tbuckley/cabot-search huggingface dataset:
PWE-059 Noroviral 3C Protease: A Target for Development of An Effective Antiviral Agent
Authors: N Tan, JJ Tan, JB Cooper
Journal: Gut (2016)

<h3>Introduction</h3> Norovirus is the most common cause of viral gastroenteritis in man. It affects approximately 267 million people/annum and, although usually self-limiting, infection is still associated with around 200,000 deaths/annum. Norovirus infection has a significant, detrimental impact on societal infrastructure; it is the leading pathogen responsible for forced-ward closures in the NHS. There are no specific treatments available; the most promising target for antiviral therapy is noroviral 3 C protease (3 CLpro) which processes the polyprotein essential for the production of viral proteins. Inhibiting 3 CLpro would stop viral replication. This study focused on the function of 3 CLpro, especially the cleavage sites from its precursor. <h3>Methods</h3> The wild-type (WT) 3 CLpro sequence was altered with a cysteine to alanine base substitution to create a 3 CLpro mutant with greatly reduced catalytic activity. The mutant was expressed in <i>E.coli</i> and purified using ion exchange and size-filtration chromatography. Protein expression was confirmed by gel electrophoresis and Western blotting. The specificity of 3 CLpro was studied using a spectrophotometric assay and the rates of reaction of mutant and WT 3 CLpro with substrate were compared. The chemical composition of mutant and WT 3 CLpro were examined using mass spectroscopy. <h3>Results</h3> Western blot analysis showed multiple bands indicating that both WT and mutant 3 CLpro appeared to be cleaved out of their precursor. Enzyme kinetic studies, however, confirmed that mutant 3 CLpro had negligible catalytic activity; the WT 3 CLpro’s turnover rate of catalytic activity was 25 times faster than that of mutant 3 CLpro. Mass spectrometry of mutant 3 CLpro generated a mass spectrum and transformed to a protein mass of 18,747.5. This confirmed the identity of noroviral 3 CLpro, which is 19 kDA. <h3>Conclusion</h3> Mutant 3 CLpro was still cleaved out of its precursor despite the fact that it has negligible catalytic activity. The most likely explanation is that the cleavage was effected by an <i>E.coli</i> protease, possibly a metalloprotease, acting at the upstream and downstream boundaries thereby releasing the processed mutant 3 CLpro. The fact that mutant 3 CLpro can be cleaved out of its precursor by host-cell proteases raises the possibility that WT 3 CLpro could also be processed by exogenous proteases, rather than cleaving itself from its precursor. If this action by host cell proteases occurs <i>in vivo</i>, then it might indicate that the norovirus 3 CLpro is only needed for the cleavage of polyproteins within the newly formed virions, which do not have access to host cell proteases. This has significant implications for future research. <h3>Disclosure of Interest</h3> None Declared
Genomic- and Transcriptomic Profiling Of Acute Lymphoblastic Leukemia With Dicentric Chromosomes
Authors: Linda Holmfeldt, Paolo Vignali, Debbie Payne-Turner, Jing Ma, Guangchun Song, Pankaj Gupta, Michael Rusch, Jinghui Zhang, Nyla A. Heerema, Susana C Raimondi, Andrew J. Carroll, Stephen P. Hunger, Mignon L. Loh, Charles G. Mullighan
Journal: Blood (2013)
Optimization of Rituximab for Treatment of DLBCL in Young, High-Risk Patients-Results of the Dense-R-CHOEP Trial of the German High-Grade Lymphoma Study Group
Authors: Norbert Schmitz, Maike Nickelsen, Marita Ziepert, Mathias Haenel, Andreas Viardot, Martin H. Dreyling, Peter Borchmann, Carsten Bokemeyer, Christian Peschel, Hans-Heinrich Wolf, Rolf Mahlberg, Michael Pfreundschuh, Bertram Glass
Journal: Blood (2015)
Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1<sup>+</sup>monocytes
Authors: Takeshi Fujisawa, Keqing Wang, Xi-Lin Niu, Stuart Egginton, Shakil Ahmad, Peter Hewett, Christopher D. Kontos, Asif Ahmed
Journal: Cardiovascular Research (2016)

Atherosclerosis is a chronic inflammatory disease occurring within the artery wall. A crucial step in atherogenesis is the infiltration and retention of monocytes into the subendothelial space of large arteries induced by chemokines and growth factors. Angiopoietin-1 (Ang-1) regulates angiogenesis and reduces vascular permeability and has also been reported to promote monocyte migration in vitro. We investigated the role of Ang-1 in atherosclerosis-prone apolipoprotein-E (Apo-E) knockout mouse.Apo-E knockout (Apo-E-/-) mice fed a western or normal chow diet received a single iv injection of adenovirus encoding Ang-1 or control vector. Adenovirus-mediated systemic expression of Ang-1 induced a significant increase in early atherosclerotic lesion size and monocyte/macrophage accumulation compared with control animals receiving empty vector. Ang-1 significantly increased plasma MCP-1 and VEGF levels as measured by ELISA. FACS analysis showed that Ang-1 selectively increased inflammatory Gr1+ monocytes in the circulation, while the cell-surface expression of CD11b, which mediates monocyte emigration, was significantly reduced.Ang-1 specifically increases circulating Gr1+ inflammatory monocytes and increases monocyte/macrophage retention in atherosclerotic plaques, thereby contributing to development of atherosclerosis.
Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Receptor Upregulation
Authors: Sophie Bernichtein, Natascha Pigat, Nicolas Barry Delongchamps, Florence Boutillon, Virginie Verkarre, Philippe Camparo, Edouard Reyes-Gomez, Arnaud Méjean, Stéphane M. Oudard, Eve M. Lepicard, Mélanie Viltard, Jean-Claude Souberbielle, Gérard Friedlander, Thierry Capiod, Vincent Goffin
Journal: Cancer Research (2016)

Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355-65. ©2016 AACR.
Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth
Authors: Mónica Romero-López, Andrew L. Trinh, Agua Sobrino, Michaela M.S. Hatch, Mark T. Keating, Cristhian Fimbres, David E. Lewis, Paul D. Gershon, Elliot L. Botvinick, Michelle Digman, John S. Lowengrub, Christopher C.W. Hughes
Journal: Biomaterials (2016)
Same-Day Discharge After Percutaneous Coronary Intervention—Reply
Authors: Adhir Shroff, Ian C. Gilchrist, Sunil V. Rao
Journal: JAMA Cardiology (2016)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Cardiology journal
Parathyroid Hormone-Induced Modulation of the Bone Marrow Microenvironment Reduces Leukemic Stem Cells in Murine Chronic Myelogenous-Leukemia-Like Disease Via a TGFbeta-Dependent Pathway
Authors: Daniela S. Krause, Keertik Fulzele, Andre Catic, Michael Hurley, Sanon Lezeau, Robert Hasserjian, Joy Wu, Paola Divieti-Pajevic, Richard A. Van Etten, Ernestina Schipani, David T. Scadden
Journal: Blood (2011)
Efficacy of Imatinib-Based Therapy in a Patient with Resistant NUP214-ABL1 T-Cell Acute Lymphoblastic Leukemia.
Authors: Jacques Delaunay, Raouf Ben Abdelali, Cyrille Touzeau, Patrice Chevallier, Guillaume Thierry, Steven Le Gouill, Sameh Ayari, Jean-Luc Harousseau, Elisabeth Macintyre, Herve Avet Loiseau, Herve Dombret, Pascaline Talmant
Journal: Blood (2007)
FRI0577 A National Electronic Health Record-Enabled Registry in Rheumatology: The Acr's Rheumatology Informatics System for Effectiveness (RISE)
Authors: J. Yazdany, S. Kazi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In 2014, the ACR launched the Rheumatology Informatics System for Effectiveness (RISE), a national electronic health record (EHR)-enabled registry. RISE passively collects data from EHRs of participating practices, provides advanced quality measurement and data analytic capacities, and can be used to fulfill national quality reporting requirements. Here we detail the characteristics of practices participating in RISE, patient characteristics and performance on several nationally endorsed quality measures. <h3>Methods</h3> RISE is a national Qualified Clinical Data Registry (QCDR), allowing collection of data on quality of care without individual patient informed consent. Participating practices enter a Data Use Agreement with the ACR, after which local data are mapped, validated and uploaded regularly to the central registry. Practices can access an analytics dashboard that allows review of up-to-date information on quality measures by provider and practice as well as national benchmarks. RISE currently includes data on numerous quality measures regarding rheumatoid arthritis (RA), drug safety, osteoporosis prevention and treatment, low back pain, and preventive health care (e.g. smoking, blood pressure management). We analyzed data between October 1, 2014 and September 30, 2015 to characterize practices and patients captured in RISE. We also calculated performance on several RA quality measures endorsed by the National Quality Forum (DMARD use, disease activity measurement, functional status measurement). <h3>Results</h3> During the dates examined, RISE included data on 239,302 patients, including 60,354 with RA (Table). Three hundred twelve clinicians across 55 sites contributed data to RISE. Characteristics of patients in RISE are summarized in the Table. For the subset of patients with RA, 50.7% of patients had a disease activity score recorded, 53.2% had a functional status score recorded, and 82.1% were taking a DMARD, as defined by national quality measures. For DMARDs, 34.4% of patients with RA were on brand name biologic or small molecule drug at their last encounter, and 67.0% were receiving a non-biologic DMARD. <h3>Conclusions</h3> The ACR9s national EHR-enabled registry will provide critical infrastructure for improving quality of care in rheumatology and will serve as a unique data source to generate new knowledge regarding rheumatic disease. Data validation and mapping is ongoing and RISE will be available to both the research and clinical community to use to advance rheumatology. <h3>Disclosure of Interest</h3> None declared
Central Line-Associated Blood Stream Infections Following Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: Incidence, Risk Factors, and Impact On Survival
Authors: Joshua Lukenbill, Lisa Rybicki, Mikkael A. Sekeres, Alexander Copelan, Omer Zaman, Housam Haddad, Hien K. Duong, Brian T. Hill, Matt Kalaycio, Ronald Sobecks, Rabi Hanna, Thomas Fraser, Megan DiGiorgio, Brian J. Bolwell, Edward A. Copelan
Journal: Blood (2012)
Lymphoma Occurring Over the Age of 90: Clinical Presentation and Outcome
Authors: Adrien Trebouet, Tony Marchand, Richard Lemal, Emmanuel Gyan, Florence Broussais, Yann Guillermin, Hélène Monjanel, Gilles Salles, Steven Le Gouill, Stephanie Boulanger, Sandra Leguyader, Albert Collignon, Delphine Rossille, Catherine Thieblemont, Thierry Lamy, Roch Houot
Journal: Blood (2012)
Allogeneic Hematopoetic Stem Cell Transplantation (SCT) In Children with ALL: Outcome of Matched Sibling Donor SCT (MSD-SCT) Is Equivalent to Unrelated Well Matched Donor HSCT (MD-HSCT) A Report From the Prospective International Multicenter Trial ALL-SCT-BFM 2003
Authors: AndrÉ Schrauder, Arend von Stackelberg, Martin Schrappe, Thomas Klingebiel, Peter Bader, Wolfram Ebell, Rupert Handgretinger, Karl-Walter Sykora, Johanna Schrum, Bernhard Kremens, Karoline Ehlert, Michael Albert, Roland Meisel, Güungör Tayfun, Wolfgang Holter, Brigitte Strahm, Bernd Gruhn, Ansgar S Schulz, Martin Zimmermann, Ulrike Pötschger, Christina Peters
Journal: Blood (2010)
Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing
Authors: James R Price, Kevin Cole, Andrew Bexley, Vasiliki Kostiou, David W Eyre, Tanya Golubchik, Daniel J Wilson, Derrick W Crook, A Sarah Walker, Timothy E A Peto, Martin J Llewelyn, John Paul
Journal: The Lancet Infectious Diseases (2016)

BackgroundHealth-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus, but the dearth of evidence from non-outbreak situations means that routine health-care worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place.MethodsIn this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission.FindingsBetween Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7–37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8–50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162–399) at a rate of 38 (IQR 34–42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected.InterpretationIn the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains.FundingUK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England.
AVE5026: A Novel, Extractive Heparinoid with Enriched Anti-Xa Activity and Enhanced Antithrombotic Activity.
Authors: Debra Hoppensteadt, Josephine Cunanan, Eric Geniaux, Martin Lorenz, Christian Viskov, Pascal Ythier-Moury, Jean-Francois Brin, Walter Jeske
Journal: Blood (2007)
Phase 1 Study of Tazemetostat (EPZ-6438), an Inhibitor of Enhancer of Zeste-Homolog 2 (EZH2): Preliminary Safety and Activity in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) Patients
Authors: Vincent Ribrag, Jean-Charles Soria, Jean-Marie Michot, Anna Schmitt, Sophie Postel-Vinay, Fontanet Bijou, Blythe Thomson, Heike Keilhack, Stephen J. Blakemore, Larisa Reyderman, Pavan Kumar, Greg Fine, Alice McDonald, Peter T Ho, Antoine Italiano
Journal: Blood (2015)
Ten Year-Long Term Survival After up-Front Autologous Stem Cell Transplantation in Multiple Myeloma: Results From Two Prospective Clinical Trials
Authors: Elena Zamagni, Francesco Di Raimondo, Francesca Patriarca, Patrizia Tosi, Annalisa Pezzi, Claudia Cellini, Paola Tacchetti, Sonia Ronconi, Silvestro Volpe, Lucia Pantani, Lucio Catalano, Mauro Fiacchini, Emanuele Angelucci, Luciano Masini, Alessandro Gozzetti, Piero Galieni, Beatrice Zannetti, Franco Narni, Annamaria Brioli, Carolina Terragna, Antonio Lazzaro, Katia Mancuso, Catello Califano, Antonio Ledda, Nicoletta Testoni, Michele Baccarani, Michele Cavo
Journal: Blood (2012)
Diagnosis and Treatment of Polycythemia Vera (PV) in Russian Federation: Single Center Experience
Authors: Irina N. Subortseva, Tamara I Kolosheinova, Elena I Pustovaya, Elena K. Egorova, Alla M. Kovrigina, Ulia V Pliskunova, Tatiana V Makarik, Adham O Abdullaev, Anait L. Melikyan
Journal: Blood (2015)
Chemotherapy-Only Preparative Regimen for T-Cell Depleted Hematopoietic Stem Cell Transplantation of Patients with Fanconi Anemia From Alternative Donors
Authors: Farid Boulad, Stella M. Davies, David A. Williams, David A Margolis, Elizabeth G Klein, Leslie E. Lehmann, Christine Duncan, Eva C. Guinan, Parinda A. Mehta
Journal: Blood (2012)
Final Results of Lower Dose Fludarabine (F) and Cyclophosphamide (C), and High Dose Rituximab (R), (FCR-Lite) for Patients with Untreated Chronic Lymphocytic Leukemia (CLL).
Authors: Ahmad A. Tarhini, S. Land, L. Pietragallo, A. Laman, M. Sulecki, S. Marks, D. Meisner, P.M. Schaefer, Kenneth A. Foon
Journal: Blood (2007)
AB0127 The Frequency of Nuerological Involvement in Sjögren's Syndrome: A Single Center Experience
Authors: A. Şahin, M. Şahin, A. Camcı, D. Seven, D. Seven
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Sjögren9s syndrome is an autoimmune rheumatic disease that affects many glandular and extra-glandular tissues (1). Autoantibodies (mainly anti-Ro-SS-A and anti-La-SS-B) contribute to playing roles in its clinical pictures (2). Central and peripheral nervous system involvement may be seen as different sign, symptoms and varying its frequencies (2). <h3>Objectives</h3> The aim of this study is to investigate the frequency of neurological and other involvement patterns of the Sjögren9s syndrome (SjS). <h3>Methods</h3> Between June 2015 and December 2015, fifty-eight-SjS patients that following-up at Cumhuriyet University Medical Faculty Rheumatology-Internal Medicine Department were evaluated in the study. The clinical complaints, glandular and extra-glandular findings, age, sex, other epidemiological data, ANA, RF, anti-Ro/La, C3, C4, IgG, IgA, IgM levels were recorded. <h3>Results</h3> The mean age of the patients was 47.8±1.3 years, and the mean age at diagnosis was 46.8±1.2 years. Of the SjS patients, fifty-four (93.1%) were female and four (6.9%) were male. The frequencies of the clinical symptoms were as follows arthralgia in 81%, arthritis in 48.3%, skin dryness in 50%, rashes (including palpable purpuric lesions) in 17.2%, biopsy proven vasculitic lesions in 5.2%. The frequencies of the neurological symptoms were as follows headaches in 32.8%, localized numbness in 5.2%, seizure in 1.7%, paresthesia in 3.4%, diffuse nonfocal symptoms in 1.7% (Figure 1). The total frequency of neurological involvement was 24.1% in SjS patients. Peripheral nervous system involvement in 8.6%. The findings of the magnetic resonans imaging of the patient with neurological involvement were as non-spesific gliotic lesions in 21.4%, periventricular lesions in 28.6%, paranchymal vasculitic lesions in 35.7%, multiple sclerosis-like plaques in 14.3%. There was found that anti-Ro positivity in 58.6%, anti-La in 19.2%, RF in 51.7%, ANA in 48.3%, low complement levels in 15.5%. However, anti-Ro positivity was lower in patient with neurological involvement than in patient without neurological involvement (p=0.025). <h3>Conclusions</h3> The neurological involvement should be kept in mind when the patient has been diagnosed as SjS. It can be seen than it is expected. In addition, further studies need to be done to evaluate the role of anti-Ro autoantibody in SjS patients with neurological involvement. <h3>References</h3> Mavragani CP, Moutsopoulos HM. Sjogren syndrome. CMAJ 2014 Oct 21;186(15):E579–86. doi: 10.1503/cmaj.122037. Epub 2014 Feb 24. Soliotis FC, Mavragani CP, Moutsopoulos HM. Central nervous system involvement in Sjogren9s syndrome. Ann Rheum Dis 2004 Jun;63(6):616–20. <h3>Acknowledgement</h3> We would like to thank to Ziynet Çınar, M.D. for her statistical analysis <h3>Disclosure of Interest</h3> None declared
Biological and Clinical Relevance of Surrogate Markers of IgVH Mutational Status in B-Cell Chronic Lymphocytic Leukemia.
Authors: Fortunato Morabito, Marta Lionetti, Giovanna Cutrona, Katia Todoerti, Serena Matis, Massimo Gentile, Mauro Spriano, Vincenzo Callea, Gianluca Festini, Stefano Molica, Giorgio Lambertenghi Deliliers, Manlio Ferrarini, Antonino Neri
Journal: Blood (2008)