tbuckley/cabot-search huggingface dataset:
Abstract 16771: Longitudinal Segmental Shape Analysis of the Remodeling Left Ventricle in Chronic Mitral Regurgitation
Authors: Daniella Corporan, Muralidhar Padala
Journal: Circulation (2020)

Introduction: Severe mitral regurgitation (MR) initiates left ventricular (LV) dilatation, but preserves systolic function. Due to preserved EF, patients are not referred for correction of their MR, and the ventricle continues to enlarge. Identifying patients at risk of heart failure, just from assessing LV size is challenging. In this study, we sought to investigate if ventricular shape and sphericity can represent the pathological remodeling process in this disease. Methods: Sixty adult rats (N=60) were induced with severe MR by puncturing the mitral valve leaflet with a 23G needle on the beating heart, using echo guidance (Fig.A1). Transthoracic echocardiography was performed at 2, 10, 20, and 40 weeks (n=15 rats/group) for analysis of the left ventricular shape. Fifteen healthy rats (N=15) were used as a sham group for comparison. Results: Severe MR was confirmed in all the rats in the MR group with a MR jet area of 40.99±9.40% ( Fig.A2 ), MR volume of 119.50±32.43μl ( Fig.A3 ), and pulmonary flow reversal ( Fig.A4 ). None of these were observed in the control group. LV dilation was observed in MR rats compared to sham ( Fig.B ). Diastolic sphericity index, LV area, and diastolic apical area index was significantly increased at 2, 10, 20, and 40 weeks after MR compared to sham (p&lt;0.05) ( Fig.C1-C3 ). Systolic sphericity index was not significantly increased compared to sham at any time-point ( Fig.D1 ). LV area was unchanged at 2 weeks, and was significantly increased at 10, 20, and 40 weeks ( Fig.D2 ). Systolic apical area index was significantly increased at 2, 20, and 40 weeks compared to sham (p&lt;0.05) ( Fig.D3 ). Conclusions: Analysis of left ventricular shape and its longitudinal changes can help detect remodeling patterns that are not visible using traditional functional indices.
A <i>Cutibacterium acnes</i> antibiotic modulates human skin microbiota composition in hair follicles
Authors: Jan Claesen, Jennifer B. Spagnolo, Stephany Flores Ramos, Kenji L. Kurita, Allyson L. Byrd, Alexander A. Aksenov, Alexey V. Melnik, Weng R. Wong, Shuo Wang, Ryan D. Hernandez, Mohamed S. Donia, Pieter C. Dorrestein, Heidi H. Kong, Julia A. Segre, Roger G. Linington, Michael A. Fischbach, Katherine P. Lemon
Journal: Science Translational Medicine (2020)

Cutimycin, a thiopeptide antibiotic produced by the skin commensal Cutibacterium acnes , reduces Staphylococcus colonization of human skin hair follicles.
Diagnostic accuracy of content‐based dermatoscopic image retrieval with deep classification features
Authors: P. Tschandl, G. Argenziano, M. Razmara, J. Yap
Journal: British Journal of Dermatology (2018)

Background: Automated classification of medical images through neural networks can reach high accuracy rates but lack interpretability. Objectives: To compare the diagnostic accuracy obtained by using content based image retrieval (CBIR) to retrieve visually similar dermatoscopic images with corresponding disease labels against predictions made by a neural network. Methods: A neural network was trained to predict disease classes on dermatoscopic images from three retrospectively collected image datasets containing 888, 2750 and 16691 images respectively. Diagnosis predictions were made based on the most commonly occurring diagnosis in visually similar images, or based on the top-1 class prediction of the softmax output from the network. Outcome measures were area under the ROC curve for predicting a malignant lesion (AUC), multiclass-accuracy and mean average precision (mAP), measured on unseen test images of the corresponding dataset. Results: In all three datasets the skin cancer predictions from CBIR (evaluating the 16 most similar images) showed AUC values similar to softmax predictions (0.842, 0.806 and 0.852 versus 0.830, 0.810 and 0.847 respectively; p-value>0.99 for all). Similarly, the multiclass-accuracy of CBIR was comparable to softmax predictions. Networks trained for detecting only 3 classes performed better on a dataset with 8 classes when using CBIR as compared to softmax predictions (mAP 0.184 vs. 0.368 and 0.198 vs. 0.403 respectively). Conclusions: Presenting visually similar images based on features from a neural network shows comparable accuracy to the softmax probability-based diagnoses of convolutional neural networks. CBIR may be more helpful than a softmax classifier in improving diagnostic accuracy of clinicians in a routine clinical setting.
Abstract 17116: Incidence and Costs of Major Atherothrombotic Vascular Events Among Patients With Peripheral Artery Disease After Revascularization
Authors: Marc P Bonaca, Connie N Hess, Akshay Kharat, Urvi Desai, Dejan Milentijevic, François Laliberté, Peter R Zuckerman, John Benson, Patrick Lefebvre, william R hiatt
Journal: Circulation (2020)

Introduction: Peripheral artery disease (PAD), frequently requiring lower-extremity revascularization (LER), is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major amputation of vascular etiology, myocardial infarction [MI], ischemic stroke [IS], cardiovascular [CV] death). Understanding the incidence and healthcare costs of such events in PAD patients post-revascularization may be important in translation. Methods: Patients with PAD who underwent LER were identified from Optum Clinformatics Data Mart claims database (Q1 2014 - Q2 2019). The first LER was considered index. Patients were required to be ≥50 years old at index with ≥6 months of prior health plan enrollment. Patients with IS, atrial fibrillation (AF), venous thromboembolism (VTE), intracranial hemorrhage, ESRD, or oral anticoagulant (OAC) use pre-index; or diagnoses of MI 30 days or ALI 14 days pre-index were excluded. Patients were followed until the earliest of 1) end of enrollment/data; 2) diagnosis of AF or VTE; or 3) OAC use. For each major vascular event, the incidence rate was assessed as the number of first events divided by patient-years of observation. Event-related healthcare costs per-patient-year (PPY) were also reported. Results: Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event over a median follow-up of 1.0 years (IQR: 0.4-2.1). The composite event incidence rate was 13.81 per 100 patient years [ALI: 5.51; lower-limb amputation: 5.15; MI: 3.19; IS: 2.06; CV-related death: 0.88]. PPY event-related costs ranged from $57,825 for IS to $108,302 for lower-limb amputation (Figure). Conclusions: One in six PAD patients have a major atherothrombotic vascular event within one year post-LER. Costs of these events are high, particularly for limb complications. Therefore, reducing the rate of such events could reduce the overall healthcare costs for this population.
Monogenic Diabetes: From Genetic Insights to Population-Based Precision in Care. Reflections From a <i>Diabetes Care</i> Editors’ Expert Forum
Authors: Matthew C. Riddle, Louis H. Philipson, Stephen S. Rich, Annelie Carlsson, Paul W. Franks, Siri Atma W. Greeley, John J. Nolan, Ewan R. Pearson, Philip S. Zeitler, Andrew T. Hattersley
Journal: Diabetes Care (2020)

Individualization of therapy based on a person's specific type of diabetes is one key element of a "precision medicine" approach to diabetes care. However, applying such an approach remains difficult because of barriers such as disease heterogeneity, difficulties in accurately diagnosing different types of diabetes, multiple genetic influences, incomplete understanding of pathophysiology, limitations of current therapies, and environmental, social, and psychological factors. Monogenic diabetes, for which single gene mutations are causal, is the category most suited to a precision approach. The pathophysiological mechanisms of monogenic diabetes are understood better than those of any other form of diabetes. Thus, this category offers the advantage of accurate diagnosis of nonoverlapping etiological subgroups for which specific interventions can be applied. Although representing a small proportion of all diabetes cases, monogenic forms present an opportunity to demonstrate the feasibility of precision medicine strategies. In June 2019, the editors of Diabetes Care convened a panel of experts to discuss this opportunity. This article summarizes the major themes that arose at that forum. It presents an overview of the common causes of monogenic diabetes, describes some challenges in identifying and treating these disorders, and reports experience with various approaches to screening, diagnosis, and management. This article complements a larger American Diabetes Association effort supporting implementation of precision medicine for monogenic diabetes, which could serve as a platform for a broader initiative to apply more precise tactics to treating the more common forms of diabetes.
Abstract 15857: SARS-Cov-2 Genes Encode <i> I <sub>to</sub> </i> -like Potassium Channels: Linkage Between Viroporins and High Mortality Rate in COVID-19 Patients With Pre-existing Cardiovascular Diseases
Authors: Iuliia Polina, Jae Hwi Sung, Bong Sook Jhun, Jin O-uchi
Journal: Circulation (2020)

Introduction: COVID-19 patients with pre-existing cardiovascular diseases (CVDs) have a higher risk for severe illness, cardiac damage, and death. Therefore, strategies for cardiovascular protection in COVID-19 are urgently needed until a reliable and effective treatment for COVID-19 (e.g., vaccine) is established. Because angiotensin-converting enzyme 2 (ACE2) is overexpressed in the cardiovascular system during CVD, COVID-19 patients with pre-existing CVDs may have higher risk for direct SARS-CoV-2 infection into the heart. However, the specific molecular mechanisms linking SARS-CoV-2 and cardiac risk are still unclear. Previous studies for SARS suggest that several SARS-CoV-1 genes [Envelope (E) protein, open reading frame (ORF) 3a, and ORF8a] have the potential to form viral channels (i.e., “viroporins”) in host cells and dysregulate host-cell functions. Hypothesis: SARS-CoV-2 genes encode viroporins, which can be expressed in the heart after infection and dysregulate cardiac electrophysiology and contractility. Methods: Individual SARS-CoV-2 genes were expressed in HEK293T cells via plasmids vector and the transfected cells were used for biochemical and electrophysiological assays. Results: By database analysis, we found that ORF3a and E from SARS-CoV-2 share over 85% similarity to those in SARS-CoV and maintain the critical sequences for ion channel functions. Both SARS-CoV-2-ORF3a and E protein form K + channels with similar channel properties of the endogenous transient outward K + current ( I to ), which can be activated during the initial repolarization phase of an action potential (AP) in cardiomyocytes. A computational model of human ventricular myocytes (O'Hara-Virag-Varro-Rudy Model) with increased I to amplitude suggests that the expression of these viroporins may increase Ca 2+ transient (CaT) amplitude at the baseline, but decrease CaT in response to increased heart rate. Conclusion: SARS-CoV-2 genes encode K + channels, which may dysregulate AP and Ca 2+ handing in cardiomyocytes, thus promoting decreased cardiac contractility and increased susceptibility to arrhythmias. Targeting these viroporins may reduce the risk of sudden cardiac death and cardiac damage in COVID-19 patients with pre-existing CVDs.
COVID-19–Associated Nonocclusive Fibrin Microthrombi in the Heart
Authors: Melanie C. Bois, Nicholas A. Boire, Andrew J. Layman, Marie-Christine Aubry, Mariam P. Alexander, Anja C. Roden, Catherine E. Hagen, Reade A. Quinton, Christopher Larsen, Young Erben, Ramanath Majumdar, Sarah M. Jenkins, Benjamin R. Kipp, Peter T. Lin, Joseph J. Maleszewski
Journal: Circulation (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.
Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans
Authors: Xiao Wang, Huimin Wang, Bolin Xu, Dong Huang, Chao Nie, Longjun Pu, Gregory J.M. Zajac, Han Yan, Jingru Zhao, Fangyuan Shi, Brian T. Emmer, Jia Lu, Rui Wang, Xiaohui Dong, Jianye Dai, Wenjing Zhou, Chu Wang, Ge Gao, Yan Wang, Cristen Willer, Xiangfeng Lu, Yuangang Zhu, Xiao-Wei Chen
Journal: Cell Metabolism (2020)
Abstract 13167: Early Mobilization in Postoperative Cardiac Surgical Patients
Authors: Michael Goldfarb, Diana Dima, Yves Langlois
Journal: Circulation (2020)

Introduction: Early mobilization (EM) is recommended by cardiac surgical societies. However, the optimal method of EM delivery has yet to be determined. Our objective was to assess whether a bedside nurse-driven EM strategy is safe and associated with improved outcomes following cardiac surgery. Methods: Consecutive post-cardiac surgery patients in a cardiovascular intensive care unit (CVICU) at an academic tertiary care centre from 2017 to 2019 prior to and after EM program implementation were reviewed. Postoperative cardiac surgery patients were initially managed in a general ICU and transferred to the CVICU when hemodynamic stability was achieved, typically postoperative day 1 or 2. Functional status was assessed by the nurse on CVICU admission using the Level of Function (LOF) Mobility Scale, which ranges from LOF 0 (bed immobile) to LOF 5 (walks &gt; 50 feet). The nurse uses the LOF score to guide twice-daily level-specific mobility activities. The primary outcome was hospital length of stay. Results: There were 504 patients included in the study (preintervention, N=329; Intervention, N=175). There was no difference in age, sex or comorbid illness between the groups (Table). The LOF was 4.7 ± 0.5 prior to surgery, 3.4 ± 1.1 on CVICU admission, and 4.3 ± 0.6 on CVICU discharge in patients undergoing EM. Patients were mobilized during nearly all mobilization opportunities (98.7%; 685/694). Adverse events were rare (0.4%; 8 events/1901 mobilization activities), minor and transient. There was no difference is postoperative hospital length of stay, in-hospital mortality, discharge home or 30-day hospital re-admission (all P&gt;0.05). Conclusion: A nurse-driven EM program was safe and associated with improvement in functional status in postoperative cardiac surgery patients. The EM program was not associated with improved short-term outcomes. Further studies are needed to understand optimal delivery of EM in cardiac surgical patients.
Molecular Recurrence-Free Survival (MRecFS) Following Imatinib Vs. Nilotinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Matched Analysis of Patients in EURO-SKI and Enestfreedom
Authors: Markus Pfirrmann, Francois-Xavier Mahon, Joelle Guilhot, Johan Richter, Francis J. Giles, Andreas Hochhaus, Jerald P. Radich, David M Ross, Giuseppe Saglio, Weiping Deng, Darshan Dalal, Susanne Saussele
Journal: Blood (2017)
Abstract 14938: Impact of Cerebrovascular Comorbidity on Prognosis in Patients Undergoing Percutaneous Coronary Intervention: 1-year Data From Japanese Multi-center Registry
Authors: Khlood Ahmed
Journal: Circulation (2020)

Background: Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data has been found about the impact of stroke with underlying cardiac disease. This study’s objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. Methods and Results: This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age73.5±9.6, 69.7(±11.5) respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p&lt;0.0001). During the one-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p&lt;0.0001),cardiac death amounted for 2.2% and 1.2% respectively (P&lt;0.0001), recurrent stroke for 3.1% and 1.2% (P&lt;0.0001), non-cardiac death for 3.6% and 1.54% (P&lt;0.0001),and finally, hemorrhagic complications with 2.6% and 1.3% (p&lt;0.0001).Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p&lt;0.0001). Cox hazard analysis also revealed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR=1.457, 95%CI=1.036–2.051, p=0.031), thus proving it to be a crucial predictor on cardiac prognosis. Conclusion: History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence, thus highlighting urgent need for comprehensive prevention of cardiac and cerebrovascular diseases
YAP/TAZ Transcriptional Coactivators Create Therapeutic Vulnerability to Verteporfin in EGFR-mutant Glioblastoma
Authors: Krishanthan Vigneswaran, Nathaniel H. Boyd, Se-Yeong Oh, Shoeb Lallani, Andrew Boucher, Stewart G. Neill, Jeffrey J. Olson, Renee D. Read
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Glioblastomas (GBMs), neoplasms derived from glia and neuroglial progenitor cells, are the most common and lethal malignant primary brain tumors diagnosed in adults, with a median survival of 14 months. GBM tumorigenicity is often driven by genetic aberrations in receptor tyrosine kinases, such as amplification and mutation of EGFR. Experimental Design: Using a Drosophila glioma model and human patient–derived GBM stem cells and xenograft models, we genetically and pharmacologically tested whether the YAP and TAZ transcription coactivators, effectors of the Hippo pathway that promote gene expression via TEA domain (TEAD) cofactors, are key drivers of GBM tumorigenicity downstream of oncogenic EGFR signaling. Results: YAP and TAZ are highly expressed in EGFR-amplified/mutant human GBMs, and their knockdown in EGFR-amplified/mutant GBM cells inhibited proliferation and elicited apoptosis. Our results indicate that YAP/TAZ-TEAD directly regulates transcription of SOX2, C-MYC, and EGFR itself to create a feedforward loop to drive survival and proliferation of human GBM cells. Moreover, the benzoporphyrin derivative verteporfin, a disruptor of YAP/TAZ-TEAD–mediated transcription, preferentially induced apoptosis of cultured patient-derived EGFR-amplified/mutant GBM cells, suppressed expression of YAP/TAZ transcriptional targets, including EGFR, and conferred significant survival benefit in an orthotopic xenograft GBM model. Our efforts led us to design and initiate a phase 0 clinical trial of Visudyne, an FDA-approved liposomal formulation of verteporfin, where we used intraoperative fluorescence to observe verteporfin uptake into tumor cells in GBM tumors in human patients. Conclusions: Together, our data suggest that verteporfin is a promising therapeutic agent for EGFR-amplified and -mutant GBM.
Abstract 16616: Assessment of Lipid Rich Plaque Containing Necrotic Core Using a Multi-Modality Near-Infrared Autofluorescence and Optical Coherence Tomography Imaging System
Authors: Kohei Watanabe, Joseph A Gardecki, Kensuke Nishimiya, Zhonglie Piao, Daisuke Yamada, Guillermo J Tearney
Journal: Circulation (2018)

Introduction: Optical coherence tomography (OCT) is thought to be capable of identifying lipid-rich plaque (LRP). However, several histopathological correlative studies have shown that LRP assessment by OCT alone may be indecisive for identifying advanced plaque containing a necrotic core. This study aims to investigate the feasibility of multi-modality OCT-near-infrared autofluorescence (NIRAF) imaging to identify advanced necrotic-core LRP. Methods: We constructed a new fully integrated multi-modality OCT-NIRAF imaging system and catheter that allows simultaneous and co-registered acquisition of OCT and NIRAF data. NIRAF excitation was 635nm and emission was collected between 690-750nm. OCT-NIRAF pullback imaging was performed with excised human cadaver coronary arteries during saline perfusion. Subsequently, H&amp;E sections were obtained and co-registered (longitudinally and azimuthally) with corresponding OCT-NIRAF images, using the known pullback distances, and anatomic landmarks and features such as calcium nodules seen in the OCT and histopathology images. In addition, a bench top confocal microscope was used to obtain images of NIRAF on corresponding unstained, formalin-fixed, paraffin-embedded slides. Results: A total of 187 histopathological sections and corresponding OCT-NIRAF images from 13 cadaver coronary arteries from 5 patients were imaged and analyzed. Several LRP that were identified by histopathology in these arteries showed regions with evidence of necrotic core with hemosiderin granules that had significantly higher catheter-based NIRAF than regions without hemosiderin granules. Confocal NIRAF microscopy also showed that regions of high NIRAF were associated with accumulation of hemosiderin in corresponding histological sections. Conclusions: This study provides suggestive data that an integrated OCT-NIRAF imaging system and catheter may be able to be used to identify advanced LRP that contains a necrotic core with hemosiderin granules. Future investigation of NIRAF from cadaver arteries from additional patients is merited to robustly confirm these findings.