tbuckley/cabot-search huggingface dataset:
Abstract 363: Systems Network Genomic Analysis Reveals the Role Of MURC/Cavin-4 in Cardiac Ischemia/reperfusion Injury
Authors: Masahiro Nishi, Takehiro Ogata, Naohiko Nakanishi, Yusuke Higuchi, Akira Sakamoto, Yumika Tsuji, Satoaki Matoba
Journal: Circulation Research (2019)

Background: Ischemia/reperfusion (I/R) injury is a critical issue in the development of treatment strategies for ischemic heart disease. Muscle-restricted coiled-coil protein (MURC)/Cavin-4, which is a component of caveolae, is involved in the pathophysiology of dilated cardiomyopathy and cardiac hypertrophy. However, the role of MURC in cardiac I/R injury remains unknown. Objective: To elucidate the role of MURC in cardiac I/R injury. Methods and Results: The systems network genomic analysis based on PC-corr network inference on microarray data between wild-type and MURC knockout (KO) mouse hearts described a network of discriminating genes associated with reactive oxygen species (ROS). To demonstrate the prediction, we investigated the effect of MURC deletion in cardiac I/R injury. MURC deletion in IR-injured mouse hearts decreased infarct size and preserved heart contraction with the inhibition of ROS production and ROS-related gene expressions such as EGR1 and DDIT4 as well as EGR1 protein level. PC-corr network inference integrated with a protein-protein interaction network prediction showed that MURC is also involved in the apoptotic pathway. We confirmed the upregulated activity of STAT3, which is a transcription factor of anti-apoptotic signaling, with the increase of BCL2 mRNA expression and protein level and the decrease of cleaved Caspase 3 protein level in MURC KO compared with WT mouse hearts after I/R. TUNEL assay showed that MURC modulates the apoptosis in cardiomyocytes exposed to hydrogen peroxide. STAT3 inhibitor cancelled the cardioprotective effect of MURC deletion in I/R-injured heart and the anti-apoptotic effect of MURC knockdown in cardiomyocytes. Conclusions: Our findings suggest that MURC plays a pivotal role in the regulation of ROS-induced cell death and STAT3-meditated anti-apoptotic signaling in cardiac I/R injury. MURC may be a therapeutic target for cardiac I/R injury.
Developing and operationalizing a safety culture across a hematology/oncology ambulatory network.
Authors: Tony Philip, Karen Gleason, Jenny Paul Valadez, Keasha Guerrier, Sony Abraham
Journal: Journal of Clinical Oncology (2019)

250 Background: The “Safety Belongs to Me” (SBTM) campaign is an initiative that evaluates safety systems utilized by the Medical Oncology ambulatory network. The SBTM project aims to identify, report, and resolve current and future safety risks by implementing weekly interdisciplinary conference calls across the network. In addition it deploys a highly reliable reporting structure for departmental stakeholders (i.e. Administration, Nursing Administration, Materials Operations, Laboratory, and Pharmacy.) Thereby increasing situational awareness, and prevention of complacency as it relates to patient and employee safety risks. Methods: Methodologies utilized include six sigma tools (Kano analysis, etc.) improvement science tools (PDSA, process maps, and driver diagrams), and surveys. These were used to illustrate how principles of process improvement can be utilized to provide an effective framework for systematic innovation in healthcare. Weekly safety calls were started March 2019 after clinical and administrative leadership completed IHI safety culture training. Results: Since implementation of weekly safety calls, an average 13.2 safety issues identified/week with 3.6 issues/week needing follow up for resolution. There has been an increasing trend in safety issues identified and decreasing trend in new safety issues for follow up. Conclusions: The development of a reporting platform augmented a pre-existing process to escalate safety concerns and events within the medical oncology network. This collaborative has facilitated a formalized safety culture that has increased the identification of both potential and existing safety concerns.
Abstract 143: Surface Modification of Stem Cell Exosomes Myocardial Infarction Specific Peptides for Non-invasive Delivery to Ischemic Myocardium
Authors: Vandana Mallaredy
Journal: Circulation Research (2019)

Exosomes are under extensive investigation as a next generation therapeutic agent for clinical applications in various diseases. Stem cell-derived exosomes have been shown to provide post-MI cardiac repair in small and large animals, however, their multi-dose application is limited to single intra-myocardial delivery. In this study, we investigated the heart homing peptide, CRPPR (Cys-Arg-Pro-Pro-Arg) modified mouse Embryonic Stem Cells (mESCs) exosomes as efficient strategy for intravenous delivery of exosomes to ischemic myocardium. In order to target the infarcted heart, we fabricated the exosomes with CRPPR peptide. These peptides are MI-specific peptides, identified by phage display in earlier studies. For this study, we constructed a plasmid expressing fusion protein consisting of Green Fluorescent Protein (GFP), CRPPR and a truncated lactadherin that gets expressed on the surface of exosomes. The plasmid was transfected into the mESCs, followed by puromycin selection. The modified CRPPR exosomes released from the cells were collected by ultracentrifugation and displayed intense GFP- fluorescence indicating efficient CRPPR tagging of exosomes. The CRPPR exosomes were characterized by Nanosight, Electron microscopy and western blotting. MI was performed by LAD ligation and GFP-CRPPR tagged exosomes were intravenously (i.v) injected at a dose of 10 10 particles per mouse and their tissue distribution was evaluated. Interestingly, unmodified exosomes were rapidly cleared from the circulation within 1 hr after i.v injection in mice whereas exosomes modified with CRPPR were still detectable. At tissue level, there was an increased accumulation of the CRPPR exosomes in the heart compared to the unmodified exosomes. In conclusion, we report developing heart homing exosomes that may efficiently delivers the therapeutic payload of embryonic stem cells to the ischemic region of the heart.
T cells redirected against Igβ for the immunotherapy of B cell lymphoma
Authors: Dongpeng Jiang, Xiaopeng Tian, Xiaosen Bian, Tingting Zhu, Huimin Qin, Ruixi Zhang, Yang Xu, Zhansheng Pan, Haiwen Huang, Jianhong Fu, Depei Wu, Jianhong Chu
Journal: Leukemia (2019)
Taking the Air Out of Oxygen Supplementation in Individuals With Diabetes and Acute Coronary Syndromes
Authors: David Aguilar, Vijay Nambi
Journal: Diabetes Care (2019)

Oxygen supplementation has been a cornerstone in the initial treatment of individuals with acute coronary syndrome. While consensus for oxygen supplementation exists for patients with hypoxia, oxygen supplementation has also been routinely used in those presenting with acute myocardial infarction (MI) with normal oxygen saturations based on the rationale that oxygen therapy could improve oxygen supply to the ischemic myocardium, thereby reducing the infarct size and complications. Indeed, reports of oxygen supplementation to relieve angina pectoris were described as early as 1900 (1). These reports were followed by small studies that suggested benefit with oxygen supplementation in acute MI, but these studies were limited by lack of randomization and unblinded end point ascertainment (2–4). Nonetheless, supplemental oxygen was incorporated into routine clinical practice, as evidenced in 2007 cardiology practice guidelines that recommended routine supplemental oxygen to all patients with acute coronary syndrome during the first 6 h after presentation (5). This widespread belief in oxygen was highlighted in a survey of emergency department, cardiology, and ambulance staff in which 98% of respondents reported using oxygen supplementation for suspected MI and 55% believed oxygen reduced the risk of death (6).

Despite the ubiquitous use of oxygen, there were early reports of potential harm with high-dose oxygen supplementation in individuals with acute MI (7). Over 40 years ago, the first randomized trial of high-dose oxygen in patients with an acute MI demonstrated that oxygen-treated patients had …
Ixazomib in Previously Untreated Indolent B-Cell Non-Hodgkin Lymphoma
Authors: Solomon A. Graf, Ryan C. Lynch, David G. Coffey, Mazyar Shadman, Sandra Kanan, Edward N. Libby, Edus H. Warren, Colin Godwin, Ted Gooley, Jonathan R. Fromm, Ajay K. Gopal
Journal: Blood (2018)
Visualizing treatment patterns and survival in metastatic breast cancer.
Authors: Aidan Gilbert, Courtney Williams, Pravinkumar Kandhare, Arie Nakhmani, Stephen C. Meersman, Elizabeth Garrett-Mayer, Melinda Kaltenbaugh, Andres Azuero, Stacey A. Ingram, Mark E. Burkard, Smita Bhatia, Kelly Kenzik, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

316 Background: Optimal treatment sequencing (i.e., the order in which drugs are given) for metastatic breast cancer (MBC) is unknown. We aimed to develop an approach to visualize treatment patterns and survival in MBC. Methods: This retrospective study utilized ASCO’s CancerLinQ Discovery® database generated from electronic health records. Subjects included 3,312 women aged ≥18 years who were diagnosed with and received treatment for MBC after 1980. Hormone receptor (HR) status was determined by concordant diagnosis and treatment records. Human epidermal growth factor (HER2) status was determined by delivery of HER2-targeted therapy. Ordered and administered treatments were included. We created spatiotemporal plots of treatment patterns for HR+/HER2-, HER2+, and triple negative (TN) MBC. Individuals were represented on the Y-axis, and time on the X-axis with development of MBC aligned at time 0. Treatment classes were identified by colors: hormone therapies in shades of red, chemotherapies in shades of blue, HER2-targeted therapies in shades of green, and novel therapies in shades of orange. Concurrent treatments were represented by split bars. An overlaid Kaplan-Meier curve allowed for observations about the relationship between survival and treatment. Results: We developed a novel visualization approach to simultaneously display heterogeneous, longitudinal treatments and survival. Median survival after first documentation of MBC was 3.1 (IQR 1.4-7.2), 1.3 (IQR 0.6-2.8), and 2.6 (IQR 1.0-5.2) years for HR+/HER2-, TN, and HER2+ MBC, respectively. Patients with longer survival often had long duration of initial therapy, suggesting a more indolent or responsive disease. Substantial heterogeneity in treatment sequencing was observed for HR+HER2- and TN cohorts. In the HER2+ cohort, HER2-targeted therapy was commonly administered for the duration of treatment with more homogeneous sequencing. Conclusions: This novel visualization approach allows for observing the relationship between treatment patterns and survival, which is challenging to demonstrate with traditional quantitative methods. This approach can generate hypotheses regarding impact of treatment patterns on survival.
The Mantle Cell Lymphoma Response to VCR Protocol Associated with Its Sensitivity to Hypomethylation Regulation-a Collateral Study on VCR Phase I Trial
Authors: Jeffrey J Pu, Matthew Nemesure, W. Christopher Ehmann, David F Claxton, Joseph J Drabick, Anna C Salzberg, Yuka I Kawasawa, Elliot Epner
Journal: Blood (2018)
Impact of burn-out syndrome in oncology staff and its improvement through specific interventions.
Authors: Alberto Jacobo Cunquero Tomas, Inmaculada Ortega, Teresa Fernández, Miriam Lobo De Mena, Mireia Gil Raga, Vega Iranzo, Cristina Caballero Diaz, Ana Gomez, Ana Blasco, Carlos Camps
Journal: Journal of Clinical Oncology (2019)

249 Background: Burn-Out Syndrome (BOS) is defined by: emotional and physical exhaustion; cynicism and depersonalization; and no personal nor professional fulfillment. With increasing incidence, it impacts negatively in the patient attention quality and the quality of institutional processes. Few experiences reported about its incidence and impact in Medical Oncology. Lack of resources for its diagnosis and management. Our objective was to determine the incidence of the BOS in our workers, analyze its causes and try to reduce in 20% the percentage of workers suffering or at risk of suffering BOS. Developed as a Quality Training Program (ASCO - ECO Foundation) project. Methods: 23 nurses/nurse-assistants Medical Oncology Department at University General Hospital of Valencia fulfilled anonymized questionnaire with personal details, GHQ-12 evaluation and Maslach index questions, at baseline and after intervention. Causes of BOS analyzed and process map and Ishikawa fish-bone scheme designed. Interventions carried in consequence. Results: 23 subjects, 87% women, 47 year-old median age. 14 nurses, 8 working in the clinic. 90% with more than 5 years of experience in Oncology. At baseline, 75% GHQ-12 good health. Maslech index: 70%, 45% and 55% in risk (medium+high) of BOS related to exhaustion, depersonalization or fulfillment, respectively. In exhaustion, 35% medium risk, 35% high risk of BOS. After priority-matrix development, ergonomy tips and self-improvement tools were identified as the adequate interventions to improve exhaustion risk. After ergonomy tips intervention, 90% GHQ-12 good health, 15% exhaustion medium risk, 50% exhaustion high risk, 65% at risk of BOS related to exhaustion. An improvement of 5% lowering the risk of suffering Burn-Out Syndrome among our workers was achieved Conclusions: BOS risk is complex due to answer subjectivity. We have healthier workers (GHQ-12), but although levels of exhaustion have decreased mildly, those who were already exhausted are worse than before (Maslach Index). Possible causes: renovation work on Clinic, labor instability, local holidays during project. Additional self-improvement tools sessions are now being held.
Reducing radiation oncology time to treatment for definitive cancers.
Authors: Ronald Young, Naichang Yu, Molly Patt
Journal: Journal of Clinical Oncology (2019)

84 Background: Time to first treatment intervention has been associated with improved patient outcomes. Although, radiation therapy is not always the first treatment intervention, a reduced time to treatment for radiation therapy patients reduces the anxiety and worry of the patient and their family. At the Cleveland Clinic, TTT is considered an important metric that is reviewed by our Cancer Committee and is considered within our tumor boards as well as our multi-disciplinary clinics. Methods: A value stream mapping exercise starting at the time of diagnosis and ending at the first scheduled treatment date allowed us to understand where our opportunities were to improve our TTT. Analytics and reporting was developed to track and report objective data that was incorporated into our operational huddles. Process improvements were implemented to improve clinical template access for our physicians, we eliminated the sequential nature of insurance authorization after consult and created reporting tools that our teams could monitor our success. Results: We improved our median time of consult to first treatment by 29% . Driving our consults to treatment times down a full 4 days on average. We have sustained this improvement with team based visual management boards, team huddles and incorporating TTT into our culture. Conclusions: Radiation therapy time to treat was reduced with the use of continuous improvement tools, analytics, and team based huddles.
Distress Screening Scores of Malignant and Benign Hematology Patients: Results of a Pilot Project.
Authors: Linda McLellan, Brad Pohlman, Lisa Rybicki, Larry Foster, Shawnda Tench, Michele Cooper, Millie McKenzie, Megan Kilbane, Cheryl Wright, Julie Dimitrov, Julianne Bauer, Jane Dabney, Barbara Savage, Christa Poole, Rene' Barrat-Gordon, Karen Fireman, Brian J. Bolwell
Journal: Blood (2012)
Marrow Blast Percentage Impact on High-Grade Myelodysplastic Syndrome By the Revised International Prognostic Scoring System
Authors: Omar Alkharabsheh, Mrinal M. Patnaik, Naseema Gangat, Kebede H. Begna, Hassan B. Alkhateeb, Mithun Vinod Shah, William J. Hogan, Rong He, Patricia Greipp, Phuong L. Nguyen, Mark R. Litzow, Aref Al-Kali
Journal: Blood (2018)
Abstract 518: Pharmacological Inhibition of Human Antigen R (HuR) Blunts fibroblast Activation and Cardiac Fibrosis
Authors: Lisa C Green, Sarah R Anthony, Samuel Slone, Perwez Alam, Liang Xu, Michael Tranter
Journal: Circulation Research (2019)

Myocardial fibrosis is associated with many cardiac diseases and often leads to a worsened prognosis. In a healthy heart, cardiac fibroblasts are responsible for maintaining the extracellular matrix (ECM). In response to stress or injury, however, the fibroblasts activate to myofibroblasts and begin proliferating, migrating, and depositing excess ECM. This leads to decreased compliance and contractility of the myocardium, furthering the progression to heart failure. Dampening the chronic activation of fibroblasts, therefore, is an attractive target for future cardiac therapeutics. Human Antigen R (HuR) is an RNA binding protein known to stabilize mRNA through binding to AU rich regions in the 3’UTR. Our lab has previously utilized a myocyte-specific knockout of HuR to show that HuR plays an important role in cardiac fibrosis through mediating TGFβ gene expression in the myocytes. Additionally, pharmacological inhibition of HuR markedly reduced interstitial cardiac fibrosis in an 11-week transverse aortic constriction (TAC) mouse model of heart failure, quantifying the fibrosis with Masson’s Trichrome Stains, western blots, and qPCR of profibrotic markers. The goal of this work is to identify the functional role of HuR in mediating pro-fibrotic gene expression and ECM remodeling activity in cardiac fibroblasts. Our results demonstrate that HuR inhibition blunts the activation and wound healing activity of primary adult cardiac fibroblasts. Specifically, utilizing an in vitro scratch/wound healing assay we show that HuR inhibition significantly prolongs wound closure time and blunts the expression of profibrotic genes (e.g. collagen1a1, periostin, TGFb, fibronectin). Ongoing studies will determine the effect of HuR inhibition in a two-week isoproterenol pump (30mg/kg/day) model. Quantification of fibrosis and upstream signaling of fibroblast activation, such as TGFβ-dependent phosphorylation of SMAD2/3, will be assessed to determine the role of HuR in the initiation of fibrotic signaling.
Genetic correlates of social stratification in Great Britain
Authors: Abdel Abdellaoui, David Hugh-Jones, Loic Yengo, Kathryn E. Kemper, Michel G. Nivard, Laura Veul, Yan Holtz, Brendan P. Zietsch, Timothy M. Frayling, Naomi R. Wray, Jian Yang, Karin J. H. Verweij, Peter M. Visscher
Journal: Nature Human Behaviour (2019)
Quality of Life Among Adolescents with Beta-Thalassemia Major (TM) in Qatar
Authors: Abdulqadir Jeprel Nashwan, Mohamed A Yassin, Ganga Babu, Sindhumole LK Nair, Izette Libo-on, Hothaifah Hijazi, Vincenzo De Sanctis, Ashraf Tawfiq Soliman
Journal: Blood (2018)
Abstract P339: Impaired Cardiac Autonomic Modulation in Adolescents: Role of Insomnia Symptoms, Objective Short Sleep Duration and Night-To-Night Sleep Variability
Authors: Julio Fernandez-Mendoza, Fan He, Duanping Liao, Alexandros N Vgontzas, Edward O Bixler
Journal: Circulation (2018)

Introduction: Impaired cardiac autonomic modulation (CAM), as measured by heart rate variability (HRV), has been associated with increased risk of cardiovascular morbidity. Inadequate sleep has been shown to contribute to impaired CAM, however, it is not clear what sleep problems are independently associated with impaired CAM in adolescents, a population in which insomnia symptoms, short sleep duration and night-to-night sleep variability are highly prevalent. Hypothesis: Insomnia symptoms, objective short sleep duration and high sleep variability are independently associated with worse HRV indices in adolescents. Methods: Data from the Penn State Child Cohort, a randomly-selected sample of 421 adolescents (12-23y) was used. Insomnia symptoms were defined by the presence of self-reported difficulties falling and/or staying asleep on the Pediatric Sleep Questionnaire. All subjects underwent 9-hour, in-lab polysomnography (PSG) and wore an actigraphy (ACT) monitor in the non-dominant wrist for 7 days. Mixed-effect regression models predicting HRV indices included insomnia symptoms, PSG sleep duration and ACT sleep duration and its variability (standard deviation) adjusted for each other as well as for sex, race, age, body mass index, and apnea/hypopnea index. Results: Shorter PSG sleep duration and higher ACT sleep variability were independently associated with decreased parasympathetic and increased sympathetic nervous activity [e.g., SDNN: 2.05±0.70, p&lt;0.01 and -4.50±1.14, p&lt;0.01 and Log-HF: 0.10±0.03, p&lt;0.0 and -0.10±0.05, p=0.05, respectively], while ACT sleep duration or self-reported insomnia symptoms were not [e.g., SDNN: -0.57±0.84, p=0.49 and 0.90±1.26, p=0.47 and Log-HF: -0.06±0.04, p=0.12 and 0.05±0.06, p=0.37, respectively]. Conclusions: Objective, but not subjective, measures of sleep are associated with impaired CAM in adolescents. Interestingly, short PSG sleep duration and high ACT sleep variability are independently associated with impaired CAM, which indicates that these two objective measures may help identify distinct sleep phenotypes associated with increased cardiovascular risk in adolescents. Future studies should examine whether a more severe type of insomnia symptoms, i.e., chronic insomnia, is associated with impaired CAM in adolescents.
Working Toward Better Metrics for Nonventilator Hospital-Acquired Pneumonia
Authors: Jonathan Baghdadi, Anthony D. Harris
Journal: JAMA Network Open (2019)

Wenjing Ji, PhD; Caroline McKenna, MPH; Aileen Ochoa, MPH; Haiyan Ramirez Batlle, MD; Jessica Young, PhD; Zilu Zhang, MS; Chanu Rhee, MD, MPH; Roger Clark, DO; Erica S. Shenoy, MD, PhD; David Hooper, MD; Michael Klompas, MD, MPH; for the CDC Prevention Epicenters Program
Targeting Ras-Signalling Pathway to Strike Hsf1 and Induce Apoptosis in Chronic Lymphocytic Leukemia
Authors: Flavia Raggi, Federica Frezzato, Veronica Martini, Filippo Severin, Valentina Trimarco, Emanuele Favero, Andrea Visentin, Monica Facco, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2018)
Estimand Framework in AML Based on a Randomized, Placebo-Controlled, Phase 3 Study Investigating the Effect of Adding Midostaurin to Standard Chemotherapy in Patients with Newly Diagnosed AML without a FLT3 Mutation
Authors: Bourras-Rezki Bengoudifa, Hans Weber, Insa Gathmann, Albert Hoenekopp, Noah Berkowitz
Journal: Blood (2018)
Polymeric Immunoglobulin A1 Controls Erythroblast Proliferation and Accelerates Erythropoiesis Recovery in Anemia
Authors: Séverine Coulon, Michael Dussiot, Damien Grapton, Thiago Maciel, Pamella Huey Mei Wang, Celine Callens, Bertrand Arnulf, Patrick Mayeux, Benhamou Marc, Michel Cogné, Renato Monteiro, Olivier Hermine, Ivan Cruz Moura
Journal: Blood (2011)
IL6 -174 G/C and Fibrinogen-β-455 G/A Polymorphisms in Ischemic Cerebrovascular Disease (ICD).
Authors: Vanessa Moreno B, Arantxa Garcia-Raso, Maria Jose Garcia-Bueno, Carmen Sanchez, Dolores Subira, Raquel Mata, Pilar Llamas, Jose Martinez
Journal: Blood (2006)
DNA extraction for human microbiome studies: the issue of standardization
Authors: K. Leigh Greathouse, Rashmi Sinha, Emily Vogtmann
Journal: Genome biology (2019)

Among the laboratory and bioinformatic processing steps for human microbiome studies, a lack of consistency in DNA extraction methodologies is hindering the ability to compare results between studies and sometimes leading to errant conclusions. The purpose of this article is to highlight the issues related to DNA extraction methods and to suggest minimum standard requirements that should be followed to ensure consistency and reproducibility.
Predictors of Spleen and Anemia Response to Specific Drugs in Primary Myelofibrosis
Authors: Domenico Penna, Natasha Szuber, Terra L. Lasho, Christy Finke, Rangit Reddy Vallapureddy, Curtis A. Hanson, Rhett P. Ketterling, Animesh Pardanani, Naseema Gangat, Ayalew Tefferi
Journal: Blood (2018)