tbuckley/cabot-search huggingface dataset:
Nuclear receptor ERRα contributes to castration-resistant growth of prostate cancer via its regulation of intratumoral androgen biosynthesis
Authors: Zhenyu Xu, Taiyang Ma, Jianfu Zhou, Weijie Gao, Youjia Li, Shan Yu, Yuliang Wang, Franky Leung Chan
Journal: Theranostics (2020)

Enhanced intratumoral androgen biosynthesis and persistent androgen receptor (AR) signaling are key factors responsible for the relapse growth of castration-resistant prostate cancer (CRPC). Residual intraprostatic androgens can be produced by de novo synthesis of androgens from cholesterol or conversion from adrenal androgens by steroidogenic enzymes expressed in prostate cancer cells via different steroidogenic pathways. However, the dysregulation of androgen biosynthetic enzymes in CRPC still remains poorly understood. This study aims to elucidate the role of the nuclear receptor, estrogen-related receptor alpha (ERRα, ESRRA), in the promotion of androgen biosynthesis in CRPC growth. Methods: ERRα expression in CRPC patients was analyzed using Gene Expression Omnibus (GEO) datasets and validated in established CRPC xenograft model. The roles of ERRα in the promotion of castration-resistant growth were elucidated by overexpression and knockdown studies and the intratumoral androgen levels were measured by UPLC-MS/MS. The effect of suppression of ERRα activity in the potentiation of sensitivity to androgen-deprivation was determined using an ERRα inverse agonist. Results: ERRα exhibited an increased expression in metastatic CRPC and CRPC xenograft model, could act to promote castration-resistant growth via direct transactivation of two key androgen synthesis enzymes CYP11A1 and AKR1C3, and hence enhance intraprostatic production of dihydrotestosterone (DHT) and activation of AR signaling in prostate cancer cells. Notably, inhibition of ERRα activity by an inverse agonist XCT790 could reduce the DHT production and suppress AR signaling in prostate cancer cells. Conclusion: Our study reveals a new role of ERRα in the intratumoral androgen biosynthesis in CRPC via its transcriptional control of steroidogenic enzymes, and also provides a novel insight that targeting ERRα could be a potential androgen-deprivation strategy for the management of CRPC.
TCT-17 Current Perspectives On Stent Fractures: Trends, Characteristics And Outcomes From The Food And Drug Administration Manufacturer And User Facility Device Experience Database
Authors: Alfazir Omar, Hironori Kitabata, Lakshmana Pendyala, Israel Barbash, Salem Badr, Joshua P. Loh, Marco A. Magalhaes, Sa'ar Minha, Hideaki Ota, Fang Chen, Rebecca Torguson, Kenneth Kent, Augusto Pichard, Lowell F. Satler, William O. Suddath, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
TCT-326 Major predictors of long-term clinical outcomes after percutaneous coronary intervention for coronary bifurcation lesions with 2-stent strategy: Patient-Level Analysis of the Korean Bifurcation Pooled Cohorts
Authors: Ji-Hoon Jang, Dong-Kie Kim, Pil Sang Song, Doo-Il Kim, Joo Myung Lee, Young Bin Song, Joo-Yong Hahn, Seung-Hyuck Choi, Hyo-Soo Kim, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2016)
Research Priorities for Heart Failure With Preserved Ejection Fraction
Authors: Sanjiv J. Shah, Barry A. Borlaug, Dalane W. Kitzman, Andrew D. McCulloch, Burns C. Blaxall, Rajiv Agarwal, Julio A. Chirinos, Sheila Collins, Rahul C. Deo, Mark T. Gladwin, Henk Granzier, Scott L. Hummel, David A. Kass, Margaret M. Redfield, Flora Sam, Thomas J. Wang, Patrice Desvigne-Nickens, Bishow B. Adhikari
Journal: Circulation (2020)

Heart failure with preserved ejection fraction (HFpEF), a major public health problem that is rising in prevalence, is associated with high morbidity and mortality and is considered to be the greatest unmet need in cardiovascular medicine today because of a general lack of effective treatments. To address this challenging syndrome, the National Heart, Lung, and Blood Institute convened a working group made up of experts in HFpEF and novel research methodologies to discuss research gaps and to prioritize research directions over the next decade. Here, we summarize the discussion of the working group, followed by key recommendations for future research priorities. There was uniform recognition that HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach in both humans and animal models to improve understanding of mechanisms and treatment of HFpEF. It was recognized that advances in the understanding of basic mechanisms and the roles of inflammation, macrovascular and microvascular dysfunction, fibrosis, and tissue remodeling are needed and ideally would be obtained from (1) improved animal models, including large animal models, which incorporate the effects of aging and associated comorbid conditions; (2) repositories of deeply phenotyped physiological data and human tissue, made accessible to researchers to enhance collaboration and research advances; and (3) novel research methods that take advantage of computational advances and multiscale modeling for the analysis of complex, high-density data across multiple domains. The working group emphasized the need for interactions among basic, translational, clinical, and epidemiological scientists and across organ systems and cell types, leveraging different areas or research focus, and between research centers. A network of collaborative centers to accelerate basic, translational, and clinical research of pathobiological mechanisms and treatment strategies in HFpEF was discussed as an example of a strategy to advance research progress. This resource would facilitate comprehensive, deep phenotyping of a multicenter HFpEF patient cohort with standardized protocols and a robust biorepository. The research priorities outlined in this document are meant to stimulate scientific advances in HFpEF by providing a road map for future collaborative investigations among a diverse group of scientists across multiple domains.
Effective targeting of intact and proteolysed CDCP1 for imaging and treatment of pancreatic ductal adenocarcinoma
Authors: Thomas Kryza, Tashbib Khan, Simon Puttick, Chao Li, Kamil A Sokolowski, Brian WC Tse, Tahleesa Cuda, Nicholas Lyons, Madeline Gough, Julia Yin, Ashleigh Parkin, Elena I Deryugina, James P. Quigley, Ruby H. P. Law, James C. Whisstock, Andrew D. Riddell, Andrew P. Barbour, David K. Wyld, Paul A. Thomas, Stephen Rose, Cameron E. Snell, Marina Pajic, Yaowu He, John D. Hooper
Journal: Theranostics (2020)

Background: CUB domain-containing protein 1 (CDCP1) is a cell surface receptor regulating key signalling pathways in malignant cells. CDCP1 has been proposed as a molecular target to abrogate oncogenic signalling pathways and specifically deliver anti-cancer agents to tumors. However, the development of CDCP1-targeting agents has been questioned by its frequent proteolytic processing which was thought to result in shedding of the CDCP1 extracellular domain limiting its targetability. In this study, we investigated the relevance of targeting CDCP1 in the context of pancreatic ductal adenocarcinoma (PDAC) and assess the impact of CDCP1 proteolysis on the effectiveness of CDCP1 targeting agents. Methods: The involvement of CDCP1 in PDAC progression was assessed by association analysis in several PDAC cohorts and the proteolytic processing of CDCP1 was evaluated in PDAC cell lines and patient-derived cells. The consequences of CDCP1 proteolysis on its targetability in PDAC cells was assessed using immunoprecipitation, immunostaining and biochemical assays. The involvement of CDCP1 in PDAC progression was examined by loss-of-function in vitro and in vivo experiments employing PDAC cells expressing intact or cleaved CDCP1. Finally, we generated antibody-based imaging and therapeutic agents targeting CDCP1 to demonstrate the feasibility of targeting this receptor for detection and treatment of PDAC tumors. Results: High CDCP1 expression in PDAC is significantly associated with poorer patient survival. In PDAC cells proteolysis of CDCP1 does not always result in the shedding of CDCP1-extracellular domain which can interact with membrane-bound CDCP1 allowing signal transduction between the different CDCP1-fragments. Targeting CDCP1 impairs PDAC cell functions and PDAC tumor growth independently of CDCP1 cleavage status. A CDCP1-targeting antibody is highly effective at delivering imaging radionuclides and cytotoxins to PDAC cells allowing specific detection of tumors by PET/CT imaging and superior anti-tumor effects compared to gemcitabine in in vivo models. Conclusion: Independent of its cleavage status, CDCP1 exerts oncogenic functions in PDAC and has significant potential to be targeted for improved radiological staging and treatment of this cancer. Its elevated expression by most PDAC tumors and lack of expression by normal pancreas and other major organs, suggest that targeting CDCP1 could benefit a significant proportion of PDAC patients. These data support the further development of CDCP1-targeting agents as personalizable tools for effective imaging and treatment of PDAC.
Online patient feedback is positive, but not used effectively
Authors: Rob Cook, Peter Davidson, Alicia White
Journal: BMJ (2020)

The study Powell J, Atherton H, Williams V, et al. Using online patient feedback to improve NHS services: the INQUIRE multimethod study. Health Serv Deliv Res 2019;7:38. This project was funded by the NIHR Health Services and Delivery Research programme (project number HS&amp;DR 14/04/48). To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000861/online-patient-feedback-is-mostly-positive-but-is-not-being-used-effectively
Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study
Authors: Haiyan Qiu, Junhua Wu, Liang Hong, Yunling Luo, Qifa Song, Dong Chen
Journal: The Lancet Infectious Diseases (2020)

Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19.
Exercising Heart and Head in Managing Coronavirus Disease 2019 in Wuhan
Authors: Roy H. Perlis
Journal: JAMA Network Open (2020)

Jianbo Lai, MSc; Simeng Ma, MSc; Ying Wang, MSc; Zhongxiang Cai, MD; Jianbo Hu, MSc; Ning Wei, MD; Jiang Wu, MD; Hui Du, MD; Tingting Chen, MD; Ruiting Li, MD; Huawei Tan, MD; Lijun Kang, MSc; Lihua Yao, MD; Manli Huang, MD; Huafen Wang, BD; Gaohua Wang, MD; Zhongchun Liu, MD; Shaohua Hu, MD
Changing the editorial process at JCI and JCI Insight in response to the COVID-19 pandemic
Authors: Rexford S. Ahima, Sarah Jackson, Arturo Casadevall, Gregg L. Semenza, Gordon Tomaselli, Kathleen L. Collins, Andrew P. Lieberman, Donna M. Martin, Pavan Reddy
Journal: Journal of Clinical Investigation (2020)

The editors of JCI and JCI Insight are revisiting our editorial processes in light of the strain that the COVID-19 pandemic places on the worldwide scientific community. Here, we discuss adjustments to our decision framework in light of restrictions placed on laboratory working conditions for many of our authors.
PLAQUE MORPHOLOGY PREDICTORS OF SIDE BRANCH OCCLUSION AFTER MAIN VESSEL STENTING IN CORONARY BIFURCATION LESION: OPTICAL COHERENCE TOMOGRAPHY IMAGING STUDY
Authors: Takahiro Yoshimura, Yuliya Vengrenyuk, Jacobo Pena, Jossef Amirian, Safwan Kezbor, Choudhury Hasan, Joseph Sweeny, George Dangas, Usman Baber, Pedro R. Moreno, Jagat Narula, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2016)
Paneth cells promote angiogenesis and regulate portal hypertension in response to microbial signals
Authors: Mohsin Hassan, Sheida Moghadamrad, Marcel Sorribas, Sergi G. Muntet, Philipp Kellmann, Coralie Trentesaux, Marie Fraudeau, Paolo Nanni, Witold Wolski, Irene Keller, Siegfried Hapfelmeier, Noah F. Shroyer, Reiner Wiest, Beatrice Romagnolo, Andrea De Gottardi
Journal: Journal of Hepatology (2020)
PROGNOSTIC VALUE OF SEGMENT INVOLVEMENT SCORE COMPARED TO OTHER MEASURES OF CORONARY ATHEROSCLEROSIS BY COMPUTED TOMOGRAPHY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chadi Ayoub, Fernanda Erthal, Mahmoud Abdelsalam, Mohammad H. Murad, Zhen Wang, Patricia Erwin, Graham S. Hillis, Leonard Kritharides, Benjamin Chow
Journal: Journal of the American College of Cardiology (2017)
Lung Recruitability in COVID-19–associated Acute Respiratory Distress Syndrome: A Single-Center Observational Study
Authors: Chun Pan, Lu Chen, Cong Lu, Wei Zhang, Jia-An Xia, Michael C. Sklar, Bin Du, Laurent Brochard, Haibo Qiu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

majority (67-85%) of critically ill patients who
The role of tumor-stroma interactions on desmoplasia and tumorigenicity within a microengineered 3D platform
Authors: Harpinder Saini, Kiarash Rahmani Eliato, Jaimeson Veldhuizen, Azadeh Zare, Mayar Allam, Casey Silva, Alex Kratz, Danh Truong, Ghassan Mouneimne, Joshua LaBaer, Robert Ros, Mehdi Nikkhah
Journal: Biomaterials (2020)
A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles
Authors: Li Wang, Robert P. Sebra, John P. Sfakianos, Kimaada Allette, Wenhui Wang, Seungyeul Yoo, Nina Bhardwaj, Eric E. Schadt, Xin Yao, Matthew D. Galsky, Jun Zhu
Journal: Genome Medicine (2020)

Abstract Background Patient stratification based on molecular subtypes is an important strategy for cancer precision medicine. Deriving clinically informative cancer molecular subtypes from transcriptomic data generated on whole tumor tissue samples is a non-trivial task, especially given the various non-cancer cellular elements intertwined with cancer cells in the tumor microenvironment. Methods We developed a computational deconvolution method, DeClust, that stratifies patients into subtypes based on cancer cell-intrinsic signals identified by distinguishing cancer-type-specific signals from non-cancer signals in bulk tumor transcriptomic data. DeClust differs from most existing methods by directly incorporating molecular subtyping of solid tumors into the deconvolution process and outputting molecular subtype-specific tumor reference profiles for the cohort rather than individual tumor profiles. In addition, DeClust does not require reference expression profiles or signature matrices as inputs and estimates cancer-type-specific microenvironment signals from bulk tumor transcriptomic data. Results DeClust was evaluated on both simulated data and 13 solid tumor datasets from The Cancer Genome Atlas (TCGA). DeClust performed among the best, relative to existing methods, for estimation of cellular composition. Compared to molecular subtypes reported by TCGA or other similar approaches, the subtypes generated by DeClust had higher correlations with cancer-intrinsic genomic alterations (e.g., somatic mutations and copy number variations) and lower correlations with tumor purity. While DeClust-identified subtypes were not more significantly associated with survival in general, DeClust identified a poor prognosis subtype of clear cell renal cancer, papillary renal cancer, and lung adenocarcinoma, all of which were characterized by CDKN2A deletions. As a reference profile-free deconvolution method, the tumor-type-specific stromal profiles and cancer cell-intrinsic subtypes generated by DeClust were supported by single-cell RNA sequencing data. Conclusions DeClust is a useful tool for cancer cell-intrinsic molecular subtyping of solid tumors. DeClust subtypes, together with the tumor-type-specific stromal profiles generated by this pan-cancer study, may lead to mechanistic and clinical insights across multiple tumor types.
Zoonotic tuberculosis—a call for an open One Health debate
Authors: Alimuddin Zumla, Dorothy Yeboah-Manu, Anita L Michel, Esam I Azhar, Jordi B Torrelles, Simeon I Cadmus, Sharon L Kendall, Jeremiah M Chakaya, Ben Marais, Richard Kock
Journal: The Lancet Infectious Diseases (2020)
CD8<sup>+</sup> T-cell plasticity regulates vascular regeneration in type-2 diabetes
Authors: Cai Liang, Kevin Y. Yang, Vicken W. Chan, Xisheng Li, Tiffany H.W. Fung, Yalan Wu, Xiao Yu Tian, Yu Huang, Ling Qin, James Y.W. Lau, Kathy O. Lui
Journal: Theranostics (2020)

In this study, we observe that the ischemic tissues of type-2 diabetic (T2D) patients and mice have significantly more CD8+ T-cells than that of their normoglycemic counterparts, respectively. However, the role of CD8+ T-cells in the pathogenesis of diabetic vascular complication has been less studied. Methods: We employed loss-of-function studies in mouse models using the non-lytic anti-CD8 antibody that blocks tissue infiltration of CD8+ T-cells into the injured tissue. We also performed genome-wide, single-cell RNA-sequencing of CD8+ T-cells to uncover their role in the pathogenesis of diabetic vascular diseases. Results: The vascular density is negatively correlated with the number of CD8+ T-cells in the ischemic tissues of patients and mice after injury. CD8+ T-cells or their supernatant can directly impair human and murine angiogenesis. Compared to normoglycemic mice that can regenerate their blood vessels after injury, T2D mice fail in this regeneration. Treatment with the CD8 checkpoint blocking antibody increases the proliferation and function of endothelial cells in both Leprdb/db mice and diet-induced diabetic Cdh5-Cre;Rosa-YFP lineage-tracing mice after ischemic injury. Furthermore, single-cell transcriptomic profiling reveals that CD8+ T-cells of T2D mice showed a de novo cell fate change from the angiogenic, tissue-resident memory cells towards the effector and effector memory cells after injury. Functional revascularization by CD8 checkpoint blockade is mediated through unleashing such a poised lineage commitment of CD8+ T-cells from T2D mice. Conclusion: Our results reveal that CD8+ T-cell plasticity regulates vascular regeneration; and give clinically relevant insights into the potential development of immunotherapy targeting vascular diseases associated with obesity and diabetes.
EMERGENCY ROOM EVALUATION OF PATIENTS WITH CARDIAC COMPLAINTS AND NEW LEFT BUNDLE BRANCH BLOCK: THE UTILITY OF THE SGARBOSSA AND MODIFIED SGARBOSSA CRITERIA
Authors: Supreeti Behuria, Joseph C. Yu, Rajbir Sidhu, Perry Fisher, Deepika Misra, Paul (Pavol) Schweitzer, Yumiko Kanei
Journal: Journal of the American College of Cardiology (2017)
REPEAT PULMONARY VALVE REPLACEMENT: SIMILAR INTERMEDIATE-TERM OUTCOMES BETWEEN SURGICAL AND TRANSCATHETER PROCEDURES
Authors: Hope Caughron, Norihiko Kamioka, Dennis Kim, Stamatios Lerakis, Altayyeb Yousef, Aneesha Maini, Shawn Reginauld, Anurag Sahu, Subhadra Shashidharan, Maan Jokhadar, Fred Rodriguez, Wendy Book, Michael McConnell, Peter Block, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2018)
TCT-68 Clinical Outcomes According to Fractional Flow Reserve or Instantaneous Wave-Free Ratio in Deferred Lesions
Authors: Joo Myung Lee, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Doyeon Hwang, Jonghanne Park, Ahn Chul, Bon-Kwon Koo
Journal: Journal of the American College of Cardiology (2017)
Covid-19: how to be careful with trust and expertise on social media
Authors: Sue Llewellyn
Journal: BMJ (2020)

Three times in one day I received the same warning from different groups of friends, through various channels.It came through email, Facebook, and WhatsApp, and I also saw it circulating widely on Twitter.I replied thanking them, saying that I knew they wanted to help (we all do) but that, actually, the warning wasn't true and could even be dangerous.I felt almost unkind by pointing out that holding your breath wasn't a test for covid-19.And that drinking lots of water wouldn't help it go away.
TCT-457 Severe Mitral Stenosis in Patients With Severe Mitral Annular Calcification: An Area of Unmet Need
Authors: Rayji Tsutsui, Eli Simsolo, Yoshihito Saijo, Kinjal Banerjee, James Gentry, Rishi Puri, Grant Reed, Amar Krishnaswamy, Marc Gillinov, Zoran Popovic, Samir Kapadia
Journal: Journal of the American College of Cardiology (2019)
Obesity Treatment Among Adolescents
Authors: Michelle I. Cardel, Mark A. Atkinson, Elsie M. Taveras, Jens-Christian Holm, Aaron S. Kelly
Journal: JAMA Pediatrics (2020)

Obesity in adolescence has reached epidemic proportions around the world, with the prevalence of severe obesity increasing at least 4-fold over the last 35 years. Most youths with obesity carry their excess adiposity into adulthood, which places them at increased risk for developing obesity-driven complications, such as type 2 diabetes and cardiovascular disease, and negatively affects social and emotional health. Given that adolescence is a unique transition period marked by significant physiologic and developmental changes, obesity-related complications can also negatively affect adolescent growth and developmental trajectories.
Ellagic acid-Fe@BSA nanoparticles for endogenous H<sub>2</sub>S accelerated Fe(III)/Fe(II) conversion and photothermal synergistically enhanced chemodynamic therapy
Authors: Qingqing Tian, Lu An, Qiwei Tian, Jiaomin Lin, Shiping Yang
Journal: Theranostics (2020)

: Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H
Increased mTOR activation in idiopathic multicentric Castleman disease
Authors: Daniel J. Arenas, Katherine Floess, Dale Kobrin, Ruth-Anne Langan Pai, Maya B. Srkalovic, Mark-Avery Tamakloe, Rozena Rasheed, Jasira Ziglar, Johnson Khor, Sophia A. T. Parente, Sheila K. Pierson, Daniel Martinez, Gerald B. Wertheim, Taku Kambayashi, Joseph Baur, David T. Teachey, David C. Fajgenbaum
Journal: Blood (2020)
Small Data Challenges of Studying Rare Diseases
Authors: Aya A. Mitani, Sebastien Haneuse
Journal: JAMA Network Open (2020)

Shirisha Avadhanula, MD; Wendy J. Introne, MD; Sungyoung Auh, PhD; Steven J. Soldin, PhD; Brian Stolze, MSc; Debra Regier, MD; Carla Ciccone, MS; Fady Hannah-Shmouni, MD; Armando C. Filie, MD; Kenneth D. Burman, MD; Joanna Klubo-Gwiezdzinska, MD, PhD, MHSc
TCT-246 Temporal Trends and Outcomes of Percutaneous Coronary Interventions in Nonagenarians – A National Perspective
Authors: Kashish Goel, Tanush Gupta, Dhaval Kolte, Sahil Khera, Deepak Bhatt, Rajiv Gulati, Malcolm Bell, Chet Rihal, David Holmes
Journal: Journal of the American College of Cardiology (2017)
Greater Than Minimal Risk, No Direct Benefit – Bridging Drug Trials and Novel Therapy in Pediatric Populations
Authors: Benjamin S. Wilfond, Devan M. Duenas, Liza-Marie Johnson
Journal: The American Journal of Bioethics (2020)

"Greater Than Minimal Risk, No Direct Benefit – Bridging Drug Trials and Novel Therapy in Pediatric Populations." The American Journal of Bioethics, 20(4), pp. 102–103
THE IMPACT OF MULTIVESSEL VERSUS SINGLE VESSEL APASM AS ASSESSED BY THE INTRACORONARY ACETYLCHOLINE PROVOCATION TEST ON 3 YEARS CLINICAL OUTCOMES IN KOREAN PATIENTS
Authors: Ji Young Park, Seung-Woon Rha, Byoung Geol Choi, Jae Woong Choi, Sung Kee Ryu, Se Yeon Choi, Yoonjee Park, Akkala Goud, Hu Li, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Cheol Ung Choi, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2014)