tbuckley/cabot-search huggingface dataset:
Abstract 18927: Systolic Blood Pressure (SBP) <130 mmHg and Outcomes in Patients With Heart Failure and Preserved Ejection (HFpEF) and Hypertension (HTN)
Authors: Apostolos Tsimploulis, Phillip H Lam, Poonam Bhyan, Daniel J Dooley, Prakash Deedwania, Selma Mohammed, Gurusher Panjrath, Javed Butler, Ioannis E Kanonidis, Cherinne Arundel, Charity J Morgan, Farooq H Sheikh, Gaby A Weissman, Wilbert S Aronow, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2017)

Background: According to 2017 update of 2013 ACCF/AHA HF guideline, SBP should be lowered to <130 mmHg in euvolemic patients with HFpEF and persistent HTN. Methods: In Medicare-linked OPTIMIZE-HF r...
Optimal Treatment of Patients With Left Ventricular Dysfunction and Severe Coronary Artery Disease
Authors: Michael J. Domanski, Michael E. Farkouh
Journal: Circulation (2018)

oronary artery disease (CAD) is the most common cause of left ventricular dysfunction and heart failure (ischemic cardiomyopathy [ICM]).The increasing sophistication of coronary artery bypass grafting (CABG) and percutaneous intervention (PCI) raises important questions about the appropriate role of revascularization, CABG, or PCI in treating patients with ICM.Understandings now in hand provide guidance regarding clinical decision making, underscore areas of uncertainty, and point to next steps in the quest to better understand the role of revascularization in these patients. CABG VERSUS OPTIMAL MEDICAL THERAPY FOR THE TREATMENT OF PATIENTS WITH ICMThe STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study) 1 examined long-term outcomes in patients with left ventricular ejection fraction ≤35%, CAD without left main coronary artery stenosis ≥50%, New York Heart Association Functional Class 2 or 3 heart failure, and Canadian Cardiovascular Society Angina Class ≤2 randomized to Optimal Medical Therapy (OMT) or to OMT and CABG.A primary outcome event (death from any cause) occurred in 58.9% of patients with CABG plus OMT and 66.1% of patients randomized to OMT only (hazard ratio for CABG versus OMT, 0.84; 95% CI, 0.73-0.97;P=0.02).These data provide high-quality evidence that revascularization with CABG improves outcomes in patients with ICM with suitable anatomy.It is important to note that the benefit was present in the group as a whole despite the early risk accompanying surgery.
Using a Deep Learning Algorithm and Integrated Gradients Explanation to Assist Grading for Diabetic Retinopathy
Authors: Rory Sayres, Ankur Taly, Ehsan Rahimy, Katy Blumer, David Coz, Naama Hammel, Jonathan Krause, Arunachalam Narayanaswamy, Zahra Rastegar, Derek Wu, Shawn Xu, Scott Barb, Anthony Joseph, Michael Shumski, Jesse Smith, Arjun B. Sood, Greg S. Corrado, Lily Peng, Dale R. Webster
Journal: Ophthalmology (2018)

To understand the impact of deep learning diabetic retinopathy (DR) algorithms on physician readers in computer-assisted settings.Evaluation of diagnostic technology.One thousand seven hundred ninety-six retinal fundus images from 1612 diabetic patients.Ten ophthalmologists (5 general ophthalmologists, 4 retina specialists, 1 retina fellow) read images for DR severity based on the International Clinical Diabetic Retinopathy disease severity scale in each of 3 conditions: unassisted, grades only, or grades plus heatmap. Grades-only assistance comprised a histogram of DR predictions (grades) from a trained deep-learning model. For grades plus heatmap, we additionally showed explanatory heatmaps.For each experiment arm, we computed sensitivity and specificity of each reader and the algorithm for different levels of DR severity against an adjudicated reference standard. We also measured accuracy (exact 5-class level agreement and Cohen's quadratically weighted κ), reader-reported confidence (5-point Likert scale), and grading time.Readers graded more accurately with model assistance than without for the grades-only condition (P < 0.001). Grades plus heatmaps improved accuracy for patients with DR (P < 0.001), but reduced accuracy for patients without DR (P = 0.006). Both forms of assistance increased readers' sensitivity moderate-or-worse DR: unassisted: mean, 79.4% [95% confidence interval (CI), 72.3%-86.5%]; grades only: mean, 87.5% [95% CI, 85.1%-89.9%]; grades plus heatmap: mean, 88.7% [95% CI, 84.9%-92.5%] without a corresponding drop in specificity (unassisted: mean, 96.6% [95% CI, 95.9%-97.4%]; grades only: mean, 96.1% [95% CI, 95.5%-96.7%]; grades plus heatmap: mean, 95.5% [95% CI, 94.8%-96.1%]). Algorithmic assistance increased the accuracy of retina specialists above that of the unassisted reader or model alone; and increased grading confidence and grading time across all readers. For most cases, grades plus heatmap was only as effective as grades only. Over the course of the experiment, grading time decreased across all conditions, although most sharply for grades plus heatmap.Deep learning algorithms can improve the accuracy of, and confidence in, DR diagnosis in an assisted read setting. They also may increase grading time, although these effects may be ameliorated with experience.
CCR5 delta32 Cord &amp; Haploidentical Grafts: Allogeneic Stem Cell Transplant for HIV+ /AML Patient: A Case Report from the Impaact P1107 Observational Study
Authors: Jingmei Hsu, Marshall Glesby, Tsiporah B. Shore, Catherine Small, Usama Gergis, Sebastian A. Mayer, Adrienne A. Phillips, Lawrence D. Petz, Renee Browning, Meredith Warshaw, Deborah Persaud, Bryson Yvonne, Koen Van Besien
Journal: Blood (2018)
FRI0396 The atm kinase and pten, drive myofibroblasts differentiation by activating the tgfΒ autocrine loop
Authors: S. Xu, I. Papaioannou, M. Ponticos, C. Denton, A. Wells, E. Renzoni, D. Abraham
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Pulmonary fibrosis is a major cause of mortality in scleroderma (SSc) and Idiopathic Pulmonary Fibrosis (IPF). Fibrosis is driven by Inappropriate myofibroblast differentiation and persistence. Understanding this process, is vital for developing an effective treatment. Angiotensin II, is implicated in fibroblast activation in the heart and kidney, through interactions with growth factors (e.g. EGF and TGFβ). <h3>Objectives</h3> We examined the role of Angiotensin II in myofibroblast activation in the lung. <h3>Methods</h3> Lung fibroblasts were isolated from SSc, IPF, or control patient lungs (6 each). Fibroblasts were also cultured from PTEN null and wild-type mice. Protein expression after angiotensin II treatment (AngII) was investigated by western blotting. Myofibroblast differentiation and function was assayed through the contraction of 3D collagen gels and scratch migration assays. The signalling pathways involved were dissected using specific inhibitors: PI3-kinase/AKT (wortmannin, LY294002), TGFβ (1d11 neutralising antibody, SB431542 ALK5 inhibitor) Ataxia-Telangiectasia Mutated (ATM – Ku55933), AngII (Losartan). <h3>Results</h3> SSc and IPF lung fibroblasts showed increased AKT phosphorylation and suppressed PTEN expression (p&lt;0.05). Their phenotype was more myofibroblast-like, with higher αSMA expression (p&lt;0.05), increased collagen gel contraction (control; 207±14 vs SSc; 93±15 vs IPF 91±21, p&lt;0.05), and enhanced migratory capacity (p&lt;0.05). PTEN-null fibroblasts showed a similar phenotype. AngII treatment activated AKT, suppressed PTEN and induced myofibroblast differentiation in normal lung fibroblasts. In both AngII-treated and PTEN lung fibroblasts AKT activation required the ATM kinase. Inhibition of AKT either with PI3K or ATM inhibitor abrogated these effects. The increased expression of Myofibroblast-related genes after AngII treatment, was also blocked by inhibition of TGFβ with a neutralising antibody or an ALK5 inhibitor. AKT phosphorylation on the other hand was only partially blocked was partially blocked by TGFβ inhibition. <h3>Conclusions</h3> Our data demonstrate for the first time that AngII signals via the ATM kinase, which together with PTEN suppression are essential for the activation of AKT by AngII. AngII promotes myofibroblast differentiation, by stimulating the fibroblast TGFβ autocrine loop through AKT. Our data shows that activation of AKT through ATM and PTEN, may serve as the molecular link between pulmonary hypertension and lung fibrosis in fibrotic diseases. <h3>Acknowledgements</h3> Arthritis Research UK, Royal Free Hospital Charity and Scleroderma Research UK. <h3>Disclosure of Interest</h3> None declared
Abstract 12403: Association of Visceral Adipose Tissue, Metabolic Risk Factors, and Subclinical Atherosclerosis in Mexican Americans
Authors: Clarence Gill, Kristina P Vatcheva, Nahid J Rianon, Miryoung Lee, Beverly Smulevitz, David D McPherson, Joseph B McCormick, Susan P Fisher-Hoch, Susan T Laing
Journal: Circulation (2017)

Excess visceral adipose tissue (VAT) is considered to be a primary driver for the cardiometabolic complications of obesity; VAT-associated CVD risk appears to vary by race. Mexican Americans have a...
Abstract IA17: Liquid biopsies: Concepts and applications
Authors: Anamaria A. Camargo
Journal: Clinical Cancer Research (2018)

Abstract The presence of cell-free DNA (cfDNA) in human blood was first described in 1948 by Mandel and Métais, but mutated KRAS DNA sequences derived from tumor cells were first reported in the plasma of patients with pancreatic cancer almost 50 years later. Since then, our ability to analyze cfDNA has significantly improved with the development of molecular technologies, such as digital PCR and next-generation sequencing, which enable the detection of circulating tumor DNA molecules (ctDNA) with high specificity and sensitivity. ctDNA is shed into the bloodstream by cells undergoing apoptosis or necrosis and genomic profiles of ctDNA have been shown to closely match those of the corresponding tumors. Recent studies have demonstrated the translational potential of ctDNA detection—commonly referred to as liquid biopsies—for diagnosis and prognosis, for treatment decision, and for monitoring residual disease, treatment response, and disease progression. This is an opportune time to discuss how liquid biopsies can be exploited to guide cancer patient care and ultimately be integrated into clinical practice. Citation Format: Anamaria A. Camargo. Liquid biopsies: Concepts and applications [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA17.
Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain
Authors: Diego F. Niño, Qinjie Zhou, Yukihiro Yamaguchi, Laura Y. Martin, Sanxia Wang, William B. Fulton, Hongpeng Jia, Peng Lu, Thomas Prindle, Fan Zhang, Joshua Crawford, Zhipeng Hou, Susumu Mori, Liam L. Chen, Andrew Guajardo, Ali Fatemi, Mikhail Pletnikov, Rangaramanujam M. Kannan, Sujatha Kannan, Chhinder P. Sodhi, David J. Hackam
Journal: Science Translational Medicine (2018)

Necrotizing enterocolitis–induced brain injury in mice can be prevented with an oral nanotherapeutic that targets microglia.
Performance of colorectal cancer screening in the European Union Member States: data from the second European screening report
Authors: Carlo Senore, Partha Basu, Ahti Anttila, Antonio Ponti, Mariano Tomatis, Diama Bhadra Vale, Gugliemo Ronco, Isabelle Soerjomataram, Maja Primic-Žakelj, Emilia Riggi, Joakim Dillner, Miriam Klara Elfström, Stefan Lönnberg, Rengaswamy Sankaranarayanan, Nereo Segnan
Journal: Gut (2018)

Objective To present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs). Design Cross-sectional study. We analysed key performance indicators—participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC—based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols. Results Participation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%–71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%–66.6%), and it showed a positive correlation (ρ=0.842, p&lt;0.001) with participation in breast cancer screening in the same areas. Screening performance showed a large variability. Compliance with referral for colonoscopy (total colonoscopy (TC)) assessment ranged between 64% and 92%; TC completion rate ranged between 92% and 99%. PR and DR of advanced adenomas and CRC were higher in FIT, as compared with gFOBT programmes, and independent of the protocol among men, older subjects and those performing their first screening. Conclusions The variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management.
Decompensated Liver Disease due to Primary Hepatic Amyloidosis: Is Liver Transplantation Still Mandatory?
Authors: Mar Riveiro‐Barciela, Merche Gironella, Alicia Senín, María‐Teresa Salcedo, Xavier Merino‐Casabiel, Lluis Castells, Rafael Esteban, Maria Buti, Fernando Martínez‐Valle
Journal: Hepatology (2018)

Riveiro‐Barciela, Mar; Gironella, Merche; Senín, Alicia; Salcedo, María‐Teresa; Merino‐Casabiel, Xavier; Castells, Lluis; Esteban, Rafael; Buti, Maria; Martínez‐Valle, Fernando Author Information
Abstract 14946: Loss-framed Financial Incentives and Personalized Goal Setting Increase Physical Activity in Ischemic Heart Disease Patients Using Wearable Devices: The ACTIVE REWARD Randomized Clinical Trial
Authors: Neel P Chokshi, Srinath Adusumalli, Dylan S Small, Alexander Morris, Jordyn Feingold, YoonHee P Ha, Charles A Rareshide, Victoria Hilbert, Mitesh S Patel
Journal: Circulation (2017)

Introduction: Physical activity programs reduce morbidity and mortality in ischemic heart disease (IHD) patients. Most patients, however, are unable to access such programs and obtain enough physic...
Abstract 17543: The Chicken or the Eggs? Examining the Causal Relationship Between the Development of Atrioventricular Valve Regurgitation and Ventricular Dysfunction in Patients With Functionally Single-Ventricle Physiology
Authors: Yasuhiro Kotani, Devin Chetan, Selvi Senthilnathan, Arezou Saedi, Christopher A Caldarone, Glen S Van Arsdell, Luc Mertens, Osami Honjo
Journal: Circulation (2015)

Introduction: Development of atrioventricular valve regurgitation (AVVR) with or without ventricular dysfunction (VD) often occurs during the first 6 months of life and has a significant impact on outcomes for single-ventricle patients. Yet, it is not well known whether AVVR causes VD or vice versa. Thus, we sought to identify the timing and causal relationship between AVVR and VD. Methods: Among 156 consecutive single-ventricle patients who had staged palliation (2005- 2012), 28 who had AVV repair at the time of stage II (n=24, 86%) or inter-stage (n=4, 14%) were reviewed. Diagnosis included HLHS in 17 (61%) patients, tricuspid atresia in 2 (7%), and others in 9 (32%). Ventricular morphology was left-dominant in 6 (21%) patients and right-dominant in 22 (79%). AVV morphology included mitral in 6 (21%) patients, tricuspid in 18 (64%), and common in 4 (14%). Serial echocardiograms were reviewed to identify the timing of development of AVVR and/or VD. Results: After stage I palliation, ventricular end-diastolic dimension (VEDD) z-score significantly increased from 4.01 to 5.69 (p&lt;0.01) AVVR (Figure). By the time of stage II palliation, VEDD further increased and subsequent AVV annular dilation occurred, resulting in 23 patients with significant AVVR. None of the patients, however, had significant VD before stage II palliation/AVV repair, but 9 patients developed significant VD after AVV repair. Conclusions: Ventricular dilation occurred immediately after stage I palliation and continued until stage II palliation. Secondary annular dilation occurred inter-stage and this further triggered the development of AVVR. Tangible ventricular dysfunction was not seen before AVV repair, however, important ventricular dysfunction was unmasked after volume unloading surgery. Heart failure management and early intervention to significant AVVR may reduce the incidence of ventricular dysfunction following AVV repair.
The Transcription Factor Ets1 Suppresses T Follicular Helper Type 2 Cell Differentiation to Halt the Onset of Systemic Lupus Erythematosus
Authors: Chan Johng Kim, Choong-Gu Lee, Ju-Yang Jung, Ambarnil Ghosh, Syed Nurul Hasan, Sung-Min Hwang, Hyeji Kang, Changhon Lee, Gi-Cheon Kim, Dipayan Rudra, Chang-Hee Suh, Sin-Hyeog Im
Journal: Immunity (2018)
Unsupervised analysis of the extent, organization and phenotype of tumor-infiltrating lymphocytes in breast cancer identifies two major clusters
Authors: C. Solinas, F. Richard, S. Garaud, P. De Silva, A. de Wind, G. Van Den Eyden, C. Gu-Trantien, M. Langouo Fontsa, G. Noël, A. Boisson, C. Naveaux, H. Duvillier, L. Craciun, D. Larsimont, K. Willard-Gallo
Journal: Annals of Oncology (2018)

Background: Heterogeneous expression of immune checkpoint molecules by tumor-infiltrating lymphocytes (TIL) and within tertiary lymphoid structures (TLS) was previously demonstrated in breast cancer (BC). This study analyzed primary breast tumors for: TIL and TLS; LAG3 and TIM3 expression; and other clinicopathological parameters. Methods: A cohort of untreated primary BC (N = 95) was prospectively analyzed. Hierarchical unsupervised clustering was performed on: the % of CD4+ and CD8+ TIL expressing LAG3 and TIM3 in fresh BC tissues (flow cytometry, FC); the % of stromal (str), intratumoral and global TIL, CD3+, CD4+, CD8+, CD20+ cells, and number of TLS scored on matched tissue sections dual-stained by immunohistochemistry (IHC; CD3/CD20; and CD4/CD8); age; estrogen receptor (ER) status; and BC clinical subtype. FC data was analyzed using Kaluza™ software. IHC stained tissues were evaluated by two pathologists blinded to the clinical data. Tumors were categorized as TILneg (<10% str-TIL), TILint (>10% and <50% str-TIL) and TILhi (>50% str-TIL) on IHC slides. Continuous marker data was scaled and z-scores were computed on log2transformed data. Clustering was based on Euclidian distances and Wald criteria. Results: Tumors in this cohort contain a majority of luminal BC (66%). Analysis of all parameters using the gap statistical method identified two optimal clusters, which were classified as TIL-poor and TIL-rich BC. The TIL-rich group (24%) contains the majority of TILhi tumors with increased numbers of TLS and fewer patients >70 years old, compared to the predominant TIL-poor group. LAG3 and TIM3 are expressed on T cells in a small fraction of BC in both TIL-rich and TIL-poor clusters, but rarely co-expressed by T cell subpopulations in the same tumors. LAG3 expression tends to be more frequently associated with TILint triple negative BC (TNBC). A higher proportion of TIL-rich tumors was found to express TIM3. Conclusions: Our study identified TIL-poor and TIL-rich immune clusters in primary BC. TIL-rich BC has heterogeneous TIM3 and sporadic LAG3 expression. TILint TNBC from the TIL-poor cluster frequently express LAG3. These data suggest that LAG3 and TIM3 screening may be important for BC immunotherapy. Legal entity responsible for the study: Molecular Immunology Unit, Institut Jules Bordet (Brussels). Funding: Les Amis de l'Institut Jules Bordet. Disclosure: All authors have declared no conflicts of interest.
Osteosarcoma cell intrinsic PD-L2 signals promote invasion and metastasis via the RhoA-ROCK-LIMK2 and autophagy pathways
Authors: T. Ren, B. Zheng, W. Guo
Journal: Annals of Oncology (2018)

Background: Known as co-stimulatory molecule, programmed death ligand-2 (PD-L2) contributes to T-cell exhaustion by interaction with programmed death-1 (PD-1) receptor, but its tumor cell intrinsic signal effects has been little investigated. Methods: PD-L2 expression was detected by immunohistochemistry in 18 pairs of primary osteosarcoma tissues and matching lung metastasis tissues. We also investigated the effects of PD-L2 knockdown on osteosarcoma both in vitro and in vivo. Results: In our study, PD-L2 expression was elevated in lung metastases compared with primary osteosarcoma according to an immunohistochemistry assay. Wound healing and transwell assays revealed that PD-L2 knockdown leads to inhibition of migration and invasion of human osteosarcoma cells in vitro. Mechanistically, we demonstrated that PD-L2 knockdown attenuated migration and invasion by inactivating RhoA-ROCK-LIMK2 signaling, suppressing epithelial-mesenchymal transition (EMT), and inhibiting autophagy by decreasing beclin1 expression. In support of these observations, beclin1 knockdown also inhibited activation of the RhoA-ROCK-LIMK2 pathway, leading to autophagy inhibition-induced blockade of migration and invasion. Depletion of PD-L2 in KHOS cells markedly weakens pulmonary metastatic potential in vivo by orthotopic transplantation of nude mice. Conclusions: Our study reveals a pro-metastatic functional mechanism for PD-L2 in osteosarcoma. Furthermore, we demonstrate a regulatory role for PD-L2 on autophagy as well as a relationship between autophagy and metastasis in osteosarcoma, which may represent a potential therapeutic target for osteosarcoma. Legal entity responsible for the study: Tingting Ren. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Prevalence of chronic rhinosinusitis in the general population based on sinus radiology and symptomatology
Authors: Dirk Dietz de Loos, Evelijn S. Lourijsen, Maarten A.M. Wildeman, Nicole J.M. Freling, Marije D.J. Wolvers, Sietze Reitsma, Wytske J. Fokkens
Journal: Journal of Allergy and Clinical Immunology (2018)