tbuckley/cabot-search huggingface dataset:
Genetic Analysis of Plasmablastic Lymphomas in HIV (+) Patients Reveals Novel Driver Regulators of the Noncanonical NF-κB Pathway
Authors: Munevver Cinar, Hsiao-Rong Rong, Iloabueke Chineke, Abner Louissaint, Jennifer Rose Chapman-Fredricks, Francisco Vega, Clifford James Gunthel, Cassandra Love, Marina Mosunjac, Christopher R Flowers, Sandeep Dave, Izidore S. Lossos, Leon Bernal-Mizrachi
Journal: Blood (2018)
Pediatric high-grade glioma resources from the Children’s Brain Tumor Tissue Consortium
Authors: Heba Ijaz, Mateusz Koptyra, Krutika S Gaonkar, Jo Lynne Rokita, Valerie P Baubet, Lamiya Tauhid, Yuankun Zhu, Miguel Brown, Gonzalo Lopez, Bo Zhang, Sharon J Diskin, Zalman Vaksman, Jennifer L Mason, Elizabeth Appert, Jena Lilly, Rishi Lulla, Thomas De Raedt, Allison P Heath, Alex Felmeister, Pichai Raman, Javad Nazarian, Maria Rita Santi, Phillip B Storm, Adam Resnick, Angela J Waanders, Kristina A Cole
Journal: Neuro-Oncology (2019)
Integration of pathology within the multidisciplinary cancer care team.
Authors: Elana Plotkin, Timothy Craig Allen, Sandra Brown, Pablo Gutman, Dana Herndon, Jan A. Nowak, Jeremiah Martin, Mohamed Mohamed, Marianne Gandee, Lorna Lucas
Journal: Journal of Clinical Oncology (2019)

49 Background: In an era of precision medicine the role of pathology in the diagnosis/management of cancer is evolving. Pathologists are positioned at the intersection of multiple points along the cancer care continuum. Starting at diagnosis pathologists provide expert interpretation and may recommend biomarker testing to guide treatment decisions. Methods: ACCC joined with partners AMP, ASCP, and CAP administered a survey in June 2018. 659 responses were received from a multidisciplinary group and a variety of cancer program settings. Results: Respondents reported that breakdowns in communication are most likely to occur when selecting and ordering biomarker tests (78%) and when reporting the results of the tests (34%). The top 5 challenges reported were coverage/reimbursement, insufficient quantity of material, turnaround time, test selection/ordering, and communication across the multidisciplinary team. There were sizable gaps in regular ordering of NGS among those with 1 tumor board (28%), 2-3 tumor boards (42%) and 4+ tumor boards (64%). Current use of liquid biopsy remains low with the majority (52%) reporting that clinicians rarely order ctDNA testing (12% “routinely”). Time to receiving test results varied with 58% reporting 5-10 business days, 19% reporting &lt;5 business days and 24% &gt;10 business days. 43% indicated pathologists are authorized to order all types of cancer biomarker tests. 56% have molecular pathologists on staff, 24% have a cancer genetics team. 62% report pathology has access to all inpatient records (38% outpatient records). Conclusions: Programs viewed as having integrated pathology participation feature pathologists leading institutional biomarker testing protocols, active participation at tumor boards and standardized reflexive testing pathways that reduce waste &amp; turnaround time. Full integration is a critical piece to ensure patients receive appropriate and timely care.
Rheumatoid Arthritis Morning Stiffness Is Associated With Synovial Fibrin and Neutrophils
Authors: Dana E. Orange, Nathalie E. Blachere, Edward F. DiCarlo, Serene Mirza, Tania Pannellini, Caroline S. Jiang, Mayu O. Frank, Salina Parveen, Mark P. Figgie, Ellen M. Gravallese, Vivian P. Bykerk, Ana‐Maria Orbai, Sarah L. Mackie, Susan M. Goodman
Journal: Arthritis & Rheumatology (2019)

Objective Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom. Methods Data on patient‐reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Synovium was scored for 10 histopathologic features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells, detritus, neutrophils, and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays. Results Stiffness severity and morning stiffness duration were both significantly associated with DAS28 ( P = 0.0001 and P = 0.001, respectively). None of the synovial features examined were associated with patient‐reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly associated ( P &lt; 0.0001) with patient‐reported morning stiffness of ≥1 hour, such that 73% of patients with both synovial fibrin and neutrophils reported morning stiffness of ≥1 hour. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells ( P = 0.008). DNase I treatment of necrotic neutrophils abrogated the delay in fibrinolysis. Conclusion In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil‐enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiologic phenomena.
Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States
Authors: Sikander Ailawadhi, Sri Lekha Bodepudi, Zan Tahir Shareef, Fabiola Coromoto Cardozo, Salman Ahmed, Prachi Jani, Shishir David, Vivek Roy, Aneel Paulus, Victoria R. Alegria, Vivek Kumar, Meghna Ailawadhi, Prakash Vishnu, Sonikpreet Aulakh, Rami Manochakian, Asher A. Chanan-Khan, Taimur Sher
Journal: Blood (2018)
Haplo-SCT Mediates Stronger GVL Effect Than HLA-Matched Sibling Allograft By Significantly Reducing Leukemia Burden
Authors: Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Huan Chen, Chen-Hua Yan, Kaiyan Liu, Xiao-Jun Huang
Journal: Blood (2018)
Imaging Morphologic Changes On Platelet and Monocyte Surfaces In Heparin-Induced Thrombocytopenia (HIT)
Authors: Lubica Rauova, Yanjun Zhang, Vincent M. Hayes, Chandrasekaran Nagaswami, Douglas B. Cines, Jing-fei Dong, Mortimer Poncz, John W. Weisel
Journal: Blood (2013)
Abstract 153: Dexamethasone Inhibits Regeneration and Causes Ventricular Aneurysm in the Neonatal Porcine Heart After Myocardial Infarction
Authors: Lei Ye, Zhonghao Tao Tao, Sze Jie Loo, Liping Su, Shihua Tan, Desiree Abdurrachim, Janise Lalic, Teck Hock Lee, Rusan Tan, Stuart Alexander Cook
Journal: Circulation Research (2019)

Background: The adult mammalian heart has limited ability to repair itself following injury. Zebrafish, newts and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. More recently, we demonstrated that the hearts of neonatal pigs (2-day old) have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth. The current study aims to determine whether acute inflammation is required for CM regeneration after myocardial infarction (MI). Methods: We examined the role of acute inflammation on regenerative capacity of the neonatal pig heart (ages: 2 days postnatal) by intramuscular injection of dexamethasone (Dex) during the first week post-MI surgery. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance (CMR) imaging. Bromodeoxyuridine pulse-chase labeling, histology, and immunohistochemistry were performed to study CM cytokinesis and to quantify myocardial fibrosis. Results: After MI, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day old pigs. In contrast, piglets received Dex injection developed ventricular aneurysm and did not recover function. Dex limited CM cytokinesis via inhibiting aurora-B protein expression and caused mature scar and thinned walls at infarct site. Conclusions: Dex suppresses acute inflammation, inhibits CM regeneration, and causes ventricular aneurysm in neonatal pig hearts after MI.
Front Line Treatment of Elderly Patients with Acute Promyelocytic Leukemia: Long-Term Results of the German AML Cooperative Group
Authors: Eva Lengfelder, Benjamin Hanfstein, Claudia Haferlach, Jan Braess, Utz Krug, Karsten Spiekermann, Torsten Haferlach, Karl-Anton Kreuzer, Hubert Serve, Heinz A. Horst, Susanne Schnittger, Philipp Erben, Bernhard J Woermann, Wolfgang E. Berdel, Maria-Christina Sauerland, Achim Heinecke, Wolf-Karsten Hofmann, Rüdiger Hehlmann, Wolfgang Hiddemann, Thomas Buchner
Journal: Blood (2011)
Cannabis Use Is Associated With Increased Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Findings From the T1D Exchange Clinic Registry
Authors: Gregory L. Kinney, Halis K. Akturk, Daniel D. Taylor, Nicole C. Foster, Viral N. Shah
Journal: Diabetes Care (2019)

OBJECTIVE We examined the frequency of diabetic ketoacidosis (DKA) in cannabis users compared with nonusers in the T1D Exchange clinic registry (T1DX). RESEARCH DESIGN AND METHODS The association between cannabis use by total substance score for cannabis (TSC) and DKA in the past 12 months was examined using a logistic regression model adjusted for potential confounders among adults in the T1DX. RESULTS Of 932 adults with type 1 diabetes, 61 had a TSC &amp;gt;4, which classified them as moderate cannabis users. Adjusting for sex, age at study visit, and HbA1c, cannabis use was associated with a twofold increase in risk for DKA among adults with type 1 diabetes (odds ratio 2.5 [95% CI 1.0–5.9]). CONCLUSIONS Cannabis use was associated with an increased risk for DKA among adults in the T1DX. Providers should inform their patients of the potential risk of DKA with cannabis use.
Increased Charlson Comorbidity Index (CCI) Is Not Associated with Inferior Clinical Outcomes in Patients with Mantle Cell Lymphoma (MCL)
Authors: Derrick Ridley, Subir Goyal, Oscar Calzada, Michael C Churnetski, Jean L. Koff, Mary Jo Lechowicz, Christopher R Flowers, Jonathon B. Cohen
Journal: Blood (2018)
Bosutinib As Therapy For Chronic Phase Chronic Myeloid Leukemia Following Resistance Or Intolerance To Imatinib: 48-Month Update
Authors: Tim H. Brümmendorf, Jorge E. Cortes, H. Jean Khoury, Hagop M. Kantarjian, Dong-Wook Kim, Maureen G. Conlan, Eric Leip, Kathleen Turnbull, Carlo Gambacorti-Passerini, Jeff H. Lipton
Journal: Blood (2013)
Alternate Donor HSCT for Fanconi Anemia (FA): Results of a Total Body Irradiation (TBI) Dose De-Escalation Study.
Authors: Margaret L. MacMillan, Bruce R. Blazar, Todd E. DeFor, Kathryn R. Dusenbery, Jakub Tolar, Heather Zierhut, John E. Wagner
Journal: Blood (2007)
Evaluation of Interventions for Implementation of Thromboprophylaxis in Hospitalized Medical and Surgical Patients At Risk for Venous Thromboembolism: A Systematic Review and Metaanalysis
Authors: Jacqueline M. Cohen, David Morrison, Ian Shrier, Vicky Tagalakis, Jessica D. Emed, William Geerts, Andre Roussin, Susan R. Kahn
Journal: Blood (2011)
Acute Right Ventricular Restrictive Physiology After Repair of Tetralogy of Fallot
Authors: Rajiv R. Chaturvedi, Darryl F. Shore, Christopher Lincoln, Sharon Mumby, Michael Kemp, J. Brierly, Andrew Petros, John M.G. Gutteridge, James Hooper, Andrew N. Redington
Journal: Circulation (1999)

Background —Acute right ventricular (RV) restrictive physiology after tetralogy of Fallot repair results in low cardiac output and a prolonged stay in the intensive care unit (ICU). However, its mechanism remains uncertain. Methods and Results —In the first 24 hours after tetralogy of Fallot repair (n=11 patients), serial prospective measurements were performed of cardiac troponin T, indexes of NO production (NO 2 − and NO 3 − combined as NOx), and iron metabolism and antioxidants. RV diastolic function was assessed by transthoracic Doppler echocardiography. Patients who had a long stay in the ICU were characterized by restrictive RV physiology (nonrestrictive group [n=7]: 3.0±0.6 days [mean±SD]; restrictive group [n=4]: 10.7±3.1 days). Troponin T peak concentration and the area under its concentration-time curve (AUC) were higher in the restrictive RV group (peak: restrictive group 17.0±2.8 μg/L, nonrestrictive group 10.4±4.6 μg/L, P &lt;0.03; AUC: restrictive group 268.8±73.6 μg · h −1 · L −1 , nonrestrictive group 136.2±48.3 μg · h −1 · L −1 , P &lt;0.03). Plasma NOx/creatinine concentrations were higher in the restrictive group than the nonrestrictive group at 2 hours after bypass (restrictive group 1.3±0.4, nonrestrictive group 0.8±0.2; P =0.04) but were similar by 24 hours. Iron loading peaked 2 to 10 hours after bypass and was more severe in the restrictive group (peak transferrin saturation: restrictive group 83.9±13.0%, nonrestrictive group 58.3±16.2%, P =0.05; minimum total iron-binding capacity: restrictive group 0.59±0.21%, nonrestrictive group 0.76±0.06%, P =0.04; minimum iron-binding antioxidant activity to oxyorganic radicals: restrictive group 9.5±22.4%, nonrestrictive group 50.6±11.4%, P =0.01). Conclusions —After tetralogy of Fallot repair, acute restrictive RV physiology is associated with greater intraoperative myocardial injury and postoperative oxidative stress with severe iron loading of transferrin.
Abstract 606: Stimulation of Cardiomyocyte a- and b-Adrenoceptors Uniquely Regulates Exosome Generation and miRNA Content
Authors: Jin-Sook Kwon, Walter J Koch
Journal: Circulation Research (2019)

Background and Purpose: Influence of adrenoceptor (AR) signaling for the regulation of exosomes secreted from cardiomyocytes is unknown and since catecholamines are increased in heart failure (HF), there is interest in uncovering whether α- or β-ARs can induce specific changes in circulating blood exosomes in HF. In this study, we have evaluated whether α- or β-AR stimulation of neonatal rat ventricle myocytes (NRVMs) can alter the number, size or microRNA (miR) content of secreted exosomes. Methods and Results: The number and size distribution of exosomes from NRVMs were evaluated by Nanosight NS300. Phenylephrine (PE, 10 uM for 3 days), an α-AR agonist, increased exosome number significantly of NRVM compared than vehicle (PBS) treatment group (Veh: 7.82X10 8 ± 5.06X10 7 and PE: 10.09X10 8 ± 15.0 X10 7 / 1X10 6 NRVMs, n=3) but Isoproterenol (ISO, 1uM), a β-AR agonist, did not. Both agonists had no effect on exosome size distribution. After purifying total RNA from secreted exosomes, we evaluated the expression level of 37 candidate miR’s, which were selected from previous microarray data. ISO treatment decreased 14 miR’s (miR-222, -106a, -292a, -181b, -210, -489, -214, -1947, -195, -17, -7b, -93, -532 and -19a) and PE increased 5 miR’s (miR-20a, -210, -17-1, -Let7a, and 146b). Importantly, PE or ISO regulated any identical miR’s. As a control for treatment effects, we found that PE and ISO elevated myocyte mRNA levels of ANP and BNP to similar degrees. Conclusions: Both α- and β-AR agonists are can stimulate cardiomyocyte hypertrophy to similar degrees, however they have distinct regulatory patterns for secreted exosomes. This includes the number produced and more importantly, miR content. These miR’s and exosomes found in circulating blood may be able to distinguish and be biomarkers for different modes of maladaptive cardiac hypertrophy and HF.
Abstract 424: Postnatal Resetting of Cardiomyocytes Toward Ground State as a Principal Step in Heart Maturation
Authors: Li Wang, Zheng Li, Fang Yao, Peng Yu, Dandan Li, Zongna Ren, Bingying Zhou
Journal: Circulation Research (2019)

The mammalian postnatal heart undergoes orchestrated and systematic changes to culminate in functional maturation, yet little is known about the cellular and molecular foundations underlying these processes. Here, we reported that cardiomyocytes (CMs) epigenetically and transcriptionally shut down cardiac gene expression immediately after birth, and reset into a ground state with potential enhancers for further programming CMs into distinct subtypes during heart maturation. Large-scale single-cell RNA-sequencing and genetic lineage tracing confirmed the presence of a postnatal ground state of CMs (pngCMs) that were in highest abundance around postnatal day 7 (P7), and recapitulated the developmental route of postnatal CM development. Importantly, this fate resetting mechanism used by CMs was conserved in neonatal heart regeneration upon surgical resection. Furthermore, P7-pngCMs exhibited remarkable regenerative capacity in infarcted hearts. Collectively, our data uncovered CM fate resetting as a pivotal mechanism in postnatal heart development and regeneration, and supported a new model to understand how organs adapt to abrupt environmental changes to gain maturity upon birth.
Novel Evidence That Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells (HSPCs) During Intravascular Hemolysis Requires Attenuation Of The SDF-1–CXCR4 Retention Axis Of HSPCs In Bone Marrow Niches – Implications For Paroxysmal Nocturnal Hemoglobinuria-Induced Mobilization of HSPCs
Authors: Kasia Mierzejewska, Ahmed Abdel-Latif, Gabriela Schneider, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak
Journal: Blood (2013)
Abstract 306: DJ-1 Preserves Mitochondrial Function in the Ischemic Heart by Reducing the Glycation of Complex I
Authors: Yvanna Pantner, Yuuki Shimizu, Rohini Polavarapu, Lian Li, Lih-Shen Chin, John Calvert
Journal: Circulation Research (2019)

Background: DJ-1 is a cytoprotective protein implicated in many cellular processes, including the oxidative stress response and the glycative stress pathway. DJ-1 has proteolytic activity when cleaved under conditions of oxidative stress. We recently found that the cleaved form of DJ-1 attenuates ischemia-reperfusion (I/R)-induced heart failure by reducing glycative stress. Mitochondrial electron transport proteins are susceptible to glycative stress. Here, we sought to determine if DJ-1 regulates the glycation of Complex I after I/R injury. Methods and Results: Initial studies found that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of advanced glycation end products and carboxymethyl-lysine (CML) following I/R.Additionally, CML was shown to be bound to complex I at higher levels in DJ-1 KO hearts. This corresponded with reduced Complex I activity and reduced mitochondrial oxygen consumption in the presence of Complex I substrates. To confirm an association between DJ-1 and Complex I, wildtype animals were subjected to I/R injury and co-immunoprecipitation revealed higher levels of DJ-1 bound to Complex I after I/R. To further determine if DJ-1 influences the glycation of Complex I, an adenoviral approach (AAV9-CMV-DJΔc) was used to over-express the cleaved form of DJ-1. Under I/R conditions, mitochondrial CML levels were attenuated in hearts treated with AAV9-CMV-DJΔc compared to hearts treated with a control virus. Moreover, mitochondria from AAV9-CMV-DJΔc treated hearts showed improved Complex I activity and oxygen consumption. Conclusion: These data demonstrate that DJ-1 plays a role in maintaining Complex I efficiency when under ischemic conditions. In elucidating a specific mechanism for DJ-1’s role in attenuating ischemia-reperfusion-induced heart failure, these data break new ground for potential therapeutic strategies using DJ-1 as a target.
Identifying levels of financial toxicity and unmet needs in cancer patients receiving financial assistance: Exploring trends in populations lacking adequate resources to overcome healthcare barriers.
Authors: Brittnee Barris, Katie Deehr, Eric Anderson, Kathleen D. Gallagher, Shonta Chambers, Alan James Balch
Journal: Journal of Clinical Oncology (2019)

151 Background: The inability to afford healthcare has a widespread effect on cancer patients, notably impacting treatment decisions and outcomes. Patients receiving financial assistance to offset medication costs still face challenges overcoming cost of care barriers. This study investigated sources of concern and financial stress among racial groups and identified solutions to address patients’ needs beyond medication-related costs. Methods: This cross-sectional study utilized secondary survey data collected from cancer patients who received co-payment and/or financial aid from PAF in 2018. Respondents answered questions describing their financial distress and the COmprehensive Score for financial Toxicity (COST) tool (0-44 with lower scores indicating worse toxicity). Descriptive statistics were calculated using means and standard deviations (SD) for continuous variables and frequencies for categorical variables. Two sample t-tests were used for bivariate comparisons between racial groups. Results: Of 494 cancer patients surveyed, 72% were Caucasian, 11% were African American (AA), and 71% indicated a household income of &lt; $48,000. Although this population received financial assistance, cost of medications was still a major barrier to adhering to treatment (59% vs 69%). AA patients reported greater financial burden caused by cost of deductibles/copay/coinsurance (58% vs 50%) and treatment costs not covered by insurance (49% vs 21%). AA patients highly rated day-to-day living expenses as an unmet need (64% vs 40%). COST scores differed significantly between Caucasian (mean 17.7, SD 8.6) and AA cohorts (mean 12.1, SD 8.6; p &lt; .001), driven by the inability to meet monthly expenses at all (35% vs 11%). Of AA, 80% felt they do not have enough money in savings/retirement to cover treatment costs. Overall, the AA cohort reported higher frustration with not being able to work or contribute as much as usual (45% vs 26%). Conclusions: Under-resourced AA cancer patients identify a need for a comprehensive approach to cost of care conversation, to drive better adherence and improved treatment outcomes.