tbuckley/cabot-search huggingface dataset:
Abstract 304: Pgc1a Activation by Pterostilbene Ameliorates Acute Doxorubicin Cardiotoxicity via Reducing Mitochondrial Oxidative Stress Through Enhancing Ampk and Sirt1 Cascades
Authors: Dong Liu, Shubin Qiao, Jiansong Yuan
Journal: Circulation Research (2019)

Background: Doxorubicin (DOX) is a widely used and potent anticancer agent, but DOX dose-dependently induced cardiotoxicity greatly limits its use in clinic. Pterostilbene, a natural analog of resveratrol, is a known antioxidant and exerts myocardial protection. The present study explored the actions and detailed mechanisms of pterostilbene on DOX-treated cardiomyocytes. Experimental Approach: We investigated the effects of pterostilbene on established acute DOX-induced cardiotoxicity models in both H9c2 cells treated with 1 μM DOX and C57BL/6 mice with DOX (20 mg/kg cumulative dose) exposure. Cell viability, ATP content, oxidative parameters, transmission electron microscopy, western blot analyses were respective performed. AMPK and SIRT1 siRNA, Compound C and EX527 treatment were further conducted to elucidate the underlying mechanism about the involvement of AMPK, SIRT1 and PGC1α cascades. Key Results: Pterostilbene markedly upregulated the cell viability and ATP content in DOX-treated H9c2 cells. Both in vitro and in vivo studies revealed that pterostilbene inhibited the acute DOX exposure-caused oxidative stress and mitochondrial morphological disorder via the PGC1α upregulation through activating AMPK and via PGC1α deacetylation through enhancing SIRT1. However, these effects were partially reversed by knockdown of AMPK or SIRT1 in vitro and treatment of Compound C or EX527 in vivo . Conclusion and Implications: Our results indicate that pterostilbene protects cardiomyocytes from acute DOX exposure-induced oxidative stress and mitochondrial damage via PGC1α upregulation and deacetylation through activating AMPK and SIRT1 cascades.
Abstract 603: Differential Proteoform Regulation in Cardiac Aging
Authors: Erin Yu Han, Rushita Bagchi, Edward Lau, Maggie PY Lam
Journal: Circulation Research (2019)

Background: The aging heart is prone to diseases and injuries, and is associated with changes in gene expression and alternative splicing. The goal of our study is to identify changes in protein isoforms in cardiac aging and explore their roles in age-related processes. Methods: Left ventricles (LV) from young (12 weeks) and old (78 weeks) C57BL/6J mice (male and female) were collected and stored at -80 °C until use. LV proteins were extracted, reduced, and alkylated. Proteins were digested with trypsin or chymotrypsin and the tryptic or chymotryptic peptides were desalted using C18 spin columns followed by injection into an Easy-nLC 1200 liquid chromatography system coupled to a high-resolution Q-Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometer for LC-MS/MS analysis. To quantify isoform expression, MS spectra were searched against a custom peptide isoform database generated from a publicly available ENCODE RNAseq dataset (accession ENCSR000BYQ) on normal C57BL/6J heart (8 weeks) through an in-house computational workflow. Protein isoform expression was compared between the young and old heart samples. Results: Our experiments identified over 1,200 proteins (FDR &lt; 0.05) in young and aged mouse LV tissue, including 65 isoform-specific tryptic and chymotryptic peptide sequences originating from 45 alternatively spliced genes that are not currently documented in the commonly utilized protein sequence database SwissProt. The detected protein isoforms include TMED2, TOM1 and TACC2. Our preliminary analysis suggests widespread proteome changes between young and aged hearts, which may have implication on energetics and fibrotic changes in cardiac aging. Conclusion: We report the first large-scale survey on the expression of canonical and alternative protein isoforms in the aging LV proteome. The identification of age-associated alternative isoforms suggests a potential mechanism for protein function regulation in the aging heart and may have implications for age-related disease processes.
Got stage fright? A fellow-led initiative to improve cancer staging documentation.
Authors: Ana I. Velazquez Manana, Rahul Banerjee, Swetha Kambhampati, Anna Parks, Sam Brondfield, Claire Mulvey, Pelin Cinar
Journal: Journal of Clinical Oncology (2019)

310 Background: Accurate cancer staging is essential for estimating prognosis, guiding treatment, populating cancer registries, and assessing clinical trial eligibility. Hence, timely staging of new solid oncology patients (NSOP) is an ASCO QOPI priority. At our institution, baseline review of staging documentation revealed fellows staged only 47% of NSOP, generally as unstructured free text. During the 2017-18 academic year, our structured electronic medical record (EMR) staging tool (ST) was used in only 11% of NSOP. We used Quality Improvement (QI) methods to improve structured EMR staging documentation rates of NSOP seen by fellows during the 2018-19 academic year. Methods: A fellow focus group identified poor integration of the EMR ST as root cause of our low staging rates. We set a cumulative goal of 70% structured EMR staging of NSOP within 1 month of initial visit as our target (50% increase from baseline). We incorporated the EMR ST into our visit workflow and used promotional flyers and fellow orientation to introduce our QI initiative. Staging rates were tracked by EMR-generated reports. We used periodic emails and QI-specific boards to disseminate progress among our oncology practices. Fellows were anonymously surveyed for feedback. Results: Over an 8-month period, the cumulative rate of NSOP staging by fellows increased from 47% to 70% (Table). Statistical process control analysis showed special-cause variation in July 2018 (low performance) and December 2018 (high performance). Fellow feedback highlighted the educational value of this QI intervention and identified incomplete workup as a barrier to staging. Conclusions: Our fellow-led QI intervention achieved our goal of leveraging an existing EMR tool to increase staging documentation. In addition, this QI intervention facilitated fellow education and use of data for clinical and research purposes. Future steps include ensuring sustainability and expansion into our hematology clinics. [Table: see text]
Abstract 313: Inhibition of Resistin Protects against Heart Failure Injury by Targeting Gadd45α
Authors: Baoyin Zhao, Djamel Lebeche
Journal: Circulation Research (2019)

Background: Resistin is an adipocyte-secreted hormone, increased Resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. However, the role of Resistin in heart failure is still unclear. The aim of the present study is to investigate the molecular mechanisms underlying Resistin’s action in heart failure. Methods: C57BL/6 (WT) and Resistin knockout (RKO) mice were used. A mice transverse aortic constriction (TAC) induced heart failure model was established, and cardiac function and hemodynamic changes were measured by echocardiography and left ventricular pressure volume loops. A recombinant adeno-associated virus 9 (AAV9) vector was used to deliver resistin gene into the myocardium. RNA sequence was used to determine differentially expressed mRNA in heart from RKO and WT mice subjected to TAC or sham surgeries. Quantitative real-time PCR (qRT-PCR) and Western blot analyses were used to verify the expression levels of various fibrosis-related factors (collagen I, Fibronectin, and CTGF) and hypertrophy-related markers (ANF, β-MHC and Acta1). Results: Resistin inhibition attenuated while resistin overexpression (via AAV9-Resistin) exacerbated TAC-induced hypertrophy and cardiac dysfunction in WT and Resistin KO mice. Improvement in cardiac function was associated with decreased myocardial fibrosis as evidenced by histology and decreased mRNA levels of collagen I, fibronectin and CTGF in RKO-TAC hearts compared to WT or RKO-AAV9. In addition, myocardial tissue expression levels of ANF, β-MHC and Acta1 were also reduced in the RKO-TAC hearts. RNA sequencing analysis reveals that Gadd45a was significantly increased in RKO-TAC mice. The expression level of Gadd45a was verified by qRT-PCR and Western blot. Gadd45a expression was significantly downregulated in the RKO-TAC hearts following AAV9-Resistin delivery, suggesting that Resistin may control the regulation of Gadd45a. Conclusions: Resistin gene knockout increased Gadd45a expression in mouse model of heart failure, significantly reduced myocardial fibrosis and hypertrophy and improved heart function. The results of this study indicate that inhibition of resistin is a potential therapeutic method for treating heart failure.
Reactivation of Hepatitis B Virus Infection in Aplastic Anemia Patients Receiving Immunosuppressive Therapy
Authors: Hua Yin, Suli Wang, Xingyu Lu, Wenyi Shen, Ruinan Lu, Yu Zhu, Kourong Miao, Ming Hong, Shuai Wang, Jianfu Zhang, Chun Qiao, Yujie Wu, Xuemei Wu, Guangsheng He, Jianyong Li
Journal: Blood (2018)
Correction: Aortic dissection
Authors: Christoph A. Nienaber, Rachel E. Clough, Natzi Sakalihasan, Toru Suzuki, Richard Gibbs, Firas Mussa, Michael P. Jenkins, Matt M. Thompson, Arturo Evangelista, James S. M. Yeh, Nicholas Cheshire, Ulrich Rosendahl, John Pepper
Journal: Nature Reviews Disease Primers (2016)
Hypnotism and Its Application to Practical Medicine.
Journal: JAMA (1897)

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 737: <i>N</i> -ethylmaleimide sensitive factor (NSF) is Essential in Necrotic Cell Death
Authors: Emma K Murray, Alyssa A Lombardi, Jonathan P Lambert, John W Elrod
Journal: Circulation Research (2019)

Necrotic cell death is the main way in which cells die during myocardial infarction (MI) and heart failure (HF), yet the molecular mechanisms regulating necrotic cell death are poorly defined. To elucidate the key regulators of plasma membrane rupture during necrotic cell death a genome-wide shRNA loss-of-function screen was performed which identified components of SNARE-mediated membrane fusion as potential facilitators of Ca 2+ and ROS-induced necrosis. To examine if the SNARE machinery is involved in cellular necrosis we targeted N-ethylmaleimide sensitive Factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of NSF from 3T3 fibroblasts by CRISPR-Cas9n (Nsf -/- ), inhibited membrane rupture and improved cell viability following Ca 2+ overload (ionomycin), ROS (H 2 O 2 ), and necroptotic (TNFa, CHX, zVAD)-induced cell death but did not alter apoptotic (staurosporine) cellular demise. We next created a cardiac-specific conditional Nsf knockout mouse model to determine if NSF contributes to myocyte death during IR injury. Loss of NSF in cardiomyocytes did not alter baseline cardiac function or structure. Currently, studies are underway to determine if NSF contributes to necrotic cell as occurs in IR injury and heart failure. In summary, our results suggest that NSF is an important molecular component of membrane rupture and pathogenic cell death.
Early Hepatitis C Viral Response (EVR) to Peginterferon Alfa 2a and Ribavirin in Patients with β Thalassemia.
Authors: Paul Harmatz, Nancy F. Olivieri, Elliott Vichinsky, Janet Kwiatkowski, Patricia Giardina, Farrukh Shah, Wright C. Elizabeth, Melody Cunningham, Jonas Maureen
Journal: Blood (2004)
ASXL1 exon 12 Mutations Are Frequent in AML with Intermediate Risk Karyotype and Are Independently Associated with An Extremely Poor Outcome
Authors: Susanne Schnittger, Christiane Eder, Tamara Alpermann, Annette Fasan, Vera Grossmann, Alexander Kohlmann, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: Blood (2011)
Bisphosphonates for Postmenopausal Osteoporosis
Authors: Kristine E. Ensrud, Carolyn J. Crandall
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
Molecular Predictors Of Response To Lenalidomide In Myeloid Malignancies
Authors: Zaher K. Otrock, Bartlomiej P Przychodzen, Holleh D Husseinzadeh, Hideki Makishima, Brittney Dienes, Naoko Hosono, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2013)
Prevalence of Folic Acid Deficiency and Cost Effectiveness of Folic Acid Testing: A Single Center Experience
Authors: Karina Diaz, Zhu Na, Sorab Gupta, Vikram Arya, Lourdes Martinez, Supreet Dhaliwal, Nora Ajdir, Bhavita Gaglani, Shradha Ahuja, Ilmana Fulger
Journal: Blood (2018)
Final Analysis of a Randomized Comparison of ABVD Chemotherapy with a Strategy That Includes Radiation Therapy (RT) in Patients with Limited-Stage Hodgkin Lymphoma (HL): NCIC CTG/ECOG HD.6
Authors: Ralph M. Meyer, Mary Gospodarowicz, Joseph M. Connors, Robert G Pearcey, Woodrow A Wells, Jane N. Winter, Sandra J. Horning, A. Rashid Dar, Chaim Shustik, Douglas A. Stewart, Michael Crump, Marina S Djurfeldt, Bingshu E Chen, Lois E Shepherd
Journal: Blood (2011)
Abstract 441: The Role of Brown Adipose Tissue in Aging-Induced Cardiovascular Impairments
Authors: Eaman Abay, Megan M Mansour, Carmem Peres Valgas Da Silva, Lisa A Baer, Vikram Shettigar, Kristin I Stanford, Mark T Ziolo
Journal: Circulation Research (2019)

Adults age 65 and older are the fastest-growing demographic in the United States population and pose a significant healthcare challenge. Among several other physiological changes, aging is notably associated with an increased risk of developing cardiovascular disease. Aging leads to a decrease in brown adipose tissue (BAT), a thermogenic tissue rich in mitochondria that converts chemical energy into thermal energy. Importantly, BAT plays a role in combatting metabolic and cardiovascular impairments. Thus, while it is known that aging is associated with both impaired cardiovascular function as well as decreased BAT mass, the specific role of BAT in age-induced impairments in cardiac function remains unknown. For this study, we utilized an old C57BL/6 mouse population (18 months of age) that was divided to sham-operated (control), +BAT (mice surgically transplanted with BAT), and -BAT (or BATless; mice in which BAT was surgically removed) groups. Echocardiography was performed before (baseline) and 3 months after surgery (BAT transplantation or removal). Our data show that mice transplanted with BAT had enhanced cardiac function compared to control, suggesting that increasing BAT mass can reverse age-induced cardiac dysfunction. Moreover, removal of BAT not only resulted in a further deterioration of cardiac function but also adverse remodeling, suggesting that a decrease in BAT is detrimental to the heart. In conclusion, the decrease in BAT as we age plays a significant role in the cardiac dysfunction with senescence and that increasing BAT mass may be a novel therapeutic approach.
Eosinophil Differentiation and Viability in Hypereosinophilia Is Impaired By Genetic and Pharmacologic Targeting of LCP1 and PKC Beta
Authors: Guangxin Ma, Deniz Gezer, Oliver Herrmann, Andreas Reiter, Mohamad Jawhar, Mirle Schemionek, Tim H. Brümmendorf, Steffen Koschmieder, Nicolas Chatain
Journal: Blood (2018)
Metoprolol for the Prevention of Acute Exacerbations of COPD
Authors: Mark T. Dransfield, Helen Voelker, Surya P. Bhatt, Keith Brenner, Richard Casaburi, Carolyn E. Come, J. Allen D. Cooper, Gerard J. Criner, Jeffrey L. Curtis, MeiLan K. Han, Umur Hatipoğlu, Erika S. Helgeson, Vipul V. Jain, Ravi Kalhan, David Kaminsky, Robert Kaner, Ken M. Kunisaki, Allison A. Lambert, Matthew R. Lammi, Sarah Lindberg, Barry J. Make, Fernando J. Martinez, Charlene McEvoy, Ralph J. Panos, Robert M. Reed, Paul D. Scanlon, Frank C. Sciurba, Anthony Smith, Peruvemba S. Sriram, William W. Stringer, Jeremy A. Weingarten, J. Michael Wells, Elizabeth Westfall, Stephen C. Lazarus, John E. Connett
Journal: New England Journal of Medicine (2019)

Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.
An initiative to improve mortality index in gynecologic oncology.
Authors: Jolyn Sharpe Taylor, Jennifer F. Miller, Edith K. Ballard, Tricia K. Blanco, Karen L. Brown, Corrine C. Byrd, Anita Holloway, Arletta Smith, Anne Park, Katherine Cain, Claire Marten, Roshonda Finch, Van Nguyen, Donna Fleming, Charles F. Levenback, Karen H. Lu, Kathleen M. Schmeler
Journal: Journal of Clinical Oncology (2019)

256 Background: The mortality index (MI) is a quality metric that measures the ratio of actual mortality to expected mortality among inpatients. Expected mortality is a probability calculation based on patient risks and comorbidities. A MI of &lt; 1.0 represents that fewer patients die while admitted to the hospital than expected. Methods: We formed a multidisciplinary team that included Gynecologic Oncology (GO), Health Information Management, Clinical Informatics, Revenue Operations, Coding and Institutional Compliance experts. Our aim was to decrease the GO MI by 10% within a year. Quality Improvement Assessment Board approval was obtained. GO clinical providers were educated on proper documentation of patient comorbidities and severity of illness. Audits of the documentation were performed by the multidisciplinary team. GO patients perceived at high-risk of inpatient mortality were identified for additional review. All GO inpatient deaths were reviewed at the monthly GO Morbidity and Mortality conference and opportunities for avoidance of inpatient death were discussed. Plan-Do-Study-Act (PDSA) cycles were repeated with adjustments made to the review and education processes. Baseline (BL) 8/2017-7/2018 and interim post-intervention (PI) 11/2018-2/2019 outcomes were compared using the Mann Whitney U test. Results: The BL median number of inpatient deaths per month was 2 (range 0-7), with a median expected mortality of 2.96 (range 1.46-5.11), and a median MI of 0.84 (range 0-1.37). The PI median number of inpatient deaths per month was 2.5 (range 2-5), with a median expected mortality of 4.24 (range 3.77-5.06), and a median MI of 0.56 (range 0.53-1.27). The number of inpatient deaths per month was similar between groups (2 vs 2.5; p = 0.49) but the expected mortality increased from to 2.96 to 4.24 (p = 0.03). MI decreased by 33% between BL and PI (0.84 vs 0.56). Conclusions: Inpatient mortality is an important quality metric. Accurate measurement of expected mortality is critical and requires proper documentation. This can be improved through education, review and frequent assessment by PDSA cycles. Our preliminary results show improvement in accurate documentation and measurement of expected mortality resulting in a decrease in MI.
The Trithorax-Group Protein ASH1L Regulates Hematopoietic Stem Cell Homeostasis Independently of Its Histone Methyltransferase Activity
Authors: Gloria Jih, Jennifer Chase, Yile Zhou, Ann Friedman, Xiaomin Feng, Manabu Nakayama, Haruhiko Koseki, Kenichi Nishioka, Gang Huang, Ivan Maillard
Journal: Blood (2018)
CAR-T cell therapy: a potential new strategy against prostate cancer
Authors: Giuseppe Schepisi, Maria Concetta Cursano, Chiara Casadei, Cecilia Menna, Amelia Altavilla, Cristian Lolli, Claudio Cerchione, Giovanni Paganelli, Daniele Santini, Giuseppe Tonini, Giovanni Martinelli, Ugo De Giorgi
Journal: Journal for ImmunoTherapy of Cancer (2019)

Prostate cancer (PCa) is one of the main causes of cancer-related death in men. In the present immunotherapy era, several immunotherapeutic agents have been evaluated in PCa with poor results, possibly due to its low mutational burden. The recent development of chimeric antigen receptor (CAR)-T cell therapy redirected against cancer-specific antigens would seem to provide the means for bypassing immune tolerance mechanisms. CAR-T cell therapy has proven effective in eradicating hematologic malignancies and the challenge now is to obtain the same degree of in solid tumors, including PCa. In this study we review the principles that have guided the engineering of CAR-T cells and the specific prostatic antigens identified as possible targets for immunological and non-immunological therapies. We also provide a state-of-the-art overview of CAR-T cell therapy in PCa, defining the key obstacles to its development and underlining the mechanisms used to overcome these barriers. At present, although there are still many unanswered questions regarding CAR-T cell therapy, there is no doubt that it has the potential to become an important treatment option for urological malignancies.