tbuckley/cabot-search huggingface dataset:
116MO Efficacy, safety, and quality of life (QoL) with futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements: FOENIX-CCA2
Authors: J. Furuse, L. Goyal, F. Meric-Bernstam, A. Hollebecque, J.W. Valle, C. Morizane, T.B. Karasic, T.A. Abrams, R.K. Kelley, P.A. Cassier, H-J. Klumpen, N. Uboha, A. Mahipal, E. Mitchell, E. Ahn, H-M. Chang, K. Masuda, Y. He, K.A. Benhadji, J.A. Bridgewater
Journal: Annals of Oncology (2020)
Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling
Authors: Naoko Yamaguchi, Junhua Xiao, Deven Narke, Devin Shaheen, Xianming Lin, Erik Offerman, Alireza Khodadadi-Jamayran, Akshay Shekhar, Alex Choy, Sojin Y. Wass, David R. Van Wagoner, Mina K. Chung, David S. Park
Journal: Circulation (2020)

Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling.
Abstract 17006: A Machine Learning Approach to Identify Predictors of Mortality in Patients With Atherosclerotic Cardiovascular Disease
Authors: Ozan Dikilitas, Baosheng He, Iftikhar Kullo
Journal: Circulation (2018)

Introduction: We investigated the predictive power of a machine learning (ML) algorithm for 5-year mortality in patients with atherosclerotic cardiovascular disease (ASCVD). Candidate features included clinical variables from the electronic health record (EHR) as well as self-reported health and lifestyle data. Methods: The study cohort included 4,689 patients (66±11 years, 62% male) with ASCVD enrolled in the Vascular Disease Biorepository, which recruits patients referred to noninvasive vascular evaluation at Mayo Clinic, Rochester, MN. Clinical variables including comorbidities, lab measurements, and medication use were obtained from the EHR using validated electronic phenotyping algorithms. Information regarding social habits, physical activity levels, and personal health was obtained from a survey filled by the participants. Mortality was ascertained from the national death index. Clinical variables (n=52) and self-reported variables related to health and lifestyle habits (n=48) were added as individual features to reinforcement learning trees (RLT), a sparse decision tree algorithm, to construct the prediction model. We assessed the impact of each feature on prediction accuracy by applying feature selection and computing variable importance (VI). Results: Features with trivial VI that made no contribution to prediction were excluded. A model with 15 features had an area under the ROC curve (AUC) of 0.82 [95% CI 0.79 - 0.83] in the test set. Among the top 10 predictors of 5-year mortality, 6 were self-reported health variables (Table) , including outlook on personal health, limitations on routine daily activities, and physical activity levels. Conclusions: A ML approach had robust discrimination (AUC 0.82) in predicting 5-year mortality in patients with ASCVD. Self-reported health variables were among the top predictive features in the final model.
Genome-wide Screens Identify Lineage- and Tumor-Specific Genes Modulating MHC-I- and MHC-II-Restricted Immunosurveillance of Human Lymphomas
Authors: Devin Dersh, James D. Phelan, Megan E. Gumina, Boya Wang, Jesse H. Arbuckle, Jaroslav Holly, Rigel J. Kishton, Tovah E. Markowitz, Mina O. Seedhom, Nathan Fridlyand, George W. Wright, Da Wei Huang, Michele Ceribelli, Craig J. Thomas, Justin B. Lack, Nicholas P. Restifo, Thomas M. Kristie, Louis M. Staudt, Jonathan W. Yewdell
Journal: Immunity (2020)
15013 Dupilumab improves signs, symptoms, and quality of life in adolescents with moderate to severe atopic dermatitis
Authors: Lawrence F. Eichenfield, Jonathan I. Silverberg, Abhijit Gadkari, Isabelle Guillemin, Zhen Chen, Ashish Bansal, Laurent Eckert, Karli Rosner
Journal: Journal of the American Academy of Dermatology (2020)
The NAB2 corepressor targets the NuRD chromatin remodeling complex to EGR1 target genes in prostate
Authors: Rajini Srinivasan, Rebecca Ward, John Svaren
Journal: Cancer Research (2007)

1611  The goal of these studies is to determine how loss of the NGF1-A binding protein (NAB2) corepressor in prostate cancer affects gene regulation and chromatin structure of Early Growth Response (EGR1) target genes. EGR1 is a transcription factor that is overexpressed in prostate cancer and progression of prostate cancer in mouse models is severely compromised in the absence of EGR1. NAB corepressors directly interact with EGR1 and are important regulators of EGR1 activity. Interestingly, while EGR1 is overexpressed in prostate cancer, NAB2 expression is low or absent in majority of prostate cancer samples. The role of EGR1 in prostate cancer progression is complex as it regulates both pro-proliferative genes, as well as genes involved in apoptotic/senescence pathways. Our analysis indicates that loss of NAB2 expression alters the balance of EGR1 target genes in favor of activation of genes involved in growth promotion. Moreover, we have recently shown that NAB2 represses EGR target genes through its association with Chromodomain Helicase DNA Binding Protein 4 (CHD4), which is a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex. The NuRD complex is one of the major histone deacetylase (HDAC)-containing complexes in the nucleus and also incorporates Metastasis-Associated Factor 1/2 (MTA1/2) as integral components. Using microarray and chromatin immunoprecipitation analyses, we have identified NAB-regulated target genes in prostate cell lines and demonstrated that EGR1, NAB2 and subunits of the NuRD complex are directly recruited to several target promoters. Many of the same genes are also derepressed by exposure to histone deacetylase inhibitors, indicating that the HDAC subunits of the NuRD complex play an important role in NAB regulation. Overall, these data indicate that loss of NAB2 results in failure to target the repressive NuRD complex to specific EGR1 target genes in prostate cancer cells.
Abstract 12739: Microrna-294 Modulates Cardiomyocyte Proliferation Following Myocardial Infarction
Authors: Mohsin Khan, Emily Nickoloff, Jennifer Johnson, Suresh K Verma, Venkata N Garikipati, Jibin Zhou, Cynthia B Alderfer, Raj Kishore
Journal: Circulation (2015)

Rationale: Embryonic heart is characteristic of rapidly dividing cardiomyocytes that give rise to sufficient numbers required to build a working myocardium. In contrast, cardiomyocytes retain some proliferative capacity in the neonates but lose most of it in adulthood. Embryonic stem cell cycle (ESCC) miRs are a class of microRNAs regulating the unique cell cycle of ESCs and their characteristic pluripotency. Nevertheless, expression of miR-294, a member of the ESCC miRs is lost during developmental transitions from the ESCs to mature cells. Effect of miR-294 to induce cardiac proliferation and heart function has not been previously studied. Objective: To determine whether miR-294 drives cardiomyocyte cell cycle reentry leading to augmentation of cardiac function after myocardial infarction. Methods and Results: miR expression analysis in the heart during development revealed elevated levels of miR-294 in the prenatal stages while the expression was lost in the neonates and adults as confirmed by qRT-PCR. Neonatal ventricular cardiomyocytes (NRVMs) were treated with miR-294 mimic to determine the effect on proliferation and cell cycle. Elevated mRNA levels of cyclins A2, E1, CDK2 together with c-myc, E2F1 and E2F3 was observed in NRVMs treated with 25nM mimic for miR-294. Additionally, miR-294 treated NRVMs showed in AKT phosphorylation along with enhanced protein levels of cyclin D1 and E2F1. Increased expression of p-histone 3, Ki67 and Aurora B kinase (G2/M) was confirmed by immunocytochemistry in NRVMs after miR-294 treatment compared to control cells. Administration of miR-294 in mice subjected to myocardial infarction demonstrated augmentation of cardiac function in mice receiving miR-294 8 weeks after injury. Increase myocyte proliferation was observed in the heart after miR-294 treatment as analyzed by BrdU uptake, p-Histone 3 and Aurora B expression by immunostaining. Concurrently, a decrease in infarct size along with decreased apoptosis was observed in the miR-294 hearts compared to the control. Conclusion: Ectopic expression of miR-294 recapitulates embryonic signaling and enhances cardiomyocyte ability to proliferate and reenter the cell cycle leading to augmented cardiac function in mice after myocardial infarction.
Congenital heart disease
Authors: Cristiane Martins
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Congenital heart disease (CHD) is the most common cause of major congenital anomalies, and is the group of malformations that contributes the most for perinatal mortality [1]. It represents an important health care issue and knowing its incidence and risk factors helps developing public and private care policies and clinical protocols. In this paper, researchers published a retrospective analysis from a tertiary hospital in Portugal regarding CHD. In this editorial, we analyze their findings and compare with other publications.
Coronary Angiography After Cardiac Arrest
Authors: J.S. Lemkes
Journal: Circulation (2020)

Despite advances in the fields of resuscitation and intensive care management, the outcome of out-of-hospital cardiac arrest remains poor.Optimal care after out-of-hospital cardiac arrest and successful resuscitation includes targeted temperature management, vital organ support, and treatment of the underlying cause of the arrest.The cause of the arrest is often unclear immediately after the event, in particular in the absence of ST-segment elevation (STE) on ECG.This lack of a definitive diagnosis can lead to uncertainty about the appropriate treatment.Patients who survive cardiac arrest have a high prevalence of coronary artery disease and if myocardial infarction is the cause of the arrest, immediate coronary angiography and percutaneous coronary intervention might improve outcome.Previous observation studies reported a survival benefit of an immediate invasive strategy in patients who were resuscitated from cardiac arrest even in the absence of STE myocardial infarction compared with historical controls. 1,2However, these outcomes might have been an effect of the observational nature of these studies, which may have resulted in selection bias that favored selecting patients who had a presumed better prognosis for immediate angiography.The first large randomized, controlled trial addressing the effect of immediate coronary angiography in patients without STE after cardiac arrest was the COACT study (Coronary Angiography After Cardiac Arrest).The COACT study randomly assigned 552 patients after cardiac arrest to either immediate coronary angiography or delayed coronary angiography after neurologic recovery and found no difference in 90-day survival. 3It has been advocated that these results should be confirmed by additional randomized studies.The international, multicentered, randomized PEARL trial (Early Coronary Angiography Versus Delayed Coronary Angiography), 4 reported in this issue, is a pilot study comparing early (<2 hours) coronary angiography versus no early coronary angiography in comatose patients resuscitated from out-of-hospital cardiac arrest without STE.The trial had slow recruitment and inclusion was terminated when 99 of the planned 226 patients were randomized.The study should therefore be considered underpowered.PEARL found no difference in the primary end point (a composite of efficacy and safety measures, including efficacy measures of survival to discharge, favorable neurologic status at discharge, echocardiographic measures of left ventricular ejection fraction >50%, and a normal wall motion score of 16 within 24 hours of admission).Adverse events including rearrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension, and pneumonia were compared between the 2 groups (55.1% versus 46.0%; P=0.64).The trial found no difference in individual efficacy
Endothelial S1P <sub>1</sub> Signaling Counteracts Infarct Expansion in Ischemic Stroke
Authors: Anja Nitzsche, Marine Poittevin, Ammar Benarab, Philippe Bonnin, Giuseppe Faraco, Hiroki Uchida, Julie Favre, Lidia Garcia-Bonilla, Manuela C.L. Garcia, Pierre-Louis Léger, Patrice Thérond, Thomas Mathivet, Gwennhael Autret, Véronique Baudrie, Ludovic Couty, Mari Kono, Aline Chevallier, Hira Niazi, Pierre-Louis Tharaux, Jerold Chun, Susan R. Schwab, Anne Eichmann, Bertrand Tavitian, Richard L. Proia, Christiane Charriaut-Marlangue, Teresa Sanchez, Nathalie Kubis, Daniel Henrion, Costantino Iadecola, Timothy Hla, Eric Camerer
Journal: Circulation Research (2020)

Rationale: Cerebrovascular function is critical for brain health, and endogenous vascular protective pathways may provide therapeutic targets for neurological disorders. S1P (Sphingosine 1-phosphate) signaling coordinates vascular functions in other organs, and S1P 1 (S1P receptor-1) modulators including fingolimod show promise for the treatment of ischemic and hemorrhagic stroke. However, S1P 1 also coordinates lymphocyte trafficking, and lymphocytes are currently viewed as the principal therapeutic target for S1P 1 modulation in stroke. Objective: To address roles and mechanisms of engagement of endothelial cell S1P 1 in the naive and ischemic brain and its potential as a target for cerebrovascular therapy. Methods and Results: Using spatial modulation of S1P provision and signaling, we demonstrate a critical vascular protective role for endothelial S1P 1 in the mouse brain. With an S1P 1 signaling reporter, we reveal that abluminal polarization shields S1P 1 from circulating endogenous and synthetic ligands after maturation of the blood-neural barrier, restricting homeostatic signaling to a subset of arteriolar endothelial cells. S1P 1 signaling sustains hallmark endothelial functions in the naive brain and expands during ischemia by engagement of cell-autonomous S1P provision. Disrupting this pathway by endothelial cell-selective deficiency in S1P production, export, or the S1P 1 receptor substantially exacerbates brain injury in permanent and transient models of ischemic stroke. By contrast, profound lymphopenia induced by loss of lymphocyte S1P 1 provides modest protection only in the context of reperfusion. In the ischemic brain, endothelial cell S1P 1 supports blood-brain barrier function, microvascular patency, and the rerouting of blood to hypoperfused brain tissue through collateral anastomoses. Boosting these functions by supplemental pharmacological engagement of the endothelial receptor pool with a blood-brain barrier penetrating S1P 1 -selective agonist can further reduce cortical infarct expansion in a therapeutically relevant time frame and independent of reperfusion. Conclusions: This study provides genetic evidence to support a pivotal role for the endothelium in maintaining perfusion and microvascular patency in the ischemic penumbra that is coordinated by S1P signaling and can be harnessed for neuroprotection with blood-brain barrier-penetrating S1P 1 agonists.
The Hippo Pathway in Liver Homeostasis and Pathophysiology
Authors: Jordan H. Driskill, Duojia Pan
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

Studies of the regenerative capacity of the liver have converged on the Hippo pathway, a serine/threonine kinase cascade discovered in Drosophila and conserved from unicellular organisms to mammals. Genetic studies of mouse and rat livers have revealed that the Hippo pathway is a key regulator of liver size, regeneration, development, metabolism, and homeostasis and that perturbations in the Hippo pathway can lead to the development of common liver diseases, such as fatty liver disease and liver cancer. In turn, pharmacological targeting of the Hippo pathway may be utilized to boost regeneration and to prevent the development and progression of liver diseases. We review current insights provided by the Hippo pathway into liver pathophysiology. Furthermore, we present a path forward for future studies to understand how newly identified components of the Hippo pathway may control liver physiology and how the Hippo pathway is regulated in the liver.
15001 Durable efficacy of certolizumab pegol dosed at 400 mg every two weeks over 128 weeks in patients with plaque psoriasis enrolled in three phase 3 trials (CIMPASI-1, CIMPASI-2, and CIMPACT)
Authors: Ken Gordon, Richard B. Warren, Alice B. Gottlieb, Andrew Blauvelt, Diamant Thaci, Yves Poulin, Marion Boehnlein, Fiona Brock, Catherine Arendt, Kristian Reich
Journal: Journal of the American Academy of Dermatology (2020)
Transition from pediatric to adult care in sickle cell disease: Establishing evidence‐based practice and directions for research
Authors: Marsha Treadwell, Joseph Telfair, Robert W. Gibson, Shirley Johnson, Ifeyinwa Osunkwo
Journal: American Journal of Hematology (2010)

Transition of young adults with sickle cell disease (SCD) from pediatric to adult medical care is an important priority, given medical advances that have transformed SCD into a lifelong chronic condition, rather than a disease of childhood. Successful transfer from pediatric to adult care has its foundation in collaboration among the young adult, the family, and the health care system to support building skills in positive disease management and independent living. Systemic issues in transition from pediatric to adult care for individuals with SCD include limited access to adult providers with the skills and/or interest in caring for people with SCD; poor communication and follow-up between pediatric and adult providers; and insurance coverage and reimbursement for care coordination. Family and patient issues in transition include lack of skill development for successful transition into adulthood; absence of financial independence; fear of the unknown; and increasing morbidity with age. The design and evaluation of successful transition programming in SCD requires clarity in conceptual frameworks and consistent measurement, both before and after transfer to adult care. Strategies used by three SCD transition programs and future directions for research and program development are presented.
Loss of Phosphatase and Tensin Homolog Promotes Cardiomyocyte Proliferation and Cardiac Repair After Myocardial Infarction
Authors: Tian Liang, Feng Gao, Jun Jiang, Yao Wei Lu, Feng Zhang, Yingchao Wang, Ning Liu, Xuyang Fu, Xiaoxuan Dong, Jianqiu Pei, Douglas B. Cowan, Xinyang Hu, Jian’an Wang, Da-Zhi Wang, Jinghai Chen
Journal: Circulation (2020)
Multi-stakeholder consensus on a target product profile for an HIV cure
Authors: Sharon R Lewin, Timothy Attoye, Cathy Bansbach, Brian Doehle, Karine Dubé, Mark Dybul, Devi SenGupta, Adam Jiang, Rowena Johnston, Rosanne Lamplough, Joseph M McCune, Gary J Nabel, Thumbi Ndung'u, John Pottage, David Ripin, James F Rooney, Izukanji Sikazwe, Moses Nsubuga, Mitchell Warren, Steven G Deeks
Journal: The Lancet HIV (2020)

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures.
Medina(0,1,0)または(0,0,1)分岐部病変に対する口側および交差薬物溶出ステント留置術法の比較
Authors: Sakamoto Yasunari, Muramatsu Toshiya, Tsukahara Reiko, Itoh Yoshiaki, Sakai Tsuyoshi, Ishimori Hiroshi, Sasao Kenichiro, Hirano Keisuke, Nakano Masatsugu, Yamawaki Masahiro, Araki Motoharu, Katoh Tamon, Takimura Hideyuki, Komatsu Ikki, Takama Takurou
Journal: Circulation (2012)
RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis
Authors: Yoonsung Song, Sungsin Jo, Jee Young Chung, Younseo Oh, Subin Yoon, Young Lim Lee, Seong Su Kim, Jae-Hyuk Yang, Kiseok Jang, Chul-Su Yang, Tae-Hwan Kim, Yong-Hee Kim
Journal: Journal of Controlled Release (2020)
Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial
Authors: Stephen A Boorjian, Mehrdad Alemozaffar, Badrinath R Konety, Neal D Shore, Leonard G Gomella, Ashish M Kamat, Trinity J Bivalacqua, Jeffrey S Montgomery, Seth P Lerner, Joseph E Busby, Michael Poch, Paul L Crispen, Gary D Steinberg, Anne K Schuckman, Tracy M Downs, Robert S Svatek, Joseph Mashni, Brian R Lane, Thomas J Guzzo, Gennady Bratslavsky, Lawrence I Karsh, Michael E Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Tracey Krupski, Brant A Inman, Michael B Williams, Michael S Cookson, Kirk A Keegan, Gerald L Andriole, Alexander I Sankin, Alan Boyd, Michael A O'Donnell, David Sawutz, Richard Philipson, Ruth Coll, Vikram M Narayan, F Peter Treasure, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney
Journal: The Lancet Oncology (2020)
Myocardial Infarct Size Reduction With Pexelizumab: The Role of Chance Is Patently Clear⁎⁎Editorials published inJACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: C. Michael Gibson, Yuri B. Pride
Journal: JACC. Cardiovascular imaging (2010)
15920 Relationship of serum glucose to efficacy and safety of tildrakizumab treatment for psoriasis in patients with and without metabolic syndrome from reSURFACE 1 and reSURFACE 2
Authors: Mark G. Lebwohl, Alan Menter, Stephen J. Rozzo, Jeff Parno, Alan M. Mendelsohn, Nehal N. Mehta, Richard G. Langley
Journal: Journal of the American Academy of Dermatology (2020)
Hypergraph learning for identification of COVID-19 with CT imaging
Authors: Donglin Di, Feng Shi, Fuhua Yan, Liming Xia, Zhanhao Mo, Zhongxiang Ding, Fei Shan, Bin Song, Shengrui Li, Ying Wei, Ying Shao, Miaofei Han, Yaozong Gao, He Sui, Yue Gao, Dinggang Shen
Journal: Medical Image Analysis (2020)
192P A multicenter crossover analysis of first and second-line FOLFIRINOX or gemcitabine plus nab-paclitaxel administered to pancreatic cancer patients: Results from the NAPOLEON study
Authors: K. Nio, H. Iguchi, M. Shimokawa, T. Shirakawa, F. Koga, Y. Ueda, J. Nakazawa, A. Komori, S. Arima, M. Fukahori, A. Makiyama, H. Taguchi, T. Honda, T. Shibuki, Y. Ide, N. Ureshino, T. Mizuta, K. Mitsugi, T. Otsuka
Journal: Annals of Oncology (2020)
Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial
Authors: Rodney P Rocconi, Elizabeth A Grosen, Sharad A Ghamande, John K Chan, Minal A Barve, Jonathan Oh, Devansu Tewari, Peter C Morris, Erin E Stevens, Justin N Bottsford-Miller, Min Tang, Phylicia Aaron, Laura Stanbery, Staci Horvath, Gladice Wallraven, Ernest Bognar, Luisa Manning, John Nemunaitis, David Shanahan, Brian M Slomovitz, Thomas J Herzog, Bradley J Monk, Robert L Coleman
Journal: The Lancet Oncology (2020)