tbuckley/cabot-search huggingface dataset:
The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy
Authors: Bernard Thienpont, Jan Magnus Aronsen, Emma Louise Robinson, Hanneke Okkenhaug, Elena Loche, Arianna Ferrini, Patrick Brien, Kanar Alkass, Antonio Tomasso, Asmita Agrawal, Olaf Bergmann, Ivar Sjaastad, Wolf Reik, Hywel Llewelyn Roderick
Journal: Journal of Clinical Investigation (2016)

Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes. This analysis revealed the pervasive loss of euchromatic H3K9me2 as a conserved feature of pathological hypertrophy that was associated with reexpression of fetal genes. In hypertrophy, H3K9me2 was reduced following a miR-217-mediated decrease in expression of the H3K9 dimethyltransferases EHMT1 and EHMT2 (EHMT1/2). miR-217-mediated, genetic, or pharmacological inactivation of EHMT1/2 was sufficient to promote pathological hypertrophy and fetal gene reexpression, while suppression of this pathway protected against pathological hypertrophy both in vitro and in mice. Thus, we have established a conserved mechanism involving a departure of the cardiomyocyte epigenome from its adult cellular identity to a reprogrammed state that is accompanied by reexpression of fetal genes and pathological hypertrophy. These results suggest that targeting miR-217 and EHMT1/2 to prevent H3K9 methylation loss is a viable therapeutic approach for the treatment of heart disease.
PWE-135 Pushing Propofol-Assisted Double Balloon Enteroscopy Out of Theatre and Into The Endoscopy Suite: Does The Pound Have Enough Pull?
Authors: H-L Ching, F Branchi, DS Sanders, D Turnbull, R Sidhu
Journal: Gut (2016)

<h3>Introduction</h3> Double balloon enteroscopy (DBE) has poorer tolerability compared to other forms of endoscopy due to procedure duration. Anaesthetic led propofol sedation in theatre is increasingly used for complex endoscopy however has cost implications. We studied the feasibility and cost effectiveness of providing an anaesthetic led propofol-based DBE service outside theatre. <h3>Methods</h3> All patients undergoing DBE with propofol between March 2013 and December 2015 were prospectively recruited. The propofol lists were carried out in an endoscopy room with anaesthetists and fully equipped with anaesthetic equipment. Patient data including hospital anxiety and depression scores (HADS) were performed prior to DBE. Pain, discomfort and distress scores were measured post-DBE (range 0–10 for each category). Costs including consumables, staffing, ward and theatre expenses were compared. <h3>Results</h3> A total of 82 patients (44% male, 79% oral DBE) were included (mean age 54±13 years). Indications for DBE included iron deficiency anaemia (37%), overt gastrointestinal bleeding (8.5%), Peutz-Jeghers syndrome (18%), abnormal radiology (2.4%), suspected Crohn’s disease (22%), suspected coeliac complications (4.8%) and small bowel tumours/masses (6.1%). The mean dose of propofol was 1089 mg±422.9 and the mean procedural time 77 mins±25. The diagnostic yield was 63%. The findings included polyps/tumours (18%), angioectasias (22%), ulcers (12%), strictures (7%), and abnormal mucosa (6%). DBE was normal in 36.5%. DBE was well tolerated with median scores for pain, discomfort and distress all being 0.2. There were no correlations between pre-DBE HADS and post-DBE pain, discomfort or distress scores (p &gt; 0.05 for all categories). Therapeutic intervention was performed in 40% which included argon plasma coagulation for angioectasias (13.4%), polypectomy (22%) and dilation of strictures (3.7%). One patient experienced transient bradycardia and required glycopyrrolate while another patient became wheezy and required nebuliser therapy post-procedure. Neither cases necessitated abandonment of DBE and were deemed non-serious adverse events. The cost of running a single DBE list with propofol is £2391 at our unit compared to a national range of £3174 - £4730 if run in theatre. Extrapolating this information would imply cost-savings of between £40,700 - £110,000 per year. <h3>Conclusion</h3> We have demonstrated that propofol-assisted DBE in an endoscopy suite is safe and feasible. It provides excellent tolerability, irrespective of pre-DBE HADS and is cost effective for the department. This allows better utilisation of theatre resources and should be encouraged nationally for other forms of complex endoscopy. <h3>Disclosure of Interest</h3> None Declared
KIR Ligand Absence in Recipients of Unrelated Donor (URD) Allogeneic Hematopoietic Cell Transplantation (HCT) Is Associated with Less Relapse and Increased Graft Versus Host Disease (GVHD).
Authors: Jeffrey S. Miller, Sarah Cooley, Peter Parham, Michael R. Verneris, Karina McQueen, Libby Guethlein, Sherif Farag, Michael Haagenson, Mary Horowitz, John Klein, Daniel J. Weisdorf
Journal: Blood (2006)
SAT0619 Relationship between HAQ Disability Scores and Measures of Observed Functional Ability in Patents with Rheumatoid Arthritis, Ostearthritis and fibromyalgia and The Association To Pain and Fatigue
Authors: K. Amris, L.E. Kristensen, E.E. Wæhrens
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Functional ability, which includes the ability to perform activities of daily living (ADL), is considered a core outcome domain in rheumatology. Recommendations for assessing ADL ability include the use of generic and diseases-specific questionnaires based on self-report and one of the most frequently used instruments is the Health Assessment Questionnaire Disability Index (HAQ-DI). Self-report reflects the person9s perception of extent of disability, which may be influenced by pain and other psychosocial factors. A poor agreement between self-reported and observed ADL ability has previously been demonstrated in rheumatic populations based on other self-report instruments. <h3>Objectives</h3> to evaluate relationships between HAQ-DI scores and measures of observed ADL ability in patients with inflammatory and non-inflammatory rheumatic diseases and the association between pain and fatigue and these disability measures. <h3>Methods</h3> patients with rheumatoid arthritis (RA), knee osteoarthritis (OA) and fibromyalgia (FM) were assessed with the HAQ-DI. The Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. Two domains of observed ADL ability were evaluated: ADL motor skills (moving self and objects) and ADL process skills (organizing and adapting actions). Pain and fatigue were assessed by 100mm visual analogue scales (VAS). The project was approved by the local ethical committee (H-B-2007–084). <h3>Results</h3> 143 women (50 with RA, 27 with knee OA, 66 with FM), mean age 51.2 (11.8) participated. Baseline characteristics and correlations are presented in table 1. Patients with FM had the highest pain, fatigue, and HAQ disability scores and the poorest performance on the AMPS. The relationships between self-reported and observed ADL motor ability were weak to moderate across all diagnostic groups; strongest in patients with knee OA. Relationships with the AMPS ADL process ability measure were weak to insignificant. Level of pain, and not fatigue, showed the strongest relationship with self-reported functional ability across all diagnostic groups. A weak to moderate relationship between pain and AMPS ADL motor ability measures were also present in patients with RA and OA, but insignificant in patients with FM (r= -0.16, p=0.195). <h3>Conclusions</h3> the relation between self-reported and observed functional ability is low across a spectrum of musculoskeletal diagnoses, even when using instruments recommended for these populations including the HAQ-DI. This has major implications on how to interpret and measure functional ability in the future as both methods should probably accompany each other. Interestingly pain was not associated with observed motor ADL ability in FM as opposed to RA and OA. <h3>Disclosure of Interest</h3> None declared
Characteristics of Atrial Fibrillation Patients Not Switched from Vka to Noac and Persistence on Vka – a Subgroup Analysis of the Prospective Dresden Noac Registry (NCT01588119)
Authors: Jan Beyer-Westendorf, Franziska Michalski, Sebastian Werth, Luise Tittl, Christina Köhler, Norbert Weiss
Journal: Blood (2014)
AB1109-HPR Comparison of Joint Position Sense at end Range and mid Range in Frozen Shoulder: Table 1.
Authors: T. Zoroglu, S. Basar
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Frozen shoulder (FS) is characterized by a painful, gradual loss of both active and passive glenohumeral motion resulting from progressive fibrosis and contracture of the glenohumeral joint capsule. Deformation of capsuloligamentous tissue is believed to stimulate mechanoreceptors in the tissue and provide the central nervous system with proprioceptive information. It was shown by studies that joint position sense acquity is good near the end of motion in healthy shoulders. There is not enough study about JPS in FS. <h3>Objectives</h3> The aim of this study is to compare the effect of mid or end range of motion on joint position sense (JPS) in patients with FS. <h3>Methods</h3> Twenty five patients with FS (21 female, 4 male; mean age 53±6 years; age range 44–67) were included in this study. Mean Body Mass Index (BMI) was 29.02±4.89. 11 dominant and 14 nondominant shoulders were measured. JPS was assessed with active repositioning process by inclinometer in flexion, elevation and rotations at mid range (MR) and end range (ER). <h3>Results</h3> Error scores at ER were lower than at MR in flexion (p=0.44), elevation (p=0.01) and internal (p=0.00) and external (p=0.19) rotations. There were significant difference in elevation and internal rotation (p&lt;0.05) (Table 1). <h3>Conclusions</h3> Our study showed that JPS at ER is better than MR. Especially elevation and internal rotation that more affected motions in FS were more sensitive to JPS. It was thought that at end ranges capsuloligamentous structure is stimulated more than mid ranges. <h3>References</h3> Neviaser, A.S. and Hannafin, J.A. (2010). Adhesive capsulitis: A review of current treatment. The American Journal of Sports Medicine, 38(11), 2346–2356. Janwantanakul P, Magarey ME, Jones MA, et al. 2001.Variation in shoulder position sense at mid and extreme rangeof motion. Arch Phys Med Rehabil 82:840–844. Lonn J, Crenshaw AG, Djupsjobacka M, et al. 2000. Positionsense testing: influence of starting position and type ofdisplacement. Arch Phys Med Rehabil 81:592–597. Yang JL, Jan MH, Hung CJ, Yang PL, Lin JJ. 2010. Reduced scapular muscle control and impaired shoulder joint position sense in subjects with chronic shoulder stiffness. Journal of Electromyography and Kinesiology,20(2), 206–11 Yang JL, Chen S, Jan MH, Lin YF. and Lin JJ. 2008. Proprioception assessment in subjects with idiopathic loss of shoulder range of motion: joint position sense and a novel proprioceptive feedback index. Journal of Orthopaedic Research, 26(9), 1218–24. <h3>Disclosure of Interest</h3> None declared
AB0023 The Regulation of Human In Vitro Th17 Cell Differentiation by Cytokines
Authors: E. Baricza, E. Lajkό, L. Kőhidai, B. Molnár-Έrsek, N. Marton, E.I. Buzás, G. Nagy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Th17 cells have a central role in inflammation via their pro-inflammatory cytokine production, such as interleukin (IL)-17A, -17F, -21, -22, tumor necrosis factor-α and the expression of master regulator transcription factor RORc. The Th17 cells have essential role in many autoimmune diseases via induction of the development of inflammation. <h3>Objectives</h3> We studied the <i>in vitro</i> Th17 cell differentiation of healthy donors and patients with rheumatoid arthritis (RA). <h3>Methods</h3> CD45RO- and CD45RO+ cells were isolated from peripheral blood mononuclear cells with a two-step negative magnetic separation. The cells were activated with anti-CD3 and anti-CD28 antibodies and treated with TGFβ (2.5 ng/ml), IL-6 (25 ng/ml), IL-1β (10 ng/ml) and IL-23 (10 ng/ml) cytokines and with an anti-IL-4 (10 μg/ml) blocking antibody. After 5 and 10 days IL-17 and IL-22 productions were measured by ELISPOT and ELISA; the RORc and Tbet expression were measured by quantitative real-time PCR methods. Cell viability was monitored by impendance-based cell analyzer (CASY-TT). <h3>Results</h3> Although anti-CD3/CD28 activation increased the IL-17 and IL-22 productions, it did not alter the RORc expression of the CD45RO- cells of healthy donors. The IL-22 production and the Tbet expression of the RORc producing cells were inhibited by TGFβ and stimulated by IL-23 treatment. The CD45RO+ cells of healthy donors expressed higher level of RORc, T-bet and IL17 without stimulation or cytokine treatment compared to the CD45RO- cells. However, there was no difference between the RORc and Tbet expression of the freshly separated CD45RO+ and CD45RO- cells of RA patients. IL-23 treatment increased both of IL-17 and IL-22 cytokine production of the differentiated CD45RO- cells. <h3>Conclusions</h3> IL-17 and IL-22 production are differently regulated during human Th17 differentiation. Our data suggest that the increased baseline RORc expression of CD45RO- cells may contribute to the accelerated Th17 differentiation in RA. <h3>Disclosure of Interest</h3> None declared
“Hierarchical” Induction and “Stochastic” Maintenance of Leukemia in An In Vivo Model of t(6;9) Positive Acute Myeloid Leukemia.
Authors: Claudia Oancea, Brigitte Rüster, Jessica Roos, Anjali Dubey, Hannelore Held, Tatjana Micheilis, Hubert Serve, Reinhard Henschler, Martin Ruthardt
Journal: Blood (2009)
THU0560 TNX-102 SL for The Treatment of fibromyalgia: Comparison of 30% Pain Responder Analysis with Omeract Draft Composite Responder Endpoint Analyses:
Authors: R.M. Gendreau, L. Arnold, D. Clauw, J. Gendreau, B. Vaughn, B. Daugherty, S. Lederman
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Novel responder definitions for fibromyalgia (FM) clinical trials have been proposed by the Outcome Measures in Rheumatology (OMERACT) FM subcommittee. These definitions include key symptom and functional domains relevant to FM patients, and were validated using outcome data from 12 previous registration trials of 4 other medications (Arnold L et al, Arth Rheum 64:885, 2012.) TNX-102 SL* is a proprietary sublingual formulation of cyclobenzaprine designed for rapid absorption and bedtime use. It showed improvements in pain and other symptoms in a Phase 2B study. This study was a 12-week, randomized, double-blind, placebo-controlled trial conducted at 17 US sites, designed to evaluate TNX as a potential treatment for FM. 205 participants were randomized (TNX=103; placebo=102). <h3>Objectives</h3> This current presentation is a retrospective analysis of the trial results using the two preferred response definitions proposed by the OMERACT committee. <h3>Methods</h3> The two OMERACT responder definitions are: the FM30 Short, which defines a responder as ≥30% reduction in pain, ≥10% improvement in physical function plus a ≥30% improvement in either sleep or fatigue, and the FM30 Long, which defines a responder as ≥30% reduction in pain, ≥10% improvement in physical function plus ≥30% improvement in any two of the following measures: sleep, fatigue, depression, anxiety or cognition. <h3>Results</h3> TNX improved multiple domains of FM. The table below compares a pain responder analysis (≥30% improvement in pain based on daily diary) to the alternative composite responder definitions proposed by OMERACT. Additional improvements noted over placebo included: FIQ-R total score (-17.2 vs. -9.1, p=0.015),PGIC response rate (30.1% vs. 16.7%, p=0.025), PROMIS sleep (-9.5 vs -6.1, p=0.004), sleep based on daily diary (change from baseline to week-12, 1.9 vs. -1.0; p&lt;0.001) and FIQ-R sleep item (-2.9 vs. -1.2; p&lt;0.0001). Systemic adverse events reported were similar to placebo. The most common local adverse event was transient tongue or mouth numbness occurring in 44% of TNX patients. <h3>Conclusions</h3> Bedtime TNX improved multiple domains of FM. Analysis by composite responder criteria developed by OMERACT suggests that the improvements in FM symptoms seen with TNX are not limited to an analgesic response, since these composite criteria all require improvement in other somatic and functional symptoms. *TNX-102 SL is an Investigational New Drug and has not been approved for any indication. <h3>Acknowledgement</h3> Supported by Tonix Pharmaceuticals, Inc. <h3>Disclosure of Interest</h3> None declared
OP0147-HPR Aerobic Capacity over 16 Years in Patients with Rheumatoid Arthritis; Relations To Risk Factors for Cardiovascular Disease
Authors: K. Hörnberg, B. Sundström, S. Wållberg Jonsson
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) suffer from increased mortality due to cardiovascular disease (CVD) (1). Aerobic capacity (VO<sub>2</sub> max) is inversely and strongly related to cardiovascular disease in the general population (2). RA patients have shown very low levels of VO<sub>2</sub> max compared to normative values of healthy adults (3), which may be of importance for the increased CVD incidence in RA. <h3>Objectives</h3> To analyse the change of VO<sub>2</sub> max over time from disease onset and associated potential risk- and health factors in patients with RA. <h3>Methods</h3> 25 patients (20 f/ 5 m), diagnosed with RA 1995–2002 were tested at disease onset (&lt;12 months from symptom onset) and after a mean of 16.2 years. Applied measurements were: sub-maximal ergometer test for VO<sub>2</sub> max, functional ability, joint- and muscle function, self-efficacy, ESR, CRP, number of tender and swollen joints and patient9s global health. At follow-up, the risk of CVD was measured as blood levels of lipids, insulin and glucose, Body mass index (BMI), waist circumference and body composition measured by Dual-energy X-ray absorbtiometry (DXA). Pulse wave analysis (PWA), was used to register early endothelial dysfunction, arterial stiffness and systolic blood pressure in aorta besides peripheral blood pressure. Carotid Intima-Media Thickness (IMT) was measured by ultrasonography. Additionally, Fatigue Severity Scale was used at follow-up. <h3>Results</h3> All measures reflecting disease activity decreased significantly during the follow-up period. VO<sub>2</sub> max was (median (IQR)) 32.3 (14.2) ml O<sub>2</sub>/kg x min at disease onset, and 33,2 (10.5) at follow-up (p&gt;0.05). Aerobic capacity at inclusion was associated with follow-up values for age (r=-.469, p=.018), VO<sub>2</sub> max (r=.557, p=.004), BMI (r=-.401, p=.047), body weight (r=-.409, p=.043), waist circumference (r=-.498, p=.011) and periferal pulse pressure (r=-.415, p=.039). Variables at disease onset associated with VO<sub>2</sub> max at follow-up were VO<sub>2</sub> max (r=.557, p=.004) and self-efficacy for function, (r=.544, p=.029). <h3>Conclusions</h3> In patients with RA followed for 16 years from disease onset, VO<sub>2</sub> max was maintained. High aerobic capacity at disease onset was associated with favourable measures of VO<sub>2</sub> max and body weight at follow-up. The variables at disease onset that best correlated with a high VO<sub>2</sub> max at follow-up were high VO<sub>2</sub> max and self-efficacy for function. Our results may be important for preventive strategies in RA. <h3>References</h3> Wallberg-Jonsson, S., et al. J Rheumatol 1997;24(3):445–451. Kodama, S., et al. JAMA 2009;301(19):2024–2035. Metsios, G.S., et al. Rheumatology (Oxford) 2015;54(12):2215–2220. <h3>Disclosure of Interest</h3> None declared
AB0484 Identification of Clinical and Serologic Factors Associated with Neutropenia in Patients with Systemic Lupus Erythematosus
Authors: M.K. Chung, H. Jeon, S.H. Kim, I.J. Kim, J. Lee
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Hematologic manifestations are common in systemic lupus erythematosus (SLE). Lymphopenia is most commonly found among leukopenia, but neutropenia is also found in about 50–60% of SLE patients. Most patients experience mild neutropenia while less than 5% of those experience moderate to severe neutropenia which can increase susceptibility to recurrent infection. Although it is crucial to understand risk factors associated with neutropenia in SLE patients, there is a paucity of clinical data regarding neutropenia in patients with SLE. <h3>Objectives</h3> This study was performed to identify the clinical and serologic factors that are associated with neutropenia in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> A total 160 admissions of 85 SLE patients between 2006 and 2013 were retrospectively reviewed. Neutropenia was defined as absolute neutrophil count (ANC) below 1,500/mm<sup>3</sup>. Baseline characteristics of the patients were compared between patients who experienced neutropenia and those without. Clinical and serological factors related to neutropenia episode during admission were analyzed using generalized estimating equation (GEE) and multivariate analysis. <h3>Results</h3> Thirty two (37.6%) patients experienced neutropenia, and neutropenia episode was found in 35 (21.9%) of admissions. Most of the neutropenia episodes were mild to moderate. Severe neutropenia of ANC&lt;500/ mm<sup>3</sup> occurred in 14.3% of the cases. Patients with neutropenia had higher frequencies of ANA (100.0 vs 86.8%, <i>P</i>=0.042) and anti-dsDNA (87.5 vs 60.4%, <i>P</i>=0.008), and satisfied more SLE classification criteria at the time of the diagnosis than those without (4.8 vs 4.1, <i>P</i>=0.014) Clinical characteristics at admission such as comorbidities, concomitant medications, and SLEDAI were not different between admissions with and without neutropenia episode. Anemia, leukopenia, thrombocytopenia and low complement levels were frequently associated with neutropenic episodes. Co-existence of chronic kidney disease (OR,16.91; 95% confidence interval (CI), 2.09–136.6; <i>P</i>=0.008) and Sjögren9s syndrome (OR, 6.48; 95% CI, 1.46–28.66; <i>P</i>=0.014) was associated with increased risk of developing neutropenia. <h3>Conclusions</h3> This study demonstrates that most of neutropenia in SLE patients occur as part of hematologic and immunologic abnormalities. SLE patients with renal damage and Sjogren9s syndrome should be closely monitored for development of neutropenia. <h3>Disclosure of Interest</h3> None declared
Single Cord Blood Transplantation Combined With An HLA Mismatched Third Party Donor For High-Risk Hematological Patients With HIV Infection
Authors: Mi Kwon, Jurgen H Kuball, Pauline Ellerbroek, Pascual Balsalobre, David Serrano, Ismael Buno, Jorge Gayoso, Koen van Besien, Lawrence D. Petz, Jose Luis Diez-Martin, Annemarie Wensing
Journal: Blood (2013)
Anti-VEGF Antibody Treatment Markedly Inhibits Tumor Growth in SCID-hu Models of Human Multiple Myeloma.
Authors: Richard A. Campbell, Eric Sanchez, Haiming Chen, Lauren Turker, Olivia Trac, Mingjie Li, Dror Shalitin, Melinda S. Gordon, Shen Pang, Benjamin Bonavida, Jonathan Said, Gregory D. Plowman, Germaine Fuh, James R. Berenson
Journal: Blood (2006)
Remarkable Differences in Cellular Activation State and Migratory and Proliferative Potential among Clonal Cells Derived from Different Tissues of Chronic Lymphocytic Leukemia Patients.
Authors: Rajendra N. Damle, Taraneh Banapour, Sonal Temburni, Tarun Wasil, Jonathan E. Kolitz, Steven L. Allen, Barbara Sherry, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2006)