tbuckley/cabot-search huggingface dataset:
Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome
Authors: Josep Ordi-Ros, Luis Sáez-Comet, Mercedes Pérez-Conesa, Xavier Vidal, Antoni Riera-Mestre, Antoni Castro-Salomó, Jordi Cuquet-Pedragosa, Vera Ortiz-Santamaria, Montserrat Mauri-Plana, Cristina Solé, Josefina Cortés-Hernández
Journal: Annals of Internal Medicine (2019)

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).6 university hospitals in Spain.190 adults (aged 18 to 75 years) with thrombotic APS.Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.Anticoagulation intensity was not measured in the rivaroxaban group.Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.Bayer Hispania.
Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses
Authors: Ciara H. O’Flanagan, Kieran R. Campbell, Allen W. Zhang, Farhia Kabeer, Jamie L. P. Lim, Justina Biele, Peter Eirew, Daniel Lai, Andrew McPherson, Esther Kong, Cherie Bates, Kelly Borkowski, Matt Wiens, Brittany Hewitson, James Hopkins, Jenifer Pham, Nicholas Ceglia, Richard Moore, Andrew J. Mungall, Jessica N. McAlpine, Sohrab P. Shah, Samuel Aparicio
Journal: Genome biology (2019)

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumor tissues and patient-derived mouse xenografts for scRNA-seq are not well understood.
Dichotomous role of TGF-β controls inducible regulatory T-cell fate in allergic airway disease through Smad3 and TGF-β–activated kinase 1
Authors: Anthony Joetham, Michaela Schedel, Fangkun Ning, Meiqin Wang, Katsuyuki Takeda, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2019)
Validation Of The Revised International Prognostic Scoring System (IPSS-R) In 1000 Newly Diagnosed MDS Patients With Low- and Intermediate-1 Risk MDS In The European Leukemianet MDS (EUMDS) Registry
Authors: Louise de Swart, Alex Smith, Tom Johnston, Detlef Haase, Jackie Droste, Pierre Fenaux, Argiris Symeonidis, Guillermo Sanz, Eva Hellström-Lindberg, Jaroslav Cermak, Ulrich Germing, Reinhard Stauder, Otilia Georgescu, Marius MacKenzie, Luca Malcovati, Mette Skov Holm, Antonio Medina Almeida, Krzysztof Madry, Borhane Slama, Agnès Guerci-Bresler, Laurence Sanhes, Odile Beyne-Rauzy, Elisa Luño, David Bowen, Theo de Witte
Journal: Blood (2013)
Abstract 517: Glutaminolysis is Required to Initiate Myofibroblast Differentiation and Persistence During Stress
Authors: Andrew A Gibb, Alyssa A Lombardi, Emma K Murray, Yinfei Tan, Pawel K Lorkiewicz, Anh T Huynh, Devin W Kolmetzky, Zolt Arany, Daniel P Kelly, Kenneth B Margulies, Bradford G Hill, John W Elrod
Journal: Circulation Research (2019)

Cardiac fibrosis occurs in ischemic heart failure, genetic cardiomyopathies, diabetes, and aging. While initially considered reparative, resident cardiac fibroblasts (CFs) activation/differentiation to myofibroblasts provide contractile and integral support; however, persistent activation leads to progressive cardiac dysfunction and maladaptive remodeling. Recent reports implicate acute and/or chronic changes in metabolism as a central driver for many cellular differentiation programs. Indeed, metabolite bioavailability is directly linked to the activity of epigenetic-modifying enzymes implicated in lineage commitment and differentiation. We recently identified αKG-dependent lysine demethylases as key contributors to myofibroblast formation. Here, TGFβ stimulated fibroblasts isolated from adult mouse hearts were subjected to next-gen sequencing methodologies (RNA-seq, ATAC-seq, and RRBS-seq) to identify dynamic modifications in chromatin architecture and DNA accessibility at gene loci critical to the myofibroblast gene program. Utilizing unbiased and stable-isotope metabolomics, we correlated chromatin remodeling with a significant decrease in abundance/utilization of s-adenosylmethionine, the methyl donor for cytosine and histone methylation. In addition, a significant increase in αKG abundance driven by enhanced glutaminolysis was observed. To investigate the significance of glutaminolysis and enhanced αKG biosynthesis, we treated CFs with a glutaminase inhibitor (CB-839) and evaluated differentiation. Treatment with CB-839 in the presence of TGFβ prevented activation of the fibrotic gene program (RT-qPCR) and myofibroblast formation. Furthermore, following TGFβ-induced differentiation, inhibition of glutaminolysis was sufficient to revert activated myofibroblasts to a quiescent non-fibrotic phenotype, even during sustained stress. Importantly, this phenomenon is reproducible in CFs derived from human HF patients. Collectively, these results suggest a primary role for metabolism in not only initiating differentiation, but also the persistence of myofibroblasts, potentially through epigenetic-dependent gene transcription, providing new therapeutic targets to treat fibrosis.
Firearms and Dementia: “A Big Deal and a Tough Issue”
Authors: Rebecca Voelker
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Systems biology and big data in asthma and allergy: recent discoveries and emerging challenges
Authors: Howard H.F. Tang, Peter D. Sly, Patrick G. Holt, Kathryn E. Holt, Michael Inouye
Journal: European Respiratory Journal (2019)

Asthma is a common condition caused by immune and respiratory dysfunction, and it is often linked to allergy. A systems perspective may prove helpful in unravelling the complexity of asthma and allergy. Our aim is to give an overview of systems biology approaches used in allergy and asthma research. Specifically, we describe recent "omic"-level findings, and examine how these findings have been systematically integrated to generate further insight.Current research suggests that allergy is driven by genetic and epigenetic factors, in concert with environmental factors such as microbiome and diet, leading to early-life disturbance in immunological development and disruption of balance within key immuno-inflammatory pathways. Variation in inherited susceptibility and exposures causes heterogeneity in manifestations of asthma and other allergic diseases. Machine learning approaches are being used to explore this heterogeneity, and to probe the pathophysiological patterns or "endotypes" that correlate with subphenotypes of asthma and allergy. Mathematical models are being built based on genomic, transcriptomic and proteomic data to predict or discriminate disease phenotypes, and to describe the biomolecular networks behind asthma.The use of systems biology in allergy and asthma research is rapidly growing, and has so far yielded fruitful results. However, the scale and multidisciplinary nature of this research means that it is accompanied by new challenges. Ultimately, it is hoped that systems medicine, with its integration of omics data into clinical practice, can pave the way to more precise, personalised and effective management of asthma.
Efficacy and Safety of Bosutinib in Chronic Phase CML Patients Developing Pleural Effusion Under Dasatinib Therapy
Authors: Mario Tiribelli, Elisabetta Abruzzese, Isabella Capodanno, Federica Sorà, Elena Trabacchi, Alessandra Iurlo, Luigia Luciano, Gianni Binotto, Massimiliano Bonifacio, Mario Annunziata, Monica Crugnola, Renato Fanin
Journal: Blood (2018)
Monoclonal B-Cell Lymphocytosis (MBL) in Blood Donors: Age- and Sex-Specific Prevalence, Clone Size, and IGHV-IGHD-IGHJ Rearrangements
Authors: Youn K. Shim, Jane Rachel, Paolo Ghia, Jeff Boren, Antonis Dagklis, Geri Venable, Fatima Abbasi, Fred Plapp, Robert Vogt, Jay E. Menitove, Gerald Marti
Journal: Blood (2011)
Abstract 478: Identifying Signaling Pathways Regulated by Trophoblasts in Placental Vascular Development Using 3D Tissue Models
Authors: Olga Kashpur, Mary C Wallingford
Journal: Circulation Research (2019)

The placenta is an essential yet transient organ that supports healthy pregnancy and normal fetal development. Placental vascular dysfunction is associated with preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets), fetal growth restriction, hemorrhaging, preterm birth, and loss of life. Placental vascular dysfunction can also negatively impact long-term maternal and offspring health, increasing risk for cardiovascular disease, coronary artery calcification, and stroke later in life. The vasculature of the maternal-fetal interface is uniquely characterized by the presence of trophoblast cells. Multiple trophoblast cell lineages serve essential functions in both the maternal vascular compartment and the feto-placental angioarchitecture. Functional roles for FGF2, VEGF, and angiopoietin signaling pathways in endothelial vasculogenesis and angiogenesis are well supported by a large body of literature, but there is a gap in knowledge of placenta-specific molecular mechanisms that account for the unique interaction of trophoblasts and endothelial cells. I hypothesize that trophoblasts generate angiogenic signals that promote vascular development at the maternal-fetal interface in both an autocrine and paracrine manner. Using 3D assays, I evaluated the role of endovascular cytotrophoblast and syncytiotrophoblast cell lines in establishment of a vascular compartment. Trophoblasts harbor intrinsic angiogenic competency evident by their ability to form angiogenic sprouts and generate 3D vascular networks under defined conditions. My current research implements 3D bioassays, bio-engineered vessels, and chemical inhibition to further investigate paracrine angiogenic signaling between trophoblasts and endothelial cells. Our work is the first to evaluate autocrine and paracrine angiogenic properties of trophoblasts under physiological 3D conditions that mimic development. When coupled with histological evaluation of human placenta, these systems will allow us to better evaluate and understand molecular mechanisms of placental vascular development and vascular dysfunction.
Phenotypical and Functional Characterization of Umbilical Cord Blood-Derived Mesenchymal Stromal Cells Expanded in the Presence of Platelet Lysate and Comparison with Their Bone Marrow-Derived Counterpart
Authors: Maria Ester Bernardo, Maria Antonietta Avanzini, Cesare Perotti, Angela Maria Cometa, Nadia Zaffaroni, Francesca Novara, Antonia Moretta, Claudia del Fante, Rita Maccario, Willem E. Fibbe, Franco Locatelli
Journal: Blood (2008)
Safety and efficacy of a modified XELOX adjuvant regimen for patients with operated stage III colon cancer: a Chinese single-center experience
Authors: Jianhong Peng, Weihao Li, Rongxin Zhang, Junzhong Lin, Jinghua Tang, Yongshan Wen, Zhenhai Lu, Xiaojun Wu, Zhizhong Pan
Journal: Cancer Communications (2019)

Abstract Background A fixed 8‐cycle oxaliplatin and capecitabine (XELOX) regimen has been the standard adjuvant therapy for patients with stage III colon cancer. However, completing the full‐cycle of oxaliplatin is often associated with severe neurotoxicity. To spare patients from the toxic effects, without comprising the required efficacy, we evaluated the safety and efficacy of a modified XELOX (mXELOX) adjuvant chemotherapy regimen with 6 cycles of oxaliplatin and a full cycle of capecitabine. Methods We retrospectively analyzed 330 eligible patients with stage III colon cancer who underwent curative tumor resection followed by mXELOX, standard XELOX or unfinished XELOX adjuvant chemotherapy between December 2007 and April 2015. Associated prognostic factors were investigated and their disease‐free survival (DFS) and overall survival (OS) rates were also determined and compared among the different regimen groups. Results Compared with the standard XELOX group, the mXELOX group had lower total incidence rates of neurotoxicity (39.3% vs. 76.2%, P &lt; 0.001), leucopenia (53.6% vs. 69.8%, P = 0.017) and thrombocytopenia (38.1% vs. 56.3%, P = 0.011). The standard XELOX and mXELOX adjuvant chemotherapy regimens presented with comparable 3‐year DFS rates (86.3% vs. 89.2%; P = 0.838) and 3‐year OS rates (92.7% vs. 97.6%; P = 0.227). Compared to unfinished XELOX chemotherapy, the oncologic benefits of the mXELOX regimen were greater for patients with T4 tumors (3‐year DFS: Hazard ratio [HR], 2.184; 95% confidence interval [CI], 1.051–4.540; P = 0.036; 3‐year OS: HR, 4.529; 95% CI 1.245–16.479; P = 0.022) and for high‐risk patients (3‐year DFS: HR, 1.962; 95% CI 0.964–3.993; P = 0.044; 3‐year OS: HR, 4.193; 95% CI 1.182–14.874; P = 0.026). Conclusions The mXELOX adjuvant chemotherapy presented a comparable survival benefit and lower incidence of toxicity than standard XELOX chemotherapy. It could be an alternative treatment for high‐risk patients with operated stage III colon cancer.
Radiation Drives the Evolution of Orthotopic Xenografts Initiated from Glioblastoma Stem–like Cells
Authors: Joseph H. McAbee, Barbara H. Rath, Kristin Valdez, Dejauwne L. Young, Xiaolin Wu, Uma T. Shankavaram, Kevin Camphausen, Philip J. Tofilon
Journal: Cancer Research (2019)

A consequence of the intratumor heterogeneity (ITH) of glioblastoma (GBM) is the susceptibility to treatment-driven evolution. To determine the potential of radiotherapy to influence GBM evolution, we used orthotopic xenografts initiated from CD133
Abstract 10395: Employee Wellness Program Can Identify Those Who May Benefit From Cholesterol Reduction Efforts
Authors: Dov Shiffman, Judy Z Louie, Michael J McPhaul, James J Devlin
Journal: Circulation (2018)

Introduction: Achieving and maintaining optimal levels of low density lipoprotein cholesterol (LDL-C) reduces risk of cardiovascular (CVD) events. However, many adults do not regularly visit a prim...
Preemptive Rituximab Infusions Efficiently Prevent Relapses In Acquired Thrombotic Thrombocytopenic Purpura. Experience Of The French Thrombotic Microangiopathies Reference Center
Authors: Miguel HIE, Julie Gay, Lionel Galicier, Francois Provot, Sandrine Malot, Pascale Poullin, Guy Bonmarchand, Alain Wynckel, Ygal Benhamou, Philippe Vanhille, Dominique Bordessoule, Jean-Paul Vernant, Agnes Veyradier, Paul Coppo
Journal: Blood (2013)
Abstract 349: Beclin1 as a Critical Regulator of the Endosomal Degradation Pathway
Authors: Mark Lampert
Journal: Circulation Research (2019)

Effective cellular quality control is crucial for cellular homeostasis and cardiac health. Defects in the pathways that regulate the removal of damaged proteins and organelles contribute to heart failure. Autophagy is well known for its role in removing protein aggregates and organelles; however, we recently found that the small GTPase Rab5 and early endosomes also participate in Parkin-mediated mitochondrial clearance. Beclin1 is a scaffolding protein which can form distinct PI3K protein complexes to regulate different processes such as autophagy. Here, we have investigated the role of Beclin1 in regulating the endosomal degradation pathway in mice. We have generated inducible cardiac-specific Beclin1 KO mice to investigate the in vivo role of Beclin1 in myocytes. We found significant contractile dysfunction as early as one week after deletion of Beclin1, which led to increased mortality. Loss of Beclin1 led to rapid development of cardiac hypertrophy as characterized by increased Myh7, Nppa, Nppb , myocyte size, and heart weight/body weight. Furthermore, we found that loss of Beclin1 led to increased inflammatory markers Il6 and Tgfb1 , as well as increased DNA damage/apoptosis in the heart. Ultrastructural analysis revealed Beclin1 deficiency led to significant myocardial disarray, demonstrating the importance of Beclin1 for proper myocyte alignment. These mice also had reduced autophagic flux but increased IGFR-beta receptor protein levels, indicating defects in both the autophagy and endosomal degradation pathways. Additionally, immunofluorescence analysis revealed that Beclin1 colocalizes with Rab5 at the early endosome in cells, and coimmunoprecipitation experiments confirmed their interaction. Together, these data establish the essential role of Beclin1 in cellular homeostasis as a central regulator of endosomal activity.
20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia
Authors: Ilse K. Luirink, Albert Wiegman, D. Meeike Kusters, Michel H. Hof, Jaap W. Groothoff, Eric de Groot, John J.P. Kastelein, Barbara A. Hutten
Journal: New England Journal of Medicine (2019)

Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce.We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima-media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents.Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) - a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter [2.59 mmol per liter]) were achieved in 37 patients (20%). Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, -0.0001 mm per year; 95% confidence interval, -0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively).In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood. (Funded by the AMC Foundation.).
Abstract 263: MYH14 Protects Against of Isoproterenol-induced Left Ventricular Hypertrophy and Fibrosis
Authors: Jessica J Wang, Sunny C Chang, Alex Tran, Jessica Sanchez, Max Yang, Kazuhiro Omi
Journal: Circulation Research (2019)

Objectives: We had previously identified Myh14 as a genetic modifier of isoproterenol-induced left ventricular hypertrophy through a genome-wide association study performed among Hybrid Mouse Diversity Panel strains. Whether left ventricular hypertrophy due to Myh14 deficiency is compensatory or maladaptive is not well established. Moreover, though MYH14 had been previously reported in the intercalated disc of cardiomyocytes, the mechanisms by which Myh14 deficiency leads to left ventricular hypertrophy is unknown. Methods: We performed RNA-seq on cardiac tissues from 12-week old male Myh14 +/+ and -/- mice that had been treated under control versus isoproterenol conditions for 3 weeks. We examined the differentially expressed genes to identify enriched gene ontology (GO) terms altered by Myh14 deficiency at the transcriptional level. Findings: Differential expression analysis showed an enrichment of transcripts coding for extracellular matrix proteins in isoproterenol treated versus control mice, many of which were further enriched in Myh14 -/- versus +/+ mice. Transcripts uniquely differentially expressed due to Myh14 deficiency were enriched for GO terms such as inorganic cation import across plasma membrane, inner ear receptor cell / neuron development, response to purine-containing compound, and sensory perception of mechanical stimulus, supporting the roles these pathways play in mediating the impact of Myh14 deficiency on cardiac remodeling. Conclusions: Our RNA-seq results suggest that MYH14 plays a protective role against mechanical stress. Future directions include elucidation of specific roles that the affected pathways play in mediating mechanical stress as a result by Myh14 deficiency as well as impact on the observed phenotype of left ventricular hypertrophy and fibrosis.
Prognostic Value of Tumor-Infiltrating TIA-1+ Cytotoxic T Cells (TIA1-CTCs) and FOXP3+ Regulatory T Cells (Tregs) in Post-Transplant Lymphoproliferative Disorder (PTLD) Following Solid Organ Transplant (SOT).
Authors: Raymond E. Tsao, Bill Richendollar, Tony Jin, Eric Hsi, Brad Pohlman
Journal: Blood (2007)