tbuckley/cabot-search huggingface dataset:
THU0420 METABOLIC SYNDROME AND TRAJECTORIES OF LOCALISED PAIN AND GENERALISED PAIN
Authors: Feng Pan, Jing Tian, Flavia Cicuttini, Graeme Jones
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Metabolic syndrome (MetS) has been suggested as having a link to the pathophysiology of pain; however, no study has assessed whether MetS and its components are associated with localised pain and generalised pain and their courses over time. <h3>Objectives</h3> To describe the associations of MetS and its components with trajectories of localised knee pain (pain severity) and generalised pain ((number of painful sites (NPS)) in a general older population. <h3>Methods</h3> 1,099 participants from a population-based older adult cohort study were recruited at baseline. 875, 768 and 563 participants attended years 2.6, 5.1 and 10.7 follow-up, respectively. Data were collected on demographic, psychological, lifestyle and comorbidities, blood pressure, glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol. MetS was defined based on the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Knee pain was measured by Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire at each time-point. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees and feet was collected by questionnaire at each time-point. Group-based trajectory modelling was applied to identify pain trajectories. Multi-nominal logistic regression was used for the analyses. <h3>Results</h3> Of 985 participants included in this study, 32% of participants had MetS and 60% had ROA at baseline. Three localised knee pain severity trajectories were identified: 'Minimal pain' (52%), 'Mild pain' (33%) and 'Moderate pain' (15%). Three NPS trajectories were identified: 'Low NPS' (12%), 'Medium NPS' (38%), and 'High NPS' (49%). In multivariable analysis without adjusting for central obesity, central obesity increased risk of belonging to both 'Mild pain' and 'Moderate pain' trajectories as compared to the 'Minimal pain' trajectory group, but MetS, hypertriglyceridemia and low HDL were only associated with 'Moderate pain' trajectory [relative risk (RR): 1.67-2.26, all P&lt;0.05]. Similarly, central obesity was also associated with both 'Medium NPS' (RR 2.35, 95%CI 1.40−3.92) and 'High NPS' trajectories (RR 3.07, 95%CI 1.85−5.08) compared to 'Low NPS' trajectory group, whereas MetS was only associated with 'High NPS' trajectory (RR 2.60, 95%CI 1.54−4.41). These associations became weak and non-significant after further adjustment for central obesity. <h3>Conclusion</h3> MetS is predominantly associated with trajectories of localised and generalised pain through central obesity, suggesting that weight management is important in the prevention and therapy of pain over time. <h3>Disclosure of Interests</h3> None declared
EASIX FOR PREDICTION OF SURVIVAL IN LOWER RISK MYELODYSPLASTIC SYNDROMES
Authors: A. M. A. Merz, U. Germing, G. Kobbe, A. Jauch, A. Radujkovic, M. Hummel, A. Benner, M. Merz, C. Müller-Tidow, P. Dreger, T. Luft
Journal: HemaSphere (2019)
Abstract 16239: Stress Hyperglycemia and Prognosis of ST-Segment Elevation Myocardial Infarction Who Underwent Primary Percutaneous Coronary Intervention in Nondiabetic Patients; Data From the INTERSTELLAR Cohort
Authors: Min Gyu Kong, Jon Suh, Hyun Woo Park, Hyung Oh Choi, Hye-Sun Seo, Yun-Hang Cho, Nae-Hee Lee
Journal: Circulation (2018)

Backgrounds: Stress hyperglycemia is common in acute ill patients and associated with poor clinical outcomes. Some studies demonstrated the association of stress hyperglycemia and poor outcomes in ...
Best practices in data analysis and sharing in neuroimaging using MRI
Authors: Thomas E Nichols, Samir Das, Simon B Eickhoff, Alan C Evans, Tristan Glatard, Michael Hanke, Nikolaus Kriegeskorte, Michael P Milham, Russell A Poldrack, Jean-Baptiste Poline, Erika Proal, Bertrand Thirion, David C Van Essen, Tonya White, B T Thomas Yeo
Journal: Nature Neuroscience (2017)
AB0724 DOSE PREGNANCY AND VAGINAL DELIVERY WORSEN ANKYLOSING SPONDYLITIS?
Authors: Jung Sun Lee, Ji Seon Oh, Wook Jang Seo, Seokchan Hong, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Ankylosing spondylitis (AS) affects the sacroiliac joints and commonly occurs in those at the reproductive age. Women with aS have a higher rate of cesarean section (CS) compared with healthy controls. <h3>Objectives</h3> This study determined the effect of pregnancy and delivery methods on aS worsening by analyzing prescription pattern. <h3>Methods</h3> Based on the Korean Health insurance Review and assessment Service claims database, subjects comprised female patients aged 20–49 years with an aS. Alteration of prescriptions was defined by changing the at two time periods of 1–2 years pre-delivery and 1-year post-delivery. We compared alteration of prescriptions between aS patients with delivery and 1:1 matched aS patients without delivery. In addition, among aS patients with delivery, alteration of prescriptions according to delivery method was evaluated. <h3>Results</h3> Among 6,821 female patients with aS, 996 patients in the delivery group were younger, had a higher proportion of non-drug use, and had lower rates of comorbidity than the no delivery group. The alteration of prescriptions did not differ between the aS with delivery and the aS without delivery groups (OR 0.76, 95% CI 0.56–1.05). Furthermore, the overall alteration of prescriptions did not differ significantly between vaginal delivery (VD) and CS (OR 0.72, 95% CI 0.45–1.14). <h3>Conclusion</h3> The rate of alteration of prescriptions was comparable between the aS patients with and without delivery. There was no association between VD and alteration of prescriptions compared with CS. Taken together, pregnancy and VD may not be assumed to be factors of aS worsening. <h3>Disclosure of interests</h3> None declared
lncRNA Gm10451 regulates PTIP to facilitate iPSCs-derived β-like cell differentiation by targeting miR-338-3p as a ceRNA
Authors: Yan Huang, Yang Xu, Yuhua Lu, Shajun Zhu, Yibing Guo, Cheng Sun, Lianchen Xu, Xiaolan Chen, Yahong Zhao, Bin Yu, Yumin Yang, Zhiwei Wang
Journal: Biomaterials (2019)

iPSCs-derived insulin-producing cell transplantation is a promising strategy for diabetes therapy. Although there have been many protocols of mature, glucose-responsive β cells induced in vitro over the past few years, many underlying problems remain to be resolved. As a crucial regulator, long noncoding RNAs (lncRNAs) participate in numerous biological processes, including the maintenance of pluripotency, and stem cell differentiation. In this study, we identified a novel lncRNA Gm10451 as a functional regulator for β-like cell differentiation. Localized to the cytoplasm, Gm10451 regulates histone H3K4 methyltransferase complex PTIP to facilitate Insulin+/Nkx6.1+ β-like cell differentiation by targeting miR-338-3p as a competing endogenous RNA (ceRNA). miR-338-3p has also been shown to suppress Nkx6.1+ early-stage β-like cell differentiation by targeting PTIP. Following transplantation into streptozotocin (STZ)-mice, Gm10451 loss in β-like cells prevented the expression of mature β-cell makers, such as Insulin, Nkx6.1, and Mafa. Accordingly, hyperglycemia in the mice was not resolved. Taken together, this study provides an efficient epigenetic target for generating more mature and functional iPSCs-derived β-like cells. We anticipate that pancreatic organoids, which are generated from human stem cells, biological materials, and epigenetic modifications, can be used in the future as a novel diabetes treatment option.
SP0159 WHAT DO WE KNOW – WHAT SHALL WE DO – WHAT DO WE TELL
Authors: Timothy R. Radstake
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> There is an increasing need for patients to be involved in research as well as matters that can influence their own clinical journey. One aspect of science that links optimal clinical care is the increased use of biomarkers for so-called personalized medicine approaches. In my presentation I will showcase the State of the Art technologies of biomarker research and how the information that comes from this can be implemented for improving clinical care. I will discuss the revolution of molecular profiling and how the large amount of data coming from these approaches is used to molecularly classify patients into molecular fingerprints. How this technology leads to a disruptive change in medicine for the coming 5-10 years. I will close of with the role of biomarkers in the treatment of diseases, trial design and drug development for the coming 5 years. <h3>Disclosure of Interests:</h3> None declared
Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion
Authors: Céline Duc, Marianne Yoth, Silke Jensen, Nolwenn Mouniée, Casey M. Bergman, Chantal Vaury, Emilie Brasset
Journal: Genome biology (2019)

For species survival, the germline must faithfully transmit genetic information to the progeny. Transposable elements (TEs) constitute a significant threat to genome stability due to their mobility. In the metazoan germline, their mobilization is limited by a class of small RNAs called PIWI-interacting RNAs (piRNAs) produced by dedicated genomic loci called piRNA clusters. Although the piRNA pathway is an adaptive genomic immunity system, it remains unclear how the germline gains protection from a new transposon invasion. To address this question, we analyze Drosophila melanogaster lines harboring a deletion within flamenco, a major piRNA cluster specifically expressed in somatic follicular cells. This deletion leads to derepression of the retrotransposon ZAM in the somatic follicular cells and subsequent germline genome invasion. In this mutant line, we identify de novo production of sense and antisense ZAM-derived piRNAs that display a germinal molecular signature. These piRNAs originated from a new ZAM insertion into a germline dual-strand piRNA cluster and silence ZAM expression specifically in germ cells. Finally, we find that ZAM trapping in a germinal piRNA cluster is a frequent event that occurs early during the isolation of the mutant line. Transposons can hijack the host developmental process to propagate whenever their silencing is lost. Here, we show that the germline can protect itself by trapping invading somatic-specific TEs into germline piRNA clusters. This is the first demonstration of "auto-immunization" of a germline endangered by mobilization of a surrounding somatic TE.
AB0128 ANTIOXIDATIVE PROTECTION AND MONOXIGENASE SYSTEM ACTIVITY OF CYTOCHROME P450 (MOG) OF NEUTROPHYLIC LEUKOCYTES (NL) FROM SYNOVIAL FLUID (SF) IN RHEUMATOID ARTHRITIS (RA)
Authors: Viktor Shishkin, Galina Kudriavtseva, Yuri Malenkov, Viktor V. Shishkin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> MOG system is present not only in the liver but also in far less quantities in other organs and tissues, including SF. <h3>Objectives:</h3> SF in RA patient contains up to 95% of NL that determines the inflammation also by inhibiting MOG. <h3>Methods:</h3> SF of knee joints of 8 patients with RA with active synovitis and 4 donors (D) were examined. NL have been isolated by standard methods. After the application of Triton-X-100 0,1% solution, NL has been centrifuged at 25000 g for 30 minutes. The supernatant has been used in the experiment. The activity of MOG has been estimated according to the level of cytochromes P450. P420 and b5 have been estimated by applying the method of differential spectrophotometry. Active forms of oxygen have been registered by applying electron paramagnetic resonance (EPR). The activity of the antioxidant enzymes - Cu-Zn superoxiddismutase (Cu-Zn SOD), Se-glutathione peroxidase (Se-GPO) and catalase (CAT) was estimated by employing classical enzymology methods. <h3>Results:</h3> It has been found out that in RA, the level of active oxygen forms increases by 68%. Meanwhile, the enzymes level of antioxidant defense is insufficient. In RA the activity of SOD, GPO and CAT enzymes is inhibited at 52, 66 and 39% respectively. In RA the activity of MOG (P450 and b5) in NL is 4 times lower than normal. The concentration of the inactive form of cytochrome P420, however, doubles. Nevertheless, their ratio P450/P420 (when normal = 5) in case of RA = 5,6 hardly ever changes. <h3>Conclusion:</h3> A fall in the level of free radical oxidation and antioxidant defense and faster generation of active oxygen forms in RA leads to NL being destroyed and creates favorable conditions for the development of autophagy and apoptosis. The oxidative stress during RA is accompanied by a fall in the activity of MOG and activation of lipid peroxidation and cytokine production in NL as shown earlier. A general fall in the activity of MOG (P-450 and b5) in NL in RA occurs against the background of enhanced conversion of P-450 into the inactive cytochrome P-420. This fact proves that the expression of isoenzymes P450s (CYPs) is reprogrammed whilst the autoimmune pathology is being developed and there is an unbalance of the immune oxygenase homeostasis in RA. <h3>Reference</h3> [1] Shishkin V. I. et al. Ann Rheum. Dis. 2016;75: sup.2 - 5832. <h3>Disclosure of Interests:</h3> None declared
Abstract 20241: Gender Disparities in Rates of Obstructive Coronary Artery Disease, Percutaneous Coronary Intervention, and Mortality in Adults With Cardiac Arrest
Authors: Linh N Tran, Puja B Parikh, Ganesh Thippeswamy, Charles Loeb, Jignesh K Patel
Journal: Circulation (2017)

Introduction: Despite many advances in the field of resuscitation, cardiac arrest (CA) continues to have high rates of mortality. No studies have examined impact of gender on presence of obstructiv...
Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension
Authors: Donald E Wesson, Vandana Mathur, Navdeep Tangri, Yuri Stasiv, Dawn Parsell, Elizabeth Li, Gerrit Klaerner, David A Bushinsky
Journal: The Lancet (2019)
Targeting subtype in ALL
Authors: Arend von Stackelberg
Journal: HemaSphere (2019)

Learning goals Genetic alterations are important prognostic factors in ALL. Affected intracellular pathways may serve as therapeutic targets. Prospective trials to prove the efficacy and safety of targeted therapies are needed. Introduction Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in children. With conventional chemotherapy, prognosis is favorable, however at the cost of acute and long-term side effects. Relapsed and refractory ALL in contrast is associated with poor prognosis. Therefore, in general, there is a medical need for targeted potentially less toxic therapy to replace toxic chemotherapy and overcome resistance. In B-cell progenitor (BCP) ALL favorable genetic alterations are hyperdiploidy or translocation t(12;21)/ETV6-RUNX1, whereas t(9;22)/BCR-ABL1, KMT2A (MLL) rearrangements, chromosome 21 amplification (iAMP21), t(17/19)/TCF3-HLF and hypodiploidy are associated with poor prognosis. Numerous additional coexisting genetic lesions have been detected involving B-cell development, proliferation and differentiation pathways that may serve as prognostic markers or therapeutic targets. In T-ALL, early T-immunophenotype (ETP) shows an immature genetic profile with stem-cell- and myeloid characteristics. Alterated pathways include NOTCH signaling, cell cycle regulation, PI3K, JAK/STAT, which may serve as therapeutic targets. Targeted treatment may however be impaired by heteroclonality of the ALL. Prospective controlled trials to prove safety and efficacy of these approaches are largely lacking.
Abstract 15314: Autoantibody Against β1-Adrenoceptor Facilitates the Activation of Regulatory T Cells (Tregs), but Attenuates the Tregs’ Cardioprotective Effects in the Presence of High Concentration
Authors: Wenli Xu, Yunhui Du, Yan Bai, Yu Dong, Wen Wang, Huirong Liu
Journal: Circulation (2016)

Introduction: Numerous studies indicate that the existence of autoantibodies and CD4+T cells dysfunction constitute the main immunological mechanism in heart failure. Autoantibody against β1-adreno...
A statistical approach for identifying differential distributions in single-cell RNA-seq experiments
Authors: Keegan D. Korthauer, Li-Fang Chu, Michael A. Newton, Yuan Li, James Thomson, Ron Stewart, Christina Kendziorski
Journal: Genome biology (2016)

The ability to quantify cellular heterogeneity is a major advantage of single-cell technologies. However, statistical methods often treat cellular heterogeneity as a nuisance. We present a novel method to characterize differences in expression in the presence of distinct expression states within and among biological conditions. We demonstrate that this framework can detect differential expression patterns under a wide range of settings. Compared to existing approaches, this method has higher power to detect subtle differences in gene expression distributions that are more complex than a mean shift, and can characterize those differences. The freely available R package scDD implements the approach.
Abstract MP092: Ultrasound Measures of Abdominal Fat Predict Gestational Insulin Resistance
Authors: Katherine H Ingram, Janeen Amason, Kareem Pierre
Journal: Circulation (2017)

Introduction: Gestational diabetes mellitus (GDM) is a serious condition affecting approximately 10% of pregnancies. Obesity, and particularly abdominal obesity, is strongly associated with insulin resistance, the hallmark characteristic of diabetes. The current standard-of-care is the use of an oral glucose test to diagnose GDM at approximately 25 weeks gestation. After diagnosis, a lifestyle intervention is prescribed. If abdominal fat can be measured during routine prenatal ultrasounds, then it may provide an option for early identification of women at high risk for GDM and, in turn, earlier intervention. Hypothesis: This pilot study tested the hypothesis that deep abdominal fat depots are predictive of gestational insulin sensitivity, regardless of overall body fat. Methods: In 31 nulliparous pregnant women (age 27±4.5, BMI 27±7.8, 71% non-hispanic white), abdominal fat was measured at 18-20 weeks gestation via ultrasound. Two measurements were collected 1 inch above the umbilicus (deep intra-abdominal (IAAT) and subcutaneous (SAT1)); two were immediately below the xyphoid process (pre-peritoneal (PPAT) and subcutaneous (SAT2)). Overall body composition was calculated via 4-compartment model from body density via air displacement plethysmography (BodPod) and body water via bioelectrical impedance (InBody 720) measured at 18-20 weeks gestation, along with post-partum bone density via DXA. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed using fasting glucose and insulin at 24-28 weeks gestation. Gestational weight gain (GWG) was monitored by medical records. After testing variables for normality, HOMA-IR was log-transformed for partial correlation and multiple regression analyses. Results: HOMA-IR was strongly correlated to overall gestational body fat ( r =.666, p =.003) and measures of regional adiposity ( r =.673 for IAAT, r =.471 for PPAT, r =.627 for SAT1, r =.627 for SAT2, p &lt;.05 for all), but not GWG ( r =.012, p =.957), when controlling for age and race. HOMA-IR remained strongly associated with IAAT and SAT1 ( r = .510 and .490, respectively, p &lt;.05 for both), but not PPAT or SAT2 ( r =.143 and .380, p =.559 and .108, respectively), when correlations were repeated controlling for age, race, and percent body fat. Multiple regression analysis revealed that IAAT and SAT1 were significant independent predictors of HOMA-IR (β= .570 and .491, respectively, p &lt;.05 for both), but not PPAT, SAT2, or overall body fat (β = -.384, .473, and -.164, respectively, p = ns for all). Conclusions: Gestational insulin resistance is strongly associated with intra-abdominal and subcutaneous adipose accumulation in the lower abdomen, independent of overall body fat. Thus, abdominal fat ultrasound measures may be a simple way to identify, early in pregnancy, those who are at high risk for gestational diabetes.
Rapid turnover of life-cycle-related genes in the brown algae
Authors: Agnieszka P. Lipinska, Martha L. Serrano-Serrano, Alexandre Cormier, Akira F. Peters, Kazuhiro Kogame, J. Mark Cock, Susana M. Coelho
Journal: Genome biology (2019)

Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, many plants and algae alternate between multicellular haploid (gametophyte) and diploid (sporophyte) generations. In many algae, gametophytes and sporophytes are independent and free-living and may present dramatic phenotypic differences. The same shared genome can therefore be subject to different, even conflicting, selection pressures during each of the life cycle generations. Here, we analyze the nature and extent of genome-wide, generation-biased gene expression in four species of brown algae with contrasting levels of dimorphism between life cycle generations. We show that the proportion of the transcriptome that is generation-specific is broadly associated with the level of phenotypic dimorphism between the life cycle stages. Importantly, our data reveals a remarkably high turnover rate for life-cycle-related gene sets across the brown algae and highlights the importance not only of co-option of regulatory programs from one generation to the other but also of a role for newly emerged, lineage-specific gene expression patterns in the evolution of the gametophyte and sporophyte developmental programs in this major eukaryotic group. Moreover, we show that generation-biased genes display distinct evolutionary modes, with gametophyte-biased genes evolving rapidly at the coding sequence level whereas sporophyte-biased genes tend to exhibit changes in their patterns of expression. Our analysis uncovers the characteristics, expression patterns, and evolution of generation-biased genes and underlines the selective forces that shape this previously underappreciated source of phenotypic diversity.
A Genetically Tractable, Natural Mouse Model of Cryptosporidiosis Offers Insights into Host Protective Immunity
Authors: Adam Sateriale, Jan Šlapeta, Rodrigo Baptista, Julie B. Engiles, Jodi A. Gullicksrud, Gillian T. Herbert, Carrie F. Brooks, Emily M. Kugler, Jessica C. Kissinger, Christopher A. Hunter, Boris Striepen
Journal: Cell Host & Microbe (2019)

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here, we derive an in vivo model of Cryptosporidium infection in immunocompetent C57BL/6 mice by isolating parasites from naturally infected wild mice. Similar to human cryptosporidiosis, this infection causes intestinal pathology, and interferon-γ controls early infection while T cells are critical for clearance. Importantly, mice that controlled a live infection were resistant to secondary challenge and vaccination with attenuated parasites provided protection equal to live infection. Both parasite and host are genetically tractable and this in vivo model will facilitate mechanistic investigation and rational vaccine design.