tbuckley/cabot-search huggingface dataset:
Abstract 557: Aging and DNA methylation in Alu and LINE-1 repeated elements
Authors: Laura Cantone, Valentina Bollati, Robert Wright, Augusto Litonjua, Letizia Tarantini, Helen Suh, David Sparrow, Pantel Vokonas, Andrea Baccarelli, Joel Schwartz
Journal: Cancer Research (2008)

Abstract DNA methylation exhibits a gradual genome-wide decrease in association with aging and the rate of decrease appears to be inversely proportional to life expectancy. The observed age-related increase in cancer incidence cannot be explained entirely by genetic mutation rates. Accumulation of epigenetic alterations during aging may contribute to determine the malignant transformation. In particular, global DNA hypomethylation, which has been associated with repetitive DNA demethylation may promote chromosomal instability. About 55% of the human genome consists of repetitive elements, which are for the most part made up of approximately 500,000 long interspersed nucleotide elements (LINE elements) and 1.4 million Alu repetitive elements, which are normally heavily methylated. DNA methylation of LINE-1 and Alu elements has shown to correlate with total 5mC content and thus used to estimate global DNA methylation. In humans, LINEs are the major source of insertional mutagenesis, being involved in both germinal and somatic mutant phenotypes. Alu retrotransposition has also been associated with human disease. However, whether LINE/Alu methylation decreases with age has never been established. We examined the epigenetic effect of aging on DNA methylation in repetitive elements Alu and LINE-1, measured in peripheral blood DNA from 693 subjects evaluated between 1999-2006 as part of the Normative Aging Study (NAS), a longitudinal study established in 1963 by the U.S. Veterans Administration. We measured DNA methylation through quantitative analysis by PCR-Pyrosequencing. Two different blood samples, taken approximately three years apart, were available for each subject. Repeated element methylation was negatively associated with age. In linear regression, we found a decrease equal to 0.016% for LINE-1 (p=0.07) and 0.015% for Alu (p=0.007), for each year increase. We did not find significant changes between repeated measures taken three years apart from each other on the same subjects. The two repeated measures showed high correlation for both Alu (n=300, r=0.46, p&amp;lt;0.001) for Alu and LINE-1 (n=303, r=0.59, p&amp;lt;0.001). DNA methylation of LINE-1 and Alu repetitive elements is inversely correlated with age, although is not captured in repeated measurements taken over a three years period. Such age-related decrease in methylation may increase the risk of mutational events potentially leading to cancer development.
Elevated Labile Plasma Iron (LPI) Levels in Patients with Lower-Risk Myelodysplastic Syndromes (MDS) Are Associated with Decreased Quality of Life and Reduced Survival
Authors: Marlijn Hoeks, Tim Bagguley, Rian Roelofs, Louise De Swart, David Bowen, Argiris Symeonidis, Corine van Marrewijk, Eva Hellström-Lindberg, Aurelia Tatic, Saskia Langemeijer, Dominic J. Culligan, Marian Macheta, Hege Garelius, Michail Spanoudakis, Sally Killick, Panagiotis Panagiotidis, Oana Stanca Ciocan, Juliet Mills, Bryson Pottinger, Sam Ackroyd, Claire Hall, Jackie Droste, Alexandra Smith, Dorine W. Swinkels, Theo M de Witte
Journal: Blood (2018)
AB0199 Endocan levels and subclinical atherosclerosis in patients with rheumatoid arthritis
Authors: G. Tuzcu, A.U. Uslu, A. Tuzcu, R. Aydogan Baykara, A. Omma, A. Kucuk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with unknown etiology. Accelerated atherosclerosis (AS) and AS with heart disease are among the major causes of morbidity and/or mortality in RA. Endothelial-specific molecule 1 (endocan) is a potential indicator of vascular events and is expressed in response to inflammatory mediators in endothelial cells. Carotid intima media thickness (cIMT) is used to detect early signs of AS but also progression in cardiovascular diseases related to AS. <h3>Objectives</h3> The aim of the present study is to evaluate the relationship of serum endocan levels with RA and cIMT as a candidate marker of diseases to be used in clinical practice. <h3>Methods</h3> The study was conducted between <sup>June 2012</sup> and March 2013 at the Rheumatology Clinics of Necmettin Erbakan Meram Medical School, Turkey. Thirty nine<sup>39</sup> RA patients, diagnosed according to the 1987 criteria of the American College of Rheumatology, and 30 age-and sex-matched healthy subjects as the control group were included in this study. <h3>Results</h3> No significant difference was detected between groups with respect to age, sex and body mass index. In the patient group the Endocan and cIMT values were found to be 14.11±3.27 ng/mL and 0.63±0.17 mm, while in the control group they were 12.10±2.92 ng/mL and 0.51±0.12 mm, the Endocan and cIMT values were significantly higher in the patient group (p=0.009 and p=0.001, respectively). Positive correlations was found between Endocan, cIMT and Disease Activity Score of 28 joints (p=0.008 and p=0.029, respectively). When assessing the endocan levels of RA patients in the study population, cut off value of 12.21 with sensitivity of 71%, specificity of 57% and p=0.012 (area under curve: 0.678, 95% confidence interval (CI) 0.555–0.805) were observed according to ROC curve analysis. <h3>Conclusions</h3> Endocan might be a useful marker to evaluate atherosclerotic lesions in patients with RA and also to assess disease severity. <h3>Disclosure of Interest</h3> None declared
Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes
Authors: Carlo Maurer, Sam R Holmstrom, Jing He, Pasquale Laise, Tao Su, Aqeel Ahmed, Hanina Hibshoosh, John A Chabot, Paul E Oberstein, Antonia R Sepulveda, Jeanine M Genkinger, Jiapeng Zhang, Alina C Iuga, Mukesh Bansal, Andrea Califano, Kenneth P Olive
Journal: Gut (2019)

Objective Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has complicated attempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples. Design We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts. Results Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes. Conclusion Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.
Abstract SY19-03: Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics
Authors: Garry P. Nolan
Journal: Cancer Research (2010)

Abstract Intracellular assays of signaling systems has been limited by an inability to correlate functional subsets of cells in complex populations based on active kinase states or other nodal signaling junctions. Such correlations could be important to distinguish changes in signaling status that arise in rare cell subsets during functional activation or in disease manifestation. We have demonstrated the ability to simultaneously detect activated kinases and phosphoproteins in simultaneous pathways in subpopulations of complex cell populations by multi-parameter flow cytometric analysis, and now via high throughput mass spectrometry at the single cell level. The focus of the presentation will be our mechanistic studies of human Follicular Lymphoma, as well as signaling of “stem cell” like cell subsets in Acute Myelogenous Leukemia and other myeloid dysplasias. The detailed, correlated datasets generated via single cell phospho-flow allows for ready representation via automated signaling network determination using Bayesian analysis. Our pursuit of deep analysis of these datasets, and the limitations of cloud computing or standard multi-CPU systems, has stimulated our development of unique computational approach using field programmable gate arrays and GPU multiprocessor architectures in the development of a ‘bioinformatics supercomputer’ and associated algorithms. By analyzing the immune system, or cancer, as individual cells we now observe structured network interactions within these tissues at a new level of clarity. I will present our initial generations of comprehensive network topology maps of signaling within, and between, primary immune subsets in normal and pathologic disease tissues in cancer. My emphasis will be on the application of these approaches directly to human samples in near-patient settings for the development of point-of-care mechanistic referencing of disease and drug action. Citation Format: Garry P. Nolan. Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY19-03
AB0695 Predictive factors of long-term clinical outcome in behcet’s syndrome patients with ocular involvement: does actually the disease tend to grow dim over time?
Authors: R. Talarico, M. Figus, C. Posarelli, A. d’Ascanio, R. Neri, C. Tani, C. Baldini, M. Mosca
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet's syndrome (BS) is a multisystemic, chronic relapsing inflammatory disease classified among the vasculitis. Eye involvement represent one of the most serious manifestation of BS and occurs in half of all patients. It seems more frequent and severe among young males and, unluckily, it still represents a significant cause of morbidity. <h3>Objectives</h3> The aims of the study were: to study the relapse rate of BS patients with ocular involvement and to identify factors able to predict long-term outcome <h3>Methods</h3> Among a cohort of 138 patients with a diagnosis of BS according the ISG criteria, 62 patients (37 males and 25 females; mean age at the onset 38±5 years) with ocular involvement were prospectively studied. The probability of clinical relapse after remission of the first ocular attack was calculated using the Kaplan-Meier method. Predictors of long-term outcome were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. <h3>Results</h3> The mean time between the first initial symptoms of BS and the onset of eye lesions was 2±2 years. The number of ocular attacks were the following: 43 posterior uveitis, 27 anterior uveitis, 26 retinal vasculitis, while panuveitis developed in 18 subjects. The cumulative relapse rates at 1 year, 3 years, and 5 years after remission of the first ocular attack were 41%, 31%, and 28%, respectively. On multivariate analysis, a younger age (&lt;30 years) at the onset of ocular involvement, male sex and medical treatments other than biological agents represent independent predictive factors for more early relapses in BS patients with ocular involvement. <h3>Conclusions</h3> The relapse rate seems to be more frequent in the first years of diseases, and probably it could be related to the fact the disease tend to grow dim over time. As literature data suggest, younger age and male sex still represent predictive factors of poor long-term clinical outcome. <h3>Disclosure of Interest</h3> None declared
Abstract 19187: Predictors of Right Ventricular Pacing in ICD Recipients Without Baseline Pacing Needs
Authors: Shadi Kalantarian, Haikun Bao, Paul W Jones, Kenneth M Stein, Daniel J Friedman, Frederick A Masoudi, Jeptha P Curtis, Joseph G Akar
Journal: Circulation (2017)

Introduction: Identifying ICD recipients who will develop a need for right ventricular pacing (RVP) would inform appropriate device selection, specifically to identify patients most suitable for du...
THU0499 The effect of concomitant type of vitamin d, biological dmards and disease activity for therapeutic effect of denosumab in osteoporosis patients with rheumatoid arthritis
Authors: S. Anno, K. Inui, T. Okano, K. Mamoto, Y. Sugioka, M. Tada, T. Koike, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoporosis is one of the major comorbidity in patients with rheumatoid arthritis (RA). There are a lot of evidence that denosumab increase bone mineral density (BMD) in patients with osteoporosis. However, there are few reports investigated the influence of denosumab in patients with RA. <h3>Objectives</h3> We evaluated the BMD change in patients with RA treated denosumab and assessed the effect of verious factors, such as the type of vitamin D, biological disease-modifying anti-rheumatic drugs (bDMARDs) use, and disease activity. <h3>Methods</h3> This study included 100 RA patients (96 female, mean age 69.9±9.3 years) treated with denosumab. BMD at the lumbar spine and proximal femoral were evaluated by dual energy X-ray absorptiometry (DXA) at baseline and 1 year after treatment. We evaluated the influence of the type of vitamin D, bDMARDs and disease activity for BMD change. <h3>Results</h3> In all patients, BMD at the lumbar spine, proximal femoral and femoral neck were significantly increased in one years (6.2%: p&lt;0.01, 4.0%: p&lt;0.01, 2.2%: p=0.04, respectively). There were no significant differences in improvement ratio of BMD between 10 patients taking active form vitamin D and 71 patients taking native form vitamin D (7.7 vs 4.4%: p=0.55, 4.3 vs 4.0%: p=0.83, 1.4 vs 4.2%: p=0.52), between 30 patients treated with bDMARDs and 57 patients treated without bDMARDs (6.4 vs 6.2%: p=0.3, 2.7 vs 4.5%: p=0.95, 1.1 vs 2.5%: p=0.2), between 61 patients in remission or low disease activity and 26 patients in moderate or high disease activity (7.2 vs 4.0%: p=0.25, 3.3 vs 5.0%: p=0.87, 1.6 vs 3.8%: p=0.98) (figure 1). <h3>Conclusions</h3> Denosumab improved BMD in patients with RA independently regardless of the type of vitamin D, bDMARDs use, disease activity. <h3>Disclosure of Interest</h3> None declared
Thalassemia Gene Therapy By In Vivo Transduction of Mobilized Hematopoietic Stem Cells (HSCs) with an Integrating Hybrid Adenovirus Vector System
Authors: Afrodite Georgakopoulou, Hongjie Wang, Chrysi Kapsali, Nikoleta Psatha, Angeliki Koufali, Chang Li, Zsuzsanna Izsvak, Achilles Anagnostopoulos, Thalia Papayannopoulou, Evangelia Yannaki, Andre Lieber
Journal: Blood (2018)
Impact of a Standardized Hydroxyurea Dose Regimen for Extreme Thrombocytosis in Children after Pancreatectomy with Islet Autotransplantation
Authors: Alexander A Boucher, Todd M. Jenkins, Lori Luchtman-Jones, Joseph S. Palumbo, Tom K Lin, Maisam Abu-El-Haija, Jaimie D Nathan
Journal: Blood (2018)
Detailed Phenotypic, Molecular and Functional Profiling of Myeloid Derived Suppressor Cells (MDSCs) in the Tumor Immune Microenvironment (TIME) of Multiple Myeloma (MM)
Authors: Cristina Pérez Ruiz, Aintzane Zabaleta, Noemi Puig, María Teresa Cedena, Juana Merino, Diego Alignani, Sonia Garate, Ibai Goicoechea, David Lara-Astiaso, Sarai Sarvide, Cirino Botta, Joaquin Martinez Lopez, Albert Oriol, Rafael Rios, Laura Rosinol, Maria-Victoria Mateos, Juan-José Lahuerta, Joan Bladé, Jesus F San-Miguel, Bruno Paiva
Journal: Blood (2018)
THU0181 Glucocorticoid use is an independent risk factor for sarcopenia in patients with rheumatoid arthritis – from the chikara study -
Authors: Y. Yamada, M. Tada, K. Mandai, N. Hidaka, K. Inui, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at higher risk of sarcopenia due to joint dysfunction and chronic inflammation. The prospective observational CHIKARA study (Correlation research of sarcopenia, skeletal muscle and disease activity in rheumatoid arthritis; registration number UMIN000023744) was started in 2016 to clarify the correlation between RA disease activity and sarcopenia. <h3>Objectives</h3> We investigated risk factors for developing sarcopenia in patients with RA. <h3>Methods</h3> We analysed baseline and 1 year data from the CHIKARA study. The body composition (body weight, muscle mass, fat mass, predicted bone mass, etc.) of 100 patients (78% women; mean age, 68 years) enrolled in this study was examined using a body composition analyzer (MC-780A; TANITA, Tokyo, Japan). Grip strength and walking speed were also measured. Laboratory data, disease activity, Health Assessment Questionnaire (HAQ) and treatment were investigated. Sarcopenia was diagnosed using the criteria of the Asia Working Group on Sarcopenia. Patients with sarcopenia onset at 1 year were detected and their characteristics were analysed. Predictors for development of sarcopenia were also investigated by uni- and multivariate analyses. <h3>Results</h3> Nine patients developed sarcopenia during 1 year. Glucocorticoid (GC) use was significantly more frequent among patients with sarcopenia onset (55.6%) than among those without sarcopenia onset (22.1%, p=0.029). Univariate analysis revealed that GC dosage (r=0.217, p=0.035), body fat mass at baseline (r=−0.211, p=0.040) and change in CRP at 1 year (r=−0.205, p=0.046) were significantly associated with sarcopenia onset. GC use &gt;2 mg/day (Odds ratio (OR) 8.0, 95% confidence interval (CI) 1.2–54.8, p=0.034) and body fat mass (OR 0.78, 95% CI 0.61–0.98, p=0.037) were detected as significant factors by multivariate analysis. (table 1) <h3>Conclusions</h3> RA patients using GC at &gt;2 mg/day or with low fat mass were more likely to develop sarcopenia. <h3>References</h3> [1] Inui K., Koike T, Tada M, et al. Sarcopenia is apparent in patients with rheumatoid arthritis, especially those with biologics -TOMORROW study-. EULAR2015abstract (AB0359). [2] Chen LK, Liu LK, Assantachai P, et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc2014;15:95–101. <h3>Disclosure of Interest</h3> None declared
Abstract 17109: Input Impedance Analysis of Pulmonary Hypertension Models Indicates That Monocrotaline and Sugen/hypoxia Induce Mechanically Different Vascular Remodeling
Authors: Takuya Nishikawa, Keita Saku, Takafumi Sakamoto, Yoshinori Murayama, Takuya Kishi, Kenji Sunagawa
Journal: Circulation (2015)

Introduction: Although complex pulmonary arterial remolding characterizes pulmonary hypertension (PH), the vascular mechanics has been evaluated by the static pressure-flow relationship (resistance, R) ignoring dynamic mechanical properties (compliance, C). We therefore evaluated pulmonary arterial input impedance (Z) capable of identifying not only resistance but also compliance in monocrotaline (MCT) and Sugen/Hypoxia (SuHx) PH models. Methods: In 6 weeks Sprague-Dawley rats, we induced PH by the subcutaneous injection of MCT (60 mg/kg) or Sugen5416 (20 mg/kg) with 3 weeks hypoxia. In anesthetized PH rats, we measured pulmonary artery flow (PAF) and pressure (PAP) at 1000 Hz for 107.52 seconds under irregular pacing. We Fourier transformed both PAF and PAP to derive ensembled power spectra and crosspower spectra and taking their ratio yielded Z. We fitted the 2-element Windkessel model to Z and estimated R and C. Results: MCT and SuHx significantly increased mean PAP (Control: 19.4±2.0, MCT: 31.3±4.0, SuHx: 39.4±6.5 mmHg, p &lt;0.01) and shifted Z upward indicating the increased R (Control: 17.8±3.3, MCT: 71.4±16.3, SuHx: 81.8±18.4 mmHg/ml/sec, p &lt;0.01). MCT and SuHx both decreased C (Control: 2.6±0.4, MCT: 1.5±0.6, SuHx: 0.9±0.2 х10 -3 ml/mmHg, p &lt;0.01). However, the time constant was higher in MCT than in SuHx (Control: 90.7±8.6, MCT: 130.0±21.5, SuHx: 92.6±2.0 msec, p &lt;0.05) (Figure). MCT predominantly remodeled resistance vessels while SuHx remodeled both resistance and compliance vessels. Conclusions: We conclude that the impedance analysis is capable of characterizing how remodeling affects vascular mechanical properties, which are not identifiable if we analyze resistance alone. Hence the impedance analysis is applicable in patients, it may serve as a new tool in functionally analyzing vascular remodeling in PH patients.
FRI0424 Comparative analysis of clinically affected and unaffected skin biopsies from scleroderma patients based on rna-sequencing
Authors: Z. Makowska, A. Buttgereit, S. Babaei, N. Limaye, C. Galant, F. Houssiau, B. Weiss, R. Lesche, F. McDonald, B. Lauwerys
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a complex chronic autoimmune disease characterised by vasculopathy, inflammation and fibrosis across different organ systems. The origin and pathogenesis of the disease are not well understood and symptoms may vary among affected individuals, complicating the diagnosis and therapy. <h3>Objectives</h3> We aimed at characterising gene expression profiles in biopsies from affected and unaffected skin of SSc patients. <h3>Methods</h3> RNA isolated from affected and unaffected skin biopsies of 23 SSc patients was analysed using polyA-selected RNA sequencing. Paired differential expression analysis was performed with DESeq2, and Molecular Signatures Database gene set collections were used for functional annotation. <h3>Results</h3> Paired analysis of SSc gene expression profiles identified over 900 genes differentially regulated between the affected and unaffected skin biopsy samples (adjusted p value&lt;0.05). Macroscopically unaffected skin samples showed clear gene expression differences from the affected skin samples, even though the histological examination showed that pathological changes were already present in most of the samples classified as unaffected. Clustering of differentially expressed genes and subsequent functional characterisation of the resulting gene modules revealed sets of co-expressed genes involved in inflammatory response, extracellular matrix interaction, metabolic function and epithelial differentiation, and highlighted the importance of a number of transcription drivers, such as serum response factor (SRF) or interferon regulatory factor 7 (IRF7). Several genes from the HOX family of transcription factors were found to be among the most significantly differentially expressed genes, pointing to an important role of wound healing and regeneration processes in SSc skin lesions. Additionally, we found significant association between expression of several proteasome subunits and the inflammation score obtained by histological assessment of the skin biopsies. <h3>Conclusions</h3> RNA sequencing analysis in paired skin biopsy samples revealed coordinated changes in the gene expression between SSc lesions and macroscopically unaffected skin, providing insights into the SSc skin pathogenesis at the molecular level. <h3>Acknowledgements</h3> The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115565, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies' in kind contribution. <h3>Disclosure of Interest</h3> None declared