tbuckley/cabot-search huggingface dataset:
AB0344 COMPARATIVE ANALYSIS OF SIDE EFFECTS BETWEEN PATIENTS TREATED WITH AND WITHOUT CORTICOSTEROID AT DMARDS-STARTING POINT. SINGLE CENTER RETROSPECTIVE REAL WORLD DATA ANALYSIS
Authors: Michihiro Ogasawara, Yosuke Shimada, Yoshiyuki Abe, Ken Yamaji, Satoshi Hori, Naoto Tamura
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In the EULAR recommendation on rheumatoid arthritis (RA) treatment, short-term steroid combination should be considered at the start of DMARDs treatment. In this study, we analyzed the present condition of steroid combined use in Japan and the actual situation of side effects in recent years. <h3>Objectives</h3> RA patients who started treatment with DMARDs at our hospital during July 2008 to April 2018, <h3>Methods</h3> A new incidence of hypertension (HTN), diabetes (DIB), dyslipidemia (HLP), infection (INF) were compared between the two groups of steroid combined use group (D_PSL) and noncombined group (D_nonPSL) and analyzed by Cox regression analysis. The cases had there complications before the start of RA treatment were excluded from the analysis. <h3>Results</h3> The number of cases of analysis was 573 (D_PSL = 216, D_nonPSL = 357, average observation period: 5.22±2.70 year), and the new incidence of each complication was INF 50/561 (D_PSL 16.2%vs. D_nonPSL 4.56%[16/351], p=0.000094), HTN 48/527 cases (13.3%[25/188] vs.6.78%[23/339], P = 0.0148), DIB 24/558 (6.16%[13/211] vs. 3.17%[11/347], p = 0.136), HLP 72/542 (15.8%[32/202] vs. 11.8%[40/340], p = 0.198). The incidence of INF was high in D_PSL group in both groups over 65 and under 65 years old (p = 0.00658, p = 0.00267), HTN was high in D_PSL group only in group over 65 years old (<i>p=</i><i>0.0276, p</i><i>=</i><i>0.0554</i>). Average starting amount of steroids was 6.07±10.2 mg, cases of non-withdrawal of steroid at 1, 2, 3 years later is 79.7%, 72.2% and 66.3% respectively. <h3>Conclusion</h3> Combined use of steroid at the start of DMARDs increased the rate of mortality of infection requiring hospitalization and hypertension. More than half of them were difficult cases of withdrawal of steroids. From the viewpoint of side effect, it is necessary to study the optimization of steroid therapy in the future. <h3>Disclosure of Interests</h3> Michihiro Ogasawara: None declared, Yosuke Shimada: None declared, Yoshiyuki Abe: None declared, Ken Yamaji: None declared, Satoshi Hori: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.
PB1754 THE PERIPHERAL CD4+CD8+ T‐CELL LEVEL OF ACUTE LEUKEMIA PATIENTS AFTER HAPLO‐HSCT IS HIGHER THAN THAT OF THESE PATIENTS AFTER HLA‐IDENTICAL‐HSCT
Authors: Y. Li, J. Dai, X. Huang
Journal: HemaSphere (2019)

Background: Nowadays, we generally think that the immune responses after the HLA‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) of acute leukemia (AL) patients mainly results from the cross reactivate by donor‐derived memory T‐cells. However, the role of thymus on immune reconstitution after haplo‐HSCT is not clearly understood yet. Aims: Regarding the development of CD4 ‐ CD8 − (double negative, DN) and CD4 + CD8 + (double positive, DP) T‐cell is associated with the function of thymus, we investigate the levels of DN and DP T‐cell in AL patients who have received the haplo‐HSCT or HLA‐identical hematopoietic stem cell transplantation (identical‐HSCT). Methods: In the 1 st to the 12 th months after hematopoietic stem cell transplantation (HSCT), the DN T‐cell and DP T‐cell levels in the peripheral blood of 77 AL patients are evaluated by flow cytometry. And 51 of these patients received haplo‐HSCT, while 26 of them received identical‐HSCT. The repeated measures one‐way ANOVA is used for statistic analysis. Results: The DP T‐cell level of AL patients after haplo‐HSCT is significantly higher than those patients after identical‐HSCT (F = 12.02, p = 0.00). however, The DN T‐cell level in these two groups of patients do not show a significantly difference (F = 0.87, p = 0.36). Furthermore, when we only look into the haplo‐HSCT group, we found that the DP T‐cell level of patients donated by the parents (n = 31) is significantly higher than that of the patients donated by the children, (n = 7, F = 6.37, p = 0.03) as well as that of the patients donated by the sister/brother(n = 13, F = 6.64, p = 0.02). Summary/Conclusion: From the data of our center, in AL patients after haplo‐HSCT show a high DP T‐cell level than these patients after identical‐HSCT, and this indicates that thymus as the human central immune organ, has a possibility to play a role in immune reconstitution after haplo‐HSCT. But the clinical significance of DP T‐cell on predicting thymus function and immune reconstitution need to be further explored with more patient data. Here, we would like to share our finding on the peripheral DP T‐cell level after haplo‐HSCT, in order to inspire further exploration with other hematologists to clarify the mechanism involve in it.
Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis
Authors: A. Green, G. Shaddick, R. Charlton, J. Snowball, A. Nightingale, C. Smith, W. Tillett, N. McHugh
Journal: British Journal of Dermatology (2019)

Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis.To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis.We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models.We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0-29·9, 30·0-34·9 and ≥ 35·0 kg m-2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m-2 : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status.In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic? There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add? Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.
The Rate of Evolution of Postmating-Prezygotic Reproductive Isolation in Drosophila
Authors: David A Turissini, Joseph A McGirr, Sonali S Patel, Jean R David, Daniel R Matute
Journal: Molecular Biology and Evolution (2017)

Reproductive isolation is an intrinsic aspect of species formation. For that reason, the identification of the precise isolating traits, and the rates at which they evolve, is crucial to understanding how species originate and persist. Previous work has measured the rates of evolution of prezygotic and postzygotic barriers to gene flow, yet no systematic analysis has studied the rates of evolution of postmating-prezygotic (PMPZ) barriers. We measured the magnitude of two barriers to gene flow that act after mating occurs but before fertilization. We also measured the magnitude of a premating barrier (female mating rate in nonchoice experiments) and two postzygotic barriers (hybrid inviability and hybrid sterility) for all pairwise crosses of all nine known extant species within the melanogaster subgroup. Our results indicate that PMPZ isolation evolves faster than hybrid inviability but slower than premating isolation. Next, we partition postzygotic isolation into different components and find that, as expected, hybrid sterility evolves faster than hybrid inviability. These results lend support for the hypothesis that, in Drosophila, reproductive isolation mechanisms (RIMs) that act early in reproduction (or in development) tend to evolve faster than those that act later in the reproductive cycle. Finally, we tested whether there was evidence for reinforcing selection at any RIM. We found no evidence for generalized evolution of reproductive isolation via reinforcement which indicates that there is no pervasive evidence of this evolutionary process. Our results indicate that PMPZ RIMs might have important evolutionary consequences in initiating speciation and in the persistence of new species.
Integrating Culture-Based Antibiotic Resistance Profiles with Whole-Genome Sequencing Data for 11,087 Clinical Isolates
Authors: Valentina Galata, Cédric C. Laczny, Christina Backes, Georg Hemmrich-Stanisak, Susanne Schmolke, Andre Franke, Eckart Meese, Mathias Herrmann, Lutz von Müller, Achim Plum, Rolf Müller, Cord Stähler, Andreas E. Posch, Andreas Keller
Journal: Genomics Proteomics & Bioinformatics (2019)

Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species, including conserved essential genes and known resistance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene-drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base, a resource available for academic research use free of charge at https://gear-base.com.
Software for the Integration of Multiomics Experiments in Bioconductor
Authors: Marcel Ramos, Lucas Schiffer, Angela Re, Rimsha Azhar, Azfar Basunia, Carmen Rodriguez, Tiffany Chan, Phil Chapman, Sean R. Davis, David Gomez-Cabrero, Aedin C. Culhane, Benjamin Haibe-Kains, Kasper D. Hansen, Hanish Kodali, Marie S. Louis, Arvind S. Mer, Markus Riester, Martin Morgan, Vince Carey, Levi Waldron
Journal: Cancer Research (2017)

Abstract Multiomics experiments are increasingly commonplace in biomedical research and add layers of complexity to experimental design, data integration, and analysis. R and Bioconductor provide a generic framework for statistical analysis and visualization, as well as specialized data classes for a variety of high-throughput data types, but methods are lacking for integrative analysis of multiomics experiments. The MultiAssayExperiment software package, implemented in R and leveraging Bioconductor software and design principles, provides for the coordinated representation of, storage of, and operation on multiple diverse genomics data. We provide the unrestricted multiple ‘omics data for each cancer tissue in The Cancer Genome Atlas as ready-to-analyze MultiAssayExperiment objects and demonstrate in these and other datasets how the software simplifies data representation, statistical analysis, and visualization. The MultiAssayExperiment Bioconductor package reduces major obstacles to efficient, scalable, and reproducible statistical analysis of multiomics data and enhances data science applications of multiple omics datasets. Cancer Res; 77(21); e39–42. ©2017 AACR.
THU0205 THE HEMATOPOIETIC STEM CELLS (HSCS) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) REPROGRAM THEIR TRANSCRIPTOME: IMPLICATIONS FOR THE PATHOGENESIS OF THE DISEASE
Authors: Aggelos Banos, Maria Grigoriou, Anastasia Filia, Pavlos Pavlidis, Lina Giannouli, Vassiliki Karali, Dionisis Nikolopoulos, Antigoni Pieta, Ioannis Mitroulis, Panayotis Verginis, Dimitrios Boumpas
Journal: Annals of the Rheumatic Diseases (2019)

Background:In SLE, all terminally differentiated blood cells demonstrate an aberrant phenotype.HSCs the most primitive cell type of the hematopoietic lineage when exposed within the bone marrow (BM) to adjuvants and inflammatory mediators change their transcriptional landscape and this may persist in the HSCs circulating in the peripheral blood or those infiltrating peripheral tissues.Within peripheral tissues these reprogramed HSCs differentiate into myeloid cells mounting enhanced protective or aberrant immune responses 1 .Objectives: To dissect whether aberrant phenotypes of blood cells in SLE could be traced back to HSCs and explore how the inflammatory environment of SLE shapes the HSC differentiation process.Methods: We analyzed the transcriptional alterations (genetic or epigenetic) of CD34 + cells in the BM of SLE patients, compared it to healthy individuals and the NZB/W lupus mice at the onset of disease (6 months).CD34 + cells were isolated from BM aspirates and peripheral blood of SLE patients (n=8) and healthy subjects (n=2) with magnetic separation (Stem Cell Technologies).mRNA was extracted and libraries were prepared.Sequencing was performed in NextSeq Illumina Platform.Alignment in human genome v.38 was done by Star package and differential expression analysis was performed by edgeR algorithm.Genes with FC!1.5/£-1.5,FDR£0.05 were considered statistically significantly up-/ down-regulated, respectively.Heatmaps were constructed in R, GO/Pathway Analysis and enrichment analysis were performed in ClueGo, RNEA, GeneMania and GSEA, respectively.Results: Overlaying the transcriptome of BM-derived CD34 + of SLE patients and healthy subjects, we identified in total 598 differentially expressed genes(DEGs) (82 up-/514 down-regulated in SLE).DEGs participate in hematopoietic cell lineage fate, regulation of stem cell differentiation, cell adhesion and cell cycle regulation.We also found evidence for cell cycle checkpoints signature which drives HSCs to experience replication stress and activate ATR pathway.Comparison of CD34 + profile between severe-moderate SLE reveals a prominent neutrophilic signature in severe disease.Comparative transcriptomic analysis of human vs murine SLE revealed a panel of common genes again related to cell proliferation, differentiation and platelet activation.Conclusion: HSCs in SLE patients and murine lupus reprogram their transcriptome in response to the inflammatory milieu within the BM, thus exiting from dormancy, differentiating to myeloid cells and mounting a DNA damage response to the replication stress.This activated phenotype renders HSCs both susceptible to cell exhaustion while at the same time priming them and their progenies towards enhanced immune responses.
SP0082 SCREENING FOR MALIGNANCIES IN SJOGREN SYNDROME AND MYOSITIS
Authors: Albert Selva-O”Callaghan
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Both myositis and Sjögren syndrome may be associated with cancer. However, there are differences between the cancer-associated myositis and cancer that appears in patients with Sjogren syndrome, and these differences make for a distinct tumor screening approach. The fact that any type of cancer -mainly of the adenocarcinoma type- can be associated with myositis -dermatomyositis, either classical or amyopathic, immune-mediated necrotizing myopathy, or polymyositis phenotypes- makes more difficult to know if an occult malignancy is present. Nevertheless, in recent years biological markers such as several autoantibodies, essentially anti-TIF1γ, but also anti-NXP2 and to some extent anti-HMGCR, and combined techniques such as PET/CT that allow to detect structural and functional changes by means of <sup>18</sup>F- Fluorodeoxyglucose and whole CT have helped the clinician to screen for an occult cancer in patients with myositis. Alternatively, the clinical situation and screening approaches in Sjögren syndrome are more focused in the detection of lymphoproliferative disorders, mostly in salivary glands (MALT type lymphoma) but also marginal zone or diffuse large B cell lymphomas. Several approaches for detecting MALT-type lymphoma or generalized lymphomas, beyond the well-known parameters such as low complement levels, cytopenias, cryoglobulins or persistent enlargement of salivary glands, are also discussed. <h3>References:</h3> [1] Selva-O"Callaghan A, Martínez-Gómez X, Trallero-Araguás E, Pinal-Fernández I. The diagnostic work-up of cancer-associated myositis. Curr Opin Rheumatol. 2018; 30:630-6 [2] Baldini C, Ferro F, Luciano N, Bombardieri S, Grossi E. Artificial neural networks help to identify disease subsets and to predict lymphoma in primary Sjögren syndrome. Clin Exp Rheumatol. 2018;36 (Suppl. 112): S137-S144 <h3>Disclosure of Interests:</h3> None declared
AB1221 VIEWS OF PRIMARY CARE PHYSICIANS AND RHEUMATOLOGISTS REGARDING SCREENING FOR HYPERLIPIDEMIA AMONG PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Iris Navarro-Millan, Anna Cornelius-Schecter, Ronan O’beirne, Melanie Morris, Geyanne Lui, Susan Goodman, Andrea Cherrington, Liana Fraenkel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Screening of hyperlipidemia in rheumatoid arthritis (RA) is suboptimal, despite RA patients' high risk for cardiovascular disease (CVD) mortality. <h3>Objectives</h3> To identify barriers to screening for hyperlipidemia among patients with RA from the viewpoint of primary care physicians (PCPs) and rheumatologists. <h3>Methods</h3> We recruited rheumatologists and PCPs nationally to participate in separate moderated structured group teleconference discussions using the nominal group technique. Participants in each group generated lists of barriers to screening for hyperlipidemia in patients with RA, then each selected the three most important barriers from this list. <h3>Results</h3> Twenty-six rheumatologists participated in 3 groups and 20 PCPs participated in groups. The resulting barriers were organized into physician-, patient- and system-level barriers. Rheumatologists prioritized physician level barriers (e.g. 'ownership' of hyperlipidemia screening), whereas PCPs prioritized patient-level barriers (e.g. complexity of RA itself). See table 1 for details. <h3>Conclusion</h3> These rheumatologists were conflicted about whether screening of CVD risk among patients with RA should fall within the role of the rheumatologist or PCPs. On the other hand, participating PCPs were concerned about the overall effect of RA and RA treatments in the context of screening hyperlipidemia. Note: RA = rheumatoid arthritis; CVD = cardiovascular disease; 0% = that sub-theme emerged during the brainstorming session but did not receive votes; " – " = the sub-theme did not emerge in the respective group. <h3>Disclosure of Interests</h3> Iris Navarro-Millan: None declared, Anna Cornelius-Schecter: None declared, Ronan O'Beirne Grant/research support from: Pfizer, Inc., Melanie Morris: None declared, Geyanne Lui: None declared, Susan Goodman Grant/research support from: Novartis: research support, Consultant for: Novartis, UCB, Pfizer: consulting, Andrea Cherrington: None declared, Liana Fraenkel: None declared
Использование количественного определения HbsAg для мониторинга противовирусной терапии хронической HBV-инфекции
Authors: I.A. Zaitsev
Journal: GASTROENTEROLOGY (2020)

В настоящее время главным нерешенным вопросом при осуществлении мониторинга противовирусной терапии хронической HBV-инфекции является отсутствие четких предикторов развития устойчивого вирусологического ответа на лечение. Эти предикторы позволили бы рано выявлять пациентов, не отвечающих на лечение пегилированным интерфероном, и прогнозировать высокую вероятность сохранения развившегося ответа на лечение нуклеоз(т)идными аналогами в случае прекращения последнего. Выходом из сложившейся ситуации может быть использование количественной оценки HBsAg, чему и посвящен данный обзор.
AB0303 METABOLIC SYNDROME IN TUNISIAN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Najah Boussetta, Sameh Sayhi, Salma Bouzid, Leila Metoui, Faida Ajili, Bassem Louzir
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The rheumatoid arthritis (RA) is responsible of a high cardiovascular morbi-mortality. This could be related to an increased prevalence of metabolic syndrome in patients with (RA) <h3>Objectives</h3> The aim of our study was to determine the prevalence of metabolic syndrome in RA, to identify factors associated with its presence and to evaluate the influence of antirheumatic drugs on its occurrence. <h3>Methods</h3> A cross-sectional study was conducted in the Internal Medicine department over a period from July 2016 to June 2017, including 50 RA patients classified according to the 1987 ACR and/or 2010 ACR/EULAR criteria. We used the National Cholesterol Education Program/Adult Panel Treatment III 2005 (NCEP/ATP III 2005) definition for the metabolic syndrome. <h3>Results</h3> There were 50 patients (sex-ratio = 0.28) with a mean age of 50.84 ± 12.52 years. The mean age at the onset of RA was 42.04 ± 12.76 years with duration of 17.52 months (0.8-120 months). The evaluation of the disease showed an average DAS28-VS score of 5.37 ± 1.24 and a significant functional impact (HAQ score ≥ 1) in 36% of patients. The prevalence of metabolic syndrome in RA was 40%. Its presence was associated with higher age (p = 0.003), greater disease activity (p=0.044), the presence of a biological inflammatory syndrome (p=0.032) and hyperuricemia (p=0.005). An association was also found with long-term corticosteroid use (p = 0.03). <h3>Conclusion</h3> Our results are consistent with most of the literature data. Throughout our study, we emphasize the importance of continuous monitoring of disease activity and the need for cortisone-sparing. <h3>References</h3> [1] Da Cunha VR, Brenol CV, Brenol JCT, Fuchs SC, Arlindo EM, Melo IMF, et al. Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and is associated with disease activity. Scand J Rheumatol. 2012; 41 (3): 186–91. [2] Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis. 2008; 196 (2): 756–63. [3] Dao H-H, Do Q-T, Sakamoto J. Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2010; 12 (6): R218. <h3>Disclosure of Interests</h3> None declared