tbuckley/cabot-search huggingface dataset:
OP0051 Dipeptidyl-Peptidase-4 (DPP4) Characterizes A Subpopulation of Fibrosis-Promoting Fibroblasts and Is A Molecular Target for The Treatment of Fibrosis
Authors: A.M. Soare, C. Dees, Y. Zhang, R. Liang, T. Wohlfahrt, S. Rauber, N. Lin, C.-W. Chen, A. Ramming, O. Distler, C. Mihai, G. Schett, J. Distler
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Dipeptidyl-peptidase-4 (DPP4/CD26) has been recently identified as a marker for a special fibroblast lineage responsible for the tissue remodeling during physiological wound healing. Fibrotic disease may be considered as a consequence of persistent, exaggerated and uncontrolled tissue repair processes. Systemic sclerosis (SSc) is associated with the highest mortality among the connective tissue disorders and effective antifibrotic therapies are still lacking. DPP4 inhibitors are already used in treatment of diabetes. <h3>Objectives</h3> The aim of the study was to characterize the DPP4 positive cells, investigate the expression of DPP4 in SSc skin and to evaluate the antifibrotic effect of DPP4 inhibitors in preclinical models of systemic sclerosis. <h3>Methods</h3> Mouse fibroblasts were isolated and DPP4 positive cells characterized by fluorescence activating cell sorting. Expression of DPP4/CD26 in human and murine skin was analyzed by immunofluorescence. DPP4 inhibitors were tested in two different concentrations administered orally (Sitagliptin 3mg/kg/d and 10mg/kg/d, Vildagliptin 1,5mg/kg/d and 15mg/kg/d) in bleomycin induced skin fibrosis and in sclerodermatous chronic graft-versus-host disease mouse model (cGvHD). The antifibrotic effect on skin was assessed by hydroxyproline assay, alpha smooth muscle cells quantification and measuring the dermal thickness. Inflammatory infiltrate was assessed by CD45 immunofluorescence staining. <h3>Results</h3> We have demonstrated that DPP4/CD26 positive cells are a unique population of cells implicated in fibrosis. DPP4/CD26 positive cells were increased not only in experimental fibrosis, but also in skin biopsies from SSc patients as compared to healthy volunteers. Treatment with DPP4 inhibitor reduced dermal thickness in both mouse models (p&lt;0.05). The differentiation of resting fibroblasts into myofibroblasts was also significantly decreased (p&lt;0.05) in all treatment groups. Hydroxyproline content of the skin diminished by 40% in comparison with NaCl injected mice or syngeneic transplanted mice. Moreover, DDP4 inhibitors reduced the inflammatory infiltrate in a dose dependent manner in the bleomycin injected skin. <h3>Conclusions</h3> DPP4/CD26 identifies a subpopulation of fibrosis-promoting fibroblasts that plays a key role in the pathogenesis of fibrosis in SSc. Moreover, inhibitors of DPP4 show a significant antifibrotic effect in several mouse models of SSc in well tolerated doses. These results may have direct clinical implications as DPP4 inhibitors are already in clinical use for diabetes. <h3>Acknowledgement</h3> AS received an EULAR Scientific Training Bursary (2014) and was an Articulum Fellow (2015). <h3>Disclosure of Interest</h3> None declared
Obtaining Patient Informed Consent (IC) for Hematopoietic Cell Transplantation. How Much Information Is Enough?.
Authors: Ariadni Hotidou, Charalambos Kartsios, Ioanna Sakellari, Panagiotis Kaloyiannidis, Athanasios Fassas, Achilles Anagnostopoulos
Journal: Blood (2004)
Voriconazole Is Safe and Effective as Prophylactic Antifungal Therapy Following Allogeneic Transplantation.
Authors: Thomas Martin, Meaghan Working, Ryan O’Malley, Joe Guglielmo, Neal Fischbach, Lloyd Damon, Willis Navarro, Lawry Kaplan, Richard Jacobs, John Andrews, Charles Linker
Journal: Blood (2004)
Acute Erythroid Leukemia (AEL) Can Be Separated Into Distinct Prognostic Subsets Based On Cytogenetic and Molecular Genetic Characteristics
Authors: Vera Grossmann, Claudia Haferlach, Susanne Schnittger, Ulrike Bacher, Franziska Poetzinger, Sandra Weissmann, Andreas Roller, Christiane Eder, Annette Fasan, Melanie Zenger, Marita Staller, Wolfgang Kern, Alexander Kohlmann, Torsten Haferlach
Journal: Blood (2012)
Hepatitis C virus infection triggers a tumor‐like glutamine metabolism
Authors: Pierre L. Lévy, Sarah Duponchel, Hannah Eischeid, Jennifer Molle, Maud Michelet, Gaëlle Diserens, Martina Vermathen, Peter Vermathen, Jean‐Francois Dufour, Hans‐Peter Dienes, Hans‐Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch
Journal: Hepatology (2016)

Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV-infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense, and neoplastic transformation. Transcript levels of glutaminolytic factors were quantified in Huh7.5 cells or primary human hepatocytes infected with the Japanese fulminant hepatitis 1 HCV strain as well as in biopsies of chronic HCV patients. Nutrient deprivation, biochemical analysis, and metabolite quantification were performed with HCV-infected Huh7.5 cells. Furthermore, short hairpin RNA vectors and small molecule inhibitors were used to investigate the dependence of HCV replication on metabolic changes. We show that HCV modulates the transcript levels of key enzymes of glutamine metabolism in vitro and in liver biopsies of chronic HCV patients. Consistently, HCV infection increases glutamine use and dependence. We finally show that inhibiting glutamine metabolism attenuates HCV infection and the oxidative stress associated with HCV infection.Our data suggest that HCV establishes glutamine dependence, which is required for viral replication, and, importantly, that glutamine addiction is a hallmark of tumor cells. While HCV induces glutaminolysis to create an environment favorable for viral replication, it predisposes the cell to transformation. Glutaminolytic enzymes may be interesting therapeutic targets for prevention of hepatocarcinogenesis in chronic hepatitis C. (Hepatology 2017;65:789-803).
A Quantitative Systems Pharmacology Model for the Coagulation Network Describes Biomarker Changes Observed in a Clinical Study with FXa Variant and Predicts Age-Associated Biomarker Variations
Authors: Satyaprakash Nayak, Dooyoung Lee, Steven Arkin, Steven W. Martin, Anne C. Heatherington, William S. Denney, Paolo Vicini, Fei Hua
Journal: Blood (2015)
Differential Development of Donor Bone Marrow-Derived Thymocytes after Allogeneic in Utero Hematopoietic Cell Transplantation in the Murine Model
Authors: Yan Li, Jesse D Vrecenak, Haying Li, Michael A Conner, Aimee G Kim, Aliza Olive, Huimin Jia, Mathew M Boelig, William Peranteau, Alan W Flake
Journal: Blood (2014)
Analysis of Both Clonal Functional and Non-Functional Immunoglobulin Heavy Chain (IgH) Rearrangements in Waldenström’s Macroglobulinemia.
Authors: Patricia Martin-Jimenez, Ana Balanzategui, Miguel E. Ocio, Miguel Alcoceba, Maria E. Sarasquete, Carmen Aguilera, Jose A. Portero, Javier Fernandez Calvo, Javier Garcia Frade, Maria C. Chillon, Guadalupe Diaz, Adriana Armellini, Ramon Garcia-Sanz, Marcos Gonzalez, J.F. San Miguel
Journal: Blood (2005)
Potent Stem Cell Mobilization with the Novel CXCR4 Antagonist POL6326 - Results of a Phase IIa Dose Escalation Study in Comparison to G-CSF
Authors: Darja Karpova, Susanne Brauninger, Eliza Wiercinska, Ariane Kraemer, Belinda Stock, Jochen Graff, Christophe Escot, Garry Douglas, Barbara Romagnoli, Eric Chevalier, Klaus Dembowsky, Leon Hooftman, Halvard Bonig
Journal: Blood (2015)
SP0166 The Interferon Pathway in Sle: from Immunology To New Insights and New Treatment
Authors: L. Rönnblom
Journal: Annals of the Rheumatic Diseases (2016)

The interferons (IFNs) consist of a large family of proteins classified as type I-III IFNs and originally defined by their capacity to interfere with viral replication. Subsequent studies revealed that IFNs also have many immunomodulatory effects and can act as immune adjuvant. Among the immunostimulatory effects by type I IFN are maturation and differentiation of dendritic cells, activation of T cells and enhanced antibody production by B cells. There are several observations suggesting an important role for the type I IFN system in the etiopathogenesis of SLE. Among these are the reported development of autoimmune diseases, including SLE, during treatment with IFN and a prominent increase in the expression of type I IFN regulated genes (an IFN signature) in cells from SLE patients. Recent data also show that the regulation of the type I IFN system is abnormal in SLE, which all together suggests that inhibition of the type I IFN system could be beneficial in SLE. Many different therapeutic targets exists and several studies are in progress aiming to block, or down-regulate, the activated type I IFN system in SLE. A number of studies with monoclonal anti-IFN-alpha antibodies have been reported, and a small study investigating vaccination with an interferon-alpha-kinoid against IFN-alpha has been published. Trials targeting the type I IFN receptor are also under way, and preliminary data was recently reported. Other possibilities include elimination of endogenous IFN inducers and inhibition of key molecules in the type I IFN signaling pathway. The results so far show that it9s possible to partially suppress the IFN signature, improve several biomarkers and reduce disease activity in a subset of SLE patients. No major safety problems have been observed so far, but complete inhibition of the type I IFN system will automatically increase the risk for severe infections. <h3>Disclosure of Interest</h3> L. Rönnblom Grant/research support from: Astra/Zeneca
Improved Heart Function after the Combined Treatment of Patients Undergoing Coronary Artery Bypass Grafting through Stem Cell Therapy and Transmyocardial Laser Revascularisation.
Authors: Marcus Stockschlaeder, Ali Ghodsizad, Emmeran Gams, L. Poll, Volker Stoldt, E. R. Piechaczek, N. Feifel, Michael Klein, Ruediger E. Scharf
Journal: Blood (2004)
SP0053 Experiences from Young Rheumatologists into EMEUNET
Authors: A. Moltό
Journal: Annals of the Rheumatic Diseases (2016)

EMEUNET, the Emerging EUlar NETwork, is a network of young clinicians and researchers in the field of rheumatology in Europe. The principal objectives of EMEUNET are: (1) To enhance the quality of education among emerging rheumatologists and researchers by, among others: –Dedicated content on the EMEUNET Website, facebook and Twitter and regular Newsletters –A network of Country Liaisons responsible for communicating EMEUNET projects/activities and documents to the national societies, and particularly to young trainees and researchers in EULAR member countries –EMEUNET initiated courses and mentoring projects –EMEUNET Observers, recruited yearly from among EMEUNET Working Group Members on the Standing Committees of EULAR –Participation in EULAR task forces for the development of EULAR recommendations –Sessions proposals for "The Young Rheumatologist" track at the EULAR Annual Congress under the umbrella of the EULAR Standing Committee for Education and Training (ESCET) (2) To promote research and create collaborations among emerging rheumatologists and researchers by, among others: –Establishing a database of young rheumatologists involved in research and of researchers working in the field of rheumatology –Supporting exchange of methodologies, technical data and knowledge as well as dissemination of documents between emerging researchers, through the EMEUNET Website, Facebook, and Twitter –Organizing together with Annals of the Rheumatic Diseases the peer-review mentoring program –Promoting networking at social events held at the EULAR and ACR Annual Congress –Organizing mentor/mentee meetings between EMEUNET members and leaders in the field at the EULAR and ACR Annual Congress None of these objectives could be fulfilled without the work and enthusiasm of the people involved in the 7 subgroups that form the Working Group of EMEUNET: Education, Peer Mentoring, Newsletters, Social Media, Visibility, Country Liaisons and Global Affairs. EMEUNET subgroups are enthusiastically engaged in several activities, and the list of current and upcoming projects has quickly expanded over the past few months. With all these initiatives and activities we hope that EMEUNET will continue to be embraced by the young rheumatology community and more and more young clinicians and researchers in rheumatology will become involved in rheumatology education, research and EULAR, making EMEUNET a successful and influential resource that fosters new and long-term collaborative endeavours and ensures that excellence in European Rheumatology and EULAR is maintained. <h3>Disclosure of Interest</h3> None declared
Fetal Origins of Mental Health: The Developmental Origins of Health and Disease Hypothesis
Authors: Kieran J. O’Donnell, Michael J. Meaney
Journal: American Journal of Psychiatry (2016)

The quality of fetal growth and development predicts the risk for a range of noncommunicable, chronic illnesses. These observations form the basis of the "developmental origins of health and disease" hypothesis, which suggests that the intrauterine signals that compromise fetal growth also act to "program" tissue differentiation in a manner that predisposes to later illness. Fetal growth also predicts the risk for later psychopathology. These findings parallel studies showing that antenatal maternal emotional well-being likewise predicts the risk for later psychopathology. Taken together, these findings form the basis for integrative models of fetal neurodevelopment, which propose that antenatal maternal adversity operates through the biological pathways associated with fetal growth to program neurodevelopment. The authors review the literature and find little support for such integrated models. Maternal anxiety, depression, and stress all influence neurodevelopment but show modest, weak, or no associations with known stress mediators (e.g., glucocorticoids) or with fetal growth. Rather, compromised fetal development appears to establish a "meta-plastic" state that increases sensitivity to postnatal influences. There also remain serious concerns that observational studies associating either fetal growth or maternal mental health with neurodevelopmental outcomes fail to account for underlying genetic factors. Finally, while the observed relation between fetal growth and adult health has garnered considerable attention, the clinical relevance of these associations remains to be determined. There are both considerable promise and important challenges for future studies of the fetal origins of mental health.
In nonischemic systolic heart failure, prophylactic ICDs did not reduce all-cause mortality compared with usual care
Authors: Ellis Lader
Journal: Annals of Internal Medicine (2016)

ACP Journal Club15 November 2016In nonischemic systolic heart failure, prophylactic ICDs did not reduce all-cause mortality compared with usual careEllis Lader, MD, FACP, FACCEllis Lader, MD, FACP, FACCNew York University School of Medicine, Kingston, New York, USA (E.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2016-165-10-055 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationKøber L, Thune JJ, Nielsen JC, et al; DANISH Investigators. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375:1221-30. https://pubmed.ncbi.nlm.nih.gov/27571011Clinical Impact RatingsCardiology: References1 Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147-239. [PMID: 23747642] Google Scholar2 Kadish A, Dyer A, Daubert JP, et al; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350:2151-8. [PMID: 15152060] Google Scholar Author, Article, and Disclosure InformationAffiliations: New York University School of Medicine, Kingston, New York, USA (E.L.)This article was published at Annals.org on 1 November 2016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 2016Volume 165, Issue 10Page: JC55KeywordsCardiomyopathiesChemoradiation therapyHazard ratioHeartHeart failureImplantable cardioverter defibrillatorsMortalityRenal failureSudden cardiac deathVentricular tachycardia ePublished: 15 November 2016 Issue Published: 15 November 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
SAT0169 Successful Extension of Tocilizumab Infusion Intervals from 4 Weeks To 6 or 5 Weeks in 90% of RA Patients with Good Response To 4 Weeks Intervals
Authors: H. Uda, O. Saiki
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> A period of 4 weeks (w) has been recommended as the interval between tocilizumab (TCZ) infusions. The cost of TCZ is very high, which makes it difficult for all patients to receive TCZ because of the associated expenses. <h3>Objectives</h3> Treating the patients with TCZ, we experienced that longer intervals than 4w were also effective. We examined whether the intervals between TCZ infusions could extend from 4w to 6w or 5w. <h3>Methods</h3> The RA patients who had shown good response and maintained low disease activity (LDA) with 8mg/kg of TCZ infusions at 4w intervals were enrolled in the study. To the eligible patients, the intervals between TCZ infusions were extended to 5w at the same TCZ dose (8mg/kg). For the patients who could maintain LDA for 6 months and more at 5w interval of TCZ infusion, the intervals between TCZ infusions were extended to 6w. We followed the patients up for 2 years and more. Good response and LDA was defined as DAS-28CRP EULAR criteria. <h3>Results</h3> One hundred patients were enrolled in the present study, and 96 patients completed the study. 93 patients maintained LDA with 8mg/kg of TCZ infusion every 5w for 6 months and more and the rest of 7 patients could not keep LDA and the intervals between TCZ infusions were shortened to 4w. The 93 patients who maintained LDA with 8mg/kg of TCZ infusion every 5w were received 8mg/kg of TCZ infusion every 6 weeks, and 62 patients maintained LDA with 6w-interval. After 2 years follow-up, 96 patients could maintain LDA and 4 patients were dropped from the study. Among 96 patients who could maintain LDA, the intervals between TCZ intervals were 6w in 62 patients, 5w in 28 patients, and 4w in 6 patients, indicating that 90% of patients who had shown good response with 4w intervals could extend the intervals between TCZ infusions from 4w to 5w or 6w. The mean baseline DAS28-CRP score in patients who could maintain LDA with TCZ infusions at 6w intervals were 2.2 and was significantly lower than that at 4 weeks interval (2.6). The frequency of adverse events with TCZ infusions at 6 weeks intervals was lower than that at 4 weeks intervals. <h3>Conclusions</h3> The present study provides evidence that most of RA patients who showed good response to TCZ infusions at 4w could extend the intervals to 6w or 5w. This finding should be of great interest for both financial and labor reasons. <h3>Disclosure of Interest</h3> None declared
Mid-Treatment Evaluation of 18-FDG-Positron Emission Tomography/Computed Tomography (PET) as Predictive Value of Response Assessment in Aggressive Non Hodgkin Lymphoma (NHL).
Authors: Patrizia Pregno, Annalisa Chiappella, Daniele Penna, Marilena Bellò, Giulia Benevolo, Barbara Botto, Roberto Freilone, Lorella Orsucci, Sabrina Scaglia, Giovanni Bisi, Umberto Vitolo, Eugenio Gallo
Journal: Blood (2007)
FOXC1, a New Prognostic Marker in Adult Acute Myeloid Leukemia (AML).
Authors: Odile Blanchet, Frederique Galopin, Derek Stirewalt, Mathilde Hunault-Berger, Annaelle Beucher, Era Pogosova-Agadjanyan, Lejla Ibricevic, Laurence Baranger, Franck Genevieve, Marc Zandecki, Norbert Ifrah, Jerald P. Radich, Philippe Guardiola
Journal: Blood (2007)
Inhibition of the B Cell Associated Tyrosine Kinase SYK as a Potential Therapeutic Target in Aggressive Lymphomas.
Authors: Francesco Bertoni, Andrea Rinaldi, Anna Sasso, Silvia Uccella, Vittoria Martin, Sara Napoli, Giancarlo Pruneri, Emanuele Zucca, Carlo Capella, Carlo V. Catapano, Maria Grazia Tibiletti, Franco Cavalli
Journal: Blood (2005)
Initial Results of the Phase I/II Panobidara Study of Panobinostat in Combination with Idarubicin and Cytarabine in Patients Aged 65 Years or Older with Newly Diagnosed Acute Myeloblastic Leukaemia (AML)
Authors: Enrique M Ocio, Pilar Herrera, Teresa Olave, Salut Brunet, Albert Oriol, Maria-Pilar Martínez-Sánchez, Miguel A. Sanz, Marta Mateos, Pilar Aliseda, Ivo J. Winiger, Sushant Hardikar, Maria Victoria Mateos, Javier Lopez, Jesús F. San-Miguel
Journal: Blood (2012)
Evaluating the Efficacy and Toxicity of Two Lenalidomide Dose Regimens for the Treatment of Older Relapsed Multiple Myeloma Patients with Co-Morbidities: A Multi-Site Study at the Veteran's Administration Hospitals
Authors: Sarvari V Yellapragada, Shayna Sarosiek, Neelima D Prabhala, Mehmet Kemalsamur, Antoun Houranieh, Saulius Girnius, Praveen Tumula, Suman Kambhampati, Nirmala Bhoopalam, Rao H Prabhala, David Roodman, Alan Lichtenstein, Nikhil C Munshi
Journal: Blood (2015)
Long-Term Mutation Follow-up of Philadelphia-Chromosome Positive Leukemia Patients Treated with Second-Generation Tyrosine Kinase Inhibitors after Imatinib Failure Shows That Newly Acquired Bcr-Abl Kinase Domain Mutations Leading to Relapse Are Mainly Detected during the First Year.
Authors: Simona Soverini, Alessandra Gnani, Sabrina Colarossi, Fausto Castagnetti, Francesca Palandri, Stefania Paolini, Cristina Papayannidis, Antonella Gozzini, Valeria Santini, Daniela Cilloni, Ester Orlandi, Serena Merante, Franca Radaelli, Michela Rondoni, Michele Malagola, Angela Poerio, Marilina Amabile, Ilaria Iacobucci, Gabriele Gugliotta, Gianantonio Rosti, Giovanni Martinelli, Michele Baccarani
Journal: Blood (2008)
Nilotinib 800 Mg Daily as Frontline Therapy of Ph + Chronic Myeloid Leukemia: Dose Delivered and Safety Profile for the GIMEMA CML Working Party.
Authors: Gianantonio Rosti, Fausto Castagnetti, Francesca Palandri, Massimo Breccia, Luciano Levato, Gabriele Gugliotta, Adele Capucci, Michele Cedrone, Carmen Fava, Tamara Intermesoli, Giovanna Rege Cambrin, Fabio Stagno, Mario Tiribelli, Marilina Amabile, Simona Luatti, Angela Poerio, Simona Soverini, Nicoletta Testoni, Giuliana Alimena, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)
Successful Unrelated Peripheral Blood Stem Cell Transplantation from Unrelated Donor for a Concomitant Paroxysmal Nocturnal Hemoglobinuria and Heterozygous α-Thalassemia Patient
Authors: Xuedong Wu, Jianyun Wen, Xuan Liu, Yanhua Wang, Linglong Lu, Na Li, Chunfu Li
Journal: Blood (2014)
Semantic realism, rigid designation, and dynamic semantics
Authors: Alice G. B. ter Meulen
Journal: Behavioral and Brain Sciences (1998)

Semantic realism fits Millikan's account of kind terms in its focus on information-theoretic abilities and strategic ways of gathering information in human communication. Instead of the traditional logical necessity, we should interpret rigid designation in a dynamic semantics as a legislative act to constrain possible ways in which our belief may change.