tbuckley/cabot-search huggingface dataset:
A3.3 Micro-RNA-34a and micro-RNA-155 unbalance is associated to IL-6/IL-6R pathway in CD14 cells and skin compartment of systemic sclerosis patients
Authors: S Alivernini, SL Bosello, B Tolusso, R Benvenuto, A Mangoni, L Bui, S Canestri, C Di Mario, G Ferraccioli
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> MicroRNAs (miRs) are post-transcriptional regulators implicated in Systemic sclerosis (SSc). MiR-34a and miR-155 are related to endothelial senescence and inflammation. The aim of the study is to investigate the expression of miR-34a and miR-155 in peripheral blood (PB) CD14 cells and in clinically involved and uninvolved skin paired samples in SSc. <h3>Materials and methods</h3> Twenty-seven patients with Raynaud phenomenon (RP) were enrolled, divided into 3 groups: long standing SSc (lsSSc) fulfilling the 1987 ACR criteria (n = 10), early SSc (eSSc) reaching 9 points using the Very Early Diagnosis of Systemic Sclerosis criteria (n = 9) and primary RP (n = 8) respectively. Matched healthy controls (HC) (n = 7) were enrolled. Immunostaining for CD68 was performed on paired skin tissues from SSc patients. miR-34a and miR-155 expression was evaluated by qPCR on CD14 cells isolated by CD14 specific microbeads from PB and on clinically involved and uninvolved skin paired samples. Using HumanTargetScan cross-referenced methodology, IL-6 receptor (IL6-R) was selected as target of miR-34a and miR-155 and experimentally confirmed by qPCR. IL-6 and IL-6R plasma levels were determined by ELISA. CD14 cells from PB of HC (n = 4) were cultured in RPMI, stimulated with IL-6 (30ng/ml) or LPS (100ng/ml) and collected after 48 h to assess miR-34a and miR-155 expression by qPCR. <h3>Results</h3> MiR-155 is over-expressed either in eSSc (p = 0.0002) and lsSSc (p = 0.04) compared to HC. MiR-34a expression is increased only in lsSSc compared to HC (p = 0.01). Primary RP patients did not differ for miR-155 and miR-34a expression from HC (p = 0.71). CD68 cells are over-represented in clinically involved skin compared to uninvolved skin paired samples (p = 0.02). MiR-34a is over-expressed in clinically involved skin samples compared to uninvolved skin (p = 0.04). IL-6R expression is significantly lower in lsSSc and eSSc patients compared to primary RP (p = 0.03 and p = 0.03). IL-6 plasma levels were higher in lsSSc (p = 0.01) as well as in eSSc (p = 0.003) compared to HC whereas no significant difference was found in IL-6R plasma levels. MiR-34a expression directly correlates with the skin score value (R = 0.52, p = 0.03) in SSc patients and with IL-6 plasma levels (R = 0.42; p = 0.01). SSc patients with digital ulcers have higher miR-34a expression than SSc patients without ulcers (p = 0.01). Finally, miR-34a and miR-155 are induced in CD14 cells by IL-6 and LPS <i>in vitro</i> stimulation. <h3>Conclusions</h3> MiR-34a and miR-155 expression is unbalanced in CD14 cells and paired skin samples of SSc patients linked to the IL-6/IL-6R pathway. MiRNA expression profile could help to differentiate patients with primary and SSc associated RP.
Abnormal Tl-201 Myocardial Scintigraphy Associated With Administration of Sodium Aurothiomalate
Authors: KEVIN C. ALLMAN, NEIL PETRY, B. PHARM, BRAHM SHAPIRO
Journal: Clinical Nuclear Medicine (1997)

A patient with strikingly reduced TI-201 myocardial retention after intramuscular administration of gold therapy(sodium aurothiomalate) is described. Following a routine Bruce protocol exercise test, postexercise scintigraphy was normal; an abnormal scan of the thorax was obtained on delayed imaging at 3 hours. This scan showed no demonstrable myocardial retention of tracer. In between the two acquisitions, the patient received 50 mg intramuscular sodium aurothiomalate for rheumatoid arthritis. A repeat scan obtained 3 days later showed a normal myocardial scintigram. It is recommended that patients receiving intramuscular gold therapy should not undergo such treatment close to the timing of TI-201 myocardial scans.
AB0310 Ra remission rates with tocilizumab therapy (lornet study: multicentre open-label, phase iv study of the quality of the life patient with severe/moderate ra with adding of tocilizumab to disease-modifying antirheumatic drugs therapy)
Authors: E. Panasyuk, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab (TCZ), anti-interleukin-6 receptor monoclonal antibody, is an active biological agent for treatment of active rheumatoid arthritis (RA). The main objective of optimal use of TCZ is searching of clinical remission of RA. <h3>Objectives</h3> To assess efficacy of TCZ by criteria of remission Disease Activity Score based on 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) evaluation. <h3>Methods</h3> The results come from LORNET study, which is multicentre open-label, phase IV study of the quality of the life patient with severe/moderate RA with adding of tocilizumab (TCZ) to disease-modifying antirheumatic drugs (DMARDs) therapy. Patient had to be naïve to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the 6-month trial. A total 201 adult patients with active RA (DAS&gt;3,2) who remained on stable doses of DMARDs and received TCZ 8 mg/kg every 4 weeks for 24 weeks (total 6 infusions) were enrolled in the study. Mean age of the patients was 49±12 years. And their mean disease duration was 7,5±6,5 years. <h3>Results</h3> Baseline characteristics of 201 patients included: mean (sd) age 49 (12). Disease duration 7,5 (6,5) years, swollen joint count (SJC)16 (9), tender joint count (TJC) 26 (13), HAQ-DI 1,93±0,6. Average disease activity score (DAS) 28 of all 201 patients significantly decreased from 6,75±0,85 (baseline) to 2,6±1,16 (week 24). DAS28 remission (DAS28&lt;2,6) rate at week 24 being achieved by 51,3%, SDAI remission – 21,4%, CDAI remission – 22,0%. HAQ-DI clinical improvements were seen in patient starting at week 4, delta HAQ-DI -0,44 (minimal clinical difference is -0,22). At week 24 delta HAQ-DI -1,09. There were registered 101 AEs in 51 (25,4%) patients. Most of AE were mild or moderate. Which were mostly high level transaminases (n=29) and respiratory infections (n=17). 73% of AEs resolved by the time of reporting. There were 15 serious AEs. <h3>Conclusions</h3> Tocilizumab in combination with DMARDs is highly effective in the treatment of moderate to severe RA. Tocilizumab infusion is applicable as primary biologic therapy for active RA. Rapid and sustained improvement was noted in quality of life. A manageable safety profile was seen over the 24-week study period. <h3>Disclosure of Interest</h3> None Declared
Abstract 2368: An online tool for the validation of survival-predicting biomarkers in non small-cell lung cancer using microarray data of 1,329 patients.
Authors: Balazs Gyorffy, Andras Lanczky
Journal: Cancer Research (2013)

Abstract To decipher the molecular basis of lung cancer and to improve treatment strategies we have to identify genes correlated to therapy response and to survival. Here, we present the development of a new, freely available online tool suitable for the real-time meta-analysis of published lung cancer microarray datasets to validate expression based survival related biomarker candidates. First we have searched the caBIG, GEO and TCGA repositories to identify datasets with published gene expression data and survival information. In this, three GEO platforms (GPL96, GPL570 and GPL3921) were considered as these possess 22,277 common probes, which were used for constructing the database. All together 1,329 NSCLC samples in 9 independent datasets were identified, 85% have overall survival and 45% progression free survival info, one-third adenocarcinomas and one-third squamous cell carcinomas, 57% male and the average overall survival is 45 months. Kaplan-Meier survival plot, and the hazard ratio with 95% confidence intervals and logrank P value are calculated and plotted in R using Bioconductor packages. To assess the prognostic value of a gene, each percentile (of expression) between the lower and upper quartiles are computed and the best performing threshold is used as the final cutoff in a Cox regression analysis. The complete meta-analysis tool can be accessed online at: www.kmplot.com/lung. We demonstrate the application of this integrative analysis pipeline by validating 22 previously published survival associated biomarkers including VEGF, ADAM28, ANXA3, CADM1, CD24, CD82, CDK1, CEA, cyclin E, ERCC1, EZH2, HER2, IFNAR2, MMP9, OPN, P16, p53R2, RAD51, S100A4, survivin, XAF1 and XIAP. Of these, high significances (p&amp;lt;1E-16) were achieved by ANXA3 (HR=0.63), CADM1 (HR=1.7), IFNAR2 (HR=0.54), RAD51 (HR=1.9) and XAF1 (HR=0.58). Five additional genes were significant: S100A4 (HR=1.46, p=3.6E-4), CD82 (HR=1.34, p=0.018), OPN (HR=1.33, p=0.02), HER2 (HR=1.3, p=0.02) and CD24 (HR=0.75, p=0.3). The remaining genes did not achieved statistical significance. In summary, we developed an online available meta-analysis tool for the validation of genes associated with survival in NSCLC. Citation Format: Balazs Gyorffy, Andras Lanczky. An online tool for the validation of survival-predicting biomarkers in non small-cell lung cancer using microarray data of 1,329 patients. [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 2368. doi:10.1158/1538-7445.AM2013-2368
SAT0513 Hospital Burden of Gout, Pseudogout and Other Crystal Arthropathies in France from 2009 to 2011:
Authors: H.K. Ea, M. Maravic
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To describe hospital economic burden of microcrystal arthropathies in France from 2010 to 2012 using French Hospital National Database <h3>Methods</h3> Data were extracted from the French Hospital National Database. We selected all adult (age &gt;18 years) hospitalizations for crystal arthropathies encoded as primary diagnosis with their corresponding ICD-10 codes. Hospital stays were classified in those related to gout, chrondrocalcinosis, or other crystal arthropathies. For each type of crystals arthropathies, we have numbered the hospitalizations, and have described the mean age and percentage of women, the mean duration of stay, and the following diagnoses encoded as secondary diagnosis either related to the metabolic syndrome (diabetes, dysplipidemia, obesity, hypertension) or to other relevant comorbidities (ischemic cardiac disease, chronic renal insufficiency, cerebrovascular disease). For economic evaluation, we used the 2012 public tariff per disease related group and did not take into account the costs related to prosthesis or materiel of osteosynthesis in the case of surgical management or those due to dialysis or stay in intensive care. The point of view is those of society. <h3>Results</h3> there were 137,734 hospitalizations involving 105,932 patients (61% for gout, 34% chondrocalcinosis, and 5% other microcrystal arthropathies). Patients with chondrocalcinosis diagnosis were older (mean age of 77.3 years versus 74.8 for other microcrystals and 72.5 for gout). Men represented 73%, 37% and 48% of the patients with gout, chondrocalcinosis and other microcrystal arthropathies, respectively. Hypertension, diabetes, dyslipidemia, cardiac ischemia, and renal failure were more frequent in patients with gout than other patients (table 1). The overall hospital costs were 562 million Euros, 71% spent on gout patients. <h3>Conclusions</h3> In terms of hospital costs, gout represented the main part of the economic burden of crystal arthropathies and a high level of diseases belonging to the metabolic syndrome. Specific therapy programs favouring adherence to treatment could diminish this hospital economic burden. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4776
Case 7-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Joseph A. Majzoub, Robert E. Scully
Journal: New England Journal of Medicine (1993)

Presentation of CaseA boy six years and two months old was admitted to the hospital because of sexual precocity, polyostotic fibrous dysplasia, and cafe-au-lait spots.The boy was born after a 37-week, uncomplicated pregnancy to a 23-year-old primigravida; he was delivered by cesarean section because of failure to progress and a decrease in the heart rate noted on the fetal monitor; the birth weight was 2.66 kg. The infant was discharged home at four days with his mother. He reached his milestones at appropriate ages; he walked at 11 months and was toilet-trained at 2 1/2 years. At the . . .
P656 THE ROLE OF SEQUENCE VARIATION IN T-CELL EPITOPES OF THE HEPATITIS B VIRUS (HBV) POLYMERASE AND ENVELOPE PROTEINS IN HBeAg CLEARANCE AND DISEASE PROGRESSION
Authors: C.-J. Huang, C.-Y. Lan, F.-Y. Sung, C.-L. Lin, C.-J. Liu, C.-F. Wu, M.-W. Yu
Journal: Journal of Hepatology (2014)
Abstract B20: GLI1 overexpression contributes to HCC recurrence partly through the induction of SNAI1-induced epithelial-to-mesenchymal transition
Authors: Xin Zheng, Xiaohong Gai, Martin Fernandez-Zapico, Lewis Roberts, Catherine Moser, Chunling Hu, Ikuo Nakamura, Abdirashid Shire, Judong Yang, Sherine Elsawa, Luciana Almada, Snorri Thorgeirsson
Journal: Cancer Research (2011)

Abstract Background/Aim: Glioma-associated oncogene 1 (GLI1) is one of the most important transcription factors in the hedgehog (Hh) signaling pathway and has been shown to be involved in embryonic development and tumor progression. The epithelial-to-mesenchymal transition (EMT) is an important cellular program which contributes to invasion and metastasis of cancer. We have previously shown that GLI1 may promote HCC metastasis via EMT. Here, we demonstrate that GLI1 upregulates SNAI1 expression, induces EMT, and promotes HCC recurrence in vivo and in vitro. Methods: Gli1 mRNA was assessed in 139 HCCs by microarray and its correlation with HCC recurrence and SNAI1 mRNA expression was analyzed. In vitro, the mRNA and protein expression of GLI1 was measured in Gli1-negative Huh7 cells transfected with GU1 and GU1-expressing SNU398 cells transfected with antisense oligonucleotides targeting GU1 (GLI1 ASO). GLI1-dependent transcriptional activity was assessed with GU reporter luciferase assay and electrophoretic mobility shift assay (EMSA). The interaction between Gli1, SNAI1 and EMT was assessed by real-time PCR, Western immunoblotting and immunofluorescence. Effects of GLI1 on proliferation, viability, migration, and invasion of tumor cells were also assessed. Results: GLI1 mRNA was detected in 74 HCC tumors and found to be upregulated in 43 (58.1 %) HCCs. Increased Gli1 mRNA in HCCs was associated with tumor recurrence after resection. There was a positive correlation between GLI1 and SNAI1 mRNA expression. In HCC cells, GLI1 overexpression increased Gli1-dependent transcriptional activity, proliferation, viability, migration, and invasion of tumor cells. GU1 also increased SNAI1 expression and induced the EMT. Opposite effects were observed in GU1-knockdown models. Conclusion: Together, these findings identify a novel mechanism mediating HCC recurrence that includes GLI1-mediated activation of EMT via upregulation of SNAI1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B20.
Abstract 4761: Glial cell derived neurotrophic factor (GDNF)-RET signaling as a target in aromatase inhibitor resistant ER-positive breast cancers.
Authors: Andrea Morandi, Lesley-Ann Martin, Qiong Gao, Alan Mackay, David Robertson, Marketa Zvelebil, Mitch Dowsett, Ivan Plaza-Menacho, Clare M. Isacke
Journal: Cancer Research (2013)

Abstract The majority of breast cancers are estrogen receptor (ER)-positive and depend on estrogen for growth and survival. Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER-positive breast cancers. Despite providing substantial improvements in patient outcome, resistance to such therapy remains a major clinical challenge. We previously showed that GDNF-RET signaling plays an important role in ER-positive breast tumors and in the response to tamoxifen treatment. Resistance to this therapy is often associated with estrogen-independent activation of ER mediated by cell surface growth factor receptors, such as RET. Here, a multidisciplinary strategy was used to address the impact of GDNF-RET signaling in the response to AI treatment. First, using 2D and 3D in vitro approaches we show that GDNF-mediated RET signaling is enhanced in a model of AI resistance. Further, GDNF-RET signaling promotes the survival of AI-resistant cells and increases resistance in AI-sensitive cells, effects that are selectively reverted by a potent RET kinase inhibitor. Second, we generated a proliferation-independent GDNF-response gene set, identified from gene expression profiling in ER-positive breast cancer cells, and demonstrated this to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to AI treatment and development of resistance. Finally, the relevance of these findings was validated by demonstrating increased RET protein expression levels in an independent cohort of AI resistant patient samples. Together these preclinical and clinical models identify GDNF-RET signaling as a key determinant of response and resistance to AIs in ER-positive breast cancers. As a consequence, RET inhibition may be of use in the clinical setting either in combination with an AI to prevent and delay the onset of resistance, or to prolong the efficacy of the AI in the recurrent and/or metastatic setting. Citation Format: Andrea Morandi, Lesley-Ann Martin, Qiong Gao, Alan Mackay, David Robertson, Marketa Zvelebil, Mitch Dowsett, Ivan Plaza-Menacho, Clare M. Isacke. Glial cell derived neurotrophic factor (GDNF)-RET signaling as a target in aromatase inhibitor resistant ER-positive breast cancers. [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 4761. doi:10.1158/1538-7445.AM2013-4761
DYNAMIC T2 SIGNAL CHANGES ON MAGNETIC RESONANCE IMAGING AFTER RADIOFREQUENCY ABLATION INJURY TO THE ATRIAL MYOCARDIUM
Authors: Allen Rassa, Eugene Kholmovski, Promporn Suksaranjit, Brent Wilson, Nazem Akoum, Nassir Marrouche, Christopher McGann
Journal: Journal of the American College of Cardiology (2015)
LEFT VENTRICULAR TRANSMURAL REPOLARIZATION GRADIENT IN HUMANS
Authors: Bich Lien Nguyen, Loredana Iannetta, Alessandro Persi, Gianfranco Piccirillo, Fabrizio Ammirati, Antonio Ciccaglioni, Nicola Alessandri, Carlo Gaudio, Paolo-Emilio Puddu
Journal: Journal of the American College of Cardiology (2016)
AB0255 The effect of biological and conventional disease-modifying anti-rheumatic drugs on fatigue in fibromyalgic rheumatoid arthritis patients
Authors: S. Hizmetli, Y. Durmaz, E. Kaptanoglu, A. K. Cengiz, H. Peksen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid Arthritis (RA) has different clinical phenotypes. RA with co-existing fibromyalgic features has been termed as fibromyalgic- RA (FRA). Fatigue is a common symptom in rheumatological diseases. <h3>Objectives</h3> The aim of this study is to evaluate the effects of biological and conventional Disease-Modifying Anti-Rheumatic Drugs (DMARD) on fatigue in FRA patients. <h3>Methods</h3> Thirty (30) RA patients who met the 2010 ACR/EULAR classification criteria were enrolled in the study. Patients who had other possible causes of fatigue were excluded. The ones who met the ACR 1990 criteria for fibromyalgia were grouped in FRA group. The FRA and non- fibromyalgic RA (non-FRA) groups were divided into subgroups according to the medications used as biological-DMARD and conventional-DMARD subgroups. Fatigue was evaluated via Multidimensional Assessment of Fatigue scale (MAF) and disease activity was assessed by using Disease Activity Score-28 (DAS 28). <h3>Results</h3> The mean MAF total score of RA patients was 21.35±15.82. Eight (26.7%) of the RA patients had co-existing FMS (FRA group). The mean MAF total score in FRA group was statistically higher than the the non-FRA group (36.56±7.10, 15.81±14.45 respectively) (p&lt;0.05). There was no correlation between MAF total score and DAS 28 score in FRA group (r=0.559, p=0.152). However a strong statistically significant positive correlation between MAF total score and DAS 28 was found in non-FRA group (r=0.550, p=0.008). In FRA group the mean MAF total score of the patients was 34.20±7.29 for the biological-DMARD subgroup and 40.50±5.76 for the conventional-DMARD subgroup. The difference between these subgroups did not reach statistical significance. However in non-FRA group mean MAF total score of the patients who were on biological DMARD therapy and conventional DMARD therapy was 2.75±3.78 and 26.70±10.12 respectively. The difference between these subgroups was statistically significant (p&lt;0.05). <h3>Conclusions</h3> Fatigue is common in RA. Fatigue becomes more prominent if there is co-existing fibromyalgia. In non-FRA patients fatigue is correlated with the disease activity however such a correlation is absent for FRA patients. In non-FRA patients biological DMARD usage improved fatigue when compared with the conventional- DMARD therapy. However biological DMARD did not have additional benefit on fatigue in FRA patients when compared with the conventional DMARD group. When dealing with fatigue in RA patients possibility of co-existing fibromyalgia must be taken into account for treatment success. <h3>Disclosure of Interest</h3> None Declared