tbuckley/cabot-search huggingface dataset:
Risk of diabetes mellitus associated with disease-modifying antirheumatic drugs and statins in rheumatoid arthritis
Authors: Gulsen Ozen, Sofia Pedro, Marie E Holmqvist, Michael Avery, Frederick Wolfe, Kaleb Michaud
Journal: Annals of the Rheumatic Diseases (2016)

Objective To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. Methods We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without baseline DM from 2000 through 2014. DM was determined by self-report or initiating DM medication. DMARDs were categorised into four mutually exclusive groups: (1) methotrexate monotherapy (reference); (2) any abatacept with or without synthetic DMARDs (3) any other DMARDs with methotrexate; (4) all other DMARDs without methotrexate; along with separate statin, glucocorticoid and hydroxychloroquine (yes/no) variables. Time-varying Cox proportional hazard models were used to adjust for age, sex, socioeconomic status, comorbidities, body mass index and RA severity measures. Results During a median (IQR) 4.6 (2.5–8.8) years of follow-up in 13 669 patients with RA, 1139 incident DM cases were observed. The standardised incidence ratio (95% CI) of DM in patients with RA (1.37, (1.29 to 1.45)) was increased compared with US adult population. Adjusted HR (95% CI) for DM were 0.67 (0.57 to 0.80) for hydroxychloroquine, 0.52 (0.31 to 0.89) for abatacept (compared with methotrexate monotherapy), 1.31 (1.15 to 1.49) for glucocorticoids and 1.56 (1.36 to 1.78) for statins. Other synthetic/biological DMARDs were not associated with any risk change. Concomitant use of glucocorticoids did not alter DM risk reduction with hydroxychloroquine (HR 0.69 (0.51 to 0.93)). Conclusions In RA, incidence of DM is increased. Hydroxychloroquine and abatacept were associated with decreased risk of DM, and glucocorticoids and statins with increased risk.
Plasma immunoprofiling of patients with high-risk diffuse large B-cell lymphoma: a Nordic Lymphoma Group study
Authors: F Pauly, K Fjordén, S Leppä, H Holte, M Björkholm, Ø Fluge, L Møller Pedersen, M Eriksson, A Isinger-Ekstrand, C A K Borrebaeck, M Jerkeman, C Wingren
Journal: Blood Cancer Journal (2016)

Plasma immunoprofiling of patients with high-risk diffuse large B-cell lymphoma: a Nordic Lymphoma Group study
L-Stereoisomer RNA Oligonucleotide Anti-SDF-1 (Nox-A12) Disrupts the Interaction of Multiple Myeloma Cells with the Bone Marrow Milieu In Vivo, Leading to Enhanced Sensitivity to Bortezomib
Authors: Aldo M Roccaro, Antonio Sacco, Phong Quang, AbdelKareem Azab, Patricia Maiso, Feda Azab, Yong Zhang, Ghayas C Issa, Yang Liu, Hai T Ngo, Anna Kruschinski, Irene M. Ghobrial
Journal: Blood (2011)
Chronic Myelomonocytic Leukemia and Related Disorders Provide Particular Disease-Specific Challenges to Effective Bone Marrow Transplant: a Multicenter Experience.
Authors: Steven E. McCormack, Yan Zhang, Ramon V. Tiu, Jaroslaw P Maciejewski, Ronald Sobecks, Javier Bolanos-Meade, Michael A McDevitt, Erica Warlick
Journal: Blood (2010)
Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial
Authors: Rakesh Popat, Sarah R Brown, Louise Flanagan, Andrew Hall, Walter Gregory, Bhuvan Kishore, Matthew Streetly, Heather Oakervee, Kwee Yong, Gordon Cook, Eric Low, Jamie Cavenagh
Journal: The Lancet Haematology (2016)
THU0617 Work Productivity and Daily Activity in Patients with Rheumatoid Arthritis in Four Phase III Randomized Clinical Trials of Baricitinib: Table 1
Authors: J.S. Smolen, A.M. DeLozier, S. de Bono, L. Yang, C. Gaich
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Baricitinib (bari), an oral JAK1 and JAK2 inhibitor, was efficacious in Ph 3 studies in patients (pts) with active RA.<sup>1–4</sup> <h3>Objectives</h3> To assess effects of bari on workplace and daily activity with the Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire in adult RA pts. <h3>Methods</h3> In 4 Ph 3 trials (table), pts completed the WPAI-RA at baseline and ∼every 4 wks. Least-squares mean (LSM) of change from baseline was compared with ANCOVA. <h3>Results</h3> Across studies, bari pts tended to have less absenteeism, presenteeism, and impairment in work productivity and daily activities at primary and final timepoints vs pts from comparator groups. <h3>Conclusions</h3> Across 4 Ph 3 studies, bari treatment improved workplace and daily activities in RA pts. <h3>References</h3> Dougados et al. Ann Rheum Dis 2015; Genovese et al. Ann Rheum Dis 2015; Taylor et al. Arthritis Rheumatol 2015; Fleischmann et al. Arthritis Rheumatol 2015 <h3>Disclosure of Interest</h3> J. Smolen Grant/research support from: AbbVie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, A. DeLozier Employee of: Eli Lilly and Company, S. de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Yang Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Gaich Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company
Effect of DECIDE (Decision-making Education for Choices In Diabetes Everyday) Program Delivery Modalities on Clinical and Behavioral Outcomes in Urban African Americans With Type 2 Diabetes: A Randomized Trial
Authors: Stephanie L. Fitzpatrick, Sherita Hill Golden, Kerry Stewart, June Sutherland, Sharie DeGross, Tina Brown, Nae-Yuh Wang, Jerilyn Allen, Lisa A. Cooper, Felicia Hill-Briggs
Journal: Diabetes Care (2016)

OBJECTIVE To compare the effectiveness of three delivery modalities of Decision-making Education for Choices In Diabetes Everyday (DECIDE), a nine-module, literacy-adapted diabetes and cardiovascular disease (CVD) education and problem-solving training, compared with an enhanced usual care (UC), on clinical and behavioral outcomes among urban African Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS Eligible participants (n = 182) had a suboptimal CVD risk factor profile (A1C, blood pressure, and/or lipids). Participants were randomized to DECIDE Self-Study (n = 46), DECIDE Individual (n = 45), DECIDE Group (n = 46), or Enhanced UC (n = 45). Intervention duration was 18–20 weeks. Outcomes were A1C, blood pressure, lipids, problem-solving, disease knowledge, and self-care activities, all measured at baseline, 1 week, and 6 months after completion of the intervention. RESULTS DECIDE modalities and Enhanced UC did not significantly differ in clinical outcomes at 6 months postintervention. In participants with A1C ≥7.5% (58 mmol/mol) at baseline, A1C declined in each DECIDE modality at 1 week postintervention (P &amp;lt; 0.05) and only in Self-Study at 6 months postintervention (b = −0.24, P &amp;lt; 0.05). There was significant reduction in systolic blood pressure in Self-Study (b = −4.04) and Group (b = −3.59) at 6 months postintervention. Self-Study, Individual, and Enhanced UC had significant declines in LDL and Self-Study had an increase in HDL (b = 1.76, P &amp;lt; 0.05) at 6 months postintervention. Self-Study and Individual had a higher increase in knowledge than Enhanced UC (P &amp;lt; 0.05), and all arms improved in problem-solving (P &amp;lt; 0.01) at 6 months postintervention. CONCLUSIONS DECIDE modalities showed benefits after intervention. Self-Study demonstrated robust improvements across clinical and behavioral outcomes, suggesting program suitability for broader dissemination to populations with similar educational and literacy levels.
Forkhead box protein‐3 (Foxp3)‐producing dendritic cells suppress allergic response
Authors: X.‐Y. Liu, L.‐Z. Xu, X.‐Q. Luo, X.‐R. Geng, Z.‐Q. Liu, L.‐T. Yang, G. Yang, S. Chen, Z.‐G. Liu, H.‐B. Li, L.‐T. Yang, T.‐G. Luan, P.‐C. Yang
Journal: Allergy (2016)

The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be upregulated by Staphylococcal enterotoxin B (SEB).The expression of Foxp3 by DCs was evaluated by real-time RT-PCR, Western blotting, flow cytometry, and chromatin immunoprecipitation assay.We observed that mice treated with SEB at 0.25-0.5 μg/mouse showed high frequencies of transforming growth factor (TGF)-β-producing CD4+ T cells and TGF-β-producing DCs in the intestine, while the IL-4+ CD4+ T cells and TIM4+ DCs were dominated in the intestine in mice treated with SEB at 1-10 μg/mouse. Treating DCs with SEB in the culture induced high levels of Foxp3 at the TGF-β promoter locus. The function of Foxp3 was blocked by STAT6 (signal transducer and activator transcription-6); the latter was induced by exposing DCs to SEB in the culture at doses of 100-400 ng/ml. Treating allergic mice with specific immunotherapy (SIT) together with SEB significantly promoted the therapeutic effects on the allergic responses than treating with SIT alone.Dendritic cells have the capacity to express Foxp3, which can be upregulated by exposure to SEB.
CDP7657, and Other Anti-CD40L Antibody Formats Lacking a Functional Fc Region, Do Not Cause Platelet Activation In Vitro
Authors: Ali Amirkhosravi, Todd Meyer, Olivier Harari, Linda Burkly, Lihe Su, Yen-Ming Hsu, Timothy Bourne, Ian Wakefield, Christopher Peters, Anthony Shock, John Francis
Journal: Blood (2010)
PWE-010 Monitoring IBD Medications in Primary Care: Audit of Practice in South West London
Authors: C Alexakis, C Oliver, E Hockney, A Amoyel, C Grayson, R Pollok, S Saxena
Journal: Gut (2016)

<h3>Introduction</h3> IBD is increasing in the UK. Primary care will likely have a greater role in the management of such patients under ‘shared-care’ protocols, particularly with regards to drug monitoring and vaccination requirements. A recent national audit indicated varied prescribing practices amongst GPs treating patients with IBD.<sup>1</sup> To address local prescribing behaviours, we audited 4 practices in SW London, against established standards for IBD care. <h3>Methods</h3> Patients with Crohn’s disease (CD) or ulcerative colitis (UC) were identified retrospectively from the records of 4 practices in SW London. Information collected included the number of patients on 5 aminosalicylates (5 ASA) and azathioprine (AZA) for the previous year. The following audit standards were generated, derived from IBD guidelines;<sup>2,3</sup> patients on 5 ASA require yearly renal function; 5 ASA should not be used in CD as maintenance therapy; prolonged (&gt;3 months) or repeated steroid courses (&gt;1/year) should be avoided; patients on AZA should have blood monitoring every 2–3 months; patients on AZA should be offered annual Pneumococcal and Influenza vaccination. <h3>Results</h3> 70 patients with UC and 45 with CD were identified. 41% UC were on maintenance 5 ASA of whom 86% had appropriate renal function monitoring. 27% CD were on 5 ASA of whom only 58% had renal function checked in the past year. 7% UC and 9% CD had prolonged steroid courses prescribed. 9% and 7% of UC and CD had repeated courses of steroids in the previous year. AZA use was equivalent in the two groups (~20%). However, appropriate blood monitoring was significantly different between UC and CD (93% UC vs 10% CD, p = 0.001). The number of patients on AZA who were offered Pneumoccocal vaccination (UC 50% vs CD 60%) and Influenza vaccination (UC 57% vs CD 20%) was considerably short of the audit standards. <h3>Conclusion</h3> This audit identifies areas of IBD practice in primary care that are performed to a high standard, namely the monitoring of blood tests in patients with UC, and the low use of steroids in both groups. There remain areas that require improvement, notably the vaccination status of patients on AZA, and the inappropriate prescribing of 5 ASA in CD. The findings should prompt improved networking between primary and secondary care, a role which could be fulfilled by an IBD specialist nurse. <h3>References</h3> 1 <i>UK IBD audit steering group</i>. IBD audit round three. RCP 2012. 2 Mowat C, <i>et al</i>. Guidelines for the management of IBD in adults. <i>Gut</i> 2011 May;<b>60</b>(5). 3 Rahier JF, <i>et al</i>. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in IBD. <i>J Crohns Colitis</i>. 2014 Jun;<b>8</b>(6). <h3>Disclosure of Interest</h3> None Declared
Sex-Related Discordance Between Aortic Valve Calcification and Hemodynamic Severity of Aortic Stenosis
Authors: Louis Simard, Nancy Côté, François Dagenais, Patrick Mathieu, Christian Couture, Sylvain Trahan, Yohan Bossé, Siamak Mohammadi, Sylvain Pagé, Philippe Joubert, Marie-Annick Clavel
Journal: Circulation Research (2016)

Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification loads than men for the same AS hemodynamic severity.We, thus, aimed to assess sex differences in aortic valve fibrocalcific remodeling.One hundred and twenty-five patients underwent Doppler echocardiography and multidetector computed tomography within 3 months before aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed, and fibrosis degree was determined. Sixty-four men and 39 women were frequency matched for age, body mass index, hypertension, renal disease, diabetes mellitus, and AS severity. Mean age (75±9 years), mean gradient (41±18 mm Hg), and indexed aortic valve area (0.41±0.12 cm2/m2) were similar between men and women (all P≥0.18). Median aortic valve calcification (1973 [1124-3490] Agatston units) and mean valve weight (2.36±0.99 g) were lower in women compared with men (both P<0.0001). Aortic valve calcification density correlated better with valve weight in men (r2=0.57; P<0.0001) than in women (r2=0.26; P=0.0008). After adjustment for age, body mass index, aortic valve calcification density, and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (P=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (P=0.01), and Masson trichrome staining revealed a greater proportion of dense connective tissue (P=0.02) in women compared with men.In this series of patients with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared with men. These findings suggest that the pathophysiology of AS and thus potential targets for drug development may be different according to sex.
Running exposure is associated with the risk of hamstring strain injury in elite Australian footballers
Authors: Joshua D Ruddy, Christopher W Pollard, Ryan G Timmins, Morgan D Williams, Anthony J Shield, David A Opar
Journal: British Journal of Sports Medicine (2016)

To investigate the association between running exposure and the risk of hamstring strain injury (HSI) in elite Australian footballers.Elite Australian footballers (n=220) from 5 different teams participated. Global positioning system (GPS) data were provided for every athlete for each training session and match for the entire 2015 season. The occurrences of HSIs throughout the study period were reported. Receiver operator characteristic curve analyses were performed and the relative risk (RR) of subsequent HSI was calculated for absolute and relative running exposure variables related to distance covered above 10 and 24 km/hour in the preceding week/s.30 prospective HSIs occurred. For the absolute running exposure variables, weekly distance covered above 24 km/hour (>653 m, RR=3.4, 95% CI 1.6 to 7.2, sensitivity=0.52, specificity=0.76, area under the curve (AUC)=0.63) had the largest influence on the risk of HSI in the following week. For the relative running exposure variables, distance covered above 24 km/hour as a percentage of distance covered above 10 km/hour (>2.5%, RR=6.3, 95% CI 1.5 to 26.7, sensitivity=0.93, specificity=0.34, AUC=0.63) had the largest influence on the risk of HSI in the following week. Despite significant increases in the RR of HSI, the predictive capacity of these variables was limited.An association exists between absolute and relative running exposure variables and elite Australian footballers' risk of subsequent HSI, with the association strongest when examining data within 7-14 days. Despite this, the use of running exposure variables displayed limited clinical utility to predict HSI at the individual level.
Precision Medicine Gets Boost
Authors: Jeff Lyon
Journal: JAMA (2016)

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Immune Tolerance Utilizing Intermediate Purity Factor VIII Concentrate in Hemophilia A Patients with High Factor VIII Titers.
Authors: Margaret A. Heisel Kurth, Beverly Christie, Vicky Hanneman, Joni Osip, Kristen Appert, Christopher L. Moertel, Jan Watterson, Maha Hag-Alshiekh
Journal: Blood (2004)
THU0018 Regulation of Xylosyltransferase-1 Expression by Fibronectin Fragment in Human Articular Chondrocytes
Authors: C.M. Lee, G.H. Park, S.Y. Lee, K.M. Son, H.S. Lee, M.H. Lee, H.S. Hwang, H.A. Kim
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Xylosyltransferase-1 (XT-1), encoded by <i>xylt1</i> gene, is an essential anabolic enzyme to catalyze the initial and rate-determining step in glycosaminoglycan chain synthesis. The effect of fibronectin fragments (FN-fs), generated by proteolytic cleavage of FN and known as damage-associated molecular pattern (DAMP) molecules, on cartilage metabolism was poorly characterized. <h3>Objectives</h3> In this study we examined 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f)-mediated XT-1 expression mechanism and its signaling pathway, determining the role of 29-kDa FN-f in cartilage matrix synthesis. <h3>Methods</h3> Human articular chondrocytes were enzymatically isolated from articular cartilage and cultured in monolayer. In 29-kDa FN-f-stimulated chondrocytes, the relative levels of mRNA and protein for XT-1 were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. In order to investigate the effects of 29-kDa FN-f on XT-1, human chondrocytes were transfected with small interfering RNAs (siRNAs) targeting TLR-2. <h3>Results</h3> The level of aggrecan and XT-1 in human osteoarthritis cartilage was significantly decreased compared to normal cartilage. XT-1 expression in cultured primary articluar chondrocytes showed a periodic oscillation in both mRNA and protein level. 29-kDa FN-f significantly suppressed the mRNA and protein levels of XT-1 at 14 h and 24 h, respectively. Knockdown of toll like receptor-2 (TLR-2) using small interference RNA revealed that the decrease of XT-1 expression by 29-kDa FN-f is mediated by TLR-2 signaling pathway. Inhibition of mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF- κB) signaling pathway restored 29-kDa FN-f-inhibited XT-1 expression. In addition, reduction of XT-1 expression by 29-kDa FN-f- was associated with activation of activator protein 1 (AP-1) signaling pathway. Finally, 29-kDa FN-f enhanced the expression of Sp3 and inhibited the expression of Sp1. Knockdown and overexpression experiments confirmed that XT-1 expression was modulated by Sp3 and Sp1, which are ubiquitous transcriptional proteins and compete for the same DNA binding site. <h3>Conclusions</h3> These results demonstrated that 29-kDa FN-f plays a detrimental role in the regulation of cartilage extracellular matrix formation including XT-1 expression. <h3>Disclosure of Interest</h3> None declared
Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic Potential of Renal Cancer
Authors: Ke Chen, Haibing Xiao, Jin Zeng, Gan Yu, Hui Zhou, Chunhua Huang, Weimin Yao, Wei Xiao, Junhui Hu, Wei Guan, Lily Wu, Jiaoti Huang, Qihong Huang, Hua Xu, Zhangqun Ye
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Deregulation or mutation of the EZH2 gene causes various tumors, including clear cell renal cell carcinoma (ccRCC). Although several splice variants of EZH2 have been identified, little is known about how EZH2 splicing is regulated or the contribution of alternative splicing to its protumorigenic functions. Experimental Design: We conducted RT-PCR, Western blot analysis, and IHC techniques to examine EZH2 and its alternative splicing transcript expression in renal cancer tissue and renal cancer cell lines. Proliferation, migration, clonogenicity, and tumorigenicity of renal cancer cells either exhibiting knockdown of EZH2 or its splicing factor SF3B3 were assessed by CCK8, Transwell assay, and murine xenograft experiments. Results: We found that the inclusion of alternative EZH2 exon 14 was significantly increased in ccRCC samples and renal cancer cell lines. In ccRCC lines, enforced expression of EZH2Δ14 inhibited, and EZH2 promoted, cell growth, migration, proliferation, and tumorigenicity in a xenograft model. Mechanistic studies demonstrated that EZH2Δ14 isoform functions as a dominant-negative inhibitor of full-length EZH2. Coexpression of EZH2Δ14 variant with full-length EZH2 not only abrogated DAB2IP and HOXA9 suppression but also inhibited EZH2-driven tumorigenesis. Strikingly, the splicing factor SF3B3 stimulates inclusion of exon14 and has pro-proliferative activity. Importantly, the upregulation of SF3B3 expression observed in clinical ccRCC samples parallels the increased inclusion of EZH2 exon14, and the SF3B3 level is associated with higher tumor stage and poor overall survival. Conclusions: These results suggest SF3B3 as a key regulator of EZH2 pre-mRNA splicing and SF3B3 may represent a novel prognostic factor and potential therapeutic target in ccRCC.
High Resolution Genome Wide DNA Methylation Analysis in a Large Trial Group Reveals a Novel Epigenetically Defined Subgroup of Myeloma Patients Characterized By Developmental Gene Hypermethylation
Authors: Martin F Kaiser, Alexander Murison, Charlotte Pawlyn, Eileen M Boyle, David C Johnson, Brian A Walker, Ping Wu, Dil Begum, Nasrin Dahir, Christopher P Wardell, Paula Proszek, David A Cairns, Walter Gregory, Graham Jackson, Roger G Owen, Gordon Cook, Mark T Drayson, Faith E Davies, Gareth J. Morgan
Journal: Blood (2014)