, Shankar S. Iyer, Nathan Basisty, Qiuxia Wu, Ik-Jung Kim, Elena Silva, Kaitlyn Vitangcol, Kyong-Oh Shin, Yong-Moon Lee, Rebeccah Riley, Issam Ben-Sahra, Melanie Ott, Birgit Schilling, Morten Scheibye-Knudsen, Katsuhiko Ishihara, Stephen R. Quake, John Newman, Charles Brenner, Judith Campisi, Eric Verdin
Journal: Nature Metabolism (2020)
Abstract #960: Finasteride in combination with NSAIDs modulates the genetic risk of prostate cancer: In vivo evidence
Authors: Bhagavathi Narayanan, Dominick Nargi, Sally Lasano, Maarten Bosland, Narayanan Narayanan
Journal: Cancer Research (2009)

Background: The Prostate Cancer Prevention Trial (PCPT) in a total of 1,626 men demonstrated that finasteride, a 5\#945; reductase inhibitor reduces prostate cancer risk by 24.8%, and however, it was associated with a risk of small increase in high-Gleason grade tumors. To enhance the efficacy of finasteride, earlier studies have successfully used finasteride with other agents such as flutamide. Based on our earlier experience in enhancing the chemopreventive effects of NSAIDs, in this study, we tested the efficacy of finasteride with celecoxib and aspirin in preclinical models to synergistically decrease prostate cancer incidence. Methods: We examined the effects of finasteride individually and in combination with celecoxib or aspirin using in vitro and in vivo models. We used murine prostate cancer cells (CaP8) deleted for Pten-/- and human benign prostate hyperplastic epithelial cells (BPH1) to understand the mechanisms. The cells were pretreated for 24h with testosterone before incubating with different doses of finasteride (15\#956;M) or aspirin (40\#956;M) or celecoxib (40\#956;M) individually and in combination (half of each of the single dose) for 48 h. Effect on cell growth, cell cycle, apoptosis, molecular targets AR, 5aR, AKT, Cyclin D1, COX-2 and serum PGE2 levels were analyzed with MTT, flow cytometry, Western blot and ELISA assays. To determine in vivo efficacy, four week old PTEN/KO mice (n=20/group) were administered orally with finasteride (72mg/kg/bw) or celecoxib (500 mg/kg/bw) individually and in combinations. The agents were administered three times in a week for a period of eight weeks and terminated at the age of 12 weeks. Histopathological analysis was performed to determine the incidence of mPIN or adenocarcinomas. Specific immunohistochemical staining was performed to detect the molecular targets. Results: In vitro studies using Cap8 and human BPH1cells showed a significant inhibitory effect on cell survival and induced cell cycle arrest at the G1-S phase transition after treatment with celecoxib and aspirin in combination with finasteride for 48h. In vivo evidence on the histological determination of mPIN showed a significant decrease in the group of mice that received finasteride in combination with celecoxib or aspirin after six 8 weeks of treatment in contrast to the mice that received finasteride alone (P  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 960.
Abstract 17174: Revisiting the QT Correction Formulas: A Generalized Additive Models for Location, Scale, and Shape Approach
Authors: Hai Nguyen, Patrick Y Jay, William Scott, Janos Molnar, Henry Huang, John C Somberg, Krishna Kishore Umapathi, Hoang H Nguyen
Journal: Circulation (2020)

Introduction: Various mathematical equations have been proposed to correct QT interval for heart rate (QTc). However, with most formulas, QTc remains dependent on heart rate (HR) especially at low and high HR values. Hypothesis: A spline correction function would perform better than standard mathematical formulas by allowing the data to determine the form of the relationship. Methods: A series of regression models using the generalized additive models for location, scale, and shape framework was applied to 10,000 completely normal electrocardiogram data from the National Health and Nutrition Examination Surveys II and III. Evaluation of the model’s performance was performed using the R 2 coefficient of determination and the root mean squared of the errors between the predicted and observed QTc. The new regression models were compared to the Bazett’s and Fredericia’s formulas, which are the 2 most widely used formulas in clinical practice. Results: When boxplots of the QTc for each formula are plotted, grouped by HR in intervals of 5 beats/minute, QTc determined by the penalized spline regression was almost heart rate independent for both male and female as the slope of the regression line was almost zero (-0.003 for female and -0.001 for male) (Figure 1 A—B). By contrast, QTc by Bazett had a positive correlation (regression slope of 0.86 for female and 0.89 for male) while Fredericia’s had a negative correlation (regression slope of -0.14 for female and -0.13 for male) with HR (Figure 1C—F). In all 3 formulas, there was no significant difference between male and female. Conclusions: A new QTc formula was developed, which is almost independent of HR thereby providing a more accurate estimate of QTc for clinical management. Automatic QTc calculation and percentiles estimation could easily be incorporated in an online calculator or app for easy integration in everyday clinical practice.
Abstract 16742: Single-Cell Transcriptional and Epigenomic Dissection of Human Heart in Health and Coronary Artery Disease Reveals Cell-type-Specific Driver Genes and Pathways
Authors: Suvi Linna Kuosmanen, Eloi Schmauch, Kyriakitsa Galani, Carles Boix, Yongjin P Park, Maija Hollmen, Jarmo Gunn, Tuomas O Kiviniemi, Guillermo Garcia-Cardena, Manolis Kellis
Journal: Circulation (2020)

Genome-wide association studies have uncovered over 200 genetic loci underlying coronary artery disease (CAD), providing great hope for a deeper understanding of the causal mechanisms leading to this disease. However, in order to understand CAD at the molecular level, it is necessary to uncover cell-type-specific circuits and to use these circuits to dissect driver variants, genes, pathways, and cell types, in normal and diseased tissues. Here, we provide the most detailed single-cell dissection of human heart cell types, using cardiac biopsies collected during open-heart surgery from healthy, CAD, and CAD-related heart failure donors, and profiling both transcriptional (scRNA-seq) and epigenomic (scATAC-seq) changes. Using this approach, we identify 12 major heart cell types, including typical cardiovascular cells (cardiomyocytes, endothelial cells, fibroblasts), rarer cell types (B cells, neurons, Schwann cells), and previously-unrecognized layer-specific epithelial and endothelial cell types. We define markers for each cell type, providing the first extensive reference set for the living human heart. In addition, we define differential gene expression patterns in CAD relative to control samples, revealing substantial differences in cell-type-specific expression of disease-related genes, emphasizing, for example, the importance of the vascular endothelium in the pathogenesis of CAD. Strikingly, further clustering of the cell types based on specific subtypes revealed important differences in their expression patterns of disease-associated genes. These changes enrich in known CAD genetic loci, enabling us to recognize their likely target genes from scRNA-seq expression changes, candidate driver variants based on scATAC-seq localization and differential DNA accessibility, and candidate upstream regulators based on their enriched motif occurrences in scATAC loci. Overall, our results highlight the relevance and potential of single-cell transcriptional and epigenomic analyses to gain new biological insights into cardiovascular disease, and to recognize novel therapeutic target genes, pathways, and the cell types where they act.
Abstract 15912: Parenteral Iron Sucrose Improves Iron Biomarkers in Pediatric Heart Failure Patients With Iron Deficiency
Authors: Michael J Lin, Richard Kronmal, Jessica Otero, Christa Kirk, Erin L Albers, Borah Hong, Joshua Friedland-Little, Mariska Kemna, Yuk M Law
Journal: Circulation (2020)

Introduction: Iron deficiency (FeD) is common in adults with heart failure and is associated with worse outcomes. Parenteral iron therapy improves outcomes in this population, but this has not been described in the pediatric population. Methods: We conducted a prospective observational cohort study of heart failure patients with FeD, defined as ferritin &lt;100 ng/mL or ferritin = 100-300 with iron saturation &lt;20%, who received parenteral iron sucrose between 01/2007-12/2019. Iron dosing and frequency were based on initial and subsequent iron profiles using a standard replacement protocol. Monthly follow-up lab and clinical data up to 6 months were obtained and analyzed to characterize the effect on iron biomarkers and association with clinical outcomes (B-type natriuretic peptide (BNP), death, transplant, and mechanical circulatory support). Results: Among 61 patients who received parenteral iron therapy, 49% were male, with a median age of 23 months (IQR 7 - 117). 30 (49%) had primary cardiomyopathy; 31 (51%) had congenital heart disease with systolic dysfunction, 14 (45%) of which with cyanotic disease. 56 (92%) of the patients had a follow-up iron profile at timepoint 1 (TP 1) at a mean of 24 SD + 9 days. The interval between the 1st dose of iron and last follow-up (TP Last) was 61 + 50 days. The cumulative number of iron doses received was 3.5 + 1.5 at TP 1 and 4.1 + 2.4 at TP Last. Figure 1 shows the trend in iron biomarkers and BNP. There was a statistically significant increase in ferritin, iron saturation and serum iron levels, as well as a decrease in BNP over time. Clinical outcomes were examined by multivariable analysis. Only an increase in ferritin was associated with a decrease in BNP (p=0.012). Conclusions: Parenteral iron therapy for FeD under a standard protocol led to improvement in iron biomarkers in children with heart failure. Our study was limited by a small sample size and further study to assess clinical outcomes specifically related to iron therapy is warranted.
Abstract 15217: Combination Phosphodiesterase V Inhibition and Low Dose B-type Natriuretic Peptide Did Not Enhance Renal Function in Acute Heart Failure
Authors: Scott Hubers, sherry benike, Christopher Scott, Bradley Johnson, Horng Chen
Journal: Circulation (2020)

Introduction: Cardiorenal dysfunction with impaired cyclic guanosine monophosphate (cGMP) response to volume load is a hallmark of heart failure. Phosphodiesterase V (PDEV) is known to be upregulated and may explain the dysfunction of renal response. Hypothesis: We tested the hypothesis that PDEV inhibition in combination with low dose intravenous (IV) B-type natriuretic peptide (BNP) would improve renal function and potentiate urinary sodium and cGMP excretion in patients with acute heart failure. Methods: Randomized open label study in 67 patients admitted to the hospital with acute heart failure. These patients were randomized to standard care, low dose IV BNP (0.005μg/kg/min), or combination low dose BNP/PDEV inhibition with sildenafil (25 mg q12 hrs) for 48 hours. Plasma and urine studies were obtained at baseline, 24 hours, and 48 hours after study drug initiation to assess renal function. The primary endpoint was the percent change in estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) from baseline to 48 hours. Changes from baseline were summarized with median and quartiles and groups were compared using two-sample t-test. [ClinicalTrials.gov Identifier: NCT00972569] Results: Baseline characteristics were similar between groups. Median age was 78 years and median ejection fraction 39%. Treatment with BNP and BNP/PDEV inhibitor significantly increased plasma cGMP at 24 hr (% increase of 25.6 (8.9, 13.1) and 60.8 (32.3, 103.8) for BNP and BNP/PDEV vs % decrease of 13.5 (-29.1, 14.2) for placebo, p=0.001). BNP levels were significantly higher in both groups at 48 hr compared with placebo. However, there was no significant change in eGFR, BUN, or urinary sodium/cGMP excretion between groups. Hypotension was more common in the BNP/PDEV inhibitor group. Conclusions: Low dose IV BNP and combination BNP/PDEV inhibition increased plasma cGMP in patients with acute heart failure but did not improve renal function or urinary sodium/cGMP excretion. Our study does not support the use of low dose IV BNP with or without PDEV inhibition to enhance renal function in patients admitted with acute heart failure.
Sustainably Powered, Multifunctional Flexible Feedback Implant by the Bifacial Design and Si Photovoltaics
Authors: Dongwuk Jung, Kwangsun Song, Hunpyo Ju, Hyeongoh Park, Jung Hyun Han, Namyun Kim, Juho Kim, Jongho Lee
Journal: Advanced Healthcare Materials (2020)

Abstract Advanced design and integration of functioning devices with secured power is of interest for many applications that require complicated, sophisticated, or multifunctional processes in confined environments such as in human bodies. Here, strategies for design and realization are introduced for multifunctional feedback implants with the bifacial design and silicon (Si) photovoltaics in flexible forms. The approaches provide efficient design spaces for flexible Si photovoltaics facing up for sustainable powering and multiple electronic components for feedback functions facing down for sensing, processing, and stimulating in human bodies. The computational and experimental results including in vivo assessments ensure feasibility of the approaches by demonstrating feedback multifunctions, power‐harvesting in milliwatts, and mechanical compatibility for operations in live tissues. This work should useful for wide range of applications that require sustainable power and advanced multifunctions.
Quantifying and leveraging predictive uncertainty for medical image assessment
Authors: Florin C. Ghesu, Bogdan Georgescu, Awais Mansoor, Youngjin Yoo, Eli Gibson, R.S. Vishwanath, Abishek Balachandran, James M. Balter, Yue Cao, Ramandeep Singh, Subba R. Digumarthy, Mannudeep K. Kalra, Sasa Grbic, Dorin Comaniciu
Journal: Medical Image Analysis (2020)