tbuckley/cabot-search huggingface dataset:
THU0395 The Prevalence of Inflammatory and Structural Lesions on MRI of The Sacroiliac Joints in Patients with Very Early Peripheral Spondyloarthritis: Table 1
Authors: G. Varkas, P. Carron, H. Cypers, L. Van Praet, D. Elewaut, L. Jans, F. Van den Bosch
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To assess the prevalence of inflammatory and structural lesions on MRI of the sacroiliacal joints (SIJ) in patients with peripheral spondyloarthritis (PSpA) in a very early stage of the disease. <h3>Methods</h3> Baseline data originated from the double-blind RCT with golimumab in 60 patients (CRESPA), who were diagnosed with PSpA and had a symptom duration &lt;3 months. MRI SIJ was performed at baseline. Peripheral arthritis, dactylitis or enthesitis combined with ≥1 SpA feature (uveitis, psoriasis, IBD, preceding infection, HLAB27 or sacroiliitis on imaging) was necessary for inclusion. However, all patients already fulfilled the classification criteria without data on imaging of the SIJ. Bone marrow edema (BME) of the SIJ was quantified using the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Besides BME of the SIJ, all MRIs were also scored for other inflammatory lesions such as enthesitis and capsulitis. Structural MRI lesions of the SIJ such as subchondral sclerosis, erosions, periarticular fat and ankylosis were also assessed. Hip evaluation consisted of the presence of joint effusion, BME, enthesitis and cortical aberrations. <h3>Results</h3> Although not the reason for encounter, 7 out of 60 patients reported ever having inflammatory back pain (IBP) at inclusion or in the past, with median Visual analogue scores (VAS) of 2.0 (range 0.0- 9.0) for back pain. Overall, 35% of patients (21/60) exhibited BME of the SIJ and fulfilled the definition of a positive MRI by ASAS, with median SPARCC score of 8.0 (range 2.0–37.0). Only 3 out of 7 patients with IBP exhibited BME on MRI SIJ. Therefore, almost 86% of patients (18/21) with active sacroiliitis did not exhibit symptoms of IBP. Median VAS back pain in patients with sacroiliitis compared to patients without sacroiliitis respectively reached 2.0 and 1.0 (P=NS). Pelvic enthesitis was present in 23.8% (5/21) of patients with an ASAS positive MRI SIJ and in 10.3% (4/39) of patients with negative MRI. None of the patients exhibited enthesitis of the L5 spinous process, iliac crest, anterior superior iliac spine or ramus pubis. The MRI features of PSpA patients are presented in Table 1. <h3>Conclusions</h3> Even in early diagnosed peripheral SpA patients, over 1/3 exhibited BME suggestive of acute sacroiliitis and structural lesions of the SI joints. Our findings underscore the importance of sacroiliitis as the cornerstone feature within the SpA-concept, even in asymptomatic patients. <h3>Disclosure of Interest</h3> None declared
P04.07 Relapse in a paucisymptomatic form of multiple sclerosis in a patient treated with nivolumab
Authors: L. Gómez Vicente, B. Rubio Viqueira, M. Jimenez de las Peñas, R. Garcia Cobos, J. Pardo Moreno, R. Arroyo Gonzalez
Journal: Neuro-Oncology (2016)
Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation
Authors: Colleen Delaney, Carolyn Brashem- Stein, Howard Voorhies, Jonathan Gutman, Mari Dallas, Shelly Heimfeld, Irwin D Bernstein
Journal: Blood (2008)
Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension
Authors: Giuseppe Faraco, Yukio Sugiyama, Diane Lane, Lidia Garcia-Bonilla, Haejoo Chang, Monica M. Santisteban, Gianfranco Racchumi, Michelle Murphy, Nico Van Rooijen, Joseph Anrather, Costantino Iadecola
Journal: Journal of Clinical Investigation (2016)

Hypertension is a leading risk factor for dementia, but the mechanisms underlying its damaging effects on the brain are poorly understood. Due to a lack of energy reserves, the brain relies on continuous delivery of blood flow to its active regions in accordance with their dynamic metabolic needs. Hypertension disrupts these vital regulatory mechanisms, leading to the neuronal dysfunction and damage underlying cognitive impairment. Elucidating the cellular bases of these impairments is essential for developing new therapies. Perivascular macrophages (PVMs) represent a distinct population of resident brain macrophages that serves key homeostatic roles but also has the potential to generate large amounts of reactive oxygen species (ROS). Here, we report that PVMs are critical in driving the alterations in neurovascular regulation and attendant cognitive impairment in mouse models of hypertension. This effect was mediated by an increase in blood-brain barrier permeability that allowed angiotensin II to enter the perivascular space and activate angiotensin type 1 receptors in PVMs, leading to production of ROS through the superoxide-producing enzyme NOX2. These findings unveil a pathogenic role of PVMs in the neurovascular and cognitive dysfunction associated with hypertension and identify these cells as a putative therapeutic target for diseases associated with cerebrovascular oxidative stress.
Improved Survival of Intravascular Large B-Cell Lymphoma (IVLBCL) by Rituximab Containing Combination Chemotherapies.
Authors: Kazuyuki Shimada, Kosei Matsue, Kazuhito Yamamoto, Naoaki Ichikawa, Masataka Okamoto, Nozomi Niitsu, Hiroshi Kosugi, Norifumi Tsukamoto, Takuhei Murase, Hiroshi Miwa, Hideki Asaoku, Ako Kikuchi, Morio Matsumoto, Yoshio Saburi, Yasufumi Masaki, Makoto Kashimura, Motoko Yamaguchi, Shigeo Nakamura, Tomoki Naoe, Kinoshita Tomohiro
Journal: Blood (2007)
General Condition and Early Complications Have in Addition to Disease- Specific Factors a Significant Impact on Outcome - Prognostic Factors Revisited in 1657 Adult ALL Patients (15–55 years).
Authors: Nicola Goekbuget, Renate Arnold, Anja Baumann, Joachim Beck, Helmut Diedrich, Mathias Freund, Andreas Hüttmann, Michael Kneba, Karl Anton Kreuzer, Lothar Leimer, Thomas Lipp, Dorle Messerer, Ralph Naumann, Albrecht Reichle, Harald Rieder, Kerstin Schäfer-Eckart, Marc Schmalzing, Mathias Schmid, Norbert Schmitz, Hubert Serve, Matthias Stelljes, Eckhard Thiel, Dieter Hoelzer
Journal: Blood (2008)
Modulation of Immune Checkpoints and Graft-versus-Leukemia in Allogeneic Transplants by Antagonizing Vasoactive Intestinal Peptide Signaling
Authors: Jian-Ming Li, Christopher T. Petersen, Jing-Xia Li, Reema Panjwani, Daniel J. Chandra, Cynthia R. Giver, Bruce R. Blazar, Edmund K. Waller
Journal: Cancer Research (2016)

The goal of allogeneic bone marrow transplantation (allo-BMT) is elimination of leukemia cells through the graft-versus-leukemia (GvL) activity of donor cells, while limiting graft-versus-host disease (GvHD). Immune checkpoint pathways regulate GvL and GvHD activities, but blocking antibodies or genetic inactivation of these pathways can cause lethal GVHD. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide that regulates coinhibitory pathways; its role in allo-BMT has not been studied. We found VIP transiently expressed in donor NK, NK-T, dendritic cells, and T cells after allo transplant, as well as host leukocytes. A peptide antagonist of VIP signaling (VIPhyb) increased T-cell proliferation in vitro and reduced IL10 expression in donor T cells. Treatment of allo-BMT recipients with VIPhyb, or transplanting donor grafts lacking VIP (VIP-KO), activated donor T-cells in lymphoid organs, reduced T-cell homing to GvHD target organs, and enhanced GvL without increasing GvHD in multiple allo-BMT models. Genetic or ex vivo depletion of donor NK cells or CD8+ T cells from allografts abrogated the VIPhyb-enhanced GvL activity. VIPhyb treatment led to downregulation of PD-1 and PD-L1 expression on donor immune cells, increased effector molecule expression, and expanded oligoclonal CD8+ T cells that protected secondary allo transplant recipients from leukemia. Blocking VIP signaling thus represents a novel pharmacologic approach to separate GvL from GvHD and enhance adaptive T-cell responses to leukemia-associated antigens in allo-BMT. Cancer Res; 76(23); 6802-15. ©2016 AACR.
Outcome of Busulfan and Fludarabine-Based Reduced Intensity Conditioning Regimen for Related and Unrelated HSCT in Fanconi Anemia Patients
Authors: Saba Azarnoush, Raphael Porcher, Regis Peffault de la Tour, Karima Yakouben, Benedicte Bruno, Marie Ouachee Chardin, Marie Robin, Andre Baruchel, Gerard Socie, Jean-Hugues Dalle
Journal: Blood (2011)
Management of psoriatic arthritis in 2016: a comparison of EULAR and GRAPPA recommendations
Authors: Laure Gossec, Laura C. Coates, Maarten de Wit, Arthur Kavanaugh, Sofia Ramiro, Philip J. Mease, Christopher T. Ritchlin, Désirée van der Heijde, Josef S. Smolen
Journal: Nature Reviews Rheumatology (2016)
Clofarabine Combinations in Acute Myeloid Leukemia (AML) Salvage: A Dose-Finding Phase I Study of Clofarabine Plus Idarubicin and Clofarabine/Idarubicin Plus Cytarabine (ara-C).
Authors: Stefan Faderl, Alessandra Ferrajoli, William Wierda, Farhad Ravandi, Zeev Estrov, Srdan Verstovsek, Deborah A. Thomas, Guillermo Garcia-Manero, Monica Kwari, Hagop M. Kantarjian
Journal: Blood (2005)
AB0106 Celecoxib Induces both Apoptotic and Autophagic Cell Death in Rheumatoid Arthritis Fibroblast-like Synoviocytes
Authors: S.-H. Kim, J. Bang, Y.S. Kim, H.-S. Kim, S.-J. Hong, S.-S. Kim, H.-J. Jeong, C.-N. Son, J.-M. Kim
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> An aggressive proliferation of synovium is the hallmark of rheumatoid arthritis (RA). Previous studies suggested that resistance of fibroblast-like synoviocytes (FLS) to apoptosis is involved in synovial hyperplasia in the patients with RA. Recently, the possibilities that autophagy regulates apoptosis resistance and hyperplasia of FLS were also presented. Selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, has been reported to affect apoptosis or autophagy in various cancer cells. <h3>Objectives</h3> The aim of this study is to investigate the influence of celecoxib on viability of RAFLS and to reveal how celecoxib affects the viability of RAFLS. <h3>Methods</h3> RA synovial tissue was obtained from patients during total knee replacement surgery or arthroscopy. FLS was cultured with celecoxib, caspase inhibitor (z-VAD-fmk) or autophagy inhibitor (3-methyladenine; 3-MA, bafilomycin A1; bafi A1, chloquine; CQ). Cell viability was measured by MTS assay and by cell count using trypan blue staining. The expression of autophagy flux (LC3, p62) and apoptosis related protein (caspase3 and poly (ADP-ribose) polymerases (PARP)) was analyzed by western blot. <h3>Results</h3> Celecoxib dose-dependently decreased cell viability (mean IC50 of 120 μM) of RAFLS. Activation of Caspase 3 and PARP cleavage were observed in RAFLS after the treatment with celecoxib. Combination treatment with caspase inhibitor and celecoxib increased cell viability than a single treatment with celecoxib. Celecoxib also increased the expression of LC3II and p62 in RAFLS. Treatment with autophagy inhibitor (3-MA, bafi A1, CQ) restored viability of RAFLS which was decreased by celecoxib. <h3>Conclusions</h3> This study demonstrates that both apoptosis and autophagy contribute to celecoxib-induced cell death in RAFLS. Further studies to identify the effects of celecoxib on chronological sequence of autophagy and apoptosis in RAFLS are need. <h3>References</h3> Kusunoki N, Yamazaki R, Kawai S. Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts. Mod Rheumatol. 2008;18(6):542–51. Audo R, Descamps V, Hahne M, Combe B, Morel J. Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther. 2007;9(6):R128. <h3>Acknowledgement</h3> None <h3>Disclosure of Interest</h3> None declared
Genome-Wide DNA Profiling Identifies a Stable Profile Although with Aberrations Targeting the Fibroblast Growth Factor Pathway in Hairy Cell Leukemia.
Authors: Francesco Forconi, Giulia Poretti, Ivo Kwee, Elisa Sozzi, Davide Rossi, Daniela Capello, Andrea Rinaldi, Emanuele Zucca, Francesco Lauria, Gianluca Gaidano, Francesco Bertoni
Journal: Blood (2007)
Outcome of BEAM-Autologous and BEAM-Alemtuzumab Allogeneic Transplantation in Relapsed Advanced Stage Follicular Lymphoma
Authors: Victor Noriega, Anjum Bashir Khan, Stephen Devereux, Robert E. Marcus, Michelle Kenyon, Victoria T Potter, Ghulam J Mufti, Antonio Pagliuca
Journal: Blood (2012)
THU0550 Early Multidisciplinary Interventions To Promote Work Participation in People with Regional Musculoskeletal Pain: A Systematic Review
Authors: A. Cochrane, N.M. Higgins, O. FitzGerald, P. Gallagher, J. Ashton, R. Breen, A. Brennan, O. Corcoran, D. Desmond
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Musculoskeletal disorders are amongst the leading causes of disability in the working age population. Whilst there is a growing body of evidence suggesting that early targeted multidisciplinary interventions can promote work retention and prevent disability, the evidence is far from conclusive as to which interventions are the most effective. <h3>Objectives</h3> To review randomised controlled trials evaluating the effectiveness of early interventions in promoting work participation in adults with regional musculoskeletal pain (RMSKP). <h3>Methods</h3> CENTRAL, MEDLINE, EMBASE, Scopus, PEDro and OT Seeker (1990 to April 2015) were searched. Reference lists of identified articles and reviews were hand searched. Only RCTs reporting on work-related outcomes were eligible for inclusion. The intervention had to include two or more elements of the biopsychosocial model delivered as an integrated programme. Participants were either experiencing difficulties at work or had less than three months sick leave as a result of their RMSKP at enrolment. Each RCT was assessed independently by two reviewers for risk of bias. Results were analysed by hazard ratios for return to work data, while continuous outcomes were analysed as mean difference (MD) with 95% confidence intervals. <h3>Results</h3> 19 RCTS were included; the considerable variation in the components employed in the interventions limited the option to pool the data statistically using meta-analysis. There was some evidence that programmes involving a stepped care approach (4 studies) increased the probability of return to work at the 12-month follow-up [HR 1.29 (95% CI, 1.03 to 1.61), p=0.03]. However, preliminary analyses indicate a lack of consistent evidence for effects on reducing sickness absences, pain reduction and functional improvement across the intervention types. <h3>Conclusions</h3> The lack of agreement as to what constitutes "early" in the context of treating RMSKP may have contributed to the rather ambiguous findings. In addition, the different health and social insurance systems across the trials have made it difficult to generalise the results. There remains a need to establish the active components that promote work retention in this population, and to identify the patients who are most likely to benefit from an integrated and cost-effective intervention. <h3>Disclosure of Interest</h3> None declared
THU0271 Impairment of GAS6/MERTK System in Lupus Nephritis
Authors: M. Bellan, M. Quaglia, F. Goegan, S. Pagani, L. Salmi, L. Castello, R. Bonometti, D. Sola, A. Gibbin, M. Pirisi, G.C. Avanzi, P. Stratta, P.P. Sainaghi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Growth Arrest-Specific 6 (Gas6) and its receptor MERTK have been involved in the regulation of inflammation and apoptosis. <h3>Objectives</h3> We evaluated if an impairment of Gas6/MERTK signalling system could be associated with Systemic Lupus Erythematosus (SLE) disease activity and, specifically, with kidney involvement. <h3>Methods</h3> Gas6 and the soluble, cleaved form of MERTK (sMER) plasma concentration were measured in 59 SLE patients and in 46 healthy controls. Clinical and laboratory data were collected. <h3>Results</h3> SLE patients had significantly higher plasma sMER concentrations (10,40 ng/ml [IQR 7,92–13,83] vs 2,65 ng/ml [2,38–3,23]) while healthy subjects showed only slightly higher plasma Gas6 concentrations than patients (22,8 ng/ml [IQR 19,2–24,7] vs 14,7 ng/ml [11,8–20,5]). Moreover, only sMER, but not Gas6, was significantly different being higher in SLE patients with renal involvement (11,3ng/mL [9,7–13,9ng/mL] vs 7,8 ng/mL [6,2–12,2ng/mL]). At univariate analysis sMER concentration was related to clinical and laboratory indexes of disease activity as SLEDAI, haemoglobin, ESR, proteinuria and creatinine plasma concentration but, at multiple regression analysis only 24 h urine protein concentration fitted the model (R=0,9751 F11,314; p&lt;0,002). <h3>Conclusions</h3> An increased sMER concentration can be detected in SLE patients, particularly those who showed renal involvement. Interestingly sMER is directly related to the degree of proteinuria, This observation suggests an increased cleavage of MERTK; on this basis an impairment of MERTK-mediated apoptotic bodies clearance could be supposed. <h3>Disclosure of Interest</h3> None declared
OC-033 Nine-Gene Signature Implicated in the Early Development of Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma (HCC)
Authors: W Fateen, H Wood, S Berri, H Thygesen, J Wyatt, M El-Meteini, C Millson, P Quirke
Journal: Gut (2016)

<h3>Introduction</h3> HCV remains the commonest cause of HCC related deaths in the west. Dysplastic nodules (DN) harbour highly relevant genomic information based on its strong potential to progress to HCC. Copy number alterations (CNA) have not been previously studied in a large cohort of HCV related DN. In this study we used next generation sequencing (NGS) to identify potential drivers of oncogenesis in a cohort of HCV related DNs and HCCs. <h3>Methods</h3> We performed low coverage next generation DNA sequencing of 116 HCCs and 49 DNs from 63 HCV infected patients to investigate their CNA profiles. Patients with a mixed aetiology of liver disease were excluded. Significant copy number gain and loss peaks were identified using GISTIC 2.0. To identify driver from passenger alterations, we stratified the peaks according to their amplitude and frequency within included samples. We also identified peaks that were inclusive of genes causally implicated in cancer, highly associated with cancer or involved in major cell signalling pathways. We further analysed the HCC-related peaks and correlated each of them to patient and tumour clinical features. This correlation was corrected for false discovery rate (FDR) using the Benjamini-Hochberg procedure. <h3>Results</h3> We identified 86 and 79 significant CNA peaks in HCC and DN respectively. The peaks were further stratified as described above which lead to recognition of a 9 gene signature highly implicated in early HCV related HCC. This included losses of ROCK1, CARS, SBDS, DUX4 and gains of NCOA2, MYC, TPO, YWHAZ and MCM4. Our data confirmed the alteration of 51 other genes in HCC but not DN. This included gains of CCND1, NFKB1/2, MUC1, FGF2/4/19 and CKS1B and losses of CDKN2A/B, KRAS, PTEN, RB1, NOTCH1, CCNA2, BMPR1B which have previously been implicated in hepatocarcinogenesis. Out of 86 HCC-related peaks, 16/86 had significant associations with clinical features after correction for FDR. Six of the above 16 peaks overlapped with 6 out of the 9 gene signature we previously identified. Genomic features strongly correlated with tumour differentiation, number of tumours per liver and overall survival. No association was found between HCV genotype or PCR quantity. <h3>Conclusion</h3> Analysis of DNA copy number profiles of a large number of HCV related DN and HCC using NGS revealed a signature of 9 genes likely to be implicated as drivers in the early development of this cancer. Our study generates a valid hypothesis and further studies are needed to confirm causality. <h3>Disclosure of Interest</h3> W. Fateen: None Declared, H. Wood: None Declared, S. Berri Employee of: Illumina, H. Thygesen: None Declared, J. Wyatt: None Declared, M. El- Meteini: None Declared, C. Millson: None Declared, P. Quirke: None Declared
Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11
Authors: Xiaochao Tan, Priyam Banerjee, Hou-Fu Guo, Stephen Ireland, Daniela Pankova, Young-ho Ahn, Irodotos Michail Nikolaidis, Xin Liu, Yanbin Zhao, Yongming Xue, Alan R. Burns, Jonathon Roybal, Don L. Gibbons, Tomasz Zal, Chad J. Creighton, Daniel Ungar, Yanzhuang Wang, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2016)

Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3–dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the pro-metastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis.
Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts
Authors: Sofia Esteves, Sara Duarte‐Silva, Patrícia Maciel
Journal: Medicinal Research Reviews (2016)

Abstract Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine–adenine–guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full‐time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches—hypothesis‐based candidate molecule testing and hypothesis‐free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.