tbuckley/cabot-search huggingface dataset:
A Comparison of Thrombolytic Therapy with Primary Coronary Angioplasty for Acute Myocardial Infarction
Authors: Nathan R. Every, Lori S. Parsons, Mark Hlatky, Jenny S. Martin, W. Douglas Weaver
Journal: New England Journal of Medicine (1996)

Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials.
SP0062 What is the Influence of the Patient Component in RA Remission Criteria?
Authors: L. Gossec
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The ACR/EULAR Boolean definition of remission in rheumatoid arthritis comprises maximal painful and swollen joint counts of 1, no acute phase reactants (maximum CRP 1 mg/dl), and a very low threshold for patient symptoms (maximal patient global assessment of 1 on a 0-10 scale). This definition of remission is extremely stringent though it can more frequently be attained for patients with recent RA than for patients with long-standing disease. Patients reaching remission for joint counts and CRP according to the ACR/EULAR Boolean definition of remission, but not remission for patient global assessment, are termed in 'near-remission'. Near-remission seems to be twice as frequent as full remission, indicating many patients who have no objective signs of inflammation, do not regard their status as optimal. This raises several questions: what explains the raised patient global assessmentin these patients without evident inflammation? Is it sub-clinical inflammation, or is it psychological distress? Is the cutoff value of 1/10 for patient global assessment too low, or is the phrasing of the patient global assessment question unclear? Indeed, patient global assessment may represent the wider impact of rheumatoid arthritis including psychological well-being and coping skills, rather than just the pathophysiological severity of the disease. And finally (and importantly for the clinician) should the management of patients in near-remission differ from the management of patients in full remission? <h3>Disclosure of Interest</h3> None Declared
A Combined Study of Tc-99m Technegas and Xe-133 Gas in Suspected Congenital Bronchial Atresia
Authors: SHIGERU KOSUDA, YOSHIKO KADOTA, SHOICHI KUSANO, ISAO SEKINE
Journal: Clinical Nuclear Medicine (2003)

KOSUDA, SHIGERU M.D.; KADOTA, YOSHIKO M.D.; KUSANO, SHOICHI M.D.; SEKINE, ISAO M.D. Author Information
P16.18 * INTEROBSERVER VARIABILITY IN THE RADIOLOGICAL ASSESSMENT OF PERFUSION MR IMAGING IN GLIOBLASTOMA MULTIFORME
Authors: M. Kerkhof, M. Vos, M. Taphoorn
Journal: Neuro-Oncology (2014)

INTRODUCTION: The limitations of conventional MR imaging for accurate tumor assessment and differentiation of true tumor progression and pseudoprogression in glioblastoma multiforme have led to the search for new imaging modalities. The perfusion MRI is a technique that is capable of quantifying microvessel density (vascularity) and permeability of brain tissue by assessment of the relative cerebral blood volume (rCBV), reflecting the degree of microvascular proliferation in tumor tissue. This study is performed to assess the interobserver variability in the radiological assessment of perfusion MR imaging in patients with glioblastoma multiforme treated with temozolomide chemoradiation. METHODS: Three radiologist evaluated the perfusion MRI of 20 patients during treatment with temozolomide chemoradiation at baseline and at 3 months and 6 months after start of treatment. The interobserver agreement is assessed by intraclass correlation coefficients between the radiologists. Results (interobserver agreement results given in ICC's will follow, study is ongoing.) CONCLUSION: The radiological assessment of perfusion MR imaging in patients with glioblastoma multiforme is …
AB1104 Can Generic PROMIS Measures Adequately Capture Fatigue in Rheumatoid Arthritis?
Authors: S.J. Bartlett, A.M. Orbai, T. Duncan, C.O. Bingham
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Fatigue is highly prevalent, disabling, and remains under-reported and undertreated in rheumatoid arthritis (RA). PROMIS measures were developed to assess common symptoms and impacts of health domains relevant to chronic conditions. PROMIS offers item banks for computer adaptive testing (CAT), paper-based short forms (SF) and single item scales. The PROMIS fatigue item bank assesses both experience (from mild tiredness to an overwhelming, sustained sense of exhaustion) and impact on physical, mental and social activities. However, it is unclear whether generic fatigue instruments are sensitive enough to assess the symptoms and impact of fatigue in RA clinical trials or to guide decision-making in clinical care. <h3>Objectives</h3> To evaluate the performance of three forms of PROMIS fatigue measures in RA patients seen in an academic inflammatory arthritis center. <h3>Methods</h3> Data are from the first 139 RA patients enrolled in an ongoing study integrating PROs into routine care at an arthritis center. Three PROMIS fatigue measures (CAT [5-8 items], 7-item SF and the single fatigue item from the Global Health scale (0-5)) were administered with other legacy measures. Routine clinical measures of disease activity were recorded. Spearman correlations were used to evaluate convergent validity and pairwise comparisons were used to examine evidence of a dose response relationship across disease activity levels. <h3>Results</h3> Participants were mostly female (81%) and white (85%) with a mean (SD) age of 56 (13) and RA duration of 12 (9) yrs. Overall mean (SD) t-scores for the PROMIS CAT and SF were 54.1 (10.2) and 53.6 (8.9); the single item was 2.6 (.9). PROMIS measures correlated highly with a fatigue VAS (.78-.87), moderately with disease activity indicators including pain (.60-.68), patient global (.66-.72), physical function (.53-.69) and CDAI (.54-.65), and weakly with MD global (.36-.39). There was evidence of a dose-response relationship in relation to disease activity levels (see table). <h3>Conclusions</h3> Our study contributes evidence of the feasibility and construct validity of using generic PROMIS fatigue instruments in RA. While the PROMIS Fatigue CAT was most strongly associated with legacy measures and offers greatest precision, the SF and single item performed adequately and are useful when paper or briefer versions are needed. Evaluation of responsiveness and validity across diverse RA patient groups and settings (trials vs clinical care, group vs. individual level change) is needed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4814
ASSOCIATION OF OBESITY WITH SURVIVAL AFTER CARDIOPULMONARY RESUSCITATION FOR IN-HOSPITAL CARDIAC ARREST: ANALYSIS OF THE 2003-2011 NATIONAL INPATIENT SAMPLE DATABASES
Authors: Tanush Gupta, Dhaval Kolte, Sahil Khera, Prakash Harikrishnan, Wilbert Aronow, Diwakar Jain, Sachin Sule, Howard Cooper, William Frishman, Sei Iwai, Deepak Bhatt, Gregg Fonarow, Julio Panza
Journal: Journal of the American College of Cardiology (2016)
A8.24 PPARβ/δ expression orchestrates the immunosuppressive effect of mesenchymal stem cells via NF-κB signalling
Authors: P Luz-Crawford, N Ipseiz, A Caicedo, C Scholtysek, C Stoll, J Loriau, G Tejedor, C Jorgensen, G Kronke, F Djouad
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> PPARβ/δ is a <i>member</i> of the PPAR transcription factor <i> family </i>expressed by several cell types including mesenchymal stem cells (MSC). PPARβ/δ modulates signal transduction by interacting with other transcription factors such as NF-κB and regulates the expression of molecules such as VCAM-1 and ICAM-1. Lately, these adhesion molecules induced by proinflammatory cytokines were described to be critical for MSC immunosuppressive functions. Therefore, we investigated the role of PPRAβ/δ as an upstream regulator of MSC immunosuppressive properties. <h3>Materials and methods</h3> MSC were isolated from the bone marrow of wildtype (MSC) and PPARβ/δ knockout mice (PPARβ/δ<sup>-/-</sup>MSC). The expression and production of immunosuppressive molecules by MSC were assessed after 24 h of culture in presence of proinflammatory cytokines by FACS analysis and ELISA, respectively. The role of NF-κB activity on adhesion molecule expression in MSC and T cell adhesion on MSC was addressed by FACS and under flow conditions, respectively. Chromatin immunoprecipitation (IP) assays were performed to study the interactions between transcription factors and co-repressors. Eventually, the therapeutic effect of PPARβ/δ<sup>-/-</sup>MSC was compared to the MSC in the collagen induced arthritis model (CIA). <h3>Results</h3> <i>In vitro</i>, PPARβ/δ<sup>-/-</sup>MSC displayed a stronger immunosuppressive effect than MSC. This was associated with a higher production of NO, expression of V-CAM and I-CAM and NF-κB activity in PPARβ/δ<sup>-/-</sup>MSC compared to MSC. Conversely, the inhibition of NF-κB activity resulted in a loss of MSC immunosuppressive functions correlated with a significant decrease of adhesion molecule expression and NO production by MSC. Under flow conditions, while T cells attach to PPARβ/δ<sup>-/-</sup>MSC significantly more than wildtype MSC, the treatment with NF-κB inhibitor significantly impaired MSC attachment potential. Chromatin IP assays revealed that MSC activation with proinflammatory cytokines maintained NF-κB p65 subunit in the κB elements of the iNOS promoter. Under the same activation conditions, the knockdown of PPARβ/δ significantly increased the retention of NF-κB p65 subunit on iNOS promoter. In addition, we showed that pro-inflammatory treatment of MSC induces the release of the co-repressor CoREST in MSC while it is constitutively absent in PPARβ/δ<sup>-/-</sup>MSC. Finally, <i>in vivo</i>, in the CIA model we found out that PPARβ/δsilencingsignificantly increased the therapeutic effect of MSC. <h3>Conclusion</h3> All together our results provide new insight into the mechanisms that mediate MSC immunosuppressive properties and highlight the role of PPARβ/δ as a potential means of enhancing MSC therapeutic potential in arthritis.
PTU-060 Phenotypic Characterisation of Inflammatory Bowel Disease in South Asians in the United Kingdom-Insights into a Shifting Landscape
Authors: C Boyd, J K Limdi
Journal: Gut (2013)

<h3>Introduction</h3> The aetiology of inflammatory bowel disease (IBD) remains elusive. The increasing incidence of IBD in developing countries and immigrant populations appears to outpace what genetic influences alone could instigate. There is a relative dearth of literature on the phenotypic characteristics of South Asian immigrant populations. The aim of our study was to define the clinical phenotype of IBD in South Asians in North-West England. <h3>Methods</h3> We conducted a retrospective study of 102 patients of South Asian origin attending IBD clinics at our hospital. Clinical data including demographics, disease characteristics (Montreal classification), treatment and blood results were obtained using electronic case records. <h3>Results</h3> Of 106 patients reviewed, 55 were male. The median age was 38 years (range 16–80) and mean disease duration was 9.5 years. Seventy-six patients had ulcerative colitis (UC) and 30 had Crohn’s disease (CD). Five patients were current or ex smokers (4.7%). Seventeen patients had extra-intestinal manifestations of IBD (16.0%). Of UC patients 37 had pancolitis, 34 left sided disease and 5 had proctitis. Of patients with CD, 3 had ileal disease, 11 colonic disease and 16 had ileocolonic disease. Five CD patients had stricturing disease, 10 had penetrating disease (6 also stricturing) and 15 had non-penetrating, non-stricturing disease. Perianal disease was noted in 3 at diagnosis and in 5 subsequently. Eighty four patients received steroids, topical steroids (31), 5-ASA (99), topical 5-ASA (31), azathioprine (56), 6- mercaptopurine (4), cyclosporine (2), methotrexate (10), infliximab (21) and adalimumab (10). Fifty eight patients received at least one immunomodulatory therapy with the median time to use being 12 months (range 0–276 months). Thirteen patients (7 CD, 3 UC) required surgery (3 total colectomy, 10 subtotal). Mean time to surgery was 4 years (range 0–13 years). Seventeen patients had disease progression leading to Montreal reclassification (median time 60 months; range 1–216 months). <h3>Conclusion</h3> We noted a higher prevalence of UC with predominantly pancolonic disease and a significant proportion of CD with penetrating or stricturing disease. The majority of patients required immunomodulatory therapy. Epidemiologic insights from such populations may provide further clues in defining an aetiological paradigm for IBD and should form an important area of further research. A case control study exploring differences is underway at our institution. <h3>Disclosure of Interest</h3> None Declared
Abstract 5143: From sequencing data to mutation spectra: a high throughput analysis pipeline.
Authors: David Jones, Adam P. Butler, Jon W. Teague, Keiran M. Raine, Andrew Menzies, John Marshall, Jonathan Hinton, Serge Dronov, Lucy Stebbings, Alagu Jayakumar, Catherine Leroy, Jorge Zamora, Manasa Ramakrishna, Elli Papaemmanuil, Helen Davies, Susanna L. Cooke, Serena Nik-Zainal, Ultan McDermott, Michael R. Stratton, Peter Campbell
Journal: Cancer Research (2013)

Abstract Advances in massively parallel sequencing technology have revolutionized the way we characterise cancer genomes and provided significant new insights to our understanding of the mechanisms that underpin oncogenesis. A diverse range of mutations types including single base-pair changes, insertions, deletions, copy number alterations and larger structural variations are common in cancer genomes. To rapidly and accurately screen next generation sequencing data for these somatic mutations in cancer, the Cancer Genome Project (CGP) has developed a high throughput analysis pipeline utilising a suite of analysis software developed by the group. Built around a compute farm of ∼2,000 nodes and using a Lustre filesystem, raw data files (BAM etc.), analysis results files and version information are efficiently stored and tracked in our archive/storage system, FileTrk. Lane data is aligned using Burrows-Wheeler Aligner (BWA) and web interfaces have been developed to allow scientific staff to rapidly QC aligned lanes. Once QC'd and desired coverage is reached, lanes are merged into a single sample BAM file and the sample is then ready for analysis. In house algorithms are used to detect point mutations (CaVEMan), structural variation breakpoints (Brass) and copy number changes (ASCAT and PICNIC), whilst Pindel is used to detect small insertions/deletions. Post-processing filters then remove false positives and the results are uploaded into a database. Mutations are annotated to the protein and RNA levels using standard nomenclature (Vagrent, in-house software). Downstream analysis software has been developed (CANDI, in-house software) which produces a range of plots to aid visualisation of mutation context and mutation spectra patterns in related cancer samples. Current IT development is focussed on converting the pipeline to produce and store VCF output, incorporate further downstream analysis software and automate data export to COSMIC and the ICGC data portal. Citation Format: David Jones, Adam P. Butler, Jon W. Teague, Keiran M. Raine, Andrew Menzies, John Marshall, Jonathan Hinton, Serge Dronov, Lucy Stebbings, Alagu Jayakumar, Catherine Leroy, Jorge Zamora, Manasa Ramakrishna, Elli Papaemmanuil, Helen Davies, Susanna L. Cooke, Serena Nik-Zainal, Ultan McDermott, Michael R. Stratton, Peter Campbell. From sequencing data to mutation spectra: a high throughput analysis pipeline. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5143. doi:10.1158/1538-7445.AM2013-5143
Long-Term Effects of Indomethacin Prophylaxis in Extremely-Low-Birth-Weight Infants
Authors: Barbara Schmidt, Peter Davis, Diane Moddemann, Arne Ohlsson, Robin S. Roberts, Saroj Saigal, Alfonso Solimano, Michael Vincer, Linda L. Wright
Journal: New England Journal of Medicine (2001)

The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known.
Baló's Concentric Sclerosis
Authors: Oliver Wengert, Eberhard Siebert
Journal: New England Journal of Medicine (2011)

A 25-year-old, left-handed patient with known relapsing–remitting MS presented with a mild, nonfluent aphasic syndrome and left facial paresis of subacute onset. MRI scans of the brain revealed a large lesion with a concentric-ring pattern.
Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation
Authors: R L Comenzo, H Hassoun, T Kewalramani, V Klimek, M Dhodapkar, L Reich, J Teruya-Feldstein, M Fleisher, D Filippa, S D Nimer
Journal: Leukemia (2005)
Abstract 4724: No-lyse no-wash immunophenotyping.
Authors: Jolene A. Bradford, Rick Kerndt
Journal: Cancer Research (2013)

Abstract Immunophenotyping whole blood is a primary application in the study of blood cell populations and their functions. Red blood cells have traditionally been removed during sample preparation by lysis methods or density-gradient selection to enable the study of nucleated cell populations. This processing of whole blood has its draw backs due to the potential loss of cells of interest thru inadvertent lysis and unintentional selection of fragile and rare cells including blast cells, cancer cells, and cancer stem cells. The application of a No-Lyse No-Wash protocol in human whole blood samples benefit from a streamlined protocol that reduces cell loss. Testing of mouse whole blood presents additional challenges for cancer researchers due to the limited sample volume available (≤100 μL/day/animal), particularly in longitudinal studies. Specifically, these small volumes limit the ability to perform immunophenotyping experiments with required controls. This work describes a No-lyse No-wash method which takes advantage of acoustic focusing technology. Immunophenotyping panels are shown for both human and mouse whole blood. A total of 10μL of whole blood is stained in a 50 μL total volume and then diluted 400-fold in PBS. A fluorescence threshold is used to distinguish the white blood cell populations from the more abundant red blood cell population. In the mouse immunophenotyping example, CD45 is used to threshold on white blood cells. For the human immunophenotyping example, a cell permeable nucleic acid stain is used to threshold on all nucleated cells. At this dilution, the coincidence of the target population with red blood cells is reduced sufficiently so scatter signals are reliable for population identification. The significantly higher sample collection rates available with acoustic cytometry allows for the acquisition of high quality data utilizing a No-lyse No-wash protocol in a timely manner. Difficult-to-collect and precious samples like mouse blood can be stained and diluted without washing or performing RBC removal procedures. Loss of cells due to sample preparation is essentially eliminated, and ability to detect the cells of interest is enabled. Citation Format: Jolene A. Bradford, Rick Kerndt. No-lyse no-wash immunophenotyping. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4724. doi:10.1158/1538-7445.AM2013-4724
Supreme Court Review of the Health Care Reform Law
Authors: Gregory D. Curfman, Brendan S. Abel, Renée M. Landers
Journal: New England Journal of Medicine (2012)

In late March, the Supreme Court will examine the constitutionality of the Affordable Care Act, potentially producing a landmark decision. The Court will determine whether, in crafting the ACA's individual mandate and Medicaid expansion, Congress exceeded its powers.
A3.05 The lung microbiome in rheumatoid arthritis and associated local/systemic autoimmunity
Authors: V Joshua, JU Scher, C Ubeda, A Artacho, L Segal, J Grunewald, AI Catrina
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Airway abnormalities and increased lung tissue citrullination is found in both RA patients and individuals at at-risk for the development of disease. Recent data suggest that the gut (Prevotella copri) and oral (Porphyromonas gingivalis) microbiome might potentially contribute to the priming of an aberrant systemic immune response characteristic of RA. Our objective was to study whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity. <h3>Materials and methods</h3> Bronchoalveolar lavage (BAL) samples from 20 subjects with RA, 10 with sarcoidosis (DC) and 24 healthy controls (HC) were obtained by research bronchoscopy. 16S rDNA sequencing was performed to define microbiota composition. Autoantibodies, including anti-CCP, RF and ACPAs were also measured in sera of RA subjects. Statistical analysis was performed using wilcoxon test and Spearman correlation. <h3>Results</h3> The16S sequencing data showed similar alpha/beta diversity between RA and DC groups, but significantly different from HC. Taxonomic comparison between groups was performed using LEfSe, which revealed several significant differences (LDA score&gt;2). Multiple taxa, including Rhanella and Rhodanobacter were present only in the RA and DC groups, but completely absent from HC (p &lt; 0.001). While RA BAL samples were enriched with Sphingobacteria, sarcoidosis BAL was enriched with Bacteroidia, Rhizobiales, Nitrospirales, and Campylobacter. Raoultella and Barnesiella correlated with CCP2 levels in BAL (rho&nbsp;= 0.49 and 0.47; p-value&nbsp;= 0.026 and 0.032). Serum levels of CCP-IgA had a negative correlation with Massilia and Tannerella (rho&nbsp;= -0.63 and 0.53; p-value 0.003 and 0.016), and a positive correlation with Vagococcus and Lactobacillus (rho= 0.59 and 0.54; p-value 0.006 and 0.014). Unclas_Lactobacillales also had a positive correlation with serum levels of RF-IgA (rho&nbsp;= 0.71; p-value &lt;0.001). Serum levels of anti-CCP2 antibodies had a positive correlation with Porphyromonas, Rahnella and Chryseobacterium (rho&nbsp;=0.46, 0.46 and 0.45; p-value&nbsp;= 0.03, 0.03 and 0.04). <h3>Conclusions</h3> Despite the relatively small number of samples analysed, several taxonomic differences were noted between groups. Correlations between relative abundance of specific taxa in RA BAL with serum autoantibodies (ie, anti-CCP) support an association between the lung microbiome and the host immune phenotype in RA. Further evaluation of functional aspects of this microbiome may provide further insights into its possible contribution to RA.