tbuckley/cabot-search huggingface dataset:
Abstract 246: Applying a Quantitative, Cell Surface Glycoproteomic Approach to Understanding the Role of Human Cardiac Fibroblasts in Advanced Heart Failure
Authors: Linda Berg Luecke, Amanda R Buchberger, Matthew Waas, Claudius Mahr, Rebekah L Gundry
Journal: Circulation Research (2019)

Heart Failure (HF) is a complex clinical syndrome defined by the heart’s inability to adequately perfuse the human body. The clinical progression of HF has been linked to the pathological activation of CF, which contributes to adverse remodeling and cardiac fibrosis. Previous studies have shown that unloading the failing heart via mechanical circulatory support devices contributes to reverse remodeling, improving both cardiac structure and function. However, despite the importance of CF in biology and disease, little is known regarding CF-specific mechanisms and functions during cardiac remodeling and reverse remodeling. Moreover, most human studies have relied on in vitro culture systems to investigate CF function, despite the fact that extended culturing leads to phenotypic changes in CF. Here, we apply state-of-the-art mass spectrometry approaches to discover and quantify cell surface and extracellular matrix (ECM) proteins to 1) develop an optimized CF culture system that allows for the preservation of their in situ phenotype and 2) study CF isolated from failing hearts, including failing hearts treated with mechanical circulatory support to identify novel targets for tracking and studying disease. To date, we have identified &gt;600 surface N- glycoproteins on primary human CF (n=12), including those with known relevance to CF ( e.g. BGN, BSG, FBN1) and those not previously described within CF ( e.g. HHIP, NFACS, GPNMB). In CF samples that were passaged ex vivo , cell surface and ECM N- glycoproteins that are associated with a phenotype switch ( e.g. COL5A1, ECM1, FBLN5, LAMB2) were detected and changes in their abundance correlated with increased expression of α-SMA. Our studies also identified cell surface and ECM proteins that have not been previously associated with the heart and those with known relevance to HF, cardiac remodeling and fibrosis ( e.g. BGN, GLUT8, ITGA11). Current efforts are underway to quantify surface proteins of interest to determine how their abundance changes during reverse remodeling in the context of HF. Overall, this work allowed for the development of an optimized CF culture system and revealed new cell-type specific molecular targets to study and track reverse remodeling in the context of advanced HF.
Abstract 407: Modeling Atrial Fibrillation in a Dish Using Atrial iPSC Derived Cardiomyocytes
Authors: Liang HONG, Meihong Zhang, Seock-Won Youn, Erin Lambers, Arvind Sridhar, Ambili Menon, Brandon Chalazan, Joseph C Wu, Jalees Rehman, Dawood Darbar
Journal: Circulation Research (2019)

Mutations in multiple genes have been linked with familial atrial fibrillation (AF) but the underlying pathophysiologic mechanisms and implications for therapy remain poorly understood. To characterize the electrophysiological phenotype of an AF-linked SCN5A mutation and assess novel mechanism-based therapies, we generated patient-specific atrial induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from a carrier with an SCN5A-E428K mutation and an unaffected family member using a differentiation protocol optimized for atrial differentiation generated atrial iPSC-CMs. The atrial iPSC-CMs carrying SCN5A-E428K displayed increased window and late Na+ current (INa,L), increased beating frequency and irregularity with triggered beats and prolongation of the action potential duration (APD) versus control atrial iPSC-CMs. The multi-electrode array (MEA) recordings of mutant atrial iPSC-CMs showed spontaneous arrhythmogenic activity with beat-to-beat irregularity. We further showed that targeted inhibition of the INa,L with ranolazine normalized the aberrant electrophysiologic phenotype in the SCN5A-E428K atrial iPSC-CMs and mexiletine reversed the sodium channel gating defects, and reduced beating frequency and irregularity. Our study illustrates the potential use of atrial iPSC-CMs for modeling AF in a dish, elucidating the underlying cellular mechanisms, and identifying novel mechanism-based therapies custom-tailored for individual patients.
Marker Chromosomes Are a New Cytogenetic Adverse Risk Factor in AML after Allo-HCT
Authors: Kyoko Fuse, Tomoyuki Tanaka, Shun Uemura, Tatsuya Suwabe, Takayuki Katagiri, Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tastuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko
Journal: Blood (2018)
Improving Nutrition to Save Lives
Authors: Bridget Kuehn
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 561: Bone Morphogenetic Protein-3b Deficiency Induces Metabolic Syndrome and Modulates Adipogenesis
Authors: Ingrid Marti-Pamies, Alex Caplan, Robrecht Thoonen, Wei Han, Patrick Seale, Emmanuel S Buys, Donald B Bloch, Marielle Scherrer-Crosbie
Journal: Circulation Research (2019)

Introduction: Bone morphogenetic proteins (BMPs) are mediators in a wide range of cellular functions, including the regulation of cell metabolism. The objective of this study was to investigate the effects of BMP-3b, a glycoprotein synthetized and secreted by adipose tissue, on cardiovascular risk factors. Methods: BMP-3b knock-out (KO) and age-matched male and female wild-type (WT) mice were weighed weekly until 6 months of age. At 6 months, fasting levels of total cholesterol, HDL-C and triglycerides were measured and glucose and insulin tolerance tests were performed. Telemetry was used to determine blood pressure and heart rate in anesthetized mice. Echocardiograms were performed under light sedation (isoflurane 1%). Mice were sacrificed and tissues were resected for gene expression analysis by qPCR. Transient transfections were performed in 3T3-L1 cells to study the interactions of BMP-3b and the C/ebp α promoter. Results: BMP3b KO mice gained more weight than WT mice. The plasma levels of total cholesterol, HDL and triglycerides were higher in BMP-3b KO mice than in WT mice. Insulin and glucose tolerant tests reveal insulin resistance and glucose intolerance in BMP-3b KO mice compared to WT mice. The basal heart rate was higher in BMP-3b KO mice than in WT mice, but no differences were observed in blood pressure. Echocardiography revealed a decrease in relative wall thickness (RWT) and left ventricular ejection fraction (LVEF), and an increase in the left ventricle end diastolic volume (LVEDV) in BMP-3b KO mice, demonstrating eccentric remodeling. Expression of genes ( Pparγ and C/ebpα ) involved in adipogenesis in white adipose tissue was higher in BMP-3b KO mice than in WT controls. Finally, transient transfection assays with 3T3-L1 cells showed that BMP-3b modulates C/ebpα promoter activity. Conclusions: The results of this study suggest that BMP-3b has an important role in the regulation of age-related weight gain, glucose metabolism and LV remodeling. Interventions that increase the level or function of BMP-3b may protect the heart from the adverse effects of cardiovascular risk factors and pathological cardiac remodeling.
Improving lung cancer screening in the HIV population.
Authors: Jose Nahun Galeas, Robert M. Grossberg, Maria Serrano, Anna Shmukler, Susan Sakalian, Vikas Mehta, Balazs Halmos, Stuart H. Packer
Journal: Journal of Clinical Oncology (2019)

69 Background: Lung cancer screening for high risk populations has a major impact in reducing mortality.In our population, HIV patients are younger (mean age 68.0 vs 56.8, p= 0.014) and have a higher percentage of advanced disease at diagnosis (49% vs 68%, p&lt; 0.001),when compared to non-HIV lung cancer patients.Due to this increased risk and aggressiveness, we embarked on a quality improvement initiative to increase screening in our HIV smoking population. Methods: Data was collected retrospectively from 10/18 to 1/19 in the HIV clinic. A multidisciplinary team was created involving thoracic oncologists, radiologists and HIV physicians to discuss methods to improve screening. We identified areas to be improved and utilized performance improvement tools such as a Pareto chart and PICK chart. Data was then collected prospectively. Results: In the initial 4 month period,among HIV positive patients 55–77 years old with significant smoking history, 13% (total n=54) of patients had a chest CT done for lung cancer screening and only 3.7% were referred for lung cancer screening during that specific period. Main barriers were lack of proper identification of screening candidates, discrepancies in smoking history within the EMR and lack of a consistent system for referral. An algorithm was created in the referral workflow, in which providers would need only to identify patients in the age group of 55-77 years old with any history of smoking and refer to a lung cancer screening program. The screening program would contact the patient and screen as per CMS guidelines. 17 Patients were referred from the HIV clinic from 4/8/19 to 5/2/19. Of these patients, 29% had a lung cancer screening CT scan done or scheduled, 18% of patients did not qualify for screening,and the remaining 53% of referrals are pending to be screened by telephone call. Further data on subsequent PDSAs and results of screening scans will be presented at the meeting. Conclusions: Modifying the screening algorithm for lung cancer in our HIV clinic by adding support from a dedicated screening program increased screening rates by 25% in the first month of intervention. Subsequent interventions include: patient education to reduce the stigma of lung cancer and EMR alerts when a patient meets criteria for screening.
Bendamustine Plus Rituximab Versus CHOP Plus Rituximab in the First-Line-Treatment of Patients with Follicular, Indolent and Mantle Cell Lymphomas: Results of a Randomized Phase III Study of the Study Group Indolent Lymphomas (StiL)
Authors: Mathias J Rummel, Ulrich von Gruenhagen, Norbert Niederle, Harald Ballo, Eckhart Weidmann, Manfred Welslau, Gerhard Heil, Christina Balser, Heinz A Duerk, Martina Stauch, Dorothea Kofahl-Krause, Ulrich Kaiser, Wolfgang Knauf, Wolfram Brugger
Journal: Blood (2008)
Genome Wide-DNA Profiling of HIV-Related Non-Hodgkin Lymphomas: Implications for Disease Pathogenesis and Histogenesis.
Authors: Francesco Bertoni, Giulia Poretti, Daniela Capello, Ivo Kwee, Clara Deambrogi, Annunziata Gloghini, Luigi Maria Larocca, Andrea Rinaldi, Davide Rossi, Emanuele Zucca, Antonino Carbone, Gianluca Gaidano
Journal: Blood (2007)
Pre-Transplant Minimal Residual Disease Detected by Multiparameter Flow Cytometric Analysis Predicts for Disease Relapse in Adult Patients with Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Stem Cell transplantation
Authors: Yi Zhou, Jeffrey L. Jorgensen, Rima M Saliba, Sa A. Wang, Gabriela Rondon, Celina Ledesma, Borje S Andersson, Marcos J de Lima, Elizabeth J Shpall, Uday Popat, Stefan O Ciurea, Amin M Alousi, Muzaffar Qazilbash, Chitra M Hosing, L. Jeffrey Medeiros, Richard Champlin, Partow Kebriaei
Journal: Blood (2011)
Global Chromatin Occupancy and Epigenetic Signature Analysis Reveal New Insights into the Function of GATA1 N-Terminus in Erythropoiesis
Authors: Te Ling, Yehudit Birger, Monika Stankiewicz, Nissim Ben-Haim, Itamar Kanter, Tomer Kalisky, Avigail Rein Gil, Neil L Kelleher, Lihua Zou, Shai Izraeli, John D. Crispino
Journal: Blood (2018)
Improve education, housing, and transport to boost young people’s health, inquiry concludes
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The UK government must overhaul housing, transport, and education policies that are currently putting young people at serious risk of ill health later in life, an independent inquiry has concluded.1

The report by the Health Foundation, produced after a major two year inquiry into young people’s future health, concludes that it is harder for young people in 2019 to access the things need to ensure their future health.

Factors such as a tough housing market, a job market where young people struggle to …
Ultrathin Strut Stents in Small Coronary Vessels—Are We There Yet?—Reply
Authors: Rosaly A. Buiten, Eline H. Ploumen, Clemens von Birgelen
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
New Paradigms in Cell Therapy
Authors: Marcin Wysoczynki, Abdur Khan, Roberto Bolli
Journal: Circulation Research (2018)

Perhaps the most important advance in the field of cell therapy for heart disease has been the recognition that all stem/progenitor cells (both adult and embryonic) fail to engraft in the heart to a significant extent and thus work via paracrine mechanisms. This fundamental advance has led to 4 new paradigms that are discussed in this review and that may importantly shape, or even revolutionize, the future of the field: (1) repeated cell therapy, (2) intravenous cell therapy, (3) immunomodulatory actions of cell therapy, and (4) new cell types. Because virtually all of our current knowledge of cell therapy is predicated on the effects of a single cell dose, the idea that the full therapeutic effects of a cell product require repeated doses is disruptive and has far-reaching implications. For example, inadequate dosing (single-dose protocols) may be responsible, at least in part, for the borderline or disappointing results obtained to date in clinical trials; furthermore, future studies (both preclinical and clinical) may need to incorporate repeated cell administrations. Another disruptive idea, supported by emerging preclinical and clinical evidence, is that intravenously injected cells can produce beneficial effects on the heart, presumably via release of paracrine factors in extracardiac organs or endocrine factors into the systemic circulation. Intravenous administration would obviate the need for direct delivery of cells to the heart, making cell therapy simpler, cheaper, safer, more scalable, and more broadly available, even on an outpatient basis. Although the mechanism of action of cell therapy remains elusive, there is compelling in vitro evidence that transplanted cells modulate the function of various immune cell types via release of paracrine factors, such as extracellular vesicles, although in vivo evidence is still limited. Investigation of the new paradigms reviewed herein should be a top priority because it may profoundly transform cell therapy and finally make it a reality.
Development Assistance for Health in Low-Income Countries—Reply
Authors: Joseph L. Dieleman, Angela E. Micah
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reasons for Increases in Complications of Diabetes—Reply
Authors: Edward W. Gregg, Israel Hora, Stephen Benoit
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 405: Functional Maturation of Human iPSC-Derived Cardiomyocytes by Prolonged 3D Culture in Engineered Cardiac Tissue Constructs
Authors: Willem J De Lange, Stanford D Mitchell, Caroline D Kreitzer, Emily T Farrell, Ying Ge, J C Ralphe
Journal: Circulation Research (2019)

The advent of human induced pluripotent stem cell (hiPSC) technology has revolutionized the way we study inherited diseases, as it allows us to study the effect of mutations in a human context. This is particularly true in the heart were species-specific differences has dramatic effects on heart rate, and expression of protein isoforms involved in excitation-contraction coupling. A major drawback of using hiPSCs is, however that cardiomyocytes derived from hiPSC (hiPSC-CM) are relatively immature, limiting their utility as a tool to study adult onset cardiac diseases. We postulated that culturing hiPSC-CM in a 3D environment in engineered cardiac tissue constructs (ECT) would promote hiPSC-CM maturation. ECTs were generated from lactate-selected day 30 hiPSCs that were mixed with isogenic hiPSC derived cardiac fibroblasts in a 10:1 ratio. Cells were mixed with fibrinogen and thrombin and seeded into molds under vacuum in FlexCell dishes to form ECT. ECTs were harvested 14-21 or 42-52 days later and subjected to functional testing, transcriptional analysis and top-down mass-spectrometry of sarcomeric proteins to assess maturation. Functionally, we found that prolonged culture of hiPSCs in ECT resulted in increased calcium transient amplitude (0.856 vs. 0.462; P &lt; 0.01) and an acceleration of calcium kinetics (calcium release time 67.7 ms vs. 109.3 ms; P &lt; 0.01 and calcium decay time 148.3 ms vs. 188.0 ms; P &lt; 0.05). This acceleration of calcium kinetics with time in culture was also true for twitch force kinetics (time to peak twitch force 178.6 ms vs. 208.0 ms; P &lt; 0.05). Furthermore, beta adrenergic stimulation had a much greater effect on twitch kinetics in older ECTs (reduction in contraction time of 26.5% vs. 7.1%; P &lt; 0.01). Transcriptional analysis revealed an increase in expression level of the beta 1 adrenergic receptor in older ECTs, while top-down mass spectrometry showed increased expression and phosphorylation of cardiac troponin I (cTnI) and mono-phosphorylated cTnI, as well as decreased phosphorylation of alpha-tropomyocin, all markers of myocardial maturation. Taken together, these data supports our hypothesis that prolonged culture of hiPSC-CM in ECT promotes maturation of the calcium handling system and the contractile apparatus.
Programmed Cell Death Receptor (PD-1), PD-1 Ligand (PD-L1) Expression and Myeloid Derived Suppressor Cells (MDSC) In Myeloid Neoplasms Implicate The Mechanism Of IMiD Treatment Of Myelofibrosis
Authors: Ajay Kundra, Stacey Baptiste, Chi Chen, Hemant Sindhu, Jen-Chin Wang
Journal: Blood (2013)
The Determination of Cardiac Output by a Continuous Recording System Utilizing Iodinated (I <sup>131</sup> ) Human Serum Albumin
Authors: WILLIAM J. MACINTYRE, WALTER H. PRITCHARD, RICHARD W. ECKSTEIN, HYMER L. FRIEDELL
Journal: Circulation (1951)

A method is outlined for the determination of cardiac output by the injection of iodinated (I 131 ) human serum albumin and continuous recording of the dilution curve. The calibration of the flow system by means of the final dilution and blood volume is discussed along with the possible application to an external measuring method. The results of eight dilution curves obtained from dogs are presented and the calculated cardiac outputs compared with the values measured by the rotameter method.
Gemtuzumab Ozagamicin Is Well Tolerated as Post-Consolidation Therapy in Childhood AML.
Authors: Henrik Hasle, Jonas Abrahamsson, Niels Clausen, Erik Forestier, Göran Gustafsson, Jesper Heldrup, Liisa Hovi, Kirsi Jahnukainen, Gudmundur Jonmundsson, Josefine Palle, Bernward Zeller
Journal: Blood (2007)