tbuckley/cabot-search huggingface dataset:
N-cadherin expression and epithelial-to-mesenchyme transition in pancreatic cancer
Authors: Yasushi Shintani, Keith R. Johnson, Margaret J. Wheelock
Journal: Cancer Research (2006)

2765   Loss of E-cadherin expression correlates with an invasive and differentiated phenotype in many carcinomas including pancreatic cancer. Furthermore, E- to N-cadherin “switching” induces epithelial-to-mesenchymal transition (EMT), while plays a crucial role during invasion and metastasis of carcinomas. We have previously shown that N-cadherin expression is associated with invasive potential in cancer. Thus, the purpose of this study was to investigate the role of N-cadherin expression in pancreatic cancer. We used the BxPC-3 pancreatic cancer cell line to generate 3 cell lines: mock transfected cells (neomycin resistance gene), N-cadherin over-expressing cells, and N-cadherin knockdown cells. We transplanted each cell line into the pancreas of nude mice (each group n=6). Examination of the abdominal cavities 8 weeks later revealed that N-cadherin overexpressing cells formed significantly more metastases to the peritoneum than did the other cell lines. Furthermore, histological examination demonstrated micro-metastases in the lung of 4 of 6 mice receiving injections of N-cadherin overexpressing BxPC-3 cells, whereas no metastases were observed in mice that received mock- or N-cadherin knockdown cells. Pancreatic cancer is characterized by an intense fibrotic reaction associated with the tumor, which contains an abundance of type I collagen. This led us to ask whether interactions with type I collagen would up-regulate N-cadherin expression BxPC-3 cells, which would be predicted to increase the metastatic potential of these cells. We found that BxPC-3 cells became flatter and more scattered, and showed increased expression of mesenchymal markers, including N-cadherin, fibronectin and vimentin when cultured on collagen. This was not seen when cells were cultured on non-coated dishes, or dishes coated with fibronectin or laminin. A modified transwell assay showed that cells were more motile in collagen coated transwell dishes as compared to fibronectin coated transwell dishes. This increased cell motility was inhibited by N-cadherin knockdown. Thus, BxPC-3 cells undergo EMT in response to collagen. Changes in phenotype include up-regulation of N-cadherin and increase motility. These data together with the vivo studies suggest that N-cadherin plays a crucial role in promoting the malignant phenotype of pancreatic cancer.
AB0917 Clinical and radiological characterisationof axial psoriatic arthritis
Authors: E. Alonso Blanco-Morales, M. Lisbona Muñoz, J. Bravo-Ferrer Acosta, R. Gil Vélez, E. Rubio Romero, J. Povedano Gómez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Defining axial involvement in psoriatic arthritis (PsA) is a challenge; thus, according to wich criteria used, the differences in prevalence of axial PsA range from 20% to 70%. Two different phenotypes have been suggested in axial PsA. One of them remind us typical Ankylosing Spondylitis (AS) with bilateral sacroiliitis according to the New York modified criteria (mNY) and a strong association with HLA-B27 and another phenotype with more indolent course, with unilateral and asymmetric sacroiliitis and a lower association to HLA B27 <h3>Objectives</h3> To define clinical and radiological characteristics of a cohort of patients with axial PsA with associated sacroiliitis in a third level hospital in southern Spain. <h3>Methods</h3> Cross-sectional study of an axial PsA cohort with sacroiliitis from a third level hospital. Demographic, clinical and radiological variables were collected. Sacroiliitis was defined as: sacroiliitis according to mNY, or unilateral sacroiliitis grade II in X-ray, and/or according to ASAS criteria of positive MRI. We excluded those patients with axial PsA without sacroiliitis according to definition. The statistical package SPSS v21 was used. The qualitative variables were analysed by the Chi2 and Fisher tests, as required. The quantitative variables were analysed by Student's T Test/Mann-Whitney U Test. Statistical significance was considered, values of p&lt;0.05 <h3>Results</h3> Of 209 patients with axial SpA with sacroiliitis according to the definition found, 39 patients with diagnosis of PsA were analysed. The main characteristics of the patients are shown in image 1. Of the 39 patients, 62% did not meet mNY criteria. Regarding the patients who met mNY criteria, those who did not comply them had the following differences (specifying the significance). The initial diagnosis was different from PsA more frequently (40% Vs. 17%, p 0.124). They presented a lower evolution of the disease (7 Vs. 13 years, p 0.052). They presented as initial symptomatology a greater frequency of peripheral arthritis (71% Vs 27%, p 0.03); and consequently, a greater presence of mixed forms (92% Vs 53%, p 0.015). They presented a lower frequency of positive HLAB27 (21 V. 60, p 0.042). No significant differences were found in reference to the presence of extra-articular involvement (dactylitis, uveitis, psoriasis, onychopathy), nor in reference to the presence of related family history (spondyloarthritis, psoriasis, uveitis). <h3>Conclusions</h3> Patients with axial PsA with sacroiliitis according to ASAS criteria of positive MRI/unilateral grade II X-ray sacroiliitis presented more peripheral joint involvement, and less association with HLA B27 compared to patients who did meet mNY criteria. A smaller proportion of patients with axial PsA that meet the mNY criteria suggests a less aggressive structural sacroiliac involvement. <h3>Disclosure of Interest</h3> None declared
Healthy infants harbor intestinal bacteria that protect against food allergy
Authors: Taylor Feehley, Catherine H. Plunkett, Riyue Bao, Sung Min Choi Hong, Elliot Culleen, Pedro Belda-Ferre, Evelyn Campbell, Rosita Aitoro, Rita Nocerino, Lorella Paparo, Jorge Andrade, Dionysios A. Antonopoulos, Roberto Berni Canani, Cathryn R. Nagler
Journal: Nature Medicine (2019)
Outcomes of Myeloma Patients with t(11;14) Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) Induction Therapy
Authors: Jonathan L Kaufman, Nisha Joseph, Vikas A. Gupta, Charise Gleason, Craig C Hofmeister, Leonard Heffner, Madhav V Dhodapkar, Sagar Lonial, Lawrence H. Boise, Ajay K Nooka
Journal: Blood (2018)
SAT0176 Contribution of cd4+ t cells decrease on clinical response to rituximab in rheumatoid arthritis
Authors: A. Bensalem, D. Mulleman, G. Thibault, N. Azzopardi, G. Paintaud, P. Goupille, D. Ternant
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Rituximab (RTX) is approved for the treatment of rheumatoid arthritis (RA), but there is a large inter-individual variability in clinical response. A better response was previously associated with a decrease in CD4+ T cell counts [1, 2]. <h3>Objectives:</h3> This study aimed at analyzing the contribution of CD4+ T cell decrease in the clinical response in RA patients treated with RTX. <h3>Methods:</h3> In this retrospective monocentric observational study, 52 patients were assessed. All patients had received 2 infusions of 1000 mg of RTX 2 weeks apart. Disease activity score in 28 joints (DAS28) was used as clinical endpoint. RTX serum concentrations, peripheral blood CD4+ counts, and DAS28 were measured before and after each RTX infusion and at 3, 6 and 9 months after last infusion. A population PK-PD model, including a physiological turnover and direct response model, was developed to estimate the probability of CD4+ counts decrease. The turnover model was used to describe the effect of RTX on CD4+ T-cell counts, and the direct model was used to describe both RTX and CD4 + T cell count effect on DAS28. <h3>Results:</h3> The probability of CD4+ counts decrease was estimated at 0.75. Patients with a CD4+ decrease had a higher &amp;x25B3;DAS28 than the patients without CD4+ decrease, with a maximal &amp;x25B3;DAS28 of -1.34 and -0.64 in patients with and without CD4+ cell decrease, respectively. Moreover, at M6, patients with CD4+ cell decrease had a median DAS28 of 3.5 (IQR: 2.7 – 4.4), among them 39.5 % with low disease activity (DAS28≤3.2) and 22.3 % in remission (DAS28&lt;2.6). At the same time point, median DAS28 of patients without CD4+ cell decrease was 4.3 (IQR: 3.5 – 5.1), among them 17.7 % with low disease activity, and 8.6 % in remission <b>(see Figure 1 Box plot of DAS28 in patients with and patients without CD4+ decrease.).</b> <h3>Conclusions:</h3> This is the first study to quantify the contribution of CD4+ T cell decrease to the clinical response in RA patients treated with RTX. <h3>References</h3> [1] Melet J, et al. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum2013. [2] Lavielle M, et al. Repeated decrease of CD4+ T-cell counts in patients with rheumatoid arthritis over multiple cycles of rituximab treatment. Arthritis Res Ther2016. <h3>Disclosure of Interest:</h3> A. Bensalem: None declared, D. Mulleman Grant/research support from: Abbvie and Nordic Pharma, Consultant for: MSD, Novartis, UCB and Pfizer, G. Thibault: None declared, N. Azzopardi: None declared, G. Paintaud Grant/research support from: Novartis, Roche Pharma, Genzyme, MSD, Chugai and Pfizer, P. Goupille Consultant for: Abbvie, Biogaran, BMS, Hospira, Janssen-Cilag, MSD, Pfizer, Sanofi-Genzyme and UCB, D. Ternant Consultant for: Amgen and Sanofi
AB1205 Precision of serum and plasma testing in anti-cardiolipin and anti-Β2 glycoprotein-1 antibodies
Authors: M.M. Pham, G. Orsolini, C.S. Crowson, M.R. Snyder, R.K. Pruthi, K.G. Moder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-cardiolipin (aCL) and anti-β2 glycoprotein-1 (β2GP1) antibody ELISA testing may be performed on serum, plasma, or both in accordance to the manufacturers' suggested protocols. There exists some variability in manufacturers' preference for serum or plasma. Various societal guidelines have published a preference for serum over plasma; however, there is scarcity of data assessing reproducibility between serum and plasma in aCL or β2GP1 testing. <h3>Objectives</h3> To determine reproducibility of aCL and β2GP1 testing between serum and plasma samples obtained in a routine clinical setting. <h3>Methods</h3> Patients with clinical serum draws for IgG/IgM aCL and β2GP1 antibodies were identified, and same-day, citrated plasma samples were obtained for repeat ELISA testing (QUANTA Lite, INOVA Diagnostics, San Diego, CA). Quantitative levels were determined for each isotype and further stratified into Negative (&lt;15.0 GPL/MPL or U/mL), Weakly Positive (15.0–39.9 GPL/MPL or U/mL), or Positive (≥40.0 GPL/MPL or U/mL) reference categories. Differences were compared using paired t-tests. Agreement between the reference categories were compared by kappa coefficients. <h3>Results</h3> Fifty patients were identified for study with 50 and 40 samples eligible for repeat aCL and β2GP1 plasma testing, respectively. Mean age was 49±18 years. 70% were female, 86% were Caucasian, 22% with systemic lupus erythematosus and 22% with antiphospholipid syndrome. As shown in Table 1, quantitative levels tended to be slightly higher in serum than plasma. Although a statistically significant difference was found for most of the antibodies tested, the difference between serum and plasma values were generally small. There was good agreement in reference category between serum and plasma. Kappa coefficients ranged from 0.70 to 1.00. <h3>Conclusions</h3> There appears good reproducibility of IgG/IgM aCL and β2GP1 antibody ELISA results between serum and plasma. <h3>References</h3> [1] Lakos G, Favaloro EJ, Pierangeli SS, et al. Arthritis &amp; Rheumatology. 2012 Jan 1;64(1):1–0. [2] Lewis DA, Pound ML, Ortel TL. Journal of Thrombosis and Haemostasis. 2006Jan 1;4(1):265–7. [3] Wong RC, Favaloro EJ, Mallon D, et al. Pathology. 2008Jan 1;40(1):58–63. [4] Wong RC, Gillis D, Sturgess A, et al. Pathology. 2004Feb 1;36(1):63–8. <h3>Acknowledgements</h3> Special thanks to Susan Hartzler, Cory Blixt, Serena Navitskas, and Diane Meier. <h3>Disclosure of Interest</h3> None declared
Is exercise therapy for femoroacetabular impingement in or out of FASHIoN? We need to talk about current best practice for the non-surgical management of FAI syndrome
Authors: Joanne L Kemp, Matthew G King, Christian Barton, Anthony G Schache, Kristian Thorborg, Ewa M Roos, Mark Scholes, Alison Grimaldi, Adam I Semciw, Matthew Freke, May Arna Risberg, Michael P Reiman, Susan Mayes, Tania Pizzari, Joshua J Heerey, Peter R Lawrenson, Lina Holm Holm Ingelsrud, Kay M Crossley
Journal: British Journal of Sports Medicine (2019)

Femoroacetabular impingement (FAI) syndrome is an important condition that can be managed by physiotherapists, together with other health professionals. ‘Failed conservative care’ for FAI syndrome is a reason for surgery being introduced into the shared decision-making process with the patient. Two recent landmark randomised controlled trials (RCTs) have brought new data to that patient-centred discussion—‘Would you consider surgery for this condition? What is the likelihood that your impairments will be appreciably improved with arthroscopic hip surgery followed by rehabilitation?’1 2 As clinicians delivering exercise therapy, we need to reflect on the question ‘are we providing high-quality, outcome driven, exercise therapy programs to these patients?’

Contemporary exercise therapy should be informed by patient needs and preferences, and address patient-specific impairments. Specific hip-related impairments in FAI syndrome include hip muscle weakness, particularly hip adductors3; lower trunk strength bilaterally3; poor dynamic single-leg balance3; and lower functional task performance3 in non-operative, preoperative and postoperative groups. None of these impairments can be corrected by surgery alone. These impairments could be best addressed with graded exercises.3 

In this editorial, we question whether the non-surgical treatment programmes evaluated in the recent RCTs included the type, dose and progression of exercises needed to generate a meaningful change in strength and function. In both studies, the physiotherapist-led groups did …
Abstract 14190: Longer Time in Therapeutic Blood Pressure Range Protects Against Major Adverse Cardiovascular Events and All-Cause Mortality in Patients With Hypertension: A Post-Hoc Analysis of SPRINT
Authors: Nayyra Fatani, Dave L Dixon, Benjamin W Van Tassell, Leo F Buckley, John Fanikos
Journal: Circulation (2018)

Introduction: Intensive blood pressure (BP) lowering reduces the risk of major adverse cardiovascular events (MACE) in high risk patients. However, BP varies over the short- and long-terms and the ...
THU0454 Increased fdg uptake of the muscles in polymyalgia rheumatica (PMR)
Authors: M.A. Cimmino, N. Vecchiola, M. Bauckneht, D. Camellino, S. Morbelli, S. Paolino, M. Cutolo, G. Sambuceti
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> PMR is an inflammatory disease affecting the shoulder and pelvic girdles of elderly patients. Its causes, development mechanisms and anatomical targets of inflammatory damage are still elusive. Synovitis, vasculitis, and bursitis have all been demonstrated in PMR but data on muscles are scanty. <h3>Objectives</h3> Our study evaluated muscular uptake at FDG-PET/CT in patients with PMR. <h3>Methods</h3> Fifty patients with PMR diagnosed according to Bird et al criteria and 50 age- and sex-matched control patients without inflammatory disorders, who underwent FDG-PET/CT to rule out malignancy, were studied. Standard FDG-PET/CT examination was performed and its results were evaluated by both qualitative scoring, on a 5-grade scale from 0 (no uptake) to 4 (clearly higher than liver uptake), and analysis of the standardised uptake value (SUV max and mean) in a ROI placed on the deltoid, byceps, gluteus and quadriceps muscles. A ROI of the joints and bursae was also designed and the SUV calculated. The muscle ROIs were positioned distant from the corresponding joints to avoid interference from possible articular or periarticular uptake. Demographic, clinical and laboratory data were collected. <h3>Results</h3> PMR patients showed an uptake higher than that of controls in the deltoid (p=0.0004), gluteus (p=0.015), and quadriceps (p=0.009), but not in the biceps (p=0.06) muscles. The semiquantitative SUV evaluation was consistent for the deltoid (SUV mean, p=0.047) and gluteus (SUV mean, p=0.01; SUV max, p=0.006) muscles. There was no correlation between muscle uptake and that of the adjoining joint. Similarly, no correlation was found between muscle uptake and demographic, clinical and laboratory (CRP, ESR) findings. <h3>Conclusions</h3> PMR show muscular inflammation at FDG-PET/CT, which does not derive from the nearby joints or periarticular tissues. A clearly defined myositis is not probable, because creatine kinase concentrations are normal in PMR. However, muscle inflammation may contribute to the global inflammatory burden and symptoms of patients with PMR. <h3>Disclosure of Interest</h3> None declared
SAT0029 Impact of glucocorticoids on sirtuin 1 expression and proinflammatory cytokine production in rats with adjuvant-induced arthritis
Authors: D. Wendling, W. Abbas, A. Kumar, S. Pasquereau, F. Verhoeven, C. Prati, C. Demougeot, G. Herbein
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sirtuin 1 (SIRT1) is a class III histone deacetylase which could play a critical role in several biological functions including lifespan, stress, and inflammation. <h3>Objectives</h3> Our main objective was to evaluate SIRT1 expression in peripheral blood mononuclear cells (PBMCs) isolated from rats with adjuvant induced arthritis (AIA) treated or not with low and high doses of glucocorticoids (GCs). Our second aim was to determine the production of proinflammatory cytokines such as tumour necrosis factor alpha (TNF), interleukin-1 beta (IL-1) and interleukin-6 (IL-6) in tissues (liver and spleen) of these rats, and to assess a potential correlation between SIRT1 expression and the production of cytokines in tissues of rats with AIA treated or not with low and high doses of glucocorticoids. <h3>Methods</h3> We performed a study on rats with AIA treated with low and high doses of prednisolone or left untreated. The SIRT1 expression was quantified in PBMCs using western blotting. Levels of proinflammatory cytokines TNF, IL-1 and IL-6 were assessed in liver and spleen from rats with AIA treated with GCs or left untreated using an ELISA assay. <h3>Results</h3> SIRT1 expression was increased in PBMCs isolated from rats with AIA treated with LD-GCs and HD-GCs compared to untreated animals. In culture, resveratrol enhanced the SIRT1 expression in PBMCs isolated from rats with AIA in a dose-dependent manner. We observed increased levels of TNF alpha in liver (correlated with SIRT1 expression) and decreased IL-6 levels in spleens (negatively correlated with SIRT1 expression) from rats with AIA treated with LD-GCs and HD-GCs compared to controls. <h3>Conclusions</h3> SIRT1 expression is increased in PBMCs isolated from rats with AIA and treated with GCs parallel to decreased levels of IL-6 in spleen and increased levels of TNF in liver. This study shows that the SIRT 1 expression is measurable in circulating PBMCs of rats with AIA and is increased under GC treatment. The potential epigenetic effect of GCs on production of proinflammatory cytokines in tissues, namely liver and spleen, is also studied. <h3>Disclosure of Interest</h3> None declared
HBV Genotype-Specific Levels of Hepatitis B Surface Antigen Improve HBV Phenotype Definition
Authors: Willem P. Brouwer, Qian Zhao, Bettina E. Hansen, Daryl Lau, Mandana Khalili, Norah A. Terrault, Adrian M. Di Bisceglie, Robert P. Perrillo, Michael W. Fried, David Wong, Jordan J. Feld, Steven H. Belle, Harry L.A. Janssen, Jianghe Niu, Asad Javaid, Bilal Nasir, Ammu Susheela, Imad Nasser, Nifasha Rusibamayila, Cara Foley, Alisha C. Stahler, Linda Stadheim, John Lake, Philip Lacher, Kathryn Rushing, Rosemary A. Nagy, Jacki Cerkoski, Debra DeMarco Shaw, Lisa Kessels, Michael K. Klebert, Seham Noureldin, Danie La, Lucie Liu, Diana Kaznowski, Jiayun Chen, Doinita Vladutu, Orlando Cerocchi, Debra Rowan, Sheila Bass, Barbara Lilly, Samuel French, Velma Peacock, Ashley Shobe, Rayshawnda Davis, Romuald Kuras, Claudia Ayala, Ivy Lau, Veronika Podolskaya, Anna von Bakonyi, Nata DeVole, Barbara McKenna, Karen Choi, Kelly Oberhelman, Sravanthi Kaza, Abigail Bowen, Sumodh Kalathil, Leslie Huddleston, Richmond Wong, A. Sidney Barritt, Tiffany Marsh, Vikki Metheny, Danielle Cardona, Velimir A. Luketic, Paula G. Smith, Charlotte Hofmann, Alycia Wolfstone, Jody Mooney, Lupita Cardona-Gonzalez, Nancy Fryzek, Elenita Rivera, Nevitt Morris, Vanessa Haynes-Williams, Amy Huang, Averell H. Sherker, Rebecca J. Torrance, Sherry R. Hall, Mary E. Valiga, Keith Torrey, Danielle Levine, James Keith, Michael Betts, Luis J. Montaner, Frani Averbach, Tamara Haller, Regina Hardison, Stephanie Kelley, Sharon Lawlor, Hsing-Hua (Sylvia) Lin, Stephen Liu, Manuel Lombardero, Andrew Pelesko, Donna Stoliker, Melissa Weiner, Ella Zadorozny
Journal: Clinical Gastroenterology and Hepatology (2019)
SAT0372 Increased carotid intima-media thickness in hyperuricemic individuals may be explained by hyperhomocysteinemia associated with renal dysfunction
Authors: S. Choi, J.H. Park, J.-S. Song, E.-J. Kang, K.-H. Lee
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Both hyperuricemia and hyperhomocysteinemia are known to be associated with the deterioration of vascular endothelial function and are regarded as important risk factors for atherosclerotic vascular diseases. However, there has been no report about the relationship between homocysteine (Hcy) and atherosclerosis in patients with hyperuricemia. <h3>Objectives</h3> In this study, we evaluated the relationship between the carotid IMT and various clinical parameters including renal function and serum Hcy level in patients with hyperuricemia, and investigated the possible mechanism of how hyperuricemia is related with the increase of carotid IMT. <h3>Methods</h3> A total of 1228 subjects who visited the health promotion centre of hospital were enrolled in this study. All subjects completed both carotid ultrasonography and laboratory measurement, including serum Hcy levels and renal function. Serum Hcy levels were measured by a competitive immunoassay using direct chemiluminescent. Carotid IMT was evaluated by B-mode carotid ultrasonography. <h3>Results</h3> Hyperuricemic patients showed higher carotid IMT values compared with normouricemic patients (1.12±0.64 mm vs. 1.02±0.50 mm, p<i>=</i>0.043). The serum Hcy levels were significantly higher in the hyperuricemic group than in the normouricemic group (13.39±4.42 μmol/L vs. 11.69±3.65 μmol/L, p<i>&lt;</i>0.001). In patients with hyperuricemia, serum uric acid levels were negatively correlated with estimated glomerular filtration rates (eGFR) (<i>γ</i>=−0.334, p<i>&lt;</i>0.001), and eGFR were negatively correlated with serum Hcy levels (; <i>γ</i>=−0.490, p<i>&lt;</i>0.001). Carotid IMT was correlated with serum Hcy levels (<i>γ</i>=0.196, p<i>=</i>0.008), and atherosclerotic changes of carotid artery measured by carotid ultrasonography increased 1.09-fold (OR, 95% CI 1.006–1.185, p<i>=</i>0.036) per 1 μmol/L difference in serum homocysteine levels. In multivariate linear regression analysis, carotid IMT was affected by reduced eGFR (<i>β</i>=−0.263, p<i>=</i>0.002). <h3>Conclusions</h3> Carotid IMT was higher in patients with hyperuricemia than in normouricemic individuals. This study suggests that impairment of the renal function in patients with hyperuricemia may induce the increase in carotid IMT via increased serum Hcy levels. <h3>Disclosure of Interest</h3> None declared