tbuckley/cabot-search huggingface dataset:
FRI0165 The Molecular Convergence of Non-Hla Ankylosing Spondylitis Risk Genes with Autoimmune Diseases
Authors: M. Uddin, D.D. O'Rielly, D. Codner, M. Hasan, D.D. Gladman, P. Rahman
Journal: Annals of the Rheumatic Diseases (2014)

Background Genome-wide association studies (GWAS) and subsequent follow up studies validated a significant number of ankylosing spondylitis (AS) loci. It is often speculated that risk loci detected from autoimmune diseases converges into shared pathways through molecular level interactions. To identify such convergence a systematic approach is required to further investigate and understand the underlying disease biology. Objectives The primary goal of this study is to show systematic molecular level convergence of AS risk genes with nine other autoimmune diseases. Methods Here we investigate 418 risk genes from ten complex autoimmune diseases (ankylosing spondylitis (AS), crohn's disease (CD), psoriasis (PS), ulcerative colitis (UC), celiac disease (CeD), multiple sclerosis (MS), primary biliary cirrhosis (PBC), rheumatoid arthritis (RA), type 1 diabetes (T1D), systemic lupus erythematous (SLE)) and their complex interactions with AS. We have used a network based method to infer connectivity between AS genes found to be associated in GWAS studies with another autoimmune risk gene set. The network is consisting of 6,998,947 pairwise interactions (symmetric gene pair interaction excluded) that is a set derived from physical protein-protein interactions (PPI), co-expression or co-localization analysis. For a given pair of disease gene set, the constructed interaction network consists of one degree connectivity for any pair of gene. Exhaustive permutation test was conducted by randomly replacing equal number of genes (50000 times, from a background of 22,695 protein coding genes) for a disease risk gene set to quantify the connectivity significance of the original risk gene sets. Results The constructed PPI network showed significantly (P<1.8x10–4) dense modular connectivity for AS genes with six autoimmune disease genes (CD, PS, UC, CeD, MS, PBC). The most significant connectivity observed (after correcting for gene number) with Crohn's disease and ulcerative colitis that is consistent with the known biology of AS where CD and UC often manifest as comorbid conditions. To better understand the shared pathway and to identify etiological genes, each gene was ranked according to their contributing connectivity of the inferred network. Apart from the shared genes (associated in multiple diseases, i.e. IL23R , TNFAIP3 ) we have also identified AS specific genes (i.e. NOS2 , GPR65 ) that are highly connected with multiple non-AS autoimmune risk genes. Conclusions We have developed a systematic approach to infer causal genes that converge at the molecular level to a common pathway involve in disease pathogenesis. The highly connected non-AS genes identified in our study should be prioritized for further investigation to identify their contribution to AS pathogenesis and to better understand the complex relationship of autoimmune diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3295
NT-01 * UTILITY OF TEMOZOLOMIDE IN THE MANAGEMENT OF ANAPLASTIC ASTROCYTOMA: A COMPARISON OF SURVIVAL IN THE ERA PRIOR TO AND FOLLOWING TEMOZOLOMIDE
Authors: I. Abuali, R. Strowd, X. Ye, S. Grossman
Journal: Neuro-Oncology (2014)

BACKGROUND: Addition of temozolomide (TMZ) to standard radiation has become common clinical practice in patients with anaplastic astrocytoma (AA). Prospective trials will ultimately inform its utility but results will not be available for years. Three retrospective studies have questioned whether TMZ improves survival over radiation alone but have methodologic limitations to their conclusions. OBJECTIVE: To determine survival trends in patients with AA prior to and following the inclusion of TMZ into standard clinical practice. METHODS: A retrospective single-institution study was conducted of all patients >18 years with newly diagnosed AA treated from Sept 1995 to Dec 2012. Based on an institutional shift toward the incorporation of TMZ into treatment regimens around Jan 2004, patients receiving treatment before (i.e. pre-TMZ) and after (i.e. post-TMZ) this time. Demographic, clinical, radiographic and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. RESULTS: A total of 196 patients were identified for inclusion; 74 pre- and 122 post-TMZ; mean age 46.5 + /-14.6 yrs; 57% male; 86% white, 9% black and 5% other ethnicity. Most tumors were supratentorial (69%) though infratentorial (4%), spinal (2%) and other locations (25%) were included. Extent of surgery included biopsy (31%), subtotal (37%) and gross total resection (32%). Chemotherapy was administered in only 12% pre-TMZ (n = 9, TMZ in 1, PCV in 2, and gliadel in 6) and 94% post-TMZ (n = 115, TMZ in all). Of all patients, 88% pre- and 54% post-TMZ were deceased. While median OS was 34.7 months pre-TMZ (95% CI 22.5-62.9) and only 28.1 post-TMZ (95% CI 19.3-40.2), only 56% of those remaining alive post-TMZ have reached median survival. CONCLUSION: The addition of TMZ to radiation for patients with AA is common. While longer OS was observed pre-TMZ, a substantial number of patients post-TMZ have not yet reached median survival and continued follow up is ongoing.
P1262 TARGETED NEXT-GENERATION SEQUENCING (NGS) REVEALS NOVEL GENOTYPE AND PHENOTYPE CORRELATIONS FOR MITOCHONDRIAL DNA DEPLETION SYNDROMES IN PEDIATRIC ACUTE LIVER FAILURE (ALF)
Authors: A.C. Valencia, T. Huang, R. Sheridan, A. Peters, K. Bove, X. Wang, A. Miethke
Journal: Journal of Hepatology (2014)
A2.36 Dynamics of T-cell subset in early ra patients treated with mtx or MTX+ANTI-TNF
Authors: Z Wigston, MH Buch, A Burska, P Emery, F Ponchel
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Introduction</h3> It has been recently established that the quantification of naïve CD4<sup>+</sup>T-cell frequency at baseline can predict the outcome of MTX treatment (1). The purpose of this study was to investigate whether T-cell subsets varied during treatment with MTX and MTX+anti-TNF. <h3>Methods</h3> Fresh blood samples were collected from 116 patients with early RA that had received no previous DMARDs: a first group received MTX (n = 67) and the second MTX+anti-TNF (n = 49). Flow cytometry was conducted at 3 monthly intervals using standard protocols. The frequency of naïve and IRC subsets were recorded as% of CD4<sup>+</sup>T-cells. Naïve T-cells decrease with age but IRC are more closely related to levels of inflammation (2). The deviation from the expected age-corrected frequency was calculated for naïve cells and used to analyse data. <h3>Results</h3> At baseline, there was no difference in the average frequency of naive CD4<sup>+</sup> T-cells and IRC between treatment groups. The average frequency of naïve CD4<sup>+</sup>T-cells increased slowly from week 26 to week 48 in the MTX group plateaued at ˜2.8 fold. In contrast, in the MTX+anti-TNF group, naïve cell frequency increases steadily from baseline up to 6.5 fold at 48 weeks. IRC marginally increased in the MTX group (1.25 fold at week 48) but were immediately reduced by half (0.46 fold) in the MTX+anti-TNF group and stayed low up to week 48 (p &lt; 0.001 at all time-points). <h3>Conclusion</h3> Results suggest an association between better inflammation control resulting in lower IRC frequency in the MTX+anti-TNF group as well as a steady increase in naïve cells frequency observed with more aggressive treatment. Considering the predictive value of naïve cell frequency at baseline (1), continued naive cells deterioration in the MTX group is an important finding suggesting lack of immune function recovery compare to the MTX+anti-TNF. <h3>References</h3> F Ponchel, <i>et al</i>. ARD. 2014;73:2047-2053 F Ponchel, <i>et</i><i>al.</i> Blood. 2002;100:4550–4556
769 FROM COMBINATION-THERAPY TO MONO-THERAPY IN TREATMENT EXPERIENCED CHB PATIENTS WITH VIRAL RESISTANCE OR PARTIAL RESPONSES: FIRST RESULTS OF AN INTERNATIONAL MULTICENTER COHORT STUDY
Authors: J. Petersen, S. Unger, M. Buti, M. Lutgehetmann, P. Lampertico, C. Sarrazin, P. Buggisch
Journal: Journal of Hepatology (2013)
Predictors of Long-Term Outcome after Percutaneous Balloon Mitral Valvuloplasty
Authors: David J. Cohen, Richard E. Kuntz, Stephen P.F. Gordon, Robert N. Piana, Robert D. Safian, Raymond G. McKay, Donald S. Baim, William Grossman, Daniel J. Diver
Journal: New England Journal of Medicine (1992)

Percutaneous balloon mitral valvuloplasty is known to produce short-term hemodynamic and symptomatic improvement in many patients with mitral stenosis. Comprehensive assessment of the clinical usefulness of balloon valvuloplasty requires evaluation of patients' long-term outcomes.
Abstract 4866: The dynamic interaction of nuclear Smads with peri- and centromeric heterochromatin is involved in the modulation of histone modification and chromatin structure
Authors: Tae-aug Kim, Jonghyun Kim, Saejung Kim, John Whang, Sato Misako, Lalage Wakefield, Larionov Vladimir, Seong-Jin Kim, John Niederhuber
Journal: Cancer Research (2010)

Abstract Smads are intracellular signaling transducers of TGF-β family ligands. Through TGF-β activation, phosphorylated R-Smads (Smad2/3) form active heteromeric complexes with co-Smad (Smad4) and translocate to the nucleus where they interact with chromatin to assemble the transcriptional machinery of various target genes. Evidence also indicates that Smads are involved in chromatin modulation via interactions with histone modifiers. The role of pre-existing nuclear Smads in chromatin modulation, however, has not been described, nor have the molecular mechanisms of their dynamic interaction with heterochromatin been elucidated. Here we report that nuclear Smads directly bind to specific sites on heterochromatin, altering chromatin architecture upon TGF-β activation. Subcellular fractionation indicates that both active and inactive nuclear Smad 2/3 remains in the biochemically insoluble fraction. We found that only non-phosphorylated Smad3 interacted with HP1α, a key component of heterochromatin under transcriptionally inactive conditions. The level of HP1α, but not HP1β and γ, was regulated in a TGF-β dependent manner in both Smad 2/3 KO MEFs and mouse mammary epithelial cells. Localization of the Smad3 in the pericentromeric heterochromatin and centromere regions of the human chromosomes suggests Smad3 may function as an organizer of chromatin architecture and chromosome assembly during mitosis. ChIP assay indicated that pericentromeric and centromeric heterochromatin bound Smads were dissociated by TGF-β activation and translocated to target gene promoter regions to activate gene transcription. Interestingly, TGF-β enhanced pericentromeric heterochromatin binding of Smad3 in a Smad3 overexpressed human breast cancer cell line, MCF10Ca1, but dramatically decreased in a cell line with deletion of MH2 domain in Smad3. Furthermore, deletion of MH2 domain markedly increased by more than 100 folds both H3 lys4 dimethylation and lys9 dimethylation in centromeric heterochromatin but diminished them in pericentromeric heterochromatin. This suggests that the MH2 domain of the Smad3 may play a critical role on modulation of heterochromatin structure in a manner that activates or represses genome wide gene transcription activity. In conclusion, these results indicate that nuclear Smads are involved in the modulation of chromatin structure through the regulation of HP1α and their direct interaction with peri- and centromeric heterochromatin. Therefore dysregulation of nuclear Smad expression may increase genomic instability. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4866.
La cholangiopancréatografie rétrograde endoscopique après 80 ans reste t'elle sûre et faisable? Résultats d'une étude cas-témoins multicentrique
Authors: P Grandval, A Laquiere, D Bernardini, H Turki, JM Gonzalez, S Di Pietro, C Boustière, R Laugier
Journal: Endoscopy (2011)

Introduction: Les indications de Cholangiografie Pancréatografie Rétrograde Endoscopique (CPRE) pour des pathologies lithiasiques et cancéreuses concernent fréquemment des patients âgés. L'analyse de la littérature montre sur des effectifs peu importants que la CPRE est sure et efficace pour le traitement de la lithiase biliaire. L'objectif de cette étude était d'analyser, chez les patients de plus de 80 ans, traités pour une pathologie lithiasique ou tumorale biliaire, les résultats de la CPRE sous anesthésie générale.
Kaiser's Project LEAN Grantees Start Community Projects
Authors: L. Baute
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Kaiser's Project LEAN Grantees Start Community Projects Get access Linda Baute Linda Baute Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 21, 1 November 1989, Pages 1612–1613, https://doi.org/10.1093/jnci/81.21.1612 Published: 01 November 1989
S30 Does Obesity Make For Worse Childhood Asthma?
Authors: SW Turner, A Mehta, JG Ayres, CN Palmer, S Mukhopadhyay
Journal: Thorax (2012)

<h3>Introduction</h3> Obesity may be important to asthma causation but the relationship between obesity and outcomes within populations of children with established asthma is inconsistent across studies. This study tested the hypothesis that obese children who have asthma have worse asthma outcomes in comparison with non-obese, non-overweight children with asthma. <h3>Methods</h3> Cross-sectionally, children with asthma were recruited from hospitals across Scotland using published methods.1 A respiratory questionnaire and quality of life questionnaire (PAQLQ) were completed with measured height, weight, spirometry and exhaled NO. Obesity was defined as body mass index (BMI) &gt;95th% and non-obese or overweight as BMI&lt;85th%. Asthma outcomes were categorised as severity (emergency prednisolone treatment, BTS treatment step, spirometry) and control (PAQLQ). <h3>Results</h3> There were 693 children recruited in whom BMI was determined in 501 including 103 who were obese and 71 overweight (ie BMI &gt;85th% but ≤95th%). In unadjusted comparisons and compared to non-obese non-overweight children, obese children had higher %FVC (mean difference 6.0% [95% CI 0.7, 11.2] p=0.026), reduced %FEV1/FVC (mean difference 4.5% [95% CI 1.2, 7.8] p=0.007), a trend for lower PAQLQ score (4.8 versus 5.8, p=0.071) and were less likely to have co-existent eczema or hayfever (OR 0.8 [0.7, 0.9] p=0.001). In the multivariate analysis and compared with non-obese non-overweight children, obese children had reduced %FEV1/FVC and also reduced risk for eczema or hayfever but not for other outcomes. <h3>Conclusion</h3> This is the first study of associations between obesity and asthma outcomes in a UK paediatric population. Although children with asthma may have slightly different physiology (i.e., obstructed lung function and reduced atopy) compared to non-obese, non-overweight individuals, these differences are unlikely to be of clinical relevance. Weight reduction interventions targeted specifically at obese children with established asthma are unlikely to improve asthma severity or control. <h3>References</h3> Turner <i>et al</i>. A methodology to establish a database to study gene environment interactions for childhood asthma. <i>BMC Medical Research Methodology</i>, 2010, 10–107.
Abstract 4940: Microrna expression profiling in adrenocortical neoplasia: Implications on tumor size and functionality
Authors: David Velázquez-Fernández, Stefano Caramuta, Deniz M Özata, Pinar Akcakaya, Anders Höög, Bertil Hamberger, Martin Bäckdahl, Catharina Larsson, Jan Zedenius, Weng-Onn Lui
Journal: Cancer Research (2011)

Abstract Background: Tumors arising from the adrenal cortex (ACT) can be hormonally hyperfunctioning or silent. This functional phenotype, as well as their size, is of clinical importance. MicroRNAs are a class of small non-coding RNAs that negatively regulates gene expression. There is increasing evidence for their significant role in tumorigenesis. Their relevance on the functional phenotype and size of these tumors has not been previously documented. Aim: To characterize differential expression patterns of microRNAs regarding the increasing size and the functional phenotypes of ACT. Methods: Seventy frozen tissue samples were included: 16 aldosterone-producing adenomas (APA), 14 cortisol producing adenomas (CPA), 14 non-hyperfunctioning adenomas (NhFA), 19 adrenocortical carcinomas (ACC) and 7 normal adrenal cortices as controls. Global microRNA expression profiles were determined using the Agilent Human microRNA microarray, and the results were verified by quantitative real-time PCR. Results: We observed distinct microRNA expression patterns among different ACT phenotypes: majority of the APA was clustered separately from NhFA and CPA, and the ACC was independently clustered apart from all benign tumors. A larger number of miRNAs were differentially expressed between APA and CPA, while a smaller subset of differently expressed microRNAs was found between functional and non-hyperfunctional adenomas. Among the benign tumors, we found miR-21 expression was significantly correlated with increasing tumor size. Conclusion: Deregulation of microRNA expression is associated with the functional phenotype and size in ACT, and these microRNAs may have implication related to the development of adrenocortical tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4940. doi:10.1158/1538-7445.AM2011-4940
Abstract P2-10-23: Lymphovascular Invasion (LVI) and Overall Survival in Node-negative and Node-positive Breast Cancer Patients: A Meta-analysis.
Authors: S Sahebjam, I Diaz-Padilla, A Ocana, B Seruga, E Amir
Journal: Cancer Research (2012)

Abstract Introduction: LVI is an important prognostic factor in patients with lymph node-negative invasive breast cancer. The prognostic value of LVI in lymph node-positive disease or in other subgroups remains unclear. Here we present a meta-analysis of studies assessing the impact of LVI on overall survival (OS) in different subgroups of breast cancer patients. Methods: A published data meta-analysis was conducted. Studies reporting hazard ratios (HR) for the association of LVI with OS in a multivariable model were included. Those not reporting HR or utilizing only univariable analyses were excluded. HR and 95% confidence intervals (CI) were extracted or computed and pooled using the DerSimonian and Laird random effects model. Subgroup analyses were conducted for the differential effect of lymph node involvement, estrogen receptor (ER) status, extent of LVI and decade in which the study was conducted (pre 1990, 1990–1999 and 2000 onwards). Results: Twenty studies comprising 40,417 patients were included in the analysis. There was marked heterogeneity in the effect size between studies (Cochran Q p &amp;lt; 0.001, I2=62%). When all studies were pooled, LVI was significantly associated with worse OS (HR:1.70 95% CI 1.49–1.95, p &amp;lt; 0.001). Among studies selecting patients by lymph node status, the association between LVI and OS was similar for lymph node positive and negative patients (HR:2.03 and 2.41 respectively, subgroup difference p = 0.56). There were no significant differences based on ER-status (subgroup difference p = 0.75) or decade of study (subgroup difference p = 0.21). Pooled assessment of the effect of extent of LVI was not possible as this parameter was not consistently reported. Conclusion: LVI is associated with similarly detrimental OS regardless of lymph-node or ER status. Improvements in adjuvant therapies over the past 20 years do not appear to have diluted the impact of LVI on OS. The marked heterogeneity in the effect size may result from differences in the extent of LVI. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-23.
SERIAL COMPUTED TOMOGRAPHY PULMONARY ARTERIAL MEASUREMENTS PREDICT SURVIVAL IN PULMONARY HYPERTENSION PATIENTS
Authors: Joseph Negusei, Rajeev Malhotra, Jackie Szymonifka, Qing Zhou, Zachary Lavender, Aaron Waxman, Marc Semigran, Quynh Truong
Journal: Journal of the American College of Cardiology (2016)
Unconscious Race and Social Class Bias in Medical Students
Authors: Z. Yang, P. Huang, X. Zhu
Journal: JAMA (2011)

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THU0130 Adherence to DMARDS in Patients with Rheumatoid Arthritis - A Multicenter Outpatient Study
Authors: K. Krueger, H. Kellner, M. Welcker, T. Schaum, I. Haug-Rost
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Abstract</h3> Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.
910 GENOTYPING OF TA DINUCLEOTIDE REPEAT, rs72258881, COULD IMPROVE THE PREDICTION OF INTERFERON-BASED CHRONIC HEPATITIS C THERAPY AND SPONTANEOUS CLEARANCE FOLLOWING rs8099917 GENOTYPING
Authors: M. Sugiyama, A. Ido, H. Tsubouchi, H. Watanabe, Y. Ueno, K. Murata, M. Korenaga, M. Mizokami
Journal: Journal of Hepatology (2013)