tbuckley/cabot-search huggingface dataset:
Pre-Transplant NPM1 Mutant Transcript Level Is Highly Predictive of Outcome after Allograft and Thresholds Are Dependent on FLT3 ITD Status
Authors: Richard Dillon, Robert K. Hills, Sylvie D Freeman, Nicola Potter, Adam Ivey, Jelena Jovanovic, Anju Kanda, Manohursingh Runglall, Nicola Foot, Laura Upton, Asim Khwaja, Jamie Cavenagh, Ruth Spearing, Alan K. Burnett, Nigel H. Russell, David Grimwade
Journal: Blood (2018)
Late Mortality and Relapse Following HLA-Identical Sibling Donor Marrow Transplantation for Chronic Myeloid Leukemia.
Authors: Edward Copelan, Pamela Crilley, Jeffrey Szer, Anthony J. Dodds, Dustin E. Stevenson, Gary Phillips, Patrick Elder, Ian Nivison-Smith, Belinda Avalos, Sam Penza, David Topolsky, R. Sobecks, Matt Kalaycio, Brian J. Bolwell
Journal: Blood (2008)
Abstract 487: Immune Response Factors in Patients With Diabetes Mellitus and Acute Coronary Syndrome
Authors: Svetlana Glova, Sergey Shlyk
Journal: Circulation Research (2019)

Purpose: To study cardiac remodeling in patients with ACS complicated with DM through analysis of laboratory parameters and echocardiogram. Methods: A total of 67 patients were prospectively enrolled (age range: from 36 to 79 years; average: 60,96 ± 9,22 years) with ACS who were admitted to Emergency Hospital. The patients were divided into 2 groups depending on the presence of DM: 23 patients with DM (age average: 65,09 ± 7,73 years) and 44 without DM (age average: 58,79 ± 9,19 years). Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high sensitive C reactive protein (hs-CRP), antibodies to LPS General Enterobacteriaceae, antibodies to LPS Re-Glycolipid were tested for all patients. Echocardiograms were obtained on all the patients, interventricular septal thickness (IVSd) and others parameters were measured by taking the mean values of three continuous heartbeat cycles in the expiratory state. All indicators were calculated using the statistics program Statistica, a P-value of &lt; 0,05 was considered statistically significant. Results: There were no significant differences in the prevalence of smoking, family history of CVD, hypertension between groups. No differences were observed in the levels of serum hs-CRP, TC, HDL-C, LDL-C; but TG levels were significantly higher in patients with DM ( 3,16 ± 2,61 mmol/l) than in controls (1,75 ± 1,33 mmol/l, p&lt;0,05). Serum antibodies to LPS General Enterobacteriaceae levels (441,52 ± 303,70 A.U.O.D) were also significantly higher in the DM group than in controls (271,41 ± 200,13 A.U.O.D, p&lt;0,05). The levels of serum antibodies to LPS General Enterobacteriaceae were positively correlated with IVSd (r = 0,765, p&lt;0,05). Conclusion: The data demonstrated, that patients with DM have a greater immune response which correlates with indicators of left ventricular remodeling. The mechanism of the cardiac function impairment, however, has not been clearly explained yet. The role of the immune response in the development of cardiac muscle remodeling is not fully understood. It Is currently considered that these changes may participate in the pathological process of left ventricular remodeling in patients with DM.
Abstract 706: Changes in Translational Efficacy During Zebrafish Heart Regeneration
Authors: Joseph A Goldman, Ariel Bazzini, Antonio Giraldez, Kenneth Poss
Journal: Circulation Research (2019)

Zebrafish are able to regenerate heart muscle after catastrophic injury. Fervent research is underway to discover critical molecules with therapeutic potential, yet many principal biological processes that underlie regeneration likely remain undiscovered. Changes in the abundance of dozens to thousands of mRNA have been reported using both targeted approaches like in-situ hybridization and unbiased approaches like RNA-seq. However, whether the abundance of mRNA represents the entirety of gene expression control remains unknown. Regulation of translation may alter the abundance of a critical protein product without requiring an intervening transcription event. Here, we have taken advantage of ribosome profiling to document the changes in translation efficiency that accompany heart regeneration. Using high-throughput sequencing of the ~28 nucleotide fragments of mRNA protected from enzymatic degradation, we find thousands of transcripts that change in their association with ribosomes. We also find that key components of the translational machinery are transcriptionally induced during regeneration, supporting a general model in which regulation of translation is a fundamental component of zebrafish heart regeneration.
Diabetes technology: specialists are blocking access for some patients, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Diabetes teams in some NHS trusts are blocking patients’ access to new technologies that could improve their care, clinical leaders have said.

A Westminster Health Forum session on diabetes and technology on 16 October heard that there was unwarranted variation across the country in access to insulin pumps and other clinically effective devices. Poorer access often stemmed from a lack of understanding among individual consultants and departments and a reluctance to offer new devices to patients, the experts said.

Partha Kar, a consultant in diabetes and endocrinology in Portsmouth and joint lead for diabetes for the NHS …
Core Binding Factor Acute Myeloid Leukemia In Pediatric Patients Of The AIEOP AML 2002/01 Trial: Screening and Prognostic Impact Of cKIT Mutations
Authors: Elena Manara, Valeria Bisio, Valzerda Beqiri, Roberto Rondelli, Giuseppe Menna, Concetta Micalizzi, Nicola Santoro, Franco Locatelli, Giuseppe Basso, Martina Pigazzi
Journal: Blood (2013)
Relationship Between Subtherapeutic Warfarin Anticoagulation and the Development of Post Thrombotic Syndrome After a First Unprovoked Deep Vein Thrombosis: Results From the REVERSE Cohort Study
Authors: Rufaro S. Chitsike, Susan R. Kahn, Michael J. Kovacs, Marisol T. Betancourt, Philip S Wells, David Anderson, Isabelle Chagnon, Gregoire Le Gal, Susan Solymoss, Mark A. Crowther, Arnaud Perrier, Richard H. White, Linda Vickars, Tim Ramsay, Marc A. Rodger
Journal: Blood (2011)
EVI1 in Acute Myeloid Leukemia Triggers Metabolic Reprograming Associated with Leukemogenesis and Increases Sensitivity to L-Aspalaginase
Authors: Yusuke Saito, Daisuke Sawa, Mariko Kinoshita, Ai Yamada, Sachiyo Kamimura, Kazuhiro Morishita, Tomoyoshi Soga, Hiroshi Moritake
Journal: Blood (2018)
Abstract 520: Cavin-2/SDPR in Cardiac Fibroblasts Modulates TGF-β/Smad Signaling and Promotes Pressure Overload-induced Fibrosis
Authors: Yusuke Higuchi, Takehiro Ogata, Naohiko Nakanishi, Masahiro Nishi, Akira Sakamoto, Yumika Tsuji, Satoaki Matoba
Journal: Circulation Research (2019)

Introduction: Heart failure (HF) is a debilitating disease associated with high morbidity and mortality. The high mortality rate reflects the inadequacy of modern therapy and calls for new treatments. A major cause of HF is the adverse tissue remodeling with fibrosis. Excessive extracellular matrix (ECM) turnover is involved in the poor outcome. Resident fibroblasts are responsible for cardiac fibrosis on pressure-overload heart failure. Caveolins and Cavins are known as caveolar-related proteins. Caveolin-1 inhibits TGF-β1-induced fibrosis in the previous reports. Although Cavin-2/Serum deprivation response protein (SDPR), which is one of the caveolar-relatedproteins, is also abundant in fibroblasts, the role of Cavin-2 in cardiac fibrosis and function remains unknown. Methods and Results: To clarify the role of Cavin-2 in the cardiac fibroblasts in the pressure-overloadedheart, we performed transverse aortic constriction (TAC) operation on SDPR flox/flox mice and fibroblast-specific Cavin-2 cKO mice (Postin Cre ; SDPR flox/flox ). Four weeks after TAC, left ventricular fractionalshortening (LVFS) was preservedwith a significant reduction of cardiac fibrosis in PostinCre; SDPRflox/flox mice. Fibrosis-associated mRNA expressions ( Col1a1 , Ctgf , Col3 ), α1 type I collagen deposition, and αSMA-positive cells were also reducedin the hearts of Cavin-2 cKO mice after TAC. Trans-differentiation of fibroblasts into activated myofibroblasts is a defining feature of fibrosis. Myofibroblasts express α-smooth muscle actin (αSMA) and secrete ECM proteins via Smad signaling. In mouse embryonic fibroblasts (MEFs),Cavin-2 deficiency reduced the levels of αSMA protein and fibrosis-associated mRNA expressions by TGF-β1 stimulation. Furthermore, TGF-β1-induced Smad2 phosphorylation was attenuatedin Cavin-2 KO MEFs compared to WT MEFs. On the other hand, adenovirus-mediated Cavin-2 overexpression significantly increased αSMA and the fibrosis-associated mRNA expressions. Conclusions: Our observations suggest that Cavin-2 contributes to the development of cardiac fibrosis through the differentiation from fibroblasts into myofibroblasts via TGF-β/Smad signaling. Cavin-2 may be a novel therapeutic target for cardiac fibrosis.
HLA-matched and HLA-haploidentical allogeneic CD19-directed chimeric antigen receptor T-cell infusions are feasible in relapsed or refractory B-cell acute lymphoblastic leukemia before hematopoietic stem cell transplantation
Authors: Xin Jin, Yaqing Cao, Luqiao Wang, Rui Sun, Lin Cheng, Xiaoyuan He, Xia Xiao, Yili Jiang, Qing Li, Huan Zhang, Wenyi Lu, Cuicui Lyu, Yanyu Jiang, Juanxia Meng, Mingfeng Zhao
Journal: Leukemia (2019)

Chimeric antigen receptor-modified T (CAR-T) cells exhibit very effective function in elimination of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) [1].In patients with a high tumor burden or who have undergone heavy treatment, it is not always possible to manufacture an effective therapeutic product [2,3].Here, we describe the first-in-human use of HLA-matched allogeneic CAR-T cells (MCART19 cells) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and expand the description of HLA-haploidentical allogeneic CAR-T cell (HCART19 cell) infusion reported in previous sporadic cases.Autologous CAR-T cells are difficult to produce due to high tumor burden or severe treatment.Eight patients with R/R B-ALL who had never received allo-HSCT received allogeneic CAR-T (allo-CART19) cell infusions.As of March 24, 2018, the median follow-up period was 10 months.All patients received more than four treatments before enrollment.One patient was PH positive (bcr-abl 190+), and seven were PH negative.Three patients had
Serotonin‐release assay‐negative heparin‐induced thrombocytopenia
Authors: Theodore E. Warkentin, Ishac Nazy, Jo‐Ann I. Sheppard, James W. Smith, John G. Kelton, Donald M. Arnold
Journal: American Journal of Hematology (2019)

Abstract Heparin‐induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet‐activating anti‐platelet factor 4 (PF4)/heparin antibodies. Pathogenic HIT antibodies can be detected by the serotonin‐release assay (SRA), a platelet activation test. We have regarded the SRA performed in our medical community (“McMaster” SRA) as having high sensitivity and specificity. Recently, the concept of “SRA‐negative HIT” has been proposed for enzyme‐immunoassay (EIA)‐positive/SRA‐negative patients with a HIT‐compatible clinical picture, who test positive in a PF4‐enhanced platelet activation assay. After identifying an index case of SRA‐negative HIT, we estimated the frequency of this condition by performing the “PF4‐SRA” (modified SRA using high concentrations of added PF4 rather than heparin) in EIA‐positive patients from a cohort study evaluating clinical and laboratory diagnosis of HIT. We defined SRA‐negative HIT as patients meeting three criteria: clinical picture compatible with HIT (4Ts ≥ 4 points); EIA‐positive (≥1.00 units); and PF4‐SRA‐positive. Among 430 patients, 35 were EIA‐positive/SRA‐positive and 27 were EIA‐positive/SRA‐negative. Among these 27 SRA‐negative patients, three were found to have subthreshold levels of platelet‐activating antibodies by PF4‐SRA, of whom one met clinical criteria for SRA‐negative HIT. Thus, based on identifying one patient with SRA‐negative HIT within a cohort study that found 35 SRA‐positive HIT patients, we estimate the sensitivity of the McMaster SRA for diagnosis of HIT to be 35/36 (97.2%; 95% CI, 85.8‐99.9%). Although the McMaster SRA is highly sensitive for HIT, occasional SRA‐negative but EIA‐positive patients strongly suspected of having HIT can have this diagnosis supported by a PF4‐enhanced activation assay such as the PF4‐SRA.
Abstract 589: Left Ventricular Unloading and Delayed Coronary Reperfusion Protects the Structural and Functional Integrity of Mitochondrial Complex 1 in a Preclinical Model of Acute Myocardial Infarction
Authors: Lija Swain, Xiaoying Qiao, Lara Reyelt, Shiva Annamalai, Paige Crowley, Courtney Boggins, Navin K Kapur
Journal: Circulation Research (2019)

Background: Mitochondrial Complex 1 (MC1) plays a key role in energy metabolism during myocardial ischemia-reperfusion injury (M-IRI). Disruption of MC1 promotes reactive oxygen species (ROS) generation and myocardial damage. We recently reported that first reducing left ventricular (LV) workload using a trans-valvular pump and delaying coronary reperfusion, known as Primary Unloading (PU), reduces infarct size in preclinical models of M-IRI. The Door to Unload Pilot Trial recently demonstrated the safety and feasibility of PU in patients with ST-segment elevation myocardial infarction (STEMI), however the cardioprotective mechanisms of PU remain poorly understood. We hypothesized that compared to immediate reperfusion (IR); PU preserves mitochondrial function in M-IRI. Results: M-IRI was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (IR, n=5) or 30 minutes of support with an Impella CP pump (PU, n=5) with persistent occlusion before reperfusion. Compared to IR, PU reduced LV stroke work by 38.4% (p=0.047) and infarct size by 41.3±5.6% (p=0.0052). Compared to IR, PU preserved gene and protein expression of specific MC1 subunits (NDUFA8 and NDUFS3). Using the Agilent Seahorse Platform, we identified that compared to IR, PU preserved function of MC1 and ATP production in mitochondria isolated from the infarct zone by 82.45±12.8% (p=0.0040, IR vs PU). Compared to IR, PU reduced levels of ROS and preserved mitochondrial membrane potential. Next, we studied the activation state of MC1 and observed that compared to IR alone, PU increased the ratio of activated A form versus de-activated D form from 2.79 ± 0.29 to 7.58 ± 0.80 (p=0.005) levels of MC1 within the infarct zone. Conclusion: We report for the first time that compared to IR, mechanically unloading the LV and delaying reperfusion protects the structural and functional integrity of mitochondrial complex 1. These findings provide new insight into the cardioprotective mechanisms of Primary Unloading and support the development of novel therapeutic approaches to improve clinical outcome for patients with STEMI.
Allogeneic HSCT Patients Receiving More RBC Transfusions Are At Increased Risk For Development Of Grade 2-4 Acute Graft-Versus-Host Disease
Authors: Cynthia R. Giver, Zahir Ali, Sheilagh Barclay, Sakura Hosaba, Qunna Li, John Roback, Edmund K. Waller
Journal: Blood (2013)
A Phase 1 Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients with Primary Central Nervous System Lymphoma (PCNSL). (CRUK/08/010)
Authors: Roderick J. Johnson, Andrew Davies, Siow-Ming Lee, Dianne Gilson, Paul Smith, Wendi Qian, Nivette Braganca, Nadjet El-mehidi, Peter Johnson
Journal: Blood (2012)
Double-Unit Cord Blood (CB) Transplantation Combined With Haplo-Identical CD34+ Cell-Selected PBSC Results In 100% CB Engraftment With Enhanced Myeloid Recovery
Authors: Juliet N Barker, Doris M Ponce, Parastoo B Dahi, Sean Devlin, Katherine L Evans, Marissa N Lubin, Richard Meagher, Lilian Reich, Hugo Castro-Malaspina, Jenna D Goldberg, Ann A. Jakubowski, Guenther Koehne, Esperanza B Papadopoulos, Miguel-Angel Perales, Craig S. Sauter, Andromachi Scaradavou, Nancy A. Kernan, Sergio A Giralt, Richard J. O'Reilly
Journal: Blood (2013)
Abstract 190: Polycystin-1 Assembles With Kv Channels to Govern Cardiomyocyte Repolarization and Contractility
Authors: Francisco Altamirano, Gabriele G Schiattarella, Kristin M French, Soo Young Kim, Felipe Engelberger, Sergii Kyrychenko, Elisa Villalobos, Dan Tong, Jay W Schneider, Cesar A Ramirez-Sarmiento, Sergio Lavandero, Thomas G Gillette, Joseph A Hill
Journal: Circulation Research (2019)

Mutations in the gene encoding polycystin-1 (PC1) underlie autosomal dominant polycystic kidney disease (ADPKD). ADPKD patients present with multiple cardiovascular co-morbidities believed to be caused by renal dysfunction. LV hypertrophy and diastolic dysfunction can manifest during childhood or in young adults prior to a formal diagnosis of hypertension, and evidence suggests that LV function is impaired in ADPKD patients with normal or moderately reduced kidney function. These facts suggest that cardiomyocyte-autonomous effects may contribute to the cardiovascular abnormalities seen in ADPKD. Contractile function (systolic and diastolic) measured by echo was significantly reduced in PC1 cKO ( Pkd1 F/F ;αMHC-Cre) mice compared with controls ( Pkd1 F/F ). PC1 cKO cardiomyocytes manifest impaired contractility and smaller and slower Ca 2+ transients. Using a multidimensional approach, we discovered that cardiomyocytes lacking PC1 have shorter action potentials (APD50/90) and decreased SERCA activity. These alterations impair EC-coupling and decrease SR Ca 2+ loading during pacing. Remarkably, square pulses under voltage clamp (-80 to +10 mV) produced Ca 2+ transients with similar amplitude between genotypes, which highlights that alterations in action potential (AP) duration drive most of the EC-coupling changes. PC1-deficient cardiomyocytes manifested an increase in outward K + currents (I to , I Kslow1/2 and I ss ) but not in inward currents (I K1 ). PC1 over-expression in HEK293T cells reduced the currents of heterologously expressed Kv4.3/2.1/1.5 channels. The inhibitory effects of PC1 on Kv4.3 currents were mediated by PC1-CT (C-terminus) through its coiled-coil domain (CCD). Interestingly, a naturally occurring human mutant PC1 R4228X , located in the CCD, manifested no suppressive effects on Kv4.3 channel. Finally, to begin to test for relevance to human pathology, we found that PC1 ablation reduces AP duration, and PC1-CT over-expression had the opposite effect in human stem cell-derived cardiomyocytes. Our findings uncover a novel role for PC1 controlling action potential duration and SERCA. PC1-deficient cardiomyocytes manifest impaired contractility, likely contributing to contractile dysfunction in ADPKD patients.
Long Term Disease Control with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: A Real Life Experience
Authors: Concetta Conticello, Marina Parisi, Salvatore Leotta, Nunziatina Laura Parrinello, Enrica Martino, Valeria Calafiore, Maria Cristina Pirosa, Urosh Markovic, Alessandra Romano, Francesco Di Raimondo
Journal: Blood (2018)
The First Report Of Differences In Fibrin Clot Nanostructure and Response To Tissue Plasminogen Activator (TPA) and Unfractionated Heparin (UFH) In Infants Compared To Adults
Authors: Vera Ignjatovic, Leonie Pelkmans, Saartje Bloemen, Vasiliki Karlaftis, Chantal Attard, Raed Al Dieri, Bas de Laat, Paul Monagle
Journal: Blood (2013)
Abstract 707: Cortical-bone Stem Cell Therapy Alters the Inflammatory Response After Myocardial Infarction
Authors: Alexander Hobby, Remus Berretta, Giulia Borghetti, Eric Feldsott, Deborah Eaton, Hajime Kubo, Sadia Mohsin, Steven Houser
Journal: Circulation Research (2019)

Ischemic heart diseases like myocardial infarction are the largest contributors to cardiovascular disease world-wide. The resulting cardiac cell death impairs function of the heart and can lead to heart failure and death. Re-perfusion of the ischemic tissue is necessary but causes damage to the surrounding tissue by re-perfusion injury and initiates a sterile inflammatory response. Cortical bone stem cells (CBSCs) have been shown to increase pump function and decrease scar size in a large animal swine model of myocardial infarction. To explore the potential cause of these changes, we hypothesized that CBSCs were altering the inflammatory response after re-perfusion thereby changing the wound healing process. To test this, we performed serial immune cell analysis of the blood and tissue from Gottingen mini-swine that underwent 90 minutes of lateral anterior descending coronary artery ischemia followed by 7 days of re-perfusion to assess changes in immune cell recruitment and phenotype. Our findings indicate that CBSCs modify the cytokines released by immune cells in the infarct, decrease macrophage infiltration of the infarct 3 days after MI, and increase the recruitment of CD4+ T-cells to the infarct zone 7 days after MI. In addition, these changes reflect a pro-healing inflammatory environment. From this data, we conclude that CBSCs are influencing immune cell recruitment dynamics and phenotype, and these changes may contribute to the decreased scar size and increased pump function seen in CBSC-treated animals.
Reply to Francesco Montorsi, Giorgio Gandaglia, Alberto Briganti’s Letter to the Editor, re: Veeru Kasivisvanathan, Armando Stabile, Joana B. Neves, et al. Magnetic Resonance Imaging-targeted Biopsy Versus Systematic Biopsy in the Detection of Prostate Cancer: A Systematic Review, Meta-analysis. Eur Urol 2019;76:284–303
Authors: Veeru Kasivisvanathan, Yemisi Takwoingi, Mark Emberton, Caroline M. Moore
Journal: European Urology (2019)
A machine-learning approach for stratifying breast cancer risk in Chinese women on the basis of epidemiological factors and mammographic density
Authors: Ziba Gandomkar, Tong Li, Zhimin Shao, Lichen Tang, Qin Xiao, Yajia Gu, Genhong Di, Claudia Mello-Thoms, Patrick Brennan
Journal: The Lancet (2019)