tbuckley/cabot-search huggingface dataset:
Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial
Authors: Lars Christian Haugli Bråten, Mads Peder Rolfsen, Ansgar Espeland, Monica Wigemyr, Jörg Aßmus, Anne Froholdt, Anne Julsrud Haugen, Gunn Hege Marchand, Per Martin Kristoffersen, Olav Lutro, Sigrun Randen, Maja Wilhelmsen, Bendik Slagsvold Winsvold, Thomas Istvan Kadar, Thor Einar Holmgard, Maria Dehli Vigeland, Nils Vetti, Øystein Petter Nygaard, Benedicte Alexandra Lie, Christian Hellum, Audny Anke, Margreth Grotle, Elina Iordanova Schistad, Jan Sture Skouen, Lars Grøvle, Jens Ivar Brox, John-Anker Zwart, Kjersti Storheim
Journal: BMJ (2019)

Abstract Objective To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). Design Double blind, parallel group, placebo controlled, multicentre trial. Setting Hospital outpatient clinics at six hospitals in Norway. Participants 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. Interventions Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. Main outcome measures The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. Results In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was −1.6 (95% confidence interval −3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was −2.3 (−4.2 to−0.4, P=0.02) for patients with type 1 Modic changes and −0.1 (−2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. Conclusions In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. Trial registration ClinicalTrials.gov NCT02323412 .
Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease
Authors: Govindarajan Thangavelu, Jing Du, Katelyn G. Paz, Michael Loschi, Michael C. Zaiken, Ryan Flynn, Patricia A. Taylor, Andrew Kemal Kirchmeier, Angela Panoskaltsis-Mortari, Leo Luznik, Kelli P. MacDonald, Geoffrey R. Hill, Ivan Maillard, David H. Munn, Jonathan S. Serody, William J. Murphy, David Miklos, Corey S. Cutler, John Koreth, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz, Carol Dahlberg, Andrew T. Miller, Bruce R. Blazar
Journal: Blood (2019)
Abstract 839: Sphingosine 1-Phosphate Receptor 1 in Cardiomyocytes Protects Against Cardiac Fibrosis
Authors: Desiree F Leach, Jayne Wolfe, Ryan Jorgensen, Bianca Lavelle, Sanjiv Shah, Lisa Wilsbacher
Journal: Circulation Research (2019)

Sphingosine 1-phosphate receptor 1 (S1P 1 , encoded by S1pr1 ) is a G protein-coupled receptor that binds the ligand S1P and signals in multiple cell types including endothelium and cardiomyocytes. We previously demonstrated that excision of S1pr1 in cardiomyocytes during embryonic development leads to ventricular noncompaction and perinatal death in most but not all mutant mice. To investigate roles for S1P 1 in adult cardiomyocytes, we used three conditional S1pr1 deletion strategies. Mice that survived early embryonic deletion of S1pr1 in cardiomyocytes using Mlc2a- Cre demonstrated interstitial cardiac fibrosis by 4 months of age. Animals with later embryonic deletion of cardiomyocyte S1pr1 using αMHC-Cre escaped the ventricular noncompaction phenotype, but they displayed significantly increased interstitial fibrosis after isoproterenol infusion. Likewise, S1pr1 excision from cardiomyocytes in adult mice using αMHC-MerCreMer led to increased cardiac fibrosis after angiotensin II infusion. In all conditional S1pr1 excision strategies, systolic function in mutant mice remained similar to control mice. Finally, we conditionally deleted the sphingosine kinases Sphk1 and Sphk2 in developing cardiomyocytes and found no reduction in survival for cardiomyocyte Sphk1/2 mutant mice. These results suggest that S1P from non-cardiomyocyte sources support cardiac development, and that cardiomyocyte S1P 1 activity protects against cardiac fibrosis.
Abstract 406: Plasminogen Regulates Mesenchymal Stem Cell-mediated Tissue Repair After Ischemia Through Cry61
Authors: Hao Duan, Zhengqiang He, Alan Mitteer, Hyun-Jun Kim, Eujing Yeo, Hongyu Han, Ling Qin, Yi Fan, Yanqing A Gong
Journal: Circulation Research (2019)

Objective: Stem cell transplantation has emerged as a promising strategy for improving post-ischemic tissue repair. However, the poor survival and persistence of the transplanted cells including mesenchymal stem cells (MSCs) in the hostile ischemic microenvironments represents a major therapeutic barrier. Previous work shows that plasminogen (Plg) promotes post-injury tissue repair by mobilizing hematopoietic stem cell from bone marrow to circulation. Here our studies aim to define the role of Plg in microenvironment-dependent, MSC-mediated tissue repair after hindlimb ischemia. Approach and Results: Our studies show that Plg stimulates MSC proliferation and migration under normoxia and promotes MSC survival under hypoxia. Hindlimb ischemia was induced in Plg-deficient (Plg -/- ) and wild-type (Plg +/+ ) mice by ligation of femoral artery, followed by injection with fLuc/tdTomato + MSCs into the ischemic limbs. Our data show that Plg deficiency abolishes MSC survival, migration, and proliferation in the ischemic limbs, and abrogates MSC-mediated blood reperfusion, neovascularization and tissue repair after ischemia, suggesting that Plg is critical for MSC-mediated tissue repair. Furthermore, multiplex cytokine array analysis identifies Cyr61, a pro-angiogenic factor, as a downstream target of Plg in MSCs. Plg cleaves and activates Cyr61, which is required for Plg-stimulated MSC survival and migration. Finally, Plg-mediated Cry61 cleavage further promotes EC migration and neovascularization in vitro and in vivo. Conclusions: Our study suggests that Plg promotes MSC survival and persistence in ischemic limbs and improves tissue repair. We identify an underlying mechanism, by which Plg induces Cyr61 cleavage and activation in MSCs, enhancing MSC survival and migration and promoting EC migration and neovascularization. Thus, targeting Plg/Cyr61 may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.
Soluble CD30 Levels Are Highest in Autoimmune Hemolytic Anemia (AIHA) and Lymphoma among the Hematologic Disorders, but Are Not Elevated in ITP.
Authors: Eugene R. Ahn, Eckhard R. Podack, Gabriella Lander, Carlos J. Bidot, Wenche Jy, Yeon S. Ahn
Journal: Blood (2004)
Successful of Chemo-Free Treatment with Dasatinib and Blinatumomab in a Pediatric EBF1-PDGFRβ Positive Acute Lymphoblastic Leukemia
Authors: Fara Petruzziello, Giovanna Giagnuolo, Giovanni Cazzaniga, Giuliana Beneduce, Franco Locatelli, Pio Stellato, Grazia Fazio, Giuseppe Mirabelli, Giuseppe Menna, Rosanna Parasole
Journal: Blood (2018)
Internet addiction severity and risk for psychopathology, serious mental illness, and suicidalities: a cross-sectional study
Authors: Wan-jun Guo, Yu-jie Tao, Xiao-jing Li, Xia Lin, Ya-jing Meng, Xia Yang, Hui-yao Wang, Ya-min Zhang, Wan-jie Tang, Qiang Wang, Wei Deng, Lian-sheng Zhao, Xiao-hong Ma, Ming-li Li, Ting Chen, Jia-jun Xu, Jing Li, Wei Hao, Sing Lee, Jeremy W Coid, Andrew J Greenshaw, Tao Li
Journal: The Lancet (2019)
Priorities for developing respiratory syncytial virus vaccines in different target populations
Authors: Simon B. Drysdale, Rachael S. Barr, Christine S. Rollier, Christopher A. Green, Andrew J. Pollard, Charles J. Sande
Journal: Science Translational Medicine (2020)

The development of an effective vaccine against respiratory syncytial virus (RSV) has been hampered by major difficulties that occurred in the 1960s when a formalin-inactivated vaccine led to increased severity of RSV disease after acquisition of the virus in the RSV season after vaccination. Recent renewed efforts to develop a vaccine have resulted in about 38 candidate vaccines and monoclonal antibodies now in clinical development. The target populations for effective vaccination are varied and include neonates, young children, pregnant women, and older adults. The reasons for susceptibility to infection in each of these groups may be different and, therefore, could require different vaccine types for induction of protective immune responses, adding a further challenge for vaccine development. Here, we review the current knowledge of RSV vaccine development for these target populations and propose a view and rationale for prioritizing RSV vaccine development.
Abstract 843: Non-oxidized Protein Kinase G 1 Alpha Antagonizes mTORC1 Signaling in a Tuberin-dependent Manner to Ameliorate Cardiac Disease
Authors: Christian U Oeing, Mark J Ranek, Brittany L Dunkerly-Eyring, David A Kass
Journal: Circulation Research (2019)

Rationale: Protein kinase G 1α (PKG1α) confers anti-hypertrophic effects in hearts subjected to mechanical and neurohumoral stress. Human heart failure with a reduced ejection fraction (HFrEF) and mouse pressure overloaded hearts present with increased mechanistic target of rapamycin complex 1 (mTORC1) activity, protein aggregation, oxidative stress, and, as we previously described, increased PKG1α disulfide dimer formation indicative of PKG1α oxidation. Recently we demonstrated that stimulation of PKG1α phosphorylates tuberin (TSC2) at one specific serine, S1365, to inhibit mTORC1 signaling and attenuate pathological hypertrophy. Objective: To determine if the redox state of PKG1α impacts its ability to target TSC2 signaling in a chronic pressure-overload mouse model exhibiting pathologic hypertrophy. We hypothesize non-oxidized PKG1α will increase TSC2 S1365 phosphorylation to antagonize mTORC1 signaling, thereby enhancing autophagic flux to clear protein aggregates, culminating in ameliorated cardiac disease. Methods and Results: Mice expressing a non-oxidizable (redox-dead) PKG1α (cysteine 42 serine, CS) knock-in mutation and wild type (WT) littermate controls were subjected cardiac pressure overload stress via transaortic constriction (TAC) or sham surgeries. Following TAC, PKG1α CS mice exhibited reduced mTORC1 activation leading to increased autophagic flux and preventing protein aggregation, compared to WT mice. PKG1α CS TAC mice had decreased expression of the hypertrophic genes, attenuated cardiac hypertrophy (p&lt;0.0001), and improve fractional shortening compared to WT TAC mice (28.14%±10.82 in WT vs. 47.42%±15.62 in CS; p&lt;0.01). Treating WT TAC mice with an mTORC1 inhibitor (everolimus) abrogated mTORC1 hyperactivation, which lead to enhanced autophagic flux, attenuated hypertrophy, and improved cardiac function. Crossing PKG1α CS mice with TSC2 S1365 phospho-null mice resulted in increased cardiac hypertrophy and reduced lifespan (p&lt;0.05). Conclusions: Preventing PKG1α oxidation attenuates mTORC1 activation to enhance autophagic flux, prevent protein aggregation, and ameliorate pathological hypertrophy in following cardiac pressure overload, dependent onTSC2 S1365 phosphorylation.
Phase I Study of Ipilimumab (Neutralizing Monoclonal Anti-CTLA4 Antibody) To Treat Relapse of Malignancy after Allogeneic Hematopoietic Stem Cell Transplantation: Evidence of Tumor Regression without Induction of GVHD.
Authors: Asad Bashey, Bridget Medina, Sue Corringham, Mildred Pasek, Ewa Carrier, Howard Streicher, Israel Lowy, James R. Mason, Robert J. Soiffer, Edward D. Ball
Journal: Blood (2006)
Timely administration of antibiotics in febrile neutropenia per updated ASCO/IDSA guidelines.
Authors: Krishna Bilas Ghimire, Po-Hung Lin, Irum Khan, Kasandra Cadman, LeeAnn Valero, Janet Golick, Maria Walker, Eileen Knightly, Jennifer Windhorst, Jovonne Owens, Patrick Joseph Fleming, Sandra Cuellar, John Crawford, Lawrence Eric Feldman, Neeta K. Venepalli
Journal: Journal of Clinical Oncology (2019)

41 Background: Current ASCO guidelines for management of febrile neutropenia (FN) recommend initial antibiotic administration within one hour of triage, and initial assessment within 15 minutes of triage for patients presenting with FN within 6 weeks of chemotherapy. The University of Illinois Cancer Center (UICC) implemented an early identification and management strategy in the ambulatory setting for FN in 2017, with success in increasing the percentage of FN patients receiving antibiotics within 2 hours from 50% to 92% over a 6 months (05/2017-11/2017) period. Given updated joint ASCO/IDSA guidelines, we aimed to increase percentage of FN patients receiving antibiotics within 1 hour from 56% to more than 90% over 16 months. Methods: A multidisciplinary team involving oncology, hematology (attendings and fellows), pharmacy, and nursing met quarterly to review FN cases including time to antibiotic administration and documentation of prompt assessment. Two Plan-Do-Study-Act (PDSA) cycles were completed, including development and deployment of an electronic medical record automated order set and targeted education for fellows and nurses. Results: Between 12/17 and 04/19, of 7 patients with FN, 100% (N = 7) received antibiotics in clinic. The percentage of FN patients receiving antibiotics within 1 hour of triage post first and second interventions was as follows: 25% (N = 1), 100% (N = 4). 100% (N = 7) of FN patients had documentation of prompt assessment, but time from triage was not specified. Conclusions: We were successful in improving the percentage of FN patients receiving antibiotics from 56% to more than 90% over 16 months. We are targeting our next PDSA cycle to increase assessments within 15 minutes of triage. Additional future interventions include tailoring antibiotics based on FN with low or high risk of complication via focus group and root case analyses discussion with our attendings, fellows, and nurses, and collaborating with ED on a standard care pathway for FN management.
Abstract 824: Thromboxane/Prostanoid Receptor Activation Increases Calpain-Mediated Proteolysis and Alters Calcium Handling and Fibrosis Following Right Ventricular Pressure Overload
Authors: James D West, Kyungsoo Kim, Toshio Suzuki, Christy Moore, Bjorn C Knollmann, Erica J Carrier
Journal: Circulation Research (2019)

In pulmonary arterial hypertension (PAH), the right ventricle undergoes remodeling and fibrosis as it struggles to adapt to the increased pressure overload. RV dysfunction and failure is the primary cause of death in PAH patients. The G protein-coupled thromboxane/prostanoid receptor (TPr) is expressed in vascular smooth muscle, myofibroblasts, and immune cells, and is upregulated in cardiomyocytes following PAH. Activation of the cardiomyocyte TPr increases intracellular calcium via G αq /IP 3 ; activation of the receptor in other cells leads to fibrosis and vasoconstriction. The TPr is activated by isoprostane as well as thromboxane, which suggests that the receptor could contribute to deleterious remodeling during cardiac stress. Our previous studies demonstrate that TPr antagonism prevents RV fibrosis and dilatation in murine models of PAH, without affecting pressures. Because the TPr can signal through Gq, we hypothesized that its activation in PAH causes changes in cardiomyocyte calcium-handling proteins which contribute to remodeling and failure. In this study, we used pulmonary arterial banding (PAB) to induce fixed pressure overload of the RV. Mice were treated for 4 weeks past PAB with normal drinking water or water containing 25 mg/kg/day of the TPr antagonist ifetroban, and either underwent pressure-volume catheterization and whole RV evaluation, or cardiomyocytes were isolated for calcium handling and protein. PAB caused an increase in cardiomyocyte resting (end-diastolic) intracellular calcium, which was ameliorated in mice given TPr antagonist. The increased intracellular calcium following PAB was associated with increased activity of the calcium-activated protease calpain, also blocked with TPr antagonism. There was no decrease in caffeine-mediated release of calcium from the sarcoplasmic reticulum (SR) at 4 weeks past PAB, and phosphorylation of phospholamban was increased, suggesting compensation to drive calcium into the SR. Our findings suggest that TPr activation produces alterations in RV calcium handling, signaling, and calpain activity that contribute to deleterious remodeling and early failure in pressure overload. Therapeutic TPr antagonism may help preserve RV function in patients with PAH.
Hematopoietic Stem Cell Transplantation in Children with Refractory Acute Lymphoblastic Leukemia
Authors: Yasuhiro Okamoto, Yozo Nakazawa, Masami Inoue, Kenichiro Watanabe, Hiroaki Goto, Nao Yoshida, Maiko Noguchi, Atsushi Kikuta, Koji Kato, Yoshiko Hashii, Yoshiko Atsuta, Motohiro Kato
Journal: Blood (2018)
Intraclonal Diversification Occurs in Chronic Lymphocytic Leukemia Expressing B Cell Receptors Belonging to the IGHV4 Gene Family
Authors: Filippo Vit, Francesca Maria Rossi, Tiziana D'Agaro, Tamara Bittolo, Antonella Zucchetto, Erika Tissino, Federico Pozzo, Pietro Bulian, Massimo Degan, Eva Zaina, Ilaria Cattarossi, Paola Nanni, Hillarj Chivilò, Giovanni Francesco D'Arena, Enrico Santinelli, Annalisa Chiarenza, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Giovanni Del Poeta, Valter Gattei, Riccardo Bomben
Journal: Blood (2018)
Gender dysphoria researchers did not veer from research norms, says ethics review
Authors: Jacqui Wise
Journal: BMJ (2019)

The UK Health Research Authority has concluded that the team carrying out a controversial study offering puberty blockers to adolescents with gender dysphoria worked in accordance with recognised practice for health research and, in some areas, such as patient involvement and transparency, were ahead of normal practice at the time.1

The arm’s length body of the Department of Health and Social Care for England found no cause for the study to be reviewed further by a research ethics committee or to be considered for suspension or termination. It also found no cause for concern about the oversight of the study by the sponsor or chief investigator.

Several concerns had been raised about the study “Early pubertal suppression in a carefully selected group of adolescents with gender identity disorders” undertaken at London’s Tavistock and Portman NHS Foundation Trust.23

The study, which started recruitment in 2011, involved the use of gonadotrophin releasing hormone analogue (GnRHa) to suppress puberty in 44 people aged between 11 and …
Supplementation with Selenium As Prevention for the Development of Mucositis in Patients Undergoing HSCT. Results of a Pilot Study
Authors: Olga Cantu Rodriguez, David Gomez-Almaguer, Cesar Homero Gutierrez Aguirre, Consuelo Mancias, Luz del Carmen Tarín Arzaga, Andrés Gómez-De León, Miguel Herrera-Rojas, Lourdes Garza-Ocañas, Jose Angel Hawing
Journal: Blood (2018)
Abstract MP111: Loss of Myosin Binding Protein H-like Causes Cardiacconduction Abnormalities
Authors: David Y Barefield, Ibrahim Tahtah, Jordan Sell, Michael Broman, Brigitte Laforest, Sean Yamakawa, Megan Puckelwartz, Andrew Wasserstrom, Elizabeth M McNally
Journal: Circulation Research (2020)

A premature truncation variant in MYBPHL in humans and a loss of Mybphl in mice associates with dilated cardiomyopathy (DCM), atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL) and is expressed highly in the atria and in foci throughout the ventricle. We hypothesize that MyBP-HL is required for proper formation and function of the conduction system. Surface telemetry found atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a faster atrial relative refractory period and atrial tachycardia in Mybphl -null mice. Ca 2+ transient analysis revealed that isolated Mybphl -null atrial cardiomyocytes had an increased occurrence of triggered Ca 2+ waves and more heterogenous Ca 2+ release than wild-type (WT) controls. Super-resolution microscopy revealed ryanodine receptor disorganization in Mybphl het and null atrial cardiomyocytes compared to WT controls. Immunofluorescence microscopy in WT adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles showed 10% as many MyBP-HL-positive cells compared to WT. Lightsheet microscopy of perinatal day 5 hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the Cntn2-positive ventricular conduction system in WT hearts, but this association was not apparent in Mybphl heterozygous null hearts. These data, abnormal Ca 2+ release, shorter atrial refractory period, and atrial dilation could account for the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene could cause ventricular arrhythmias.
HHV-6 Viremia Is Frequent but the Incidence of Encephalitis Is Low in Double-Unit Cord Blood Transplant Recipients Transplanted without ATG
Authors: Amanda L. Olson, Parastoo B. Dahi, Junting Zheng, Sean Devlin, Marissa N. Lubin, Anne Marie Gonzales, Sergio A. Giralt, Doris M. Ponce, Nancy A. Kernan, Andromachi Scaradavou, Genovefa Papanicolaou, Juliet N. Barker
Journal: Blood (2012)
Discrepant Mutational Composition between Myeloid Sarcoma and Bone Marrow Leukemia Revealed through Targeted Next Generation Sequencing
Authors: Sze Hwei Lee, Tai-Chung Huang, Yuan Chang-Tsu, Yuan-Yeh Kuo, Rung-Jing Chiou, Yi-Kuang Chuang, Hwei-Fang Tien, Jih-Luh Tang
Journal: Blood (2018)
Preliminary Results From a Phase III Trial of Imatinib Versus Imatinib in Combination with Cytarabine in Patients with First Chronic Phase Myeloid Leukemia
Authors: Noortje Thielen, Bronno van der Holt, Jan J Cornelissen, Rianne Ammerlaan, Pieter Sonneveld, Marie José Kersten, J.H. Frederik Falkenburg, Harm Sinnige, Martin Schipperus, Anton Schattenberg, Marinus van Marwijk Kooy, Willem Smit, Gregor Verhoef, Isabel Chu, Peter Valk, Jeroen JWM Janssen, Gert Ossenkoppele
Journal: Blood (2011)