tbuckley/cabot-search huggingface dataset:
Characterizing the interaction between radiation sensitivity and epidermal growth factor receptor inhibition in prostate cancer cell lines
Authors: Rex Cheung, Xiaochun Zhang, Matthew Wagener, Bingliang Fang, Joe Chang
Journal: Cancer Research (2005)

975  Background Radiotherapy is an accepted curative treatment modality of prostate cancer. Epidermal growth factor receptor (EGFR) pathway has rich potential to be used for targeted radiation sensitization. However, the data on the interaction between radiation sensitivity and EGFR inhibition are scarce in prostate cancer. Here we characterized the interaction of EGFR inhibition and radiation sensitivity of prostate cancer cell lines. Materials and Methods We tested the effects of epidermal growth factor (EGF) and anti-EGFR antibody (C225) on Du145 and LNCaP prostate cancer cell lines. When radiation (RAD) was used, the cells were γ-irradiated with a 137Cs source to various doses (Gy). The cell viability and growth were assessed with XTT and clonogenic assays. Optical absorption of XTT was measured at 490nm. The necrotic and apoptotic components of cell death were quantified using flow cytometry with dual propidium iodide (PI) and AnnexinV:FITC labeling. Flow cytometric DNA analysis was performed to assess the effects of treatments on the cell cycle progression. The activation of apoptotic Caspase pathways and EGFR downstream AKT and MAPK pathways was assessed using Western blot. Statistical routines included t-test and one-way ANOVA were used to compare sample means and variances. General linear model (GLM) was used to analyze the main effects and interactions of the treatment factors. Statistical significance was defined as p
OP0295-PARE ‘kweek begrip’: the launch of our creative campaign across the netherlands on world arthritis day aims to increase awareness about rmds in general and people living with rmds in particular
Authors: S. De Jong
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> With two million patients, RMDs are one of the most common chronic diseases in the Netherlands. A 2016 Nivel survey showed that 50% of all RMD patients deal with people who know too little about RMDs in order to understand their situation. RMDs are not always visible, and symptoms may vary from day to day. This often leads to friends, colleagues, neighbours and even relatives showing incomprehension. For RMD patients this can lead to loneliness, insecurity and a sense of not being accepted. Understanding RMDs and being able to show compassion starts with knowing about RMDs. <h3>Objectives</h3> By launching a national creative campaign about incomprehension, the Dutch Arthritis Foundation aims to raise general awareness of RMDs to promote understanding of people with a RMD and to reduce their sense of loneliness. <h3>Methods</h3> The Dutch Arthritis Foundation started its campaign on World Arthritis Day: ‘Grow awareness, plant a bulb!’. To ‘grow understanding’, we created two special tulip bulb fields, one online and one offline, for participants to plant the special ‘Anita Witzier’ tulip bulb. Anita Witzier is a well-known Dutch television host who suffers from rheumatoid arthritis. She has been ambassador for the Dutch Arthritis Foundation since 2001. With the help from 70% of all local RMD patient organisations and a number of garden centres, we handed out a total of 15 000 bags of tulip bulbs across the Netherlands. The campaign kick-off was on World Arthritis Day. The event, held on a tulip breeder’s field, hosted presentations about incomprehension, and served to share real-life stories. We also developed a website where people could plant bulbs digitally. Every week, participants receive a video, cartoon, update or article with information about RMDs. The campaign will run until 21 May 2018 when the (real-life) tulips will bloom in our RMD field. All participants can then visit the field to pick a bunch of flowers. <h3>Results</h3> The campaign received a great deal of national media attention on WorldArthritisDay, and featured on television programmes, in newspapers and on online platforms. 8000 people have since signed up for the online tulip field, sharing the information with others in their network. The campaign site drew 68 000 visitors between 12Oc and 31Oc tober. The campaign also resonated with people on Facebook. In October, our campaign posts reached 1,869,000 visitors, with more than 65 000 interactions (respond, share, like, watch video, conversion to campaign site). <h3>Conclusions</h3> Raising awareness for incomprehension can be difficult. A creative approach can help to kickstart a public debate. Responses generally show that people with RMDs appreciate this complicated subject being put on the map. <h3>Disclosure of Interest</h3> None declared
FRI0369 Pregnancy outcomes in women with antiphospholipid antibodies: interim results from a single centre cohort study
Authors: K. Schreiber, M. Frishman, M.J. Cuadrado, K. Breen, S. Robinson, B.J. Hunt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Persisting antiphospholipid antibodies (aPL) are associated with adverse obstetric events including recurrent miscarriage, late fetal loss or early delivery due to pre-eclampsia or placental insufficiency (obstetric APS) and also thrombosis. We are a tertiary referral centre for those with aPL, and have a management protocol for women with aPL during pregnancy and the puerperium with the aim of preventing obstetric complications and maternal thrombosis. <h3>Objectives</h3> To report the fetal and maternal outcomes from a single centre cohort of 511 pregnancies in 372 women over a period of eight years. <h3>Methods</h3> This is an ongoing retrospective observational study registered as an audit. Data was collected from clinic lists attending the pregnancy clinic at the Thrombosis centre of St. Thomas' Hospital in London, UK between Jan 2010 to December 2017. Women persistently positive for aPL were included if pregnancy outcome data was available. <h3>Results</h3> 511 pregnancies in 372 women were included in the study (table 1). The overall live birth rate was 78.9%. Pregnancy outcomes are outlined in table 2. <h3>Conclusions</h3> These results from the largest single centre cohort reported show that using our management protocol, nearly 80% of women with aPL had a successful pregnancy outcome. <h3>Disclosure of Interest</h3> None declared
AB0347 Body composition in patients with rheumatoid arthritis kazakh nationality
Authors: G. Gabdulina, A. Tokarev, D. Mussabaeva
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chronic inflammation in rheumatoid arthritis (RA) leads to a decrease in fat and muscle mass [Baker J.F., Von Feldt J. Mostoufi-Moab S. et al., 2014 Low muscle mass in RA is considered as the main criterion of sarcopenia. Recently, much attention has been paid to various phenotypes of sarcopenia, among which osteopenic sarcopenia, sarcopenic obesity and osteosarcopic obesity (most unfavourable in terms of functional disorders) are distinguished. In the modern literature there are works devoted to changes in the composition of the body in the aspect of abdominal obesity and its influence on cardiovascular risk in RA [Crowson C.S., Myasoedova E., Davis J.M., 2011). Studies with the evaluation of muscle mass and sarcopenia in RA are few. In Kazakhstan, the composition of the human body was not studied. <h3>Objectives</h3> The purpose of the study was to study the body composition (muscle and fat mass) of patients with RA of Kazakh nationality using bioelectrical impedance analysis. <h3>Methods</h3> In our study we used Bioimpedance analyzer 101 (BIA 101, Italy). Bioimpedansometry was performed in 585 participants, including 295 patients with RA and 290 of their siblings. <h3>Results</h3> In patients with RA, in contrast to the comparison group (sibs), BMI (probands – 25.34±5.1, siblings – 24.86±4.45), the girth of the waist and hips were slightly higher than those of the siblings. The ratio of RT/OB in both groups was virtually the same. At the same time, a decrease in the lean mass was found (probands – 45.37±12.2, siblings – 48.67±11.01), which, in all probability, is due to sarcopenia. The presence of sarcopenia is also confirmed by a decrease in the sarcopenia index (probands 0.6884±0.1, sibs 0.6947±0.1). On the contrary, the fat content of RA patients is higher than that of siblings. <h3>Conclusions</h3> Thus, in our patients cachexia is formed in RA, which is characterised by loss of muscle mass with the preservation or even growth of fat mass, which stabilises body mass indexes, and in some cases even leads to its increase (so-called cachexial obesity). <h3>References</h3> [1] Baker JF, Von Feldt J, Mostoufi-Moab S, et al. Deficits in muscle mass, muscle density, and modified associations with fat in rheumatoid arthritis. Arthritis Care Res (Hoboken)2014;66(11):1612–18. [2] Crowson CS, Myasoedova E, Davis JM 3rd, et al. Increased prevalence of metabolic syndrome associated with rheumatoid arthritis in patients without clinical cardiovascular disease. J Rheumatol2011;38(1):29–35. <h3>Disclosure of Interest</h3> None declared
Taming autoimmunity: Translating antigen-specific approaches to induce immune tolerance
Authors: José M. Carballido, Pere Santamaria
Journal: The Journal of Experimental Medicine (2019)

José M. Carballido, Executive Director at Novartis Institutes for BioMedical Research, and Pere Santamaria, Professor of Immunology at the University of Calgary and Founder of Parvus Therapeutics Inc., discuss the opportunities and challenges of translating antigen-specific approaches for autoimmunity with an emphasis on the need for scientific rigor in the preclinical stage.
Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer
Authors: Christophe Mariette, Sheraz R. Markar, Tienhan S. Dabakuyo-Yonli, Bernard Meunier, Denis Pezet, Denis Collet, Xavier B. D’Journo, Cécile Brigand, Thierry Perniceni, Nicolas Carrère, Jean-Yves Mabrut, Simon Msika, Frédérique Peschaud, Michel Prudhomme, Franck Bonnetain, Guillaume Piessen
Journal: New England Journal of Medicine (2019)

Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive esophagectomy results in lower morbidity than open esophagectomy is unclear.
THU0047 1,25(OH)2d3 and dexamethasone additively suppress synovial fibroblast activation by ccr6+ th memory cells and enhance the effect of tnf-alpha blockade
Authors: W. Dankers, W. Dankers, N. Davelaar, P.S. Asmawidjaja, A.M. Mus, J.M. Hazes, E.M. Colin, E. Lubberts
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Despite improvement in treatment of rheumatoid arthritis (RA) over the past decades, insufficient treatment response and treatment resistance in many patients demonstrate the need to develop new therapeutic strategies. Chronic synovial inflammation could be suppressed by targeting activation of RA synovial fibroblasts (RASF) by for example IL-17A-producing CCR6 +T helper memory (memTh) cells. Previously, we have shown that dexamethasone (DEX) combined with the active vitamin D metabolite 1,25(OH)<sub>2</sub>D<sub>3</sub> reduces pathogenicity of memTh cells. <h3>Objectives</h3> To study the additive effect of 1,25(OH)<sub>2</sub>D<sub>3</sub> and DEX on suppressing the pro-inflammatory loop between RASF and CCR6 +memTh cells and explore potential therapeutic applications. <h3>Methods</h3> CCR6 +memTh cells from PBMC of healthy donors or treatment-naïve early RA patients were cultured alone or with RASF from established RA patients for three days and treated with or without 1,25(OH)<sub>2</sub>D<sub>3</sub>, DEX or etanercept. Treatment effects were assessed using ELISA and flow cytometry. <h3>Results</h3> CCR6 +memTh produces less of the pro-inflammatory cytokines IL-17A, IL-22 and IFNγ upon exposure to 1,25(OH)<sub>2</sub>D<sub>3</sub>, and to a lesser extent by DEX. TNFα was only inhibited by the combination of 1,25(OH)<sub>2</sub>D<sub>3</sub> and DEX. In contrast, in RASF cultures DEX was the strongest inhibitor of IL-6, IL-8 and tissue-destructive enzymes. As a result, 1,25(OH)<sub>2</sub>D<sub>3</sub> and DEX additively inhibited inflammatory mediators in CCR6 +memTh RASF co-cultures. Interestingly, low doses of mainly DEX, but also 1,25(OH)<sub>2</sub>D<sub>3</sub>, combined with etanercept better suppressed synovial inflammation in this co-culture model compared to etanercept alone. <h3>Conclusions</h3> This study suggests that 1,25(OH)<sub>2</sub>D<sub>3</sub> and DEX additively inhibit synovial inflammation through targeting different pro-inflammatory mechanisms. Furthermore, low doses of DEX and 1,25(OH)<sub>2</sub>D<sub>3</sub> enhance the effect of TNFα blockade in inhibiting RASF activation, providing a basis to improve RA treatment. <h3>Disclosure of Interest</h3> None declared
The Hepatitis C Virus Care Continuum: Linkage to Hepatitis C Virus Care and Treatment Among Patients at an Urban Health Network, Philadelphia, PA
Authors: Catelyn Coyle, Anne C. Moorman, Tyler Bartholomew, Gary Klein, Helena Kwakwa, Shruti H. Mehta, Deborah Holtzman
Journal: Hepatology (2019)

Improving care and treatment for persons infected with hepatitis C virus (HCV) can reduce HCV-related morbidity and mortality. Our primary objective was to examine the HCV care continuum among patients receiving care at five federally qualified health centers (FQHCs) in Philadelphia, PA, where a testing and linkage to care program had been established. Among the five FQHCs, one served a homeless population, two served public housing residents, one served a majority Hispanic population, and the last, a "test and treat" site, also provided HCV treatment to patients. We analyzed data from electronic health records of patients tested for HCV antibody from 2012 to 2016 and calculated the percentage of patients across nine steps of the HCV care continuum ranging from diagnosis to cure. We further explored factors associated with successful patient navigation through two steps of the continuum using multivariable logistic regression. Of 885 chronically infected patients, 92.2% received their RNA-positive result, 82.7% were referred to an HCV provider, 69.4% were medically evaluated by the provider, 55.3% underwent liver disease staging, 15.0% initiated treatment, 12.0% completed treatment, 8.7% were assessed for sustained virologic response (SVR), and 8.0% achieved SVR. Regression results revealed that test and treat site patients were significantly more likely to be medically evaluated (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 1.82-4.17) and to undergo liver disease staging (aOR, 1.92; 95% CI, 1.02-2.86) than patients at the other FQHCs combined. Conclusion: In this US urban setting, over two thirds of HCV-infected patients were linked to care; although treatment uptake was low overall, it was highest at the test and treat site; scaling up treatment services in HCV testing settings will be vital to improve the HCV care continuum.
Tim Spector: Butter or margarine? Food religion challenged
Authors: Tim Spector
Journal: BMJ (2019)

Over a hundred academics recently signed a letter to British Journal of Sports Medicine and BMJ editors criticising them for their “pro-butter” stance and for publishing a “biased” editorial which claimed that the effect of saturated fats on cardiovascular health was grossly exaggerated. A rebuttal followed. What should have been a sensible scientific debate degenerated into a dispute over bias, integrity, and beliefs.

There is certainly a touch of the religious wars about these debates, and much of this is because of who controls the sacred nutritional guidelines. The current guidelines in the US and UK are similar. Both have areas of common consensus that few disagree with—such as eating fewer calories, eating more plants, eating less processed food, and drinking fewer sugary drinks—but when it comes to saturated fat, there is much less consensus.

The fat-diet-heart hypothesis is far from simple. The original idea that cholesterol in food was to blame …
Erythropoietin (EPO) Regulates Bone Mass Via EPO Receptors on Myeloid and Lymphocytic Cells
Authors: Sahar Hiram-Bab, Albert Kolomansky, Naamit Deshet-Unger, Nathalie Ben-Califa, Tamar Liron, Martina Rauner, Ben Wielockx, Moshe Mittelman, Howard S. Oster, Yankel Gabet, Drorit Neumann
Journal: Blood (2018)
FRI0449 Overlap myositis and primary myositis: clinical outcomes and prognosis
Authors: L. Nuño, B.E. Joven, P.E. Carreira, J. Martínez Barrio, V. Maldonado-Romero, C. Larena-Grijalba, I. Llorente Cubas, E.G. Tomero, M.C. Barbadillo-Mateos, P. García de la Peña Lefebvre, L. Ruiz-Gutiérrez, J.C. López-Robledillo, H. Moruno-Cruz, A. Pérez, T. Cobo-Ibáñez, R. Almodóvar González, M.J. García-de Yébenes, L. Lojo, F.J. López-Longo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Among the subtypes of idiopathic inflammatory myopathy (IIM), it has been recognised that primary polymyositis (PM) and primary dermatomyositis (DM) have a worse prognosis than overlap syndrome (OM). However, the benign course of OM has not been confirmed in other studies. The identification of specific characteristics that could allow a correct classification may be important for its prognosis. <h3>Objectives</h3> To analyse clinical characteristics and survival of patients diagnosed with OM, and to compare if there are differences with other IIM subgroups in a multicentric cohort. <h3>Methods</h3> Retrospective, multicentric longitudinal observational study of a cohort of patients followed between January 1980 and December 2014, with a diagnosis of MII. The patients were divided into 2 groups: OM and primary idiopathic inflammatory myositis (PIIM), which included PM and DM. Patients classified as OM had to meet IIM criteria and criteria for rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) or primary Sjögren’s syndrome (SS). <h3>Results</h3> The present study included a total of 348 patients (98 OM, 250 PIIM). The connective tissue diseases associated with OM were: MCTD in 32 (32.7%), SSc in 29 (29.6%), SLE in 21 (21.4%), RA in 8 (8.2%) and SS in 8 (8.2%). Patients with OM showed remarkable differences compared to PIIM. In general, OM exhibited more extramuscular involvement and more complications, with more serious infections (41% vs. 24%, p&lt;0.001) and higher mortality (31% vs. 20%, p=0.043). In the multivariate study of mortality prognostic factors, the overlap syndrome contributed significantly to a higher mortality (OR 5.56 (95%IC 2.32–13.23); p&lt;0.0001). <h3>Conclusions</h3> In the REMICAM registry of 348 inflammatory myopathies, 98 cases of myositis with overlap syndrome have been included, presenting with more extramuscular complications, more severe infections and higher mortality than other myopathies. It would be important to identify these patients at the onset of the disease, in order to closely monitor for development of possible complications. <h3>Disclosure of Interest</h3> None declared
OP0263 Claudin-11 regulates bone homeostasis via bidirectional ephb4-ephrinb2 signalling
Authors: C.-H. Lee, J.M. Baek, Y.J. Choi, W.-H. Yoo, M.S. Lee, J.-Y. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. <h3>Objectives</h3> This study was performed to identify the effects of Cldn on bone metabolism via regulation of osteoclast and osteoblast differentiation and their function <h3>Methods</h3> We performed various <i>in vitro</i> and <i>in vivo</i> studies using gain- and loss-of function of Cldn11 that is belong to the Cldn group. Osteoclast formation from bone marrow cells (BMC) and Osteoblast formation was evaluated in specific condition with over-expression or down- regulation of Cldn11. The expression of osteoclast associated gene and osteoblast related gene mRNA were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the mitogen-activated protein (MAPK)s and important signal pathways were measured using Western blot analysis. Osteoclast function was evaluated with resorption pit assay and osteoblastic effects of Cldn11 was evaluated with new bone formation of mouse calvaria. With LPS and co-treated Recombinant protein of Cldn11 on mouse calvaria, we evaluated the effects of Cldn11 on LPS induced bone loss by using histologic analysis. <h3>Results</h3> We found that Cldn11 played a negative role in receptor activator of nuclear factor kappa B ligand dependent osteoclast (OC) differentiation by downregulating the phosphorylated form of extracellular signal-regulated kinase (ERK), Bruton's tyrosine kinase, and phospholipase C gamma 2, in turn impeding c-Fos and nuclear factor of activated T cells c1 expression. Osteoblast (OB) differentiation by positive feedback of Cldn11 was achieved through the phosphorylation of Smad1/5/8, ERK, and c-Jun amino-terminal kinase. Importantly, this Cldn11-dependent dual event arose from targeting EphrinB2 ligand reverse signalling into OC and EphB4 receptor forward signalling into OB. In agreement with these <i>in vitro</i> effects, subcutaneous injection of Cldn11 recombinant protein exerted similar effects on local calvarial regions in mice. <h3>Conclusions</h3> These findings suggest that Cldn11 is a novel regulator in bone homeostasis. <h3>Disclosure of Interest</h3> None declared
Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells
Authors: Yu Yi, Hyun Jin Kim, Meng Zheng, Peng Mi, Mitsuru Naito, Beob Soo Kim, Hyun Su Min, Kotaro Hayashi, Federico Perche, Kazuko Toh, Xueying Liu, Yuki Mochida, Hiroaki Kinoh, Horacio Cabral, Kanjiro Miyata, Kazunori Kataoka
Journal: Journal of Controlled Release (2019)