tbuckley/cabot-search huggingface dataset:
Clinical trial design and new therapies for pulmonary arterial hypertension
Authors: Olivier Sitbon, Mardi Gomberg-Maitland, John Granton, Michael I. Lewis, Stephen C. Mathai, Maurizio Rainisio, Norman L. Stockbridge, Martin R. Wilkins, Roham T. Zamanian, Lewis J. Rubin
Journal: European Respiratory Journal (2018)

Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.
Diagnosis of pulmonary hypertension
Authors: Adaani Frost, David Badesch, J. Simon R. Gibbs, Deepa Gopalan, Dinesh Khanna, Alessandra Manes, Ronald Oudiz, Toru Satoh, Fernando Torres, Adam Torbicki
Journal: European Respiratory Journal (2018)

A revised diagnostic algorithm provides guidelines for the diagnosis of patients with suspected pulmonary hypertension, both prior to and following referral to expert centres, and includes recommendations for expedited referral of high-risk or complicated patients and patients with confounding comorbidities. New recommendations for screening high-risk groups are given, and current diagnostic tools and emerging diagnostic technologies are reviewed.
Pembrolizumab in Patients with Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL): Data from the Keynote-013 and Keynote-170 Studies
Authors: Philippe Armand, Scott J Rodig, Vladimir Melnichenko, Catherine Thieblemont, Krimo Bouabdallah, Gayane Tumyan, Muhit Özcan, Sergio Portino, Laura Fogliatto, Dolores Caballero, Jan Walewski, Zafer Gulbas, Vincent Ribrag, Beth A. Christian, Guilherme Fleury Perini, Gilles Andre Salles, Jakub Svoboda, Jasmine M. Zain, Sanjay S Patel, Pei-Hsuan Chen, Azra H. Ligon, Jing Ouyang, Donna S Neuberg, Robert A. Redd, Arkendu Chatterjee, Robert J Orlowski, Arun Balakumaran, Margaret A. Shipp, Pier Luigi Zinzani
Journal: Blood (2018)
Association of Chemoradiotherapy With Outcomes Among Patients With Stage I to II vs Stage III Small Cell Lung Cancer
Authors: Ahmed Salem, Hitesh Mistry, Matthew Hatton, Imogen Locke, Isabelle Monnet, Fiona Blackhall, Corinne Faivre-Finn
Journal: JAMA Oncology (2018)

There is limited evidence to guide stage I to II small cell lung cancer (SCLC) treatment.
Abstract 11584: Upright T Waves in Lead aVR are Associated with Cardiac Death or Hospitalization for Heart Failure in Prior Myocardial Infarction
Authors: Akira Tamura, Kumie Torigoe, Yoshiyuki Kawano, Kazuhiro Shinozaki, Munenori Kotoku, Junichi Kotoku
Journal: Circulation (2011)

Background: A previous study demonstrated that the upright T wave (amplitude >0 mV) in lead aVR may be a useful marker for predicting cardiovascular mortality. However, the prognostic significance of the wave in lead aVR has not yet been investigated in myocardial infarction (MI). Methods: We examined the prognostic significance of upright T waves in lead aVR in 167 patients with prior MI. The primary end point was cardiac death or hospitalization for heart failure. Results: During a follow-up period of 6.5 ± 2.8 years, 34 patients developed the primary end point. A Kaplan-Meier analysis showed that the primary event-free rate was lower in 27 patients with upright T waves in lead aVR than in 140 patients without the waves in lead aVR (p = 0.001). Univariate Cox proportional hazards regression analyses showed that age, male gender, chronic kidney disease, anterior wall MI, upright T waves in lead aVR, left ventricular ejection fraction, loop diuretic use, and spironolactone use were significantly associate...
Retraction: Inactivation of the Quinone Oxidoreductases NQO1 and NQO2 Strongly Elevates the Incidence and Multiplicity of Chemically Induced Skin Tumors
Authors: Jun Shen, Roberto J. Barrios, Anil K. Jaiswal
Journal: Cancer Research (2018)

This article (1) has been retracted at the request of the editors. Following an institutional investigation by the University of Maryland, Baltimore (Baltimore, MD), it was determined that data were falsified to generate the graphs presented in Figs. 2C and D and 3. As a result of these findings, the institution recommended retraction and, upon internal review, the editors agreed with this recommendation.A copy of this Retraction Notice was sent to the last known email address for one of the three authors. One author (A.K. Jaiswal) did not respond; the two remaining authors (J. Shen and R.J. Barrios) could not be located.
Abstract 18689: Lower Carotid Artery Compliance and Greater Carotid β-stiffness Index are Associated With Slower Processing Speed and Reduced Working Memory Performance in Older Healthy Adults
Authors: Lyndsey E DuBose, Michelle W Voss, Timothy B Weng, Kaitlyn M Dubishar, Abbi Lane-Cordova, Gardar Sigurdsson, Phillip Schmid, Gary L Pierce
Journal: Circulation (2015)

Introduction: Higher central elastic artery stiffness is associated with greater brain white matter hyperintensity volume and lower cognitive performance in older adults. However, it is unknown if higher central artery stiffness is related to regional decreases in brain white matter integrity (WMI) and reductions in working memory or processing speed. We hypothesized that greater large elastic artery stiffness would be associated with lower working memory and slower processing speed as well as lower regional WMI in older adults. Methods: In young (n=19; 23.8 ± 0.7 yrs) and older (n=22; 64.4 ± 4.2 yrs; range 60-71 yrs) healthy adults, aortic stiffness (carotid-femoral pulse wave velocity, cfPWV, via tonometry) and carotid artery compliance and β-stiffness index (carotid artery ultrasound and tonometry) were determined non-invasively. WMI was assessed by fractional anisotrophy (FA) (3T MRI) from diffusion tensor images. An N-Back task and letter and pattern comparison tests were performed as measures of working memory and processing speed, respectively. d’Prime, a measure of signal detection, was calculated on the N-Back task as a ratio of positive ‘hits’ to ‘false alarm’ responses. Results: cfPWV (8.4 ± 0.5 vs. 5.2 ± 0.2 m/sec, P&lt;0.01) and carotid β-stiffness (11.3 ± 0.9 vs. 6.1 ± 0.7 U, P&lt;0.01) were greater and carotid compliance (0.16 ± 0.02 vs. 0.07 ± 0.01 mm/mmHg, P&lt;0.01) was lower in older vs. young adults. Carotid β, but not aortic, stiffness was associated with slower processing speed on letter (10.7 ± 0.5 vs. 13.5 ± 0.6 units/ 30 sec, p&lt;0.01) and pattern (16.6 ± 0.6 vs. 22.0 ± 0.7 units/30 sec, p&lt;0.01) comparison tasks and reduced working memory (1.8 ± 0.2 vs. 3.1± 0.2, P&lt;0.01) in older vs. young adults. Lower carotid compliance was associated with slower performance on the letter (r=0.55, P&lt;0.01) and pattern (r=0.54, P&lt;0.01) tests and lower d’Prime (r=0.48, P&lt;0.05). Greater β-stiffness was related to pattern comparison scores only (r=-0.54, P&lt;0.01). Aortic stiffness, carotid compliance and β-stiffness were not related to WMI in any brain region. Conclusions: Our results suggest that lower carotid artery compliance and greater β-stiffness are associated with reduced working memory performance and slower processing speed but not regional WMI in older adults.
Astrocytes and microglia: Models and tools
Authors: Kevin A. Guttenplan, Shane A. Liddelow
Journal: The Journal of Experimental Medicine (2018)

Glial cells serve as fundamental regulators of the central nervous system in development, homeostasis, and disease. Discoveries into the function of these cells have fueled excitement in glial research, with enthusiastic researchers addressing fundamental questions about glial biology and producing new scientific tools for the community. Here, we outline the pros and cons of in vivo and in vitro techniques to study astrocytes and microglia with the goal of helping researchers quickly identify the best approach for a given research question in the context of glial biology. It is truly a great time to be a glial biologist.
Prevention of Arrhythmia Device Infection Trial
Authors: Andrew D. Krahn, Yves Longtin, François Philippon, David H. Birnie, Jaimie Manlucu, Paul Angaran, Claus Rinne, Benoit Coutu, R. Aaron Low, Vidal Essebag, Carlos Morillo, Damian Redfearn, Satish Toal, Giuliano Becker, Michel Degrâce, Bernard Thibault, Eugene Crystal, Stanley Tung, John LeMaitre, Omar Sultan, Matthew Bennett, Jamil Bashir, Felix Ayala-Paredes, Philippe Gervais, Leon Rioux, Martin E.W. Hemels, Leon H.R. Bouwels, Bob van Vlies, Jia Wang, Derek V. Exner, Paul Dorian, Ratika Parkash, Marco Alings, Stuart J. Connolly
Journal: Journal of the American College of Cardiology (2018)
Vascular Endothelial Growth Factor Receptor 3 Regulates Endothelial Function Through β-Arrestin 1
Authors: Zhiyuan Ma, Yen-Rei Yu, Cristian T. Badea, Jeffrey J. Kovacs, Xinyu Xiong, Suzy Comhair, Claude A. Piantadosi, Sudarshan Rajagopal
Journal: Circulation (2019)

Receptor signaling is central to vascular endothelial function and is dysregulated in vascular diseases such as atherosclerosis and pulmonary arterial hypertension (PAH). Signaling pathways involved in endothelial function include vascular endothelial growth factor receptors (VEGFRs) and G protein-coupled receptors, which classically activate distinct intracellular signaling pathways and responses. The mechanisms that regulate these signaling pathways have not been fully elucidated and it is unclear what nodes for cross talk exist between these diverse signaling pathways. For example, multifunctional β-arrestin (ARRB) adapter proteins are best known as regulators of G protein-coupled receptor signaling, but their role at other receptors and their physiological importance in the setting of vascular disease are unclear.We used a combination of human samples from PAH, human microvascular endothelial cells from lung, and Arrb knockout mice to determine the role of ARRB1 in endothelial VEGFR3 signaling. In addition, a number of biochemical analyses were performed to determine the interaction between ARRB1 and VEGFR3, signaling mediators downstream of VEGFR3, and the internalization of VEGFR3.Expression of ARRB1 and VEGFR3 was reduced in human PAH, and the deletion of Arrb1 in mice exposed to hypoxia led to worse PAH with a loss of VEGFR3 signaling. Knockdown of ARRB1 inhibited VEGF-C-induced endothelial cell proliferation, migration, and tube formation, along with reduced VEGFR3, Akt, and endothelial nitric oxide synthase phosphorylation. This regulation was mediated by direct ARRB1 binding to the VEGFR3 kinase domain and resulted in decreased VEGFR3 internalization.Our results demonstrate a novel role for ARRB1 in VEGFR regulation and suggest a mechanism for cross talk between G protein-coupled receptors and VEGFRs in PAH. These findings also suggest that strategies to promote ARRB1-mediated VEGFR3 signaling could be useful in the treatment of pulmonary hypertension and other vascular disease.
Chemotherapy sensitization of glioblastoma by focused ultrasound-mediated delivery of therapeutic liposomes
Authors: Alexandros Papachristodoulou, Rea Deborah Signorell, Beat Werner, Davide Brambilla, Paola Luciani, Mustafa Cavusoglu, Joanes Grandjean, Manuela Silginer, Markus Rudin, Ernst Martin, Michael Weller, Patrick Roth, Jean-Christophe Leroux
Journal: Journal of Controlled Release (2018)
Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter study
Authors: Juliana Yang, Yen-I Chen, Shai Friedland, Ian Holmes, Christopher Paiji, Ryan Law, Amy Hosmer, Tyler Stevens, Franco Matheus, Rishi Pawa, Nihar Mathur, Divyesh Sejpal, Sumant Inamdar, Tyler M. Berzin, Christopher J. DiMaio, Sanchit Gupta, Patrick S. Yachimski, Andrea Anderloni, Alessandro Repici, Theodore James, Laith H. Jamil, Mel Ona, Simon K. Lo, Srinivas Gaddam, Markus Dollhopf, Nuha Alammar, Eugenie Shieh, Majidah Bukhari, Vivek Kumbhari, Vikesh Singh, Olaya Brewer, Omid Sanaei, Lea Fayad, Saowanee Ngamruengphong, Eun Ji Shin, Todd H. Baron, Mouen A. Khashab
Journal: Endoscopy (2018)

Abstract Background Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs). Methods We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery. Results Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31). Conclusion When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events.
Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity
Authors: Bradley P. Coe, Holly A. F. Stessman, Arvis Sulovari, Madeleine R. Geisheker, Trygve E. Bakken, Allison M. Lake, Joseph D. Dougherty, Ed S. Lein, Fereydoun Hormozdiari, Raphael A. Bernier, Evan E. Eichler
Journal: Nature Genetics (2018)
Selective Autophagy Regulates Cell Cycle in Cancer Therapy
Authors: Kai Zheng, Zhendan He, Kaio Kitazato, Yifei Wang
Journal: Theranostics (2018)

Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment.Indeed, survival of many cancers exclusively relies on these proteins, and several specific inhibitors are in clinical use.Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery.However, these studies have often led to divergent rather than unifying explanations due to complexity of the autophagy signaling network, the inconsistent functions between general autophagy and selective autophagy, and the different characteristics of autophagic substrates.In this review, we highlight current data illustrating the contradictory and important role of cell cycle proteins in regulating autophagy.We also focus on how selective autophagy acts as a central mechanism to maintain orderly DNA repair and genome integrity by degrading specific cell cycle proteins, regulating cell division, and promoting DNA damage repair.We further discuss the ways in which selective autophagy may impact the cell cycle regulators, since failure to appropriately remove these can interfere with cell death-related processes, including senescence and autophagy-related cell death.Imbalanced cell proliferation is typically utilized by cancer cells to acquire resistance.Finally, we discuss the possibility of a potent anticancer therapeutic strategy that targets selective autophagy or autophagy and cell cycle together.
Role of Signal Transducing Adaptor Protein-1 (STAP-1) in Chronic Myelogenous Leukemia Stem Cells
Authors: Jun Toda, Michiko Ichii, Hirohiko Shibayama, Hideaki Saito, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Kodai Saitoh, Tadashi Matsuda, Kenji Oritani, Yuzuru Kanakura
Journal: Blood (2018)
Left Ventricular Assist Devices
Authors: Jason J. Han, Michael A. Acker, Pavan Atluri
Journal: Circulation (2018)

Ventricular assist device has rapidly emerged as a durable and safe therapy for end-stage heart failure patients with &gt;22 000 implantations to date. Though originally conceived for bridge-to-transplant indication, significant advancements in medical management as well as technology with arrivals of newer generation devices have improved patient outcomes, leading to increasing use as destination therapy. Despite such improvement, however, the burden of adverse events remains significant and defines the most pressing issue in the current state of ventricular assist device therapy. Eventual use of ventricular assist device technology as a comparable alternative to heart transplantation will ultimately rely on our ability to mitigate these risks. Therefore, this review article provides the narrative surrounding the rapid integration of this technology into the heart failure paradigm, specifically in the context of the most recent data on its outcomes and adverse event profiles. It describes ongoing investigations and general trends that may have significant implications for future improvements in device-related outcomes, as the field continues to grow as the epitome of synergy between advancements in engineering and clinical medicine.
Striking differences of distinct endothelial progenitor cell subtypes in coronary collateral formation and ischemia-mediated neovascularization: implications for therapeutic angiogenesis
Authors: Sui Ching G. Yuen, Kim H. Chan, Philippa Simpson, Zoe Clayton, Ashanti Dantanarayana, Laura Lecce, Louise Dunn, Andy Yong, Chi-Jen Hsu, Matt Guillou, Shisan Bao, Chirapan Chanwantanpipat, David Celermajer, Joseph Wu, Martin Ng
Journal: Circulation (2014)

Endothelial progenitor cells (EPCs) are strongly implicated in angiogenesis. However, results from EPC clinical trials have been underwhelming and contradictory, possibly due to the use of unselected cell populations. Two distinct EPC subtypes (early EPCs and late-outgrowth endothelial cells, OECs) have been found to exhibit different angiogenic properties in vitro but have rarely been compared in vivo. To investigate, we compare EPC properties in patients with CAD and murine models. In patients with single-vessel CAD involving the left anterior descending artery (n=26, age=63±10, male=81%) a positive correlation was found between the extent of coronary collateralization (invasively assessed) and OEC numbers (r=0.405,p=0.045), migration (r=0.578,p=0.006) and tubulogenesis (r=0.65,p=0.005). Patients with adequate vs inadequate collateralization (CFI≥0.25 vs <0.25) had better OEC characteristics (p<0.02). No correlation was found with early EPCs. Consistent with this, xenotransplantation of human OECs enhan...
In at-risk medical patients, rivaroxaban after discharge did not reduce symptomatic or fatal VTE at 45 days
Authors: Andrew Dunn, Henry S. Sacks
Journal: Annals of Internal Medicine (2018)

ACP Journal Club18 December 2018In at-risk medical patients, rivaroxaban after discharge did not reduce symptomatic or fatal VTE at 45 daysAndrew Dunn, MD, MPH, MACP, SFHM, Henry S. Sacks, PhD, MD, FACPAndrew Dunn, MD, MPH, MACP, SFHMIcahn School of Medicine at Mount Sinai, New York, New York, USA (A.D., H.S.S.)Search for more papers by this author, Henry S. Sacks, PhD, MD, FACPIcahn School of Medicine at Mount Sinai, New York, New York, USA (A.D., H.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-12-064 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSpyropoulos AC, Ageno W, Albers GW, et al; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med. 2018;379:1118-27. https://pubmed.ncbi.nlm.nih.gov/30145946Clinical Impact RatingsHospitalists: Cardiology: Infectious Disease: Neurology: Pulmonology: References1 Amin AN, Varker H, Princic N, et al. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med. 2012;7:231-8. [PMID: 22190427] Google Scholar2 Cohen AT, Harrington RA, Goldhaber SZ, et al; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-44. [PMID: 27232649] Google Scholar3 Cohen AT, Spiro TE, Büller HR, et al; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513-23. [PMID: 23388003] Google Scholar Author, Article, and Disclosure InformationAffiliations: Icahn School of Medicine at Mount Sinai, New York, New York, USA (A.D., H.S.S.)This article was published at Annals.org on 4 December 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 December 2018Volume 169, Issue 12Page: JC64KeywordsAnticoagulantsChronic obstructive pulmonary diseaseHazard ratioHemorrhageHospitalizationsInfectious diseasesProphylaxisSafetyUpper respiratory tract infectionsVenous thromboembolism ePublished: 18 December 2018 Issue Published: 18 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prognostic Model of Successful Tyrosine Kinase Inhibitors Discontinuation Based on the Russian RU-SKI Multicenter Prospective Study
Authors: Oleg Shukhov, Ekaterina Chelysheva, Anna Petrova, Anastasiya Bykova, Irina Nemchenko, Galina Gusarova, Eduard Gemdzhian, Anna G Turkina
Journal: Blood (2018)
Regression of Epithelial Cancers Following T Cell Receptor Gene Therapy Targeting Human Papillomavirus-16 E7
Authors: Scott Michael Norberg, Nisha Nagarsheth, Stacey Doran, Jennifer A Kanakry, Sabina Adhikary, Colleen Schweitzer, Stephanie H Astrow, William Faquin, Nikolaos Gkitsas, Steven Highfill, Christian S Hinrichs
Journal: Blood (2018)
Slc12a8 is a nicotinamide mononucleotide transporter
Authors: Alessia Grozio, Kathryn F. Mills, Jun Yoshino, Santina Bruzzone, Giovanna Sociali, Kyohei Tokizane, Hanyue Cecilia Lei, Richard Cunningham, Yo Sasaki, Marie E. Migaud, Shin-ichiro Imai
Journal: Nature Metabolism (2018)