tbuckley/cabot-search huggingface dataset:
P1134 DURATION OF UNDETECTABLE HCVRNA IN PATIENTS TREATED WITH FALDAPREVIR–DELEOBUVIR INTERFERON-FREE COMBINATION IS ASSOCIATED WITH SVR
Authors: J.-F. Dufour, S. Zeuzem, M. Buti, J.-P. Bronowicki, R. Buynak, B. Müllhaupt, P. Mantry, M. Bourlière, J. Taunk, J.O. Stern, R. Vinisko, W. Böcher, G. Kukolj, J.-P. Gallivan, F. Mensa
Journal: Journal of Hepatology (2014)
Prevalence and Pathologic Features of Sickle Cell Nephropathy and Response to Inhibition of Angiotensin-Converting Enzyme
Authors: Ronald J. Falk, Jon Scheinman, George Phillips, Eugene Orringer, Adrena Johnson, J. Charles Jennette
Journal: New England Journal of Medicine (1992)

Nephropathy may develop in patients with sickle cell disease. We determined the prevalence of proteinuria and renal insufficiency in a group of patients with sickle cell disease and investigated the renal pathologic changes and the effects of an angiotensin-converting—enzyme inhibitor (enalapril) on protein excretion in patients found to have nephropathy.
Abstract 4183: MicroRNA-7 targeting PSME3 inhibits the growth of non-small cell lung cancer.
Authors: Yiwei Chu
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRNAs) are a family of small non-coding RNAs that function as important regulators of multiple target genes and participate in diverse biological roles in carcinogenesis..In this study, we found that the expression of miR-7 was downregulated not only in cell lines, but also in human NSCLC tissues compared to the matched adjacent tissues, which exhibited positive correlation with tumor volume.Restoration of its expression through miR-7 mimics in NSCLC cell lines including A549 and H1299 cells inhibited cell proliferation, colony formation, and cell cycle progression in vitro. More importantly, the tumorigenicity in nude mice was reduced after administration of miR-7 in vivo, strongly indicating that miR-7 is a main tumor suppressor miRNA in NSCLC. In advance, through a series of analysis derived from bioinformatics prediction, western blot and luciferase assay, we identified a novel target of miR-7, PSME3 (a proteasome activator) to be enrolled in the regulation with tumor. Expression of PSME3 in NSCLC tumor samples was significantly upregulated compared to adjacent non-tumor tissues, exhibiting a strong inverse relation with that of miR-7. In addition, knockdown of PSME3 gene induced similar effects to overexpression of miR-7 in NSCLC cells. All these findings strongly imply that the overexpression of PSME3 resulted from miR-7 downexpression in NSCLC plays an important role in promoting cancer cell progress, and consequently results in NSCLC growth. Thus, strategies targeting PSME3 and/or miR-7 may be the promising molecular therapy in NSCLC treatment. Citation Format: Yiwei Chu. MicroRNA-7 targeting PSME3 inhibits the growth of non-small cell lung cancer. [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 4183. doi:10.1158/1538-7445.AM2013-4183
AB0794 Protein degradation markers are associated with clinical features of vasculopathy in systemic sclerosis
Authors: D. Khanna, K. Au, P. Maranian, M.K. Karsdal, D.J. Leeming
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The pathogenesis of systemic sclerosis (SSc) has 3 distinct yet overlapping pathological processes: inflammation, vasculopathy and fibrosis. Small fragments of proteins generated during lung fibrosis are released into circulation and may be assessed as biochemical markers in plasma of patients. This study assessed the association of clinical and radiological markers of vasculopathy and fibrosis vs. markers of protein degradation. <h3>Methods</h3> 55 SSc female patients with no history of clinical atherosclerosis were recruited at an academic center and underwent carotid ultrasound to assess the presence of plaque and carotid intima-media thickness (CIMT). The ultrasound was read by a single radiologist. Clinical data included modified Rodnan skin score (MRSS), pulmonary function tests (FVC% and DLCO%), and presence/absence of digital pulp ulcers. We investigated the associations between the presence/absence of carotid plaque, CIMT, clinical examination, and pulmonary tests vs. 4 novel non-invasive biomarkers. The biomarkers evaluated were protein degradation markers; type III collagen (C3M), type VI collagen (C6M), citrullinated vimentin (VICM) and versican (VCM), all degraded by metalloproteinase. EDTA plasma samples were collected from fasting patients at time of carotid ultrasound and stored at -80°C until use. C3M, C6M, VICM and VCM plasma levels were assessed using newly developed and technically robust competitive ELISAs. Spearman correlations and Student's t-test are considered significant at <i>P</i>&lt;0.10. <h3>Results</h3> The average of patients was 48 years, disease duaration of 7 years, 51% had limited SSc, and 39% of patients had presence of carotid plaque. Significant associations were noted between features of vasculopathy:1. presence of plaque vs. C6M and VICM (p&lt;0.10), and 2. presence of digital ulcers vs. C3M, C6M and VICM (p&lt;0.10). CIMT score was associated with VCM (coefficient=0.36, p=0.06). Interestingly, no significant association was seen between clinical features of fibrosis (MRSS and PFTs) vs. protein degradation markers (p&gt;0.10 for all analysis). <h3>Conclusions</h3> Protein degradation markers are associated with clinical features of vasculopathy. Prospective studies to evaluate the role of these biomarkers in SSc are needed. <h3>Disclosure of Interest</h3> D. Khanna Grant/Research support from: NIH, K. Au: None Declared, P. Maranian: None Declared, M. K. Karsdal Employee of: Nordic Bioscience, D. Leeming Employee of: Nordic Bioscience
SP0115 Prediction of Response to Therapy-Lessons from JIA
Authors: N. Wulffraat
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Juvenile Idiopathic Arthritis (JIA) is a heterogeneous disorder. The ILAR classification for JIA consists of 8 subtypes. Since the etiology of JIA is unknown this classification is mostly based on clinical phenotypes. Obviously these subtypes respond to treatment differently. A large retrospective UK cohort study showed that baseline demographic, clinical and routine laboratory parameters cannot predict disease outcome. To study response to treatment, clinical homogenous JIA subtype cohorts must be formed using validated clinical parameters and novel biomarkers. Also, stopping strategies should be employed for drugs for patients in clinical remission, induced by that drug. We recently proposed a prediction model for response (and non- response) to MTX including clinical variables, ESR and SNPs in genes coding for pathways involved in MTX metabolism. This prediction model may help to identify JIA patients not responding to MTX treatment, thus assisting clinicians in making individualised treatment decisions. Response to treatment depends on subtypes but may also depend on disease duration before a drug is initiated. Especially in SJIA drug responses seem to be more successful when started early, thus supporting the concept of a window of opportunity. Also in such strategies early withdrawal of medication after induction of remission seems more successful. However these assumptions need to be validated in larger cohorts. <h3>Disclosure of Interest</h3> None Declared
PWE-100 Increasing Weight And Body Mass Index Adversely Affect Thioguanine Nucleotide Levels In Inflammatory Bowel Disease: Abstract PWE-100 Table 1
Authors: S Subramanian, S Poon, A Kneebone, R Asher, R Jackson, B Gregg, P Collins, C Probert, M Dibb
Journal: Gut (2014)

<h3>Introduction</h3> Inflammatory bowel disease (IBD) often requires long term immunosuppressive therapy with thiopurines such as azathioprine (AZA) or mercaptopurine (MP) and anti-tumour necrosis factor (TNF) agents. Despite the variable response to thiopurines and anti-TNF agents, few predictive factors of response have been identified. A lower body mass index (BMI) has been associated with a better outcome for azathioprine therapy, infliximab and adalimumab. Obese IBD patients are more likely to have active disease or be hospitalised. This study examined the association between weight and thiopurine therapy by examining 6-thioguanine nucleotide (6-TGN) levels. <h3>Methods</h3> We conducted a retrospective analysis of patients who were treated at the Royal Liverpool University Hospital with a thiopurine. The dose of thiopurines was adjusted as tolerated to a maximum of 2.5 mg/kg for AZA and 1.5 mg/kg for MP. Eligible patients had a 6-TGN measurement with their height and weight recorded at the same time. Associations between 6-TGN, BMI, weight, patient demographics and biochemical indices were estimated using a multivariable linear regression model. Body fat index was calculated as described previously. All tests were declared statistically significant if p &lt; 0.05. <h3>Results</h3> 106 patients (48 male, 58 female) were included and contributed 133 measurements. 55% had Crohn’s disease and 45% had ulcerative colitis. 91% were on AZA and 9% were on MP. After adjustment, a one kilogram increase in weight was associated with a 1.62 unit decrease in 6-TGN levels (95% CI: 0.40 to 2.82, p = 0.0094). Body fat index correlated strongly with weight for both males and females (0.8345 and 0.8860 respectively) and a significant difference was found between BFI for each sex (p &lt; 0.001) with females, on average, having a higher BFI. Weight, BMI and BFI differed significantly across sub-therapeutic, therapeutic and supra-therapeutic 6-TGN groups (Table 1). <h3>Conclusion</h3> 6-TGN levels decreased significantly with increasing weight and BMI despite a similar weight based dosing. This may explain the previously noted adverse outcomes in obese IBD subjects and underscores the importance of thiopurine metabolite testing <h3>Disclosure of Interest</h3> S. Subramanian Speaker bureau with: Speaker honoraria from Warner Chilcott, Shire, MSD, Abbvie and Almirall, Conflict with: Conference support from Abbvie, MSD and Warner Chillcott, S. Poon: None Declared, A. Kneebone: None Declared, R. Asher: None Declared, R. Jackson: None Declared, B. Gregg: None Declared, P. Collins: None Declared, C. Probert: None Declared, M. Dibb: None Declared.
AB0757 EULAR/ACR diagnostic and classification criteria of systemic vasculitis (DCVAS) study update
Authors: J. Robson, R. Watts, P. Grayson, R. Suppiah, P. Merkel, A. Craven, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with vasculitis typically present with non-specific features, such as fever, fatigue and myalgia all of which are also common among different diseases. One of the aims of this study is to develop and validate diagnostic criteria for the primary systemic vasculitides (granulomatosis with polyangiitis [Wegeners], microscopic polyangiitis, Churg Strauss syndrome, polyarteritis nodosa, giant cell arteritis and Takayasu arteritis). We also aim to update the current 1990 ACR classification criteria, which has not been updated since the introduction of diagnostic tests such as anti-neutrophil cytoplasm antibody (ANCA). <h3>Objectives</h3> Develop and validate diagnostic and classification criteria for the systemic vasculitides. <h3>Methods</h3> Diagnostic criteria will be derived by comparing presenting features of patients with one type of vasculitis with vasculitis mimics to determine the discriminating features between the two groups. Classification criteria will be determined by comparing presenting features of patients with one type of vasculitis with those of patients with different types. Reference diagnoses will be determined using data-driven cluster analysis and compared with expert panel consensus. The recruitment target is 2000 patients with a diagnosis of vasculitis and 1500 patients with diseases which mimic vasculitis. <h3>Results</h3> By January 2012, a total of 658 patients had been recruited by 33 sites from 18 countries. The graph in figure 1 displays the numbers of patients recruited with each baseline diagnosis. <h3>Conclusions</h3> The DCVAS study is using a collaborative, international approach to identify large numbers of patients with vasculitis and mimic conditions, in order to develop new classification and diagnostic classification criteria. <h3>Disclosure of Interest</h3> None Declared
LIGADURA ENDOSCOPICA SIN RESECCION EN LESIONES SUPERFICIALES (MUCOSA, SUBMUCOSA) DEL TRACTO DIGESTIVO ALTO EN PACIENTES SELECCIONADOS
Authors: L Rivas, CF Consiglieri, G Ibañez-Sanz, S Salord, C Pons, M Miro, JM Castellví, JM Botargues, M Galan, JB Gornals
Journal: Endoscopy (2014)

Introducción: La ligadura endoscópica con bandas (LEB) de lesiones precoces del tracto GI alto (displasia o T1a-b) o subepiteliales (ej. neuroendocrino (TNE)) de reducido tamaño, se asocia a resección con electrocauterio, sin estar libre de complicaciones (10 – 20%).
Treatment of a congenital esophageal fistula by injection of autologous fat
Authors: Manuel Moretó, Javier Gabilondo, Fernando Fernandez-Samaniego
Journal: Endoscopy (2014)

The injection of autologous free fat obtained by suction-assisted lipectomy for the correction of soft tissue defects is a common procedure in plastic surgery. This procedure has also been used to prevent aspiration after vocal fold paralysis [1], and to treat vesicoureteral reflux [2]. Tracheo-esophageal fistula may present as an isolated defect or it may be associated with esophageal atresia. The treatment of congenital tracheo-esophageal fistulas is usually based on surgical procedures [3]. We present a preliminary report of a new endoscopic mode of therapy.
Pharmacokinetics, Safety, and Efficacy Of Long-Lasting Recombinant Factor IX Fc Fusion Protein (rFIXFc) In Adolescent Subjects With Hemophilia B: A Subgroup Analysis Of The B-LONG Study
Authors: Amy Shapiro, John Pasi, Johnny Mahlangu, David J. Perry, Jerry S Powell, Margaret V. Ragni, Leonard A. Valentino, Margareth Ozelo, Karen Nugent, Shuanglian Li, Aoife Brennan, Glenn F Pierce, Geoffrey Allen
Journal: Blood (2013)
THU0428 Methotrexate Use is not Associated with an Increased Risk of Lung Disease: A Meta-Analysis of Randomised Controlled Trials: Table 1.
Authors: C. Low, R. Conway, R.J. Coughlan, M.J. O'Donnell, J.J. Carey
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Methotrexate is the most widely prescribed DMARD in inflammatory arthritis, and is widely used in psoriasis and inflammatory bowel disease. A recent meta-analysis of methotrexate in rheumatoid arthritis (RA) showed that the risk of lung disease is much lower than previously thought. These results may have been affected by channelling bias as RA patients can get several forms of lung disease as a manifestation of their RA. We therefore evaluated the risk of lung disease in conditions where it is not a recognised feature of the underlying disease process. <h3>Objectives</h3> To evaluate the relative risk of pulmonary adverse events in patients with psoriatic arthritis, psoriasis and inflammatory bowel disease treated with methotrexate in double-blind randomised controlled trials. <h3>Methods</h3> We performed a systematic literature search of Pubmed and Cochrane databases with no date limits for double-blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis or inflammatory bowel disease. Studies with less than 50 subjects, of less than 12 weeks duration, or with no reporting of respiratory adverse events were excluded. Two investigators independently searched both databases. All authors reviewed selected studies. Random effects meta-analysis using the Mantel-Haenszel method was used to assess total respiratory adverse events, infectious respiratory adverse events, non-infectious respiratory adverse events, pneumonitis, and death. Results were expressed as relative risks (RR) with 95% confidence intervals. <h3>Results</h3> Our literature search returned 2968 results. A total of 7 studies, 6 with placebo comparators, met our inclusion criteria. Five hundred and four respiratory adverse events were documented in 1630 participants. One case of pneumonitis was reported in a methotrexate treated patient. No pulmonary deaths occurred. Heterogeneity across the studies was not significant (I<sup>2</sup>=0%), allowing combination of trial results. Methotrexate was not associated with an increased risk of adverse respiratory events, RR 1.03 (95% CI 0.90-1.17), respiratory infections, RR 1.02 (95% CI 0.88-1.19) or non-infectious respiratory events, RR 1.07 (95% CI 0.58-1.96). Subgroup analysis is shown in Table 1. <h3>Conclusions</h3> Our study found no increased risk of pulmonary adverse events in patients treated with methotrexate compared to placebo or active comparators. There were a small number of suitable studies but our results suggest that if adverse respiratory events occur with methotrexate use they are rare. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1801
Abstract 4928: Mechanisms of microglia-stimulated glioma invasion.
Authors: Salvatore J. Coniglio, Jeffrey E. Segall
Journal: Cancer Research (2013)

Abstract The ability of glioma tumor cells to infiltrate the surrounding brain parenchyma makes complete removal of these tumors nearly impossible. We investigated how microglia, the resident macrophages of the brain, stimulate glioma cell invasion. Coculture with microglia stimulates the invasion of GL261 glioma cells in-vitro. Pharmacological inhibition of EGFR using Iressa strongly inhibits microglia-stimulated invasion. Furthermore, we demonstrate using novel CSF-1R (c-fms) inhibitors that CSF-1R signaling is also required for microglial enhancement of glioma invasion. GL261 cells were found to constitutively secrete CSF-1, the levels of which are unaffected by EGF stimulation, EGFR inhibition or coculture with microglia. GL261 tumors orthotopically injected into the brains of C57 mice fed with the CSF-1R inhibitor PLX3397 showed a dramatic reduction in microglia/macrophages infiltration compared with tumors from animals fed control chow. Tumors from the PLX3397-fed animals also showed a 50% reduction in invasion into the parenchyma. We discovered that GL261 cell secretion of CSF-1 is involved in upregulating EGFR ligands in microglia including AREG, EREG and TGFA. Microglia isolated from GL261 tumors express AREG mRNA whereas naïve microglia from control animals do not. Depletion of AREG from microglia using siRNA interfered with their ability to promote GL261 invasion in vitro. These data indicate that during invasion, glioma and microglia cells signal to each other using EGFR Ligands and CSF-1 similar to what has been observed in breast cancer models. The results of this study indicate the possibility of inhibiting glioblastoma invasion by targeting functions of tumor-associated microglia in addition to glioma cells. Citation Format: Salvatore J. Coniglio, Jeffrey E. Segall. Mechanisms of microglia-stimulated glioma invasion. [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 4928. doi:10.1158/1538-7445.AM2013-4928
589 OXIDATIVE STRESS AND INFLAMMATION IN LIVER CIRRHOSIS: ROLE OF N-6/N-3 POLYUNSATURATED FATTY ACIDS BALANCE
Authors: V. Raparelli, L. Napoleone, O. Riggio, M. Merli, F. Angelico, C. Lucidi, V. Giannelli, R. Carnevale, P. Pignatelli, S. Basili, F. Violi
Journal: Journal of Hepatology (2012)
P426Delayed preconditioning-like protection against ischemia/reperfusion injury in the rat heart is associated with PPAR-alpha-mediated changes in metabolic genes and non-metabolic effects
Authors: T Ravingerova, S Carnicka, V Ledvenyiova, E Barlaka, E Galatou, P Mandikova, A Chytilova, M Nemcekova, F Kolar, A Lazou
Journal: Cardiovascular Research (2014)

Ischemia alters the balance between fatty acids (FA) and glucose utilization as the main ATP-producing pathways in the heart that may dramatically affect myocardial salvage upon ischemia/reperfusion (I/R). Genes encoding enzymes involved in metabolic processes are transcriptionally regulated by nuclear peroxisome proliferator-activated receptors (PPAR). PPAR-alpha isoform is mainly responsible for FA uptake/transport, beta-oxidation (FAO) and glucose transport/oxidation. During ischemia, it modulates substrates switch aimed at the adequate energy production to preserve cardiac function. However, the role of PPAR-mediated metabolic shifts in protective effects of preconditioning (PC) is relatively less investigated. We explored the effects of PPAR-alpha activation in a setting simulating a delayed PC in the rat heart and potential downstream genomic and non-genomic mechanisms involved. Animals were given PPAR-alpha agonist WY-14643 (WY, 1 mg/kg, i.p.) with or without PPAR-alpha antagonist MKK-886 (MKK), 24 hr prior to 30-min global ischemia/2-h reperfusion in Langendorff-perfused hearts. Sampling for measurement of the expression of PPAR-alpha and its target genes (MCAD, PDK-4, mCPT-1, GLUT-4) and gene of heme oxygenase-1 (HO-1) as a key antioxidative enzyme (real-time RT-PCR), as well as for the determination of levels and phosphorylation of survival proteins (Akt, eNOS) and markers of apoptosis (Bax, Bcl-2, caspase-3) was performed at baseline (prior to ischemia) and after I/R (WB analysis). Pretreatment with WY attenuated postischemic contractile dysfunction, reduced the severity of ventricular arrhythmias and limited the extent of lethal injury (infarct size). These cardioprotective effects were blunted by inhibitor of NO synthase L-NAME and reversed by MKK treatment indicating a PPAR-alpha-dependent response. Administration of WY remarkably enhanced the expression of PPAR-alpha and its target genes promoting FAO (MCAD, PDK-4 and mCPT-1) coupled with reduced expression of GLUT-4 responsible for glucose metabolism and with up-regulation of HO-1. In addition, enhanced Akt phosphorylation and eNOS expression, as well as changes in pro- and antiapoptotic markers (increased Bcl-2/Bax ratio, reduced caspase-3 cleavage) were observed in the WY-treated hearts. Up-regulation of PPAR-alpha target metabolic genes regulating FAO may underlie delayed protection in the rat heart. Potential non-metabolic effects of PPAR-alpha-mediated cardioprotection may involve activation of PI3K/Akt and its downstream targets, such as eNOS, and modulation of oxidative stress and apoptosis.
NASA-NCI Collaboration May Improve Breast Cancer Detection
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article NASA-NCI Collaboration May Improve Breast Cancer Detection Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 16, 17 August 1994, Pages 1191–1192, https://doi.org/10.1093/jnci/86.16.1191 Published: 17 August 1994
SP0206 How disability organisations can promote best practice in the design of the built environment
Authors: O. Miles-Paul
Journal: Annals of the Rheumatic Diseases (2013)

The UN-Convention on the Rights of Persons with Disabilities has given us a framework for the human rights of disabled people. Accessibility is one of the main rights and goals of this convention and challenges us more than ever to build and change our environment in a way that everybody can fully participate without discrimination. In Germany we have made some major improvements in this area so that I will present some examples of best practise how disability organisations can play a key role in making the built environment more accessible. Action plans for the implementation of the UN-Convention or negotiations for goals regarding accessibility with businesses are some of the instruments we use quite successfully. <h3>Disclosure of Interest</h3> None Declared