tbuckley/cabot-search huggingface dataset:
Direct-to-Consumer Genomewide Profiling
Authors: Talya Salz, Noel T Brewer
Journal: New England Journal of Medicine (2011)

n engl j med 364;21 nejm.org may 26, 2011 2074 controls in the genomic regions we presented, on the SNP level as evidenced by the basic allele test, and on the allele level as evidenced by the haplotype association test (Fig. 2 of our article). Imputation of classic HLA alleles, which in general are determined by appreciation of known variants only, may lead to rare alleles being missed or imputed with low confidence because of the limited size of the reference database given the highly polymorphic HLA locus.2 Since ultimately even the presence of statistically independent signals does not prove their causality, only sequence-based methods with accompanying cell and molecular biologic analyses will be able to confirm causative variants within genomic regions recognized by a genomewide association study.3 Horia C. Stanescu, M.D.
THU0093 Altered Expression of CD4+CD28- T Lymphocytes in Methotrexate Treated Rheumatoid Arthritis Patients
Authors: C. Bohόrquez, L. Ruiz, C. Garcia, A. Gόmez-La Hoz, A. Turriόn, H. Moruno, A. Pérez, A.I. Sánchez, E. Cuende, A. Movasat, F. Albarrán, M.J. Leόn, D. Díaz, J. Monserrat, M. Άlvarez-Mon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There are evidences supporting an expansion of CD4+ T lymphocytes in chronic and treated rheumatoid arthritis (RA) patients. The potential increased presence of these T cells in early RA remains elusive. <h3>Objectives</h3> Evaluate the number and distribution of circulating CD4+ T lymphocytes and their CD4+ naïve T cells (T<sub>N</sub>), central memory (T<sub>CM</sub>), non-terminated effector memory (T<sub>NTEM</sub>) and terminated effector memory (T<sub>TEM</sub>) T cells subsets according to the CD28 expression in a population of recently diagnosed DMARD naive RA patients before and along the first 6 months of methotrexate (MTX) treatment. <h3>Methods</h3> The number of circulating CD4+ T lymphocytes including their activation/differentiation stages (T<sub>N</sub>, TM, TCM and TEM subsets) and the CD28 expression, in fifty untreated patients with RA before MTX treatment and at 3 and 6 months of treatment, were assayed using multiparametric flow cytometry. We also studied twenty-four age- and sex-matched healthy subjects as controls. <h3>Results</h3> RA naïve patients show a significant (p&lt;0.05) expansion of the circulating CD4+CD28- T lymphocytes. The increased of this subset is mainly due to a significant elevator in the numbers of CD4+CD28- T naïve lymphocytes, CD4+CD28- T central memory lymphocytes and CD4+CD28- T non terminated effector memory lymphocytes. <h3>Conclusions</h3> In this work, we have found that the expansion of CD4+CD28- T lymphocytes is already detected in recently and DMARD AR naïve patients. Moreover this increase of CD28- T lymphocytes is also found in CD4+ T naïve lymphocytes. This it is possible to suggest that the expansion of CD4+CD28- occurs associated to the development of the RA as a biological hallmark of the disease. <h3>Disclosure of Interest</h3> None declared
Oral Cholecystagogue Cholescintigraphy
Authors: Joseph S. Fotos, Mark Tulchinsky
Journal: Clinical Nuclear Medicine (2015)

Intermittent unavailability of sincalide for determination of gallbladder ejection fraction (GBEF) prompted increased usage of fatty meal cholecystagogues (FMCs). The aim of this systematic review was to identify the state of current FMC options in cholescintigraphy, focusing on the quality of corresponding normal GBEF values.We performed an extensive literature search of the MEDLINE, Cochrane, and CINAHL databases without date or language restrictions with a broad spectrum of search terms. Selection criteria required both that the study use a FMC as part of a stimulated GBEF examination to gather data on normal volunteers or patients without evidence of gastrointestinal disease and that the meal used be described sufficiently for emulation. A cumulative point system was used to grade the quality of normal GBEF values: 1 point for screening ultrasound, 1 point for detailed screening questionnaire, 1 point for 20 or greater number of participants in a study, 1 additional point for 60 or greater number of participants in a study, 0.5 points for cursory screening questions, and 0 points when no screening process was mentioned. The meal was expressed in grams of fat per volume, when available.Twelve studies met inclusion criteria out of 15 studies claiming to report normal values. Two studies (17%) achieved a score of 3, 5 studies (42%) at 2 to 2.5, 3 studies (25%) at 1 to 1.5, and the remaining 2 studies (17%) at 0 to 0.5. Total number of participants examined ranged from 6 to 100. Meal composition varied widely. In 1 study, sham feeding was used. Most meals had components that could present problems to patients with relatively common dietary restrictions (ie, lactose intolerance, egg protein allergy, etc). Results for proposed normal values varied widely (from 16.3% to 85.6%). The commercial fatty meal products of Humana Infant Formula 1 and Ensure Plus offered the highest-quality normal values.There is a need to establish high-quality normal GBEF range for a ubiquitous fatty meal (ie, a meal that would be widely available, easy to prepare, inexpensive, and free of sensitivity-provoking ingredients). A corn oil emulsion, has immense potential as an ideal FMC, limited currently only by its lack of established normal values. Currently, the highest-quality normal GBEF values available for FMC exist for 2 commercial products, Humana Infant Formula 1 and Ensure Plus. However, these products may not be readily available at some institutions, and neither one is free from dietary restrictions.
FRI0100 The Role of Insulin Resistance and Inflammation on Symmetric Dimethylarginine in Rheumatoid Arthritis
Authors: T. Dimitroulas, J. Hodson, A. Sandoo, J. Smith, K. Douglas, G. Kitas
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Derangement of nitric oxide (NO) metabolism is considered one of the main mechanisms through which systemic inflammation exerts deleterious effects on vascular homeostasis in rheumatoid arthritis (RA). Symmetric dimethylarginine (SDMA) indirectly inhibits NO synthesis and predicts cardiovascular (CV) and all-cause mortality in high-risk patients and general population. <h3>Objectives</h3> We aimed to compare SDMA levels in RA patients and controls and to investigate whether SDMA is influenced by current and/or cumulative inflammatory burden as well by classical CV risk factors within RA population. <h3>Methods</h3> 201 RA patients [155 females, median age 67 (59 – 73)] were assessed at baseline (2006). Classical CV disease risk factors were recorded and systemic inflammation was determined by the measurement of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) routine biochemistry tests, inflammatory markers, glycemic profile and SDMA levels were measured by enzyme-linked immunosorbent assay in all patients and 82 controls [50 (60%) females, median age: 44 years (quartiles: 33 - 55)]. A quarterly measurement of CRP and ESR for each year the patient was in the study was used to produce average area under the curve (AAUC) for ESR and CRP. Paired analysis was employed for the comparison of SDMA in two groups and multivariate regression models were performed to identify predictors of SDMA. <h3>Results</h3> SDMA was significantly lower in RA patients in both unpaired and paired analyses (p=0.001 and p=0.005 respectively) with the magnitude of the difference being similar in both models. QUICKI (p=0.005) and disease activity score-28 (p=0.007) were positively related to SDMA whistle a negative correlation was with renal function (eGFR) (p=0.005). No significant association between SDMA and cumulative inflammatory load was established in univariable multivariable analysis. SDMA levels were not found to be significantly related to CV risk factors. <h3>Conclusions</h3> The molecular explanation of lower SDMA is unclear, but the established relationships with indices of disease activity and insulin resistance, may underline the pathogennetic role of NO pathway dysregulation in the development of atherosclerosis in RA. The biological and clinical importance of SDMA in RA remains to be evaluated in clinical and experimental studies. <h3>References</h3> Zsuga J, Török J, Magyar MT et al. Dimethylarginines at the crossroad of insulin resistance and atherosclerosis. Metabolism 2007; 56:394-9. Schepers E, Glorieux G, Dhondt A, Leybaert L, Vanholder R. Role of symmetric dimethylarginine in vascular damage by increasing ROS via store-operated calcium influx in monocytes. Nephrol Dial Transplant 2009; 24:1429-35. <h3>Disclosure of Interest</h3> None declared
THU0460 Tenascin-C in Joint Regeneration After Induced Osteoarthritis in the Newt Notophthalmus Viridescens
Authors: C. Schoenfeld, S.A. Susanto, M. Geyer, C. Schreiyäck, U. Lange, M. Looso, T. Braun, E. Neumann, U. Müller-Ladner
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In mammals tissue destruction often results in fibrotic scar tissue formation, which significantly impairs organ function. In contrast, many urodele amphibians have a remarkable regenerative capacity: Damaged tissues or even lost extremities are almost perfectly regenerated, both in function and size. We established the red-spotted newt <i>Notophthalmus viridescens</i> as a model organism to study endogenous knee joint regeneration in adult vertebrates. In this model, osteoarthritis (OA)-like symptoms can be induced by intra-articular injection of collagenase or surgical removal of articular cartilage. Treated animals primarily display joint instability and luxation, but joint functionality is completely restored after approximately 3 months. <h3>Objectives</h3> To identify key players involved in the underlying mechanisms driving knee joint regeneration using a high resolution gene analysis approach. <h3>Methods</h3> A cDNA array was performed after surgically and collagenase-induced knee damage in newts, and dysregulated candidate genes were selected. Microarray results were verified on the mRNA level by real-time PCR. Protein expression levels of the dysregulated candidates were analysed by immunohistochemistry (IHC). Additionally, <i>in vitro</i> experiments in newt-derived cell lines and primary newt cells (chondrocytes/fibroblasts) with tenascin-C (TN-C) knockdown were performed. <h3>Results</h3> Several matricellular proteins including TN-C were found to be upregulated during the regenerative process (at day 10 TN-C vs. control 22.4-fold in collagenase-induced OA model, 15.6-fold in surgically induced OA model). IHC revealed high TN-C expression in the periosteum in untreated newt legs. During the early phase of regeneration (at day 10) additional expression at the injury site (surgically induced OA) was observed. At later stages (20 and 40 days after injury) TN-C expression was detectable in regenerating tissues including articular cartilage. In adhesion experiments using the newt-derived cell line B1H1 TN-C coating had anti-adhesive properties (TN-C vs. control: 42% reduction). However, TN-C knock-down in newt cell lines and primary newt cells did not alter cellular adhesive behaviour. <h3>Conclusions</h3> TN-C plays an important role during knee joint regeneration. Further detailed studies will facilitate to identify additional molecular pathways guiding these regenerative processes unique for the newt and might allow the transfer to the development of new treatment options for human OA. <h3>Disclosure of Interest</h3> None declared
THU0474 A Phase 1 Clinical Trial of ATB-346, A Gastrointestinal-Ssafe Nonsteroidal Anti-Inflammatory Drug
Authors: J.L. Wallace
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Hydrogen sulfide (H<sub>2</sub>S) is an endogenous signaling molecule that exerts powerful anti-inflammatory and cytoprotective effects. Linking an H<sub>2</sub>S-releasing moiety to an NSAID greatly reduces the gastrointestinal (GI) damaging effects of the NSAID, as demonstrated in extensive pre-clinical testing in animal models (mouse, rat, dog). ATB-346 is an H<sub>2</sub>S-releasing derivative of naproxen; the latter is considered the most cardiovascular-safe of all NSAIDs. In addition to the a profound reduction in GI toxicity with ATB-346 (significant decreases in ulceration and bleeding throughout the GI tract), plasma levels of ATB-346-derived naproxen in rats and dogs remained elevated much longer after administration of ATB-346 when compared to equimolar doses of naproxen. ATB-346 suppresses COX-1 and COX-2 in vivo and in vitro with similar potency to naproxen, and is effective in reducing inflammation in various animal models. We now report on the first human trial of ATB-346. <h3>Methods</h3> ATB-346 was orally administered at a range of doses to healthy volunteers, both as a single dose, and as a daily (or twice-daily) dose for 14 days. Each cohort consisted of 8 subjects, with 6 receiving ATB-346 and 2 receiving placebo. A total of 8 cohorts were studied in the single-dose study (25 mg to 2000 mg), and 3 cohorts in the multiple-dose study (250 and 750 once daily, and 750 mg bid). All adverse events were recorded, and blood samples were drawn prior to and for at least 72 h after drug administration for measurement of ATB-346-derived naproxen levels. Routine cardiovascular, renal, hepatic and hematological biomarkers were monitored, along with clinical signs. Multiple ascending dose studies examined ATB-346 at doses of 250 and 750 mg once daily, and 750 mg twice daily. <h3>Results</h3> ATB-346 treatment did not produce any serious adverse events across the dose-ranges and treatment paradigms studied, nor were there any significant gastrointestinal, cardiovascular renal, or hematological findings associated with administration of this drug. As in animals, ATB-346 administration to humans resulted in a marked prolongation of therapeutically relevant levels of naproxen in the blood, supporting the possibility of once daily dosing for chronic conditions. <h3>Conclusions</h3> ATB-346 was very well tolerated and shown to be safe at all administered dose levels. These studies suggest a high level of safety of this drug, and support progression of testing to a relevant patient population in Phase 2 trials. <h3>Disclosure of Interest</h3> J. Wallace Shareholder of: Antibe Therapeutics Inc., Employee of: Antibe Therapeutics Inc.
PTH-241 ‘it made a big difference’-investigation of the patient experience of a community dietetic domiciliary service for patients at risk of malnutrition
Authors: S Kennelly, S Browne, G Flanagan-Rughaboor, D Loane, C Glennon
Journal: Gut (2015)

<h3>Introduction</h3> Early identification of patients at risk of malnutrition and onward referral to dietetic service is advocated in best practice guidelines.<sup>1</sup>Patients who are housebound are not able to attend dietitian clinic appointments require a domiciliary community dietetic service (CNDS). Data is lacking in relation to the patients’ experience of this type of service in the Irish setting. <h3>Aim</h3> To investigate patient experience and satisfaction with CNDS domiciliary service for patients at risk of malnutrition in 4 midlands counties in the Republic of Ireland (ROI). <h3>Method</h3> A random sample of patients who were actively receiving a domiciliary service from the CNDS were contacted and invited to be interviewed by an independent dietitian researcher at their home. A semi-structured interview-assisted questionnaire was used. The interview was audio-recorded and later transcribed for content analysis. <h3>Results</h3> Out of 20 patients contacted by the researcher, 12 participants (4 male, 8 female) were available to take part in the study. In 2/10 cases carers were interviewed as a proxy for patients who had advanced dementia. Average age of patients was 79 years (Range 62–94 years). All participants (n = 12) could recall the last visit they had received from the community dietitian (CD). All (n = 12) were satisfied with the service provided and many commented that a domiciliary visit made them feel supported. The majority of patients (10/12) felt they needed a domiciliary service. Most (10/12) participants could recall advice given by the CD however only half of those surveyed felt they were coping better with their diet (including supplement usage) after receiving the advice. <i>“I’ve become more aware what I should and should not do’. </i>Seven out of 12 participants felt the CNDS service had improved their overall quality of life such as improved health, energy, and appetite. <h3>Conclusion</h3> The finding that all patients receiving a domiciliary service from the CNDS are satisfied with the service and assessment carried out by the dietitan is encouraging. However the results suggest that many patients requiring a domically CNDS service still struggle to cope with dietary changes to improve nutritional intake despite receiving dietary advice and prescribed oral nutritional supplements. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Nutrition support in adults: oral nutritional support, enteral tube feeding, and parenteral nutrition (2006). London, National Institute for Health and Clinical Excellence (NICE)
Can Fenretinide Protect Women Against Ovarian Cancer?
Authors: G. DE PALO, U. VERONESI, T. CAMERINI, F. FORMELLI, G. MASCOTTI, C. BONI, V. FOSSER, M. D. VECCHIO, T. CAMPA, A. COSTA, E. MARUBINI
Journal: JNCI Journal of the National Cancer Institute (1995)
Hematopoietic Stem Cells
Authors: Peter Quesenberry, Lee Levitt
Journal: New England Journal of Medicine (1979)

(Second of Three Parts)Erythroid-Committed Stem CellsShortly after introduction of the assay for the pluripotent stem cell, evidence accumulated for the existence of an intermediate compartment of stem cells committed to erythropoiesis. There are several unique characteristics of erythropoiesis that allowed for a rather precise experimental evaluation of the system. It was noticed that induction of polycythemia in mice caused a reversible suppression of differentiated erythropoiesis.101 , 102 Marrows from animals with transfusion or posthypoxia polycythemia were found to contain no recognizable erythroid elements. Therefore, animals could be rendered plethoric and subjected to experimental manipulations, and differentiation into the erythroid line . . .
Reed-Sternberg cells in Hodgkin's cell lines HDLM, L-428, and KM-H2 are not actively replicating: lack of bromodeoxyuridine uptake by multinuclear cells in culture
Authors: SM Hsu, X Zhao, S Chakraborty, YF Liu, J Whang-Peng, MS Lok, S Fukuhara
Journal: Blood (1988)
Effect of infliximab therapy on employment, time lost from work, and productivity in patients with psoriatic arthritis
Authors: Arthur Kavanaugh, Christian Antoni, Philip Mease, Dafna Gladman, Songkai Yan, Mohan Bala, Bei Zhou, Lisa T Dooley, Anna Beutler, Cynthia Guzzo, Gerald G Krueger
Journal: Journal of the American Academy of Dermatology (2005)
PTU-089 Are clinical indices of inflammatory bowel disease activity superior to patient opinion at predicting activity as defined by faecal calprotectin?: Abstract PTU-089 Table 1
Authors: D Gracie, CJ Williams, R Sood, S Mumtaz, H Bholah, PJ Hamlin, AC Ford
Journal: Gut (2015)

<h3>Introduction</h3> The Harvey-Bradshaw index (HBI) and simple clinical colitis activity index (SCCAI) are clinical scoring systems used to estimate Crohn’s disease (CD), and ulcerative colitis (UC) activity, respectively. However, whether they are superior to the patient’s own opinion at predicting disease activity, defined by faecal biomarkers of inflammatory bowel disease (IBD) activity is unclear. We conducted a cross-sectional survey of IBD patients to assess these issues. <h3>Method</h3> Patient opinion as to whether they were, or were not experiencing a flare of disease was recorded in 245 patients. Active disease was defined as a HBI or SCCAI score of ≥5 for CD and UC respectively. Stool was collected for faecal calprotectin (FC) analysis by enzyme linked immunosorbent assay (Biohit, Finland), with patients dichotomised into those with or without active disease, using a FC of ≥200 µg/g of stool to define active disease. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of patient opinion and clinical activity indices at predicting disease activity defined by FC was calculated. A ROC curve for HBI and SCCAI against disease activity defined by FC was used to calculate the AUC for each clinical assessment index. Mean FC was compared between those with and without active disease by patient opinion and clinical indices of IBD activity by independent samples t-test. <h3>Results</h3> The sensitivity, specificity, positive and negative predictive value, overall test accuracy and AUC for each test when used to predict disease activity defined by FC is illustrated in Table 1. In CD, mean FC was lower in patients with active disease defined by HBI than those without (381 vs. 472; P = 0.368), but higher in patients with active disease defined by patient opinion than those without (474 vs. 425; P = 0.711). In contrast, mean FC was significantly higher in UC patients with active disease defined by both patient opinion and SCCAI (919 vs. 381; P &lt; 0.001 and 949 vs. 311; P &lt; 0.001 respectively). <h3>Conclusion</h3> The performance of clinical disease activity indices at predicting IBD activity was modest in UC and poor in CD when compared with faecal biomarkers of intestinal inflammation. Neither HBI nor SCCAI outperformed patient opinion in the assessment of disease activity. Faecal biomarker point of care testing may aid clinical decision making. <h3>Disclosure of interest</h3> None Declared.