tbuckley/cabot-search huggingface dataset:
08.37 Thrombospondin-1 is highly expressed by salivary gland epithelial cells of sjögren’s syndrome patients, both constitutively and upon exposure to necrotic cells debris
Authors: Aglaia G Vakrakou, Markos D Patsouras, Panagiotis G Vlachoyiannopoulos, Athanasios G Tzioufas, Menelaos N Manoussakis
Journal: Annals of the Rheumatic Diseases (2017)

<h3></h3> Sjögren's syndrome (SS) patients manifest inflammation in salivary glands (SG) and evidence of intrinsic activation in the salivary gland epithelial cells (SGEC). Recent evidence from this laboratory has indicated that the aberrant exposure of SGEC of SS patients to necrotic debris may be a major cause of inflammatory reactions via activation of inflammasome. Thrombospondin (TSP-1) is a matricellular glycoprotein with proinflammatory, antiangiogenic and proapoptotic properties. It was originally characterised as an α-granule glycoprotein in platelets, although can be synthesised and released by a variety of cell types, including epithelial cells. Herein, we assessed the expression of TSP-1 in cultured ductal SGEC lines obtained from SS patients and controls. We also sought to investigate the effect of necrotic cell debris (NEC) on mRNA synthesis and release of TSP-1, in healthy epithelium. SS patients (n=14) displayed significant upregulation of TSP-1 mRNA levels in cultured SGEC compared to controls (n=10, p=0.0005), that correlated with the severity of histopathologic lesions (tarpley score of respective SG tissue biopsy) (Kruskal-Wallis test, p=0.001). SS-SGEC (n=16) were also found to secrete constitutively more TSP-1 and IL-1β in their culture supernatants, compared to non-SS SGEC (n=15) (p=0.0001 and p=0.06, respectively). There was a positive correlation among the constitutively expressed levels of TSP-1 and IL-1β (Spearman's r=0.66 for mRNA and r=0.41 for protein). Treatment of healthy SGEC lines (n=4) with NEC led to induction of TSP-1 and IL-1β mRNA (2.1-fold and 2-fold increase, respectively), as well as protein in culture supernatants (3.0-fold and 2.5-fold increase, respectively) (for all comparisons, p&lt;0.05), that were abrogated upon pre-treatment of NEC with DNase1. Finally, immunohistochemistry analysis in SG revealed the overexpression of TSP-1 and IL-β, mainly in epithelial structures (both ductal and acinar cells) of SS patients, compared to non-SS controls. Preliminary results suggest for the first time that SGEC from SS patients manifest increased TSP-1 and IL-1β levels that correlate with severe lymphocytic infiltrates in SG. Chronic exposure to necrotic cells debris may hold a key pathogenetic role in the tissue inflammatory reactions of SS patients and may also explain the 'intrinsic activation status' that characterises the epithelia of these patients.
Abstract 16863: Racial Differences in Atrial Fibrillation Prevalence and Anticoagulation Use
Authors: Kevin L Thomas, Jonathan P Piccini, Li Liang, Paul Heidenreich, Gregg Fonarow, Eric Peterson, Clyde Yancy, Adrian Hernandez
Journal: Circulation (2012)

Background: Atrial fibrillation (AF) is common in heart failure (HF). Studies have suggested blacks are less likely to develop AF relative to whites, but less is known regarding racial differences ...
Phase 1 first-in-human (FIH) study of nesvacumab (REGN910) a fully human and selective angiopoietin-2 (Ang2) monoclonal antibody (MAb): Results from hepatocellular carcinoma (HCC) cohort.
Authors: Robin Kate Kelley, Lillian L. Siu, Katherine Van Loon, Anthony W. Tolcher, Albiruni R. A. Razak, Sharvina Ziyeh, Muralidhar Beeram, Philippe L. Bedard, Rebecca Arcos, Bo Gao, Pamela Trail, Lieve Adriaens, Carrie M. Brownstein, Israel Lowy, Kyriakos P. Papadopoulos
Journal: Journal of Clinical Oncology (2014)

2540 Background: Nesvacumab (N) is an Ang2 selective, human MAb that potently blocks signaling through the Tie2 receptor, inhibiting tumor angiogenesis and growth. In mouse xenograft models of human solid tumors, N inhibits tumor growth. In the dose-escalation (DE) portion of this trial [JCO 31, 2013 (suppl; abstr 2517)] anti-tumor activity (significant decline AFP) was observed in a patient (pt) with HCC, prompting expansion in this indication. Methods: Safety and anti-tumor activity are reported from all pts with HCC treated in the FIH trial in DE and expansion phases combined. In DE, single agent N was administered IV Q2W at 1 of 5 dose levels starting at 1 mg/kg; HCC expansion at 2 doses, 12, and 20 mg/kg Q2W, were studied. Results: 15 pts with HCC were enrolled: [11M/4F; median age 69 (range 24-82); ECOG PS 0=6/1=9; prior sorafenib 60%]. Dose levels were: 1 (n=1), 12 (n=6) and 20 mg/kg (n=8). Median number of doses administered was 8 (range 1-23). No pts experienced protocol defined DLTs. Most common adverse events (AEs) (all/related) were fatigue (8/5), diarrhea (5/0), decreased appetite (4/2), dizziness (4/0), nausea (4/2), abdominal pain (3/1), vomiting (3/1), back pain (3/0) and dyspnea (3/0); 9 grade ≥3 events reported in 7 pts, of which 3 events were assessed as treatment related: abdominal pain, infusion-related reaction, and retinal detachment, each reported in a single pt. One pt treated with 20 mg/kg experienced a non-severe lower GI bleed, assessed as not treatment related. No objective responses were observed. Two pts experienced a ≥ 50% decline in AFP (1 pt >90%). Nine of 15 pts achieved best response of SD (median duration 24 wks); 6 pts achieved SD for ≥ 20 wks. Notably, 5 of 8 pts treated at 20 mg/kg achieved best response of SD; median duration of 40 wks. Conclusions: Single-agent N up to 20mg/kg Q2W was generally tolerated in pts with HCC, with primarily mild and moderate AEs, independent of dose. SD occurred in 60% of pts across doses, with prolonged SD at highest dose. The safety profile supports combination with chemotherapy and/or other anti-angiogenic agents. Expansion in pts with HCC receiving N in addition to sorafenib is ongoing. Clinical trial information: NCT01271972.
Opportunities and Challenges for Personal Heat Exposure Research
Authors: Evan R. Kuras, Molly B. Richardson, Miriam M. Calkins, Kristie L. Ebi, Jeremy J. Hess, Kristina W. Kintziger, Meredith A. Jagger, Ariane Middel, Anna A. Scott, June T. Spector, Christopher K. Uejio, Jennifer K. Vanos, Benjamin F. Zaitchik, Julia M. Gohlke, David M. Hondula
Journal: Environmental Health Perspectives (2017)

Background: Environmental heat exposure is a public health concern. The impacts of environmental heat on mortality and morbidity at the population scale are well documented, but little is known about specific exposures that individuals experience. Objectives: The first objective of this work was to catalyze discussion of the role of personal heat exposure information in research and risk assessment. The second objective was to provide guidance regarding the operationalization of personal heat exposure research methods. Discussion: We define personal heat exposure as realized contact between a person and an indoor or outdoor environment that poses a risk of increases in body core temperature and/or perceived discomfort. Personal heat exposure can be measured directly with wearable monitors or estimated indirectly through the combination of time–activity and meteorological data sets. Complementary information to understand individual-scale drivers of behavior, susceptibility, and health and comfort outcomes can be collected from additional monitors, surveys, interviews, ethnographic approaches, and additional social and health data sets. Personal exposure research can help reveal the extent of exposure misclassification that occurs when individual exposure to heat is estimated using ambient temperature measured at fixed sites and can provide insights for epidemiological risk assessment concerning extreme heat. Conclusions: Personal heat exposure research provides more valid and precise insights into how often people encounter heat conditions and when, where, to whom, and why these encounters occur. Published literature on personal heat exposure is limited to date, but existing studies point to opportunities to inform public health practice regarding extreme heat, particularly where fine-scale precision is needed to reduce health consequences of heat exposure. https://doi.org/10.1289/EHP556
Abstract MP72: Feasibility, Safety and Acceptability of Soy-Based Diet for Pregnant Women: Preliminary Results From a Pilot Randomized Controlled Trial
Authors: Ling Shi, Vidya Iyer, Errol Norwitz, Tiffany A Moore Simas, Nirupa Matthan, Alice Lichtenstein, Laura L Hayman
Journal: Circulation (2018)

Introduction: Previous evidence suggests that soy containing foods may have beneficial effects on lipid and glycemic metabolism due to their biologically active components, including soy protein and isoflavones. Pregnancy is associated with changes in glucose and lipid metabolism, partially attributable to elevated estrogen concentrations. We have previously reported a significant, inverse association between urinary excretion of isoflavones and cardiometabolic risk markers in pregnant women, using data from the National Health and Nutrition Examination Survey (NHANES). Further studies are needed to determine the cardiometabolic health effects of soy intake in pregnant women. Hypothesis: We hypothesize that consumption of soy-based whole foods is safe and acceptable for pregnant women and has beneficial cardiometabolic health effects. Methods: A pilot randomized controlled trial (RCT) was conducted in 30 pregnant women who received counseling to consume either a high-soy or low-soy foods containing diet. Assessments (physical and anthropometric measurements, food frequency questionnaires, fasting blood samples) were conducted at 14 and 28 weeks of pregnancy, and 6 weeks’ postpartum. Monthly follow-up calls were conducted by research team coordinator to assess safety and encourage adherence. Results: Both the high-soy and low-soy groups demonstrated high adherence (80-90%), defined as consuming soy foods ≥ 15 days in the past four weeks for high-soy group and ≤ 5 days for low-soy group. Five subjects in the high-soy group reported adverse events (nausea, vomiting, diarrhea, itchy mouth); all were transient and resolved without sequelae. No adverse events were reported in the low-soy group. Skinfold thickness decreased (-4.8 mm) in the high-soy group and increased (+3.6 mm) in the low-soy group (p=0.04). There was a trend towards lower BMI in the high-soy compared to low-soy group at 28 weeks (+1.4 vs. +3.6 kg/m 2 , respectively, p=0.15) and postpartum (-1.2 vs. +0.6 kg/m 2 , respectively, p=0.14). This decrease in BMI was predominantly a loss of body fat and not lean mass. There were no significant differences between groups in fasting glucose, HDL-C, LDL-C, TG, or VLDL concentrations. Conclusions: In conclusion, results from this pilot RCT support the acceptability and safety of consuming soy-based whole foods during pregnancy. A larger-scale RCT is needed to further elucidate the effects of soy-based foods on cardiometabolic risk factors during pregnancy, as well as the transgenerational effects on their offspring.
Effects of sleep apnoea therapy on blood pressure and metabolism: a CPAP sex gap?
Authors: Frédéric Gagnadoux, Pascaline Priou, Nicole Meslier, Wojciech Trzepizur
Journal: European Respiratory Journal (2017)

Obstructive sleep apnoea (OSA) is a highly prevalent disease characterised by recurrent episodes of complete or partial upper airway obstruction during sleep, leading to intermittent hypoxia and sleep fragmentation. Most recent estimates of OSA prevalence suggest that 13% of men and 6% of women have clinically significant OSA [1, 2]. There is evidence from population-based and clinic-based cohort studies that moderate-to-severe OSA is independently associated with an increased incidence of cardiovascular events [3, 4]. Besides OSA-related variables, comorbid conditions including hypertension and metabolic dysfunction play an important role in the development of cardiovascular diseases in OSA patients [4]. In the clinical setting, it has been estimated that at least half of patients with OSA fulfil the criteria for the metabolic syndrome [5]. Furthermore, the prevalence of metabolic syndrome increases with OSA severity [5, 6]. An independent dose–response relationship has been demonstrated between OSA severity and the features of metabolic syndrome, including visceral adiposity [7], hypertension [8], metabolic dyslipidaemia [6] and impaired glucose metabolism [9, 10]. Considering cardiovascular prevention as a therapeutic objective in OSA patients, it is crucial to determine whether OSA therapy can lead to clinically relevant improvements in blood pressure, and glucose and lipid metabolism. CPAP therapy reduces blood pressure but has no impact on metabolic profile in women with sleep apnoea <http://ow.ly/AAKj30cQb6X>
Electrospun fibrous membranes featuring sustained release of ibuprofen reduce adhesion and improve neurological function following lumbar laminectomy
Authors: Shen Liu, Guoqing Pan, Guangwang Liu, José das Neves, Sa Song, Shuai Chen, Bangjun Cheng, Zhiyong Sun, Bruno Sarmento, Wenguo Cui, Cunyi Fan
Journal: Journal of Controlled Release (2017)
03.03 Serum interleukin 23 in polish patients with systemic lupus erythematosus – association with obesity and peripheral vascular disease
Authors: Katarzyna Fischer, Hanna Przepiera-Będzak, Anna Walecka, Marcin Sawicki, Lidia Ostanek, Iwona Brzosko, Marek Brzosko
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). The aim of this study was to evaluate association between serum levels of IL-23 and vascular involvement in SLE patients. <h3>Materials and methods</h3> Study was performed in 94 SLE patients (82 women and 12 men) aged 19–73 years and in 27 age and gender matched controls. Serum IL-23 was measured with ELISA method using R and D Systems tests. Carotid intima-media thickness and the presence of atherosclerotic plaques in carotid and lower extremities arteries were analysed with B-mode ultrasound. Ankle-brachial and high resistance indexes were measured with Doppler ultrasonography. We took into account classical cardiovascular risk factors (hypertension, dyslipidemia, hyperglycemia, overweight/obesity, smoking, oral contraceptives, positive family history of cardiovascular disease), selected clinical manifestations (cardiovascular, cerebrovascular, lupus nephritis, Raynaud's phenomenon, livedo reticularis, vasculitis, other thromboembolic complications), profile of autoantibodies (antinuclear, antiphospholipid, anti-neutrophil cytoplasmic, anti-endothelial cell). Statistical analysis was performed with: <i>chi</i><sup>2</sup>Yates, <i>chi</i><sup>2</sup>Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. <h3>Results</h3> Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0.0005). Patients with high levels of IL-23 more frequently developed atherosclerosis showed as the presence of plaques in right common femoral artery (OR=10.1; 95% CI:1.2–85.1) and lupus nephritis (OR=3.2; 95% CI:1.1–9.6). Among classical atherosclerotic risk factors only obesity was significantly associated with IL-23 (OR=3.8; 95% CI:1.2–12.3). Immunological characteristics significantly related to IL-23 were anti-phosphatidylethanolamine antibodies (OR=12.7; 95% CI:1.5–108.1) and anti-SS-B antibodies (OR=11.8; 95% CI:1.5–94.8). Association with anti-cardiolipin and anti-prothrombin antibodies was on the border of statistical significance (OR=2.3; 95% CI:0.9–5.7 and OR=8.4; 95% CI:1.0–71.1 respectively). <h3>Conclusions</h3> IL-23 may be involved in lupus nephritis pathogenesis. 2. IL-23 through its significant association with obesity and antiphospholipid antibodies may promote hypercoagulable state contributing to atherothrombosis development in SLE patients.
加齢とテロメア関連:炎症との密接な関係【Powered by NICT】
Authors: Zhang Jingwen, Rane Grishma, Dai Xiaoyun, K Shanmugam Muthu, Arfuso Frank, Samy Ramar Perumal, Lai Mitchell Kim Peng, Kappei Dennis, Kumar Alan Prem, Sethi Gautam
Journal: Ageing Research Reviews (2016)
SP0128 Mri of enthesitis – by conventional and whole-body mri - including quiz cases
Authors: I Eshed
Journal: Annals of the Rheumatic Diseases (2017)

Entheses are sites of attachment of tendons, ligaments, fascia, or capsule into bone, providing a mechanism for reducing stress at the bony interface. Entheses dissipate biomechanical stress and, in doing so, are thought to be subjected to repeated micro traumas. Inflammation of the entheses, enthesitis, is a well-known hallmark of spondyloarthritis (SpA), playing a central role in disease pathogenesis. It can also be associated with degenerative, endocrinologic, metabolic and traumatic conditions. Magnetic resonance imaging (MRI) is a sensitive tool for the detection of early signs of enthesitis in patients with SpA. The MRI features of enthesitis are well described, and include thickened enthesis with altered signal intensity and perientheseal soft tissue edema. Bone marrow edema and erosions at the adjacent bone appear mainly in SpA-associated enthesitis. Contrast material administration improves the reliability, sensitivity and specificity of detecting enthesitis on an MRI. Whole-body (WB) MRI allows assessment of all peripheral and axial joints and entheses from “head-to-toe” in one examination. The promising role of WBMRI in the evaluation of enthesitis in SpA and other rheumatic diseases was evaluated in several cross sectional and prospective studies. Indeed WB MRI was shown to be sensitive in the detection of inflammatory lesions, including enthesitis, on multiple sites, potentially serving as a one stop shop for the estimate of active disease load. In the current presentation, the typical imaging properties of enthesitis on conventional and WB-MRI will be presented along with several challenging quiz cases. <h3>Disclosure of Interest</h3> None declared
PTH-123 In patients with chronic diarrhoea, diagnosing bile acid diarrhoea with a positive sehcat test results in fewer subsequent investigations
Authors: J Turner, SS Pattni, RN Appleby, JR Walters
Journal: Gut (2017)

Introduction  Chronic diarrhoea is a common condition which may result from a number of different disorders, including bile acid diarrhoea. Primary bile acid diarrhoea is found in around 36% of patients with functional diarrhoea or diarrhoea-predominant irritable bowel syndrome, but is often undiagnosed. We hypothesised that a positive diagnosis of bile acid diarrhoea would reduce the need in these patients for subsequent investigations to look for alternative diagnoses.  Method  Patients previously recruited to a prospective study of chronic diarrhoea, who had SeHCAT testing and subsequent follow-up at our institution, were identified and their electronic records were reviewed. The numbers of defined investigations undertaken between 3 months and 5 years after SeHCAT were compared.  Results  90 patients were identified with primary bile acid diarrhoea (SeHCAT  15%, n=54). Follow-up had been performed on 29 and 39 respectively. There was no difference between these groups in the number of previous investigations or the date of the last contact. In the follow-up period, there was no significant difference in the proportion of these patients who had undergone endoscopic procedures (gastroscopy, colonoscopy, sigmoidoscopy). However there was a higher proportion of patients in the SeHCAT-negative group who had undergone other investigations including imaging, physiological tests and blood tests (p=0.037). Use of cross-sectional imaging was significantly higher in this group (p=0.015) with greater proportions having CT (0.44 vs. 0.10) and MRI (0.26 vs. 0.07). Ultrasound use (0.72 vs. 0.55) and the number of blood tests (median 33 vs. 21 tests per patient) were higher in the SeHCAT-negative group whereas the SeHCAT-positive group attended more clinic appointments (p=0.013).  Conclusion  A positive diagnosis of bile acid diarrhoea, made by a SeHCAT test, resulted in reduced use of diagnostic investigations over the subsequent five years.  Disclosure of Interest  J. Turner: None Declared, S Pattni: None Declared, R Appleby: None Declared, J Walters Conflict with: Intercept, Novartis, Conflict with: GE Healthcare
03.05 The tam receptors axl and mer play a protective role in a temporal and spatial manner in inflammatory arthritis
Authors: Claire E.J. Waterborg, Paqui G Través, Silke Beermann, Marije I Koenders, Greg Lemke, Fons A.J. van de Loo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by an inflammatory response in synovial joints. One family of tyrosine kinase receptors that mediates an anti-inflammatory feedback mechanism are Tyro3, Axl and Mer (gene <i>Mertk</i>; TAM). The role of TAM receptors in RA has not been elucidated and we studied the role of Axl and Mer in an experimental model of RA. <h3>Materials and methods</h3> The KRN serum transfer model of arthritis was induced by two intraperitoneal injections of arthritic K/BxN serum in <i>Axl<sup>-/-</sup></i>, <i>Mertk<sup>-/-</sup></i>, <i>Axl<sup>-/-</sup>Mertk<sup>-/-</sup></i>and wild-type (WT) mice. Ankle joints were macroscopically scored for 7 days. At day 0, 2 and 7, ankle and knee joints were isolated for histology and immunohistochemistry. <h3>Results</h3> <i>Mertk<sup>-/-</sup></i> mice had increased macroscopic ankle scores until day 4 whereas <i>Axl<sup>-/-</sup></i> mice had enhanced macroscopic scores from day 4 until day 7. Histology of ankle joints showed significantly more inflammation in <i>Mertk<sup>-/-</sup></i> mice at day 2 and increased arthritis pathology in <i>Axl<sup>-/-</sup></i>mice at day 7, reflecting macroscopic ankle scores. Histological analysis of ankle joints of <i>Axl<sup>-/-</sup>Mertk<sup>-/-</sup></i> mice at day 7 showed enhanced pathology compared to both <i>Axl<sup>-/-</sup></i> and WT mice, indicating an additive effect of Axl and Mer deficiency. In contrast to the ankle joints at day 7, enhanced macroscopic scores and arthritis pathology in knee joints of <i>Mertk<sup>-/-</sup></i>mice, compared to WT mice, was observed. To explain the discrepancy of Axl involvement between ankle and knee at day 7, we examined Axl expression in synovium before the onset of arthritis. The cells in the lining layer of ankle synovium were strikingly Axl positive whereas the synovium of the knee joints was Axl negative. <h3>Conclusions</h3> These findings identify the TAM receptors Axl and Mer as important players in arthritis. The Mer receptor plays a protective role at the onset of arthritis whereas the Axl receptor takes over this role in established disease in ankle joints. In the knee joints, however, Mer but not Axl, plays a prominent protective role, likely due to the lack of Axl in naïve knee joints. These findings highlight differences in topographically distinct synovial joints in inflammatory arthritis.