tbuckley/cabot-search huggingface dataset:
Triglyceride Paradox Is Related to Lipoprotein Size, Visceral Adiposity and Stearoyl-CoA Desaturase Activity in Black Versus White Women
Authors: Stephanie T. Chung, Celeste K.L. Cravalho, Abby G. Meyers, Amber B. Courville, Shanna Yang, Nirupa Rachel Matthan, Lilian Mabundo, Maureen Sampson, Ronald Ouwerkerk, Ahmed M. Gharib, Alice H. Lichtenstein, Alan T. Remaley, Anne E. Sumner
Journal: Circulation Research (2019)

In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index.In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels.In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007).Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.
Integrative Network Analysis of Pediatric AML Whole Genomes, cDNA Expression and Clinical Data Elements Reveals Shared As Well As t(8;21), Inv16 and MLL Specific Pathways; A Report From COG/NCI Target AML Initiative
Authors: Hamid Bolouri, Rhonda E. Ries, Ranjani Ramamurthy, Todd A. Alonzo, Jaime M. Guidry Auvil, Tanja M. Davidsen, Patee Gesuwan, Alan S. Gamis, Malcolm A. Smith, Daniela S. Gerhard, Robert J. Arceci, Soheil Meshinchi
Journal: Blood (2012)
Temporal Changes in Plerixafor Administration Do Not Impact Hematopoietic Stem Cell Mobilization Efficacy: Results of a Prospective Clinical Trial
Authors: R. Donald Harvey, Sagar Lonial, Heather Renfroe, Rajni Sinha, Christopher R Flowers, Mary Jo Lechowicz, H. Jean Khoury, Amelia Langston, Edmund K Waller, Jonathan L. Kaufman
Journal: Blood (2011)
Proteasome Activity As a Biomarker in Multiple Myeloma (MM): In MM Cells Treated with Bortezomib (BTZ) or Epoxomicin (EPX) Caspase 3/7 Activation Is Inversely Related to Baseline β1 and β5 Activity
Authors: Ping Zhou, Xun Ma, Raymond L. Comenzo
Journal: Blood (2011)
Radioimmunotherapy (RIT) with 90yttrium Zevalin Followed by BEAM Conditioning Regimen (Z-BEAM) and Autologous Stem Cell Transplantation (ASCT) for the Treatment of High Risk Relapsed/Resistant Non Hodgkin's Lymphoma (NHL)
Authors: Barbara Botto, Chiara Ciochetto, Marilena Bellò, Roberto Passera, Giulia Benevolo, Carola Boccomini, Annalisa Chiappella, Roberto Freilone, Francesca Giunta, Maura Nicolosi, Erika Orlandi, Lorella Orsucci, Clara Pecoraro, Patrizia Pregno, Anna Tonso, Gianni Bisi, Umberto Vitolo
Journal: Blood (2011)
A Phase 1 Dose Escalation Study of Infusion of Ex Vivo CD3/CD28 Costimulated Umbilical Cord Blood-Derived T Cells in Adults Undergoing Transplantation for Advanced Hematologic Malignancies
Authors: Elizabeth Hexner, Selina M. Luger, James K. Mangan, Noelle V. Frey, Grace R Jeschke, Dale Frank, Ran Reshef, Alison W. Loren, Steven C. Goldstein, Misha Rosenbach, Christopher Nowaczyk, Mindy Schuster, Edward A. Stadtmauer, Bruce L Levine, Carl H. June, Stephen G. Emerson, David L. Porter
Journal: Blood (2011)
Efficacy of Mitoxantrone and Etoposide in Patients with Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy.
Authors: Rajesh Sehgal, Wassim McHayleh, James Natale, Anastasios Raptis, Mounzer Agha, Robert L. Redner, Gene Richard, Ann Welsh, Kenneth A. Foon, Michael Boyiadzis
Journal: Blood (2007)
Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases
Authors: Elisabeth F.P. Peterse, Steffie K. Naber, Corinne Daly, Aaron Pollett, Lawrence F. Paszat, Manon C.W. Spaander, Melyssa Aronson, Robert Gryfe, Linda Rabeneck, Iris Lansdorp-Vogelaar, Nancy N. Baxter
Journal: Clinical Gastroenterology and Hepatology (2019)
Perioperative Outcomes and Trends in the Use of Robotic Colectomy for Medicare Beneficiaries From 2010 Through 2016
Authors: Kyle H. Sheetz, Edward C. Norton, Justin B. Dimick, Scott E. Regenbogen
Journal: JAMA Surgery (2019)

The use of robotic surgery for common operations like colectomy is increasing rapidly in the United States, but evidence for its effectiveness is limited and may not reflect real-world practice.To evaluate outcomes of and trends in the use of robotic, laparoscopic, and open colectomy across diverse practice settings.This population-based study of Medicare beneficiaries undergoing elective colectomy was conducted between January 2010 and December 2016. We used an instrumental variable analysis to account for both measured and unmeasured differences in patient characteristics between robotic, open, and laparoscopic colectomy procedures. Data were analyzed from January 21, 2019, to March 1, 2019.Receipt of robotic colectomy.Incidence of postoperative medical and surgical complications and length of stay.A total of 191 292 procedures (23 022 robotic procedures [12.0%], 87 639 open procedures [45.8%], and 80 631 laparoscopic colectomy procedures [42.0%]) were included. Robotic colectomy was associated with a lower adjusted rate of overall complications than open colectomy (17.6% [95% CI, 16.9%-18.2%] vs 18.6% [95% CI, 18.4%-18.7%]; relative risk [RR], 0.94 [95% CI, 0.91-0.98]). This difference was driven by lower rates of medical complications (15.5% [95% CI, 14.8%-16.2%] vs 16.9% [95% CI, 16.7%-17.1%]; RR, 0.92 [95% CI, 0.87-0.96]) because surgical complications were higher with the robotic approach (3.0% [95% CI, 2.8%-3.2%] vs 2.4% [95% CI, 2.3%-2.5%]; RR, 1.18 [95% CI, 1.04-1.35]). There were no differences in complications between robotic and laparoscopic colectomy (11.1% [95% CI, 10.5%-11.6%] vs 11.0% [95% CI, 10.8%-11.2%]; RR, 1.00 [95% CI, 0.95-1.05]). There was an overall shift toward greater proportional use of robotic colectomy from 0.7% (457 of 65 332 patients) in 2010 to 10.9% (8274 of 75 909 patients) in 2016. In hospitals with the highest adoption of robotic colectomy between 2010 and 2016, increasing use of robotic colectomy (0.8% [100 of 12 522 patients] to 32.8% [5416 of 16 511 patients]) was associated with a greater replacement of laparoscopic operations (43.8% [5485 of 12 522 patients] to 25.2% [4161 of 16 511 patients]) than open operations (55.4% [6937 of 12 522 patients] to 41.9% [6918 of 16 511 patients]).While robotic colectomy was associated with minimal safety benefit over open colectomy and had comparable outcomes with laparoscopic colectomy, population-based trends suggest that it replaced a greater proportion of laparoscopic rather than open colectomy, especially in hospitals with the highest adoption of robotics.
Abstract 229: TWEAK-Fn14 Axis: A Potential Therapeutic Target for Treating Heart Failure
Authors: Sathyadev Unudurthi, Evelyn Thomas, Nehal Patel, Alexander Winkle, Daniel Gratz, Thomas Hund
Journal: Circulation Research (2019)

Heart failure (HF) is a complex disease characterized by compromised cardiac structure and function. Previous work has identified a link between upregulation of pro-inflammatory cytokines, and HF. There is a critical need to gain better understanding of the inflammatory pathways in heart and identify novel therapeutic targets to regulate cardiac inflammation and HF Recent studies have shown that under stress macrophages are recruited to heart. These macrophages are mainly implicated in the release of inflammatory cytokines that promote cardiac fibrosis, eventually resulting in heart failure. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a multifunctional member of the TNF superfamily, which binds to fibroblast growth factor inducible 14 (Fn14), a ubiquitously expressed cell-surface receptor. The TWEAK-Fn14 axis has been previously implicated in promoting inflammation in multiple autoimmune disorders, such as rheumatoid arthritis, however, its role in heart in not well known. The objective of this study is to test the hypothesis that TWEAK-Fn14 pathway promotes cardiac inflammation under stress, and blocking this pathway could be a potential therapeutic strategy to reduce stress induced cardiac inflammation and HF. Wild type (WT) and Fn14 knock out (Fn14 -/- ) mice were subjected to pressure overload induced stress (Trans aortic constriction or TAC) for 1 or 6 weeks. A subset of WT TAC animals were treated with the Fn14 inhibitor [L524-0366] (9mg/kg, IP daily) or vehicle beginning at day 3 following TAC. Macrophage infiltration and cardiac fibrosis were quantified in ventricular sections using F4/80 and Masson Trichrome staining respectively, and cardiac function was measured by echocardiography. Levels of monocyte chemoattractant protein-1 ( mcp-1 ) were measured by quantitative PCR. Genetic or chemical inhibition of Fn14 reduced fibrosis [40% lower compared to WT TAC] and improved cardiac function [Δ EF of 21.7%, n=6 for WT TAC; Δ EF of 14.2%, n=6 for Fn14 -/- TAC; Δ EF of 48.5%, n=3 for vehicle; Δ EF of 27.9%, n=5 for drug] compared to WT. Fn14 inhibition also reduced mcp-1 expression and macrophage infiltration [53.5% lower compared to WT TAC] .These results support TWEAK/Fn14 axis as a potential therapeutic target for treating HF
Somatic Mutation of SF3B1, a Gene Encoding a Core Component of RNA Splicing Machinery, in Myelodysplasia with Ring Sideroblasts
Authors: Luca Malcovati, Elli Papaemmanuil, Eva Hellström-Lindberg, Jacqueline Boultwood, David Bowen, Paresh Vyas, Cristiana Pascutto, Matteo G Della Porta, Andrea Pellagatti, Michael J Groves, Anna L Godfrey, Ilaria Ambaglio, Anna Gallì, Erica Travaglino, Simona Conte, Sudhir Tauro, Norene Keenan, Ann Hyslop, Jonathan Hinton, Laura J Mudie, Carlo Gambacorti Passerini, Nicholas CP Cross, James S Wainscoat, Anthony R Green, P Andrew Futreal, Michael R Stratton, Peter J Campbell, Mario Cazzola
Journal: Blood (2011)
Abstract 895: The Role of Poly(rC)-Binding Protein-1 in Heart Development
Authors: Yao Wei Lu, Tiago Fernandes, Haipeng Guo, Xiaoyun Hu, Ramon A Espinoza-Lewis, Da-Zhi Wang
Journal: Circulation Research (2019)

Poly(rC)-Binding Protein-1 (Pcbp1) belongs to the KH homology superfamily of nucleic acid-binding proteins, which has been implicated in a vast array of biological processes such as iron transport, RNA processing, post-transcriptional and translational regulations. Germline deletion of Pcbp1 results in embryonic lethality before embryonic day (E) 8.5. To investigate the role of Pcbp1 in heart development, we generated cardiac-specific conditional deletion of Pcbp1 (Pcbp1-cKO) by crossing the Pcbp1-flox with cTNT-Cre mice. The observed frequencies for Pcbp1-cKO at E12.5 and E16.5 are normal, but no surviving Pcbp1-cKO mice were observed at weaning, suggesting the Pcbp1-cKO is perinatal lethal. E12.5 Pcbp1-cKO hearts are smaller with thin myocardium. At E16.5, Pcbp1 cKO hearts displayed ventricular non-compaction and abnormal ventricular apex formation. To understand molecular mechanisms, we perform RNA sequencing follow by differential gene expression analysis in Pcbp1-cKO hearts at E16.5. We found 241 genes were significantly dysregulated and identified unfolded protein response as a key pathway dysregulated. Furthermore, through alternative splicing analysis, we identified 168 uniquely spliced junctions in 139 genes. Of these, 10 differentially spliced genes are also differentially expressed. Future studies will be performed to better understand the biological function and mechanism of Pcbp1 in the heart. Together, this study suggests Pcbp1 is an important regulator of heart development.
Intensity of end-of-life (EOL) cancer care in Western Washington (WA) versus Alberta (AB), Canada (CA).
Authors: Ali Raza Khaki, Yuan Xu, Catherine R. Fedorenko, Petros Grivas, Scott David Ramsey, Winson Y. Cheung, Veena Shankaran
Journal: Journal of Clinical Oncology (2019)

89 Background: Aggressive care at the EOL may lead to unnecessary suffering and healthcare costs for patients (pts) with cancer. Despite similar populations and state-of-the-art cancer delivery systems, we hypothesize that EOL care may be more intense in the United States (US) multi-payer system vs the CA single-payer system. Using cancer registry and claims data, we compared EOL cancer care between WA and AB. Methods: Adult pts with AJCC stage II-IV solid tumors who died between 2014 and 2016 were identified from regional population-based cancer registries in WA and AB. Data sources were 1) WA State Cancer Registry (WSCR) and Western WA Cancer Surveillance System (CSS) linked to enrollment files and claims from four regional insurers and 2) CA National Ambulatory Care Reporting System (NACRS), Discharge Abstracts Database (DAD), and CT records from AB Health Services. Proportions of pts receiving chemotherapy (CT), ICU admission, or &gt; 1 ED visit in the last 30 days of life (DOL) in WA and AB were determined and compared using two sample z-test with two-tailed hypothesis (α = 0.05). Results: 11,177 AB and 7,906 WA pts met study inclusion criteria. Median age was 71 (IQR 61-79) and 75 (IQR 68-82) for AB and WA, respectively. The most common cancer types represented include lung (31% AB; 35% WA), colorectal (17% AB; 9% WA), breast (10% AB; 6% WA) and prostate (11% AB; 4% WA). A similar proportion of pts in WA and AB experienced multiple ED visits in the last 30 DOL (12.4% WA vs 12.1% AB). CT use in the last 14 and 30 DOL was greater in WA vs AB (6.3% and 13.4% vs 2.7% and 6.6%, respectively) and ICU admissions in the last 30 DOL were substantially greater in WA vs AB (19.9% vs 3.9%). Conclusions: CT use and ICU admissions in the last 30 DOL were more common in WA than AB. The lower rate of ICU admissions in AB may be due to a provincial effort to prioritize goals of care discussions . Future studies to characterize and compare drivers of inappropriately aggressive EOL care may help improve cancer care for patients (pts) in the US and AB. [Table: see text]
Generation of a New Chimeric Antigen Receptor (CAR) to Target CD23 Expressed on Chronic Lymphocytic Leukemia (B-CLL) Cells
Authors: Greta Maria Paola Giordano Attianese, Valentina Hoyos, Barbara Savoldo, Virna Marin, Malika Brandi, Andrea Biondi, Ettore Biagi, Gianpietro Dotti
Journal: Blood (2008)
Impact of Pre-Transplant Rituximab on Efficacy of Revaccination of Lymphoma Patients after Autologous Hematopoietic Stem Cell Transplantation
Authors: Elaina V. Preston, Meighan A. Palazzo, Kenneth Seier, Sean M Devlin, Sergio Giralt, Michael Scordo, Parastoo B. Dahi, Matthew J Matasar, Craig H. Moskowitz, Craig S. Sauter, Gunjan L. Shah, Miguel-Angel Perales
Journal: Blood (2018)
Conditioning Intensity Does Not Influence the Outcome of Allogeneic Stem Cell Transplantation in Myelodysplastic Syndrome. a Joint Study By the Polish Adult Leukemia Group and the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation
Authors: Lidia Gil, Jadwiga Dwilewicz-Trojaczek, Jan Styczynski, Marek Ussowicz, Krzysztof Kalwak, Ewa Gorczynska, Miroslaw Markiewicz, Monika Dzierzak-Mietla, Patrycja Zielinska, Martyna Borowczyk, Adam Nowicki, Marta Baranska, Mieczyslaw Komarnicki, Maria Bieniaszewska, Andrzej Hellmann, Grzegorz Basak, Wieslaw Wiktor Jedrzejczak, Andrzej Lange, Kazimierz Halaburda, Katarzyna Drabko, Agnieszka Zaucha-Prazmo, Beata Jakubas, Patrycja Mensah-Glanowska, Piotr Rzepecki, Anna Pieczonka, Jacek Wachowiak, Agnieszka Wierzbowska, Jaroslaw Dybko, Tomasz Wrobel, Sebastian Giebel
Journal: Blood (2014)
Abstract 491: Small Gtpase Rhoe Regulates Inflammatory Response in Myocardial Infarction
Authors: Weijia Luo, Yuan Dai, Jiangping Song, Jiang Chang
Journal: Circulation Research (2019)

Background: Myocardial infarction (MI) is a severe clinical condition caused by coronary artery thrombotic occlusion. An acute inflammatory response to MI is essential for cardiac healing, while excessive and prolonged inflammation causes cytotoxic damages and provokes adverse cardiac remodeling. In the present study, we demonstrate a novel inflammatory mediator, RhoE, and its cardioprotective role in MI. Methods: We use three genetic mouse lines in this study: global RhoE knockout, cardiac-specific RhoE haploinsufficient, and cardiac-specific RhoE overexpression mice. Cardiac function and inflammation in the first week post MI are assessed in mice receiving left anterior descending artery (LAD) ligation. Mechanistic study is conducted through a set of molecular signaling experiments including bimolecular fluorescence complementation (BiFC), immunoprecipitation, electrophoretic mobility shift assay and mRNA microarray analysis. Finally, we investigate the expression and clinical significance of RhoE in MI patients. Results: RhoE is upregulated in mouse post MI. RhoE deletion leads to upregulation of pro-inflammatory genes in mouse embryo heart. RhoE haploinsufficiency causes excessive inflammatory response with deleterious cardiac function post MI, while RhoE overexpression restrains post-MI inflammation and preserves cardiac function and survival. Mechanistically, RhoE specifically inhibits NF- κB activation in vivo and in vitro. RhoE binds to p65 and p50 individually in cytosol, blocking their dimerization and nuclear translocation. Consistent with findings in the mouse MI model, MI patients with higher RhoE expression show diminished cardiac inflammation and consequently a better prognosis. Conclusions: This study identified RhoE as a fine-tuning factor modulating post-MI inflammation. RhoE expression level in heart positively correlates with the outcomes of MI patients. Impact: The discovery of RhoE provides a potential therapeutic target for MI. RhoE abundance in the heart post-MI might be used for prognosis assessment.
Obsessive-Compulsive Behavior Isn't Necessarily a Bad Thing
Authors: Philippa Marrack
Journal: Annual Review of Immunology (2019)

It is difficult to believe that in about 1960 practically nothing was known about the thymus and some of its products, T cells bearing αβ receptors for antigen. Thus I was lucky to join the field of T cell biology almost at its beginning, when knowledge about the cells was just getting off the ground and there was so much to discover. This article describes findings about these cells made by others and myself that led us all from ignorance, via complete confusion, to our current state of knowledge. I believe I was fortunate to practice science in very supportive institutions and with very collaborative colleagues in two countries that both encourage independent research by independent scientists, while simultaneously ignoring or somehow being able to avoid some of the difficulties of being a woman in what was, at the time, a male-dominated profession.
BCR-ABL Kinase Domain Mutations Exist in Few Imatinib Treated Chronic Myeloid Leukemia (CML) Patients Exhibiting Stable Cytogenetic and Hematologic Responses
Authors: Afia Muhammad Akram, Tanveer Akhtar, Asma Chaudhary, Muhammad Mudassar Shahzad, Ahmad Mukhtar Khalid, Nadia Sajid, Muhammad Farooq Sabar, Zafar Iqbal
Journal: Blood (2018)
Abstract 446: The Impact of the Menstrual Cycle on the Cardiovascular System
Authors: Chih-Yu Chen, Chi-Wei Chang, Sheng-Hung Wang, Xiang-Yu Xie, Gin-Chung Wang
Journal: Circulation Research (2019)

The stage of the menstrual cycle is an exquisite regulation of female hormone and cardiovascular adaptation to prepare for pregnancy. However, there are still many unclear areas in the study of the influence of the menstrual cycle on cardiovascular function. Since the arterial pulse wave provides insightful information about the cardiovascular system, this study aimed to study cardiovascular adaptation in three phases of the menstrual cycle through non-invasive blood pressure and radial pulse wave measurements. In this observational study, we recruited 113 healthy women with regular menstrual cycles(25±35 days). All participants underwent blood pressure and radial pulse measurements in three stages of the menstrual cycle, including menses period, proliferative phase, and secretory phase. The Fourier series method was used to calculate the first ten harmonic amplitudes of the radial pulse wave(C1~C10). The results showed no significant systolic and diastolic changes in the three phases of menstruation. However, compared to the other two phases, women in menses period had lower C2 and higher C4, C6 and C7. (Figure 1) C4 and C7 are two indices that are inversely related to arterial stiffness and peripheral arterial impedance. Thus, during the menstrual cycle, female hormones may be involved in the regulation of vascular elasticity and peripheral vasodilatation, which in turn changed the radial pulse spectrum. In summary, the menstrual cycle has an impact on the radial pulse spectrum and could alter arterial stiffness to accommodate the physiological needs of the pre-pregnancy period.
The Pros and Cons of Splenectomy in Transfusion Dependent Thalassemia Patient
Authors: Adisak Tantiworawit, Somying Dumnil, Nichanan Osataphan, Thanawat Rattanathammethee, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Lalita Norasetthada, Pimlak Charoenkwan
Journal: Blood (2018)
Abstract 20487: H-Ras Mediates Growth and Survival while K-Ras Promotes Apoptotic Signaling in Cardiomyocytes
Authors: Dominic P Del Re, Takahisa Matsuda, Peiyong Zhai, Shumin Gao, Junichi Sadoshima
Journal: Circulation (2010)

Isoform specific functions of Ras proteins exist, yet the role of endogenous Ras isoforms in the heart remains unknown. The goal of this study was to determine the role of H- and K-Ras in the devel...