tbuckley/cabot-search huggingface dataset:
SAT0032 Ex vivo analysis of autoantigen-specific T cell responses using a multi HLA-CLASS II tetramer approach
Authors: C Gerstner, H Uchtenhagen, A Dubnovitsky, W Kwok, EA James, V Malmström
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> HLA class II tetramers allow the direct <i>ex vivo</i> enumeration and phenotypic characterization of antigen-specific T cells and have proven a useful tool in different settings, e.g. allergy and vaccination. In rheumatoid arthritis (RA), many candidate auto-antigens have been characterized and are believed to play a role in the disease. <h3>Objectives</h3> Based on flow cytometry we developed a multi HLA-class II tetramer approach that renders it possible to look at numerous specificities simultaneously and is sufficiently sensitive at the same time as auto-reactive T cells are likely to be rare. We focused on validated citrullinated T cell epitopes previously studied in RA, namely a-enolase, fibrinogen and CILP. To test the robustness and sensitivity of our multi-tetramer assay, we performed repeated experiments on PBMCs of HLA-DRB1*04:01-positive healthy controls as well as HLA-DRB1*04:01-positive RA patients. <h3>Results</h3> First, we examined the sensitivity of the panel by assessing PBMC from healthy donors and we could detect low frequencies of auto-reactive T cells in these samples (1–10 per million CD4), mostly displaying a naïve phenotype, which was in sharp contrast to influenza-specific T cells in the same donors which were 10–20 fold higher in numbers and of memory phenotype. Next, we tested the robustness of the panel by running technical repeats of all healthy donor samples, which yielded similar frequencies. Thereafter, we focused on RA patient PBMC obtained from repeated blood draws (2–4 weeks apart). Also in these samples, frequencies ranged between 1–10 tetramer-positive cells per million CD4+ T cells, i.e. similar as in healthy controls. Moreover, not all T cell specificities were present in all patients. Still, we found the frequencies to be stable in the repeated blood draws in approximately half of the individuals, implicating that frequencies close to 1 cell per million CD4+ T cells is borderline of what we can stably detect. Importantly, the patient samples utilized were not taken from time points of active disease, where we hypothesize frequencies to be elevated. This may be the case also in synovial fluid and as a proof of principle, we assessed synovial fluid samples of HLA-DRB1*04:01+ RA patients and were able to detect auto-reactive T cells at frequencies comparable to the ones found in peripheral blood. <h3>Conclusions</h3> In conclusion, we developed a sensitive tetramer panel allowing the simultaneous enumeration and phenotypic characterization of antigen-specific T cells in <i>ex vivo</i> samples from RA patients that can be used for monitoring and in-depth studying of these cells during the course of disease and treatment in individual patients. <h3>Disclosure of Interest</h3> None declared
Corrigendum to “Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma” [J Hepatol 67 (2017) 293–301]
Authors: Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
Journal: Journal of Hepatology (2017)
Abstract P327: COPa Library: A Proteomic Knowledge Base for Cardiovascular Biology and Medicine
Authors: Nobel Zong, Haomin Li, Ning Deng, Lingxuan Chen, Yueju Wang, Caiyun Fang, Rafael Jimenez, Tao Xu, Henning Hermjakob, Huilong Duan, John Yates, Rolf Apweiler, Peipei Ping
Journal: Circulation Research (2011)

We constructed the Cardiac Organellar Peptide Atlas Library (COPa library) as a targeted and interactive resource to the cardiovascular community. Annotated peptide spectra are hosted using a relational database in a modular fashion based on species (e.g. human, mouse) and organelles (e.g. mitochondria, proteasome). Within this release of COPa library, a total of 108,268 spectra have been disseminated via two avenues. A web portal was established to navigate the library via parallel set of identifiers, such as protein name, accession number, gene symbol, etc. In parallel, a web-service cyber-infrastructure was engineered to aid the annotation of mass spectra submitted via internet. The large raw spectra files are dissected into small data packages at the local PC before submission. This workflow surpasses the limitation of network bandwidth, as well as enables parallel data submission and search. A benchmark test with 897,327 ms/ms spectra showed the library searching covers 93.4% of proteins identified via database searching, as well as additional 23.9% of proteins at the same level of statistical confidence. In addition, a wiki-like web interface was embedded in the library web portal in order to facilitate the synthesis of consensus knowledge among the cardiovascular community on innovations of functional proteomics. Overall, the COPa library search supports targeted proteomic characterization, which complements database search for exploratory survey. The implementation of the COPa library-based proteomic knowledgebase leverages state-of-the-art technology and annotated datasets among the research community at large. Its application bridges discovery-driven and hypothesis-driven research while fostering translational medicine.
The influence of inflammation on mammographic breast density in women at increased risk of breast cancer.
Authors: Samir S. Ambrale, Tiffany Rounds, Betsy L Sussman, Mercedes Rincon, Despina Kontos, Brad M Keller, Yongli Ji, Brian Sprague, Marie Wood
Journal: Journal of Clinical Oncology (2015)

1566 Background: Mammographic density is an important risk factor for breast cancer but the etiology of density is not well understood. Studies suggest that inflammation may play a role in density. We evaluated the association between serum inflammatory markers and breast density in women at increased risk for breast cancer. Methods: Women previously enrolled in the University of Vermont IRB-approved High-Risk database were eligible for inclusion if they had a baseline serum sample and a mammogram available within 120 days of each other (N = 174). A subset of eligible women also had a paired serum sample and mammogram at 4 years from study entry (N = 38). Blood samples were analyzed for C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1b (IL-1b) and tumor necrosis factor-α (TNF-α). Breast density was calculated using 2 methods; the semi-automated Cumulus method and fully automated University of Pennsylvania (UPenn) method. Results: Mean age of the cohort was 46.2 (range 24-71 years) and 63.8% were premenopausal. Mean baseline density was 35.8% and 31.8% using the Cumulus and UPenn method respectively. Mean baseline values were 20,005 ng/ml for CRP, 10.6 pg/ml for TNF-α, 0.78 pg/ml for IL-1b and 0.84 pg/ml for IL-6. Body mass index correlated with CRP (spearman correlation coefficient [r] = 0.58; p< 0.0001), IL-6 (r = 0.17; p= 0.003) and TNF-α (r = 0.19; p= 0.02). Linear regression adjusted by age and BMI found that baseline IL-6 had significant association with breast density calculated by either density methods (Cumulus: β coefficient 1.62, p= 0.04; UPenn: β coefficient 1.95, p= 0.01). No other biomarker had a statistically significant relationship with density. There was no significant correlation between change in inflammatory marker levels and change in density at 4 years. Conclusions: Mammographic breast density was found to be elevated among women with higher serum IL-6 levels, a finding that supports prior data suggesting a relationship between inflammation and density. This study strengthens the evidence for consideration of anti-inflammatory agents as chemoprevention for breast cancer. Further research is needed to elucidate the mechanism by which IL-6 is associated with breast density.
THU0669 The association between harris hip score and disease activity or hip mri features in ankylosing spondylitis
Authors: Z Wu, L He, M Yang, Y Liu, D He, Y Zhang, C Wang, H Xu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hip involvement is a common clinical feature observed in ankylosing spondylitis (AS) patients and it often leads to substantial restriction of the body functions.<sup>1</sup> Hip involvement in AS is mainly assessed by radiographic changes, clinical symptoms or MRI. The Harris hip score (HHS) is a valuable assessment tool to measure health status of AS patients. However, the relationship between HHS and other clinical indices is unknown. <h3>Objectives</h3> To evaluate relationship between HHS and other commonly used clinical indices. <h3>Methods</h3> In this multicentre, observational study, AS patients with hip clinical manifestation are enrolled and randomly assigned to infliximab treatment (group I, with/without DMARDs and/or NSAIDs) or conventional therapy (group II, DMARDs and/or NSAIDs). Primary endpoint: to compare functional improvement of hip joint (HHS) between two treatment groups (infliximab and conventional therapy) at week 30. Secondary endpoint: to compare disease activity and functional improvement of AS and radiologic progression of hip joint between two treatment groups at week 30 and 52. Association between baseline HHS and disease activity measures such as Bath ankylosing spondylitis (BAS)-functional index (BASFI), BAS disease activity index (BASDAI), AS disease activity score (ASDAS), CRP and ESR was analysed using Pearson correlation coefficient. BAS metrology index (BASMI) and hip imaging functions (MRI of hip, BAS radiology hip index [BASRI-h]) were analysed using independent two-sample t-test or ANOVA based on data characteristics. <h3>Results</h3> Study is ongoing; currently, only baseline information is analyzed. Baseline demographics and disease characteristics did not show any significant difference between groups. Almost all baseline disease activity measures showed significant Pearson correlation (high correlation in BASFI=0.646) with HHS, except for BASDAI (table 1). Significant association between HHS and three MRI scores (articular cartilage stripping, bone destruction under joint surface, femoral head bone marrow cavity edema) and BASRI-h was shown (table 2). Also, significant correlation was shown between BASMI and HHS (F value [degree of freedom]=4.70 [4]; p=0.0022). <h3>Conclusions</h3> The baseline results of HHS were found to be well associated with disease activity scores like BASFI, ASDAS and BASMI and four hip imaging features in AS patients with hip involvement. <h3>References</h3> Jeong H, et al. Korean J Intern Med. 2017; 32(1): 158–164. <h3>Disclosure of Interest</h3> Z. Wu: None declared, L. He: None declared, M. Yang: None declared, Y. Liu: None declared, D. He: None declared, Y. Zhang: None declared, C. Wang Employee of: Xi9an Janssen pharmaceuticals Ltd., H. Xu: None declared
AB0996 Frequency of HLA-B*51 and the association with clinical manifestations in armenian patients with BEHÇET disease
Authors: VN Mukuchyan, A Haroyan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behçet disease (BD) is a system inflammatory disease mostly characterized by oral and genital ulcers and variable manifestations affecting other organs, mainly skin and eye. The HLA class I molecule HLA-B*51 allele is strongly associated with BD in many different ethnic groups and appears to be a significant risk factor for BD in the ancient Silk Route areas in contrast with Western and Northern Europe and U.S.<sup>1–4</sup> <h3>Objectives</h3> Our purpose was to show the frequency of presence of HLA-B*51 allele in Armenian patients with BD and estimate any correlation with common symptoms of disease depended on presence of HLA-B*51. <h3>Methods</h3> Forty-seven patients of Armenian origin (28 males 59.6% and 19 females 40.4%) fulfilling the International Criteria for BD (ICBD) with mean age 29.7±11.3 years; disease duration – 5.3±12.4 years were enrolled. We observed the clinical manifestations of BD of both HLA-B*51 carriers and non-carriers. <h3>Results</h3> HLA-B*51 was detected in 38 (80.8%) patients, of whom 25 male and 13 female (65.8% and 34.2%, respectively). Arthritis, erythema nodosum and genital ulcers were significantly more common in HLA-B*51-positive patients (83.3%, 83.3% and 80.6% respectively) than in HLA-B*51-negative ones (16.7%, p=0.032, 16.7% p=0.032 and 19.4% p=0.023 respectively). <h3>Conclusions</h3> In this ever first estimation of HLA-B*51 gene frequency in patients with BD in Armenia, our results indicated that the frequency of HLA-B*51 allele in BD is 80.8% which is higher than elsewhere (in Japan 58.9%, Iran 61.9%, Turkey 75%, Saudi Arabia 76.9% Greece 78.9%)<sup>5</sup>. Furthermore, this investigation revealed HLA-B*51 carriage much more often in male than in female BD patients. In addition HLA-B*51 carriers are in significant higher risk of development of arthritis, erythema nodosum and genital ulcers. <h3>References</h3> Ohno S, Aoki K, Sugiura S at al (1973) Letter. HLA 5and Behçet disease. Lancet 2:1383 – 1384. Ohno S, Ohguchi M, Hirose S et al (1982) Close association of HLA Bw51 with Behçet disease. Arch Ophthalmol 100:1455–1458. de Menthon M, Lavalley MP, Maldini C et al (2009) HLA-B51/B5 and the risk of Behçet disease: A systemic review and meta-analysis of case-control genetic association studies. Arthritis Rheum 61:1287–1296. Gul A, Ohno S (2012) HLA-B*51and Behçet disease. Ocul Immunol Inflamm 20:37–43. Yoshiaki Ishigatsubo. Behçet disease: from Genetics to Therapies. Springer 2015: 42–43. <h3>Disclosure of Interest</h3> None declared
AB0316 Hospital admissions of patients with rheumatoid arthritis treated with dmard
Authors: EC Cervantes Pérez, JR Maneiro, A Souto Vilas, JA Mera Varela, JJ Gόmez-Reino
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To describe hospital admissions and contributing factors in patients with rheumatoid arthritis (RA) treated biological DMARD (b-DMAR) and conventional synthetic DMARD (cs-DMAR). <h3>Methods</h3> Retrospective observational study of RA patients admitted to the hospital for any cause from 2010 to 2015. Demographic, clinical and therapeutic characteristics were collected from the medical charts. Multivariate and univariate models were used to identify variables associated with admissions for any cause, major adverse cardiovascular events (MACE), and infection. The statistical program Stata 14.0 was used for the analysis. <h3>Results</h3> In the period 2010–2015, 26% of all RA patients were treated with b-DMARD. There were a total of 1251 hospital admissions for any cause in 600 patients; 1055 admissions in 477 patients treated with cs-DMAR and 196 admissions in 123 patients treated with b-DMAR. Of the 1251 admissions, 251 were due to infections and 60 to MACE. Demographic characteristics, comorbidities and treatment are disclosed in table. In the multivariate analysis, diabetes mellitus (p&lt;0.001), and hypertension (p=0.029) were associated with admission for infections, and hypertension (p 0.011), and dyslipidemia (p=0.02) with admissions for MACE. <h3>Conclusions</h3> infections and MACE are a significant cause of hospital admission in patients with rheumatoid arthritis. Comorbidities as diabetes, hypertension and dyslipidemia but not b-DMARD are significantly associated with admission for infection or MACE. <h3>Disclosure of Interest</h3> None declared
Clinical Benefit of Eculizumab in Patients with No Transfusion History in the International Paroxysmal Nocturnal Hemoglobinuria Registry
Authors: Antonio Medina Almeida, Camille L. Bedrosian, Alexander Cole, Petra Muus, Hubert Schrezenmeier, Jeff Szer, Alvaro Urbano-Ispizua, Wendell F. Rosse
Journal: Blood (2015)
SAT0746-HPR Towards measurement of person-centered care outcomes in outpatient nurse-led clinics
Authors: V Bala, B Fridlund, K Forslind, B Svensson, P Hagell
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Person-centered care (PCC) is increasingly emphasized as a key component of effective illness management and of developing high quality of care. Despite considerable progress of PCC in many areas of care there is currently a gap and a need for means to assess PCC practice in outpatient care. In rheumatology, PCC is considered an unmet need and further development and evaluation of this approach to care is thus of high priority. <h3>Objectives</h3> To develop an instrument for measuring person-centered care from the perspective of the person with rheumatoid arthritis (RA) in nurse-led outpatient clinics. <h3>Methods</h3> A conceptual framework of PCC in the outpatient context and focusing on the meeting between the person with RA and the nurse and on the patient as an active care partner was undertaken. Based on this framework, qualitative interviews (1,2) and a literature review, a 35-item questionnaire was proposed and qualitatively tested regarding acceptability and content validity among 50 persons with RA attending a nurse-led outpatient clinic. Two versions of the questionnaire were tested: one using four response categories (0 = Totally disagree; 3 = Completely agree), and one using two response categories (0 = Disagree; 1 = Agree). Content validity was estimated by calculating Content Validity Index of the individual items (I-CVI) and of the overall instrument (S-CVI). <h3>Results</h3> Respondents found the items easy to understand (77%) and relevant (93%). Seventy-three percent of the respondents preferred the questionnaire version with four response categories. This version took a mean (SD) of 5.3 (2.5) minutes to complete. I-CVI values ranged from 0.87 to 1.00 and S-CVI was 0.94. About 80% of the respondents considered some items to be redundant. This resulted in a reduced 24-item draft questionnaire that yield a total score between 0–72. <h3>Conclusions</h3> A preliminary 24-item patient-reported PCC questionnaire was developed. Psychometric testing is needed for validation of this tool before implementation. <h3>References</h3> Bala SV, Samuelson K, Hagell P, Svensson B, Fridlund B, Hesselgard K (2012). The experience of care at nurse-led rheumatology clinics. Musculoskeletal Care 10: 202–211. Bala SV, Samuelson K, Hagell P, Fridlund B, Forslind K, Svensson B, Thomé B (2016). Journal of Clinical Nursing; doi: 10.1111/ jocn.13691. <h3>Disclosure of Interest</h3> None declared
Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis
Authors: Yingda L. Xie, Soumitesh Chakravorty, Derek T. Armstrong, Sandra L. Hall, Laura E. Via, Taeksun Song, Xing Yuan, Xiaoying Mo, Hong Zhu, Peng Xu, Qian Gao, Myungsun Lee, Jongseok Lee, Laura E. Smith, Ray Y. Chen, Joon Sung Joh, YoungSoo Cho, Xin Liu, Xianglin Ruan, Lili Liang, Nila Dharan, Sang-Nae Cho, Clifton E. Barry, Jerrold J. Ellner, Susan E. Dorman, David Alland
Journal: New England Journal of Medicine (2017)

Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid.
Evaluation of criteria for exercise-induced pulmonary hypertension in patients with resting pulmonary hypertension
Authors: Christopher J. Mullin, Steven Hsu, Kaushik Amancherla, Alison Wand, Parker Rhodes, Peter J. Leary, Monica Mukherjee, Rachel L. Damico, Todd M. Kolb, Stephen C. Mathai, Paul M. Hassoun, Ryan J. Tedford
Journal: European Respiratory Journal (2017)

Owing to the lack of a suitable definition, exercise criteria for the diagnosis of pulmonary hypertension (PH) were removed from consensus guidelines following the 4th World Pulmonary Hypertension Symposium in 2008 [1] and have remained absent following the 5th World Symposium [2] and recent European Cardiology Society/European Respiratory Society guidelines [3]. Nonetheless, there remains significant interest in properly defining an abnormal pulmonary vascular response to exercise [4–6]. Exercise-induced PH defined by the mPAP-CO relationship may lack sensitivity for detecting pulmonary vascular disease <http://ow.ly/v0r330dVzxr>
Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men
Authors: Tommi Suvitaival, Isabel Bondia-Pons, Laxman Yetukuri, Päivi Pöhö, John J. Nolan, Tuulia Hyötyläinen, Johanna Kuusisto, Matej Orešič
Journal: Metabolism (2017)
THU0644 Patient decisions related to hip and knee arthroplasty and the factors influencing them
Authors: WB Nowell, S Venkatachalam, E Harden, T Concannon
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patient-engaged research can improve the safety and satisfaction outcomes of hip and knee arthroplasty (joint replacement surgery). <h3>Objectives</h3> The objective of this study was to identify the decisions that are most important to patients when undergoing hip or knee arthroplasty and the factors they view as important in making those decisions. <h3>Methods</h3> Forty-nine U.S. participants were recruited from ArthritisPower Patient-Powered Research Network and CreakyJoints arthritis patient community to participate in structured one-hour discussions held via webinar during January to April 2016 to understand patients9 experiences with joint replacement. Patients described decisions that were most important to them and the factors they used to make those decisions. Discussions were transcribed and coded to identify themes; patient decisions and factors were identified and categorized and co-occurrence of decisions and factors was tabulated. Demographic and procedure-related characteristics were captured. <h3>Results</h3> Eight decisions emerged that were influenced by at least ten factors (Table). The most important decisions involved whether to have surgery, selection of surgery date, surgeon, facility, implant device, and ancillary health care professionals (HCPs) and services. Factors included current situation, expectations of having or not having surgery, professional and word-of-mouth familiarity with surgeon/HCP, procedure, services and device, and perceived value. Patients9 current situation and health status and their expectations of surgery were most commonly used to make decisions about whether and when to have surgery. Patients9 trust of and communication with doctors was the most commonly factor used when deciding on arthroplasty surgeon. <h3>Conclusions</h3> Arthroplasty patients are concerned about a variety of decisions. Patient-centered research should maximally address questions of importance to patients and this study is a first step in identifying and prioritizing topics that matter most to patients and the information that patients currently use to make joint replacement decisions. <h3>Acknowledgements</h3> This project was funded through a Patient-Centered Outcomes Research Institute (PCORI) Eugene Washington PCORI Engagement Award (2228-GHLF). <h3>Disclosure of Interest</h3> None declared