tbuckley/cabot-search huggingface dataset:
AB0189 Raid composite index in the evaluation of ra patients receiving biological treatment: hur-bio real-life results
Authors: A Erden, L Kilic, B Armagan, A Sari, A Akdogan, SA Bilgen, O Karadag, I Ertenli, S Kiraz, U Kalyoncu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid Arthritis Impact of Disease (RAID) is a composite index. There are seven domains of this index (pain, function, fatigue, sleep disturbance, physical wellbeing, psychological/emotional well-being and coping). Daily activity in last week is evaluated. This score, is reccommended to be used in clinical trials to measure the effect of RA. <h3>Objectives</h3> The aim of this study is to examine the relationship between RAID composite index and other indexes. <h3>Methods</h3> This study was carried out from the HUR-BIO reserved database since August, 2016. In addition to the demographic characteristics of the patients, DAS-28, HAQ-DI, pain, fatigue, Patient global Assesment (PGA), Tender joint counts (TJC), swollen joint counts (SJC), CRP and ESR are recorded. Since 2015, a RAID form is filled for our patients. While this composite scale was being created, Gazi University Turkey carried out Turkish validation, in the original study. RAID composite index includes 7 questions, each scored from 0 to 10, 0 being the best score while 10 points is worst. The relationship between RAID composite index and other indexes were studied with Spearman correlation test. <h3>Results</h3> HUR-BIO database containts 1235 RA patients as of August 2016. A RAID form was filled for 149 of these patients before initiating biological agent. 124 patients (83.2%) were female. Mean age was 49±13 years and mean disease duration was 7.8±7.2 years. Positive ACPA and RF ratios were detected as 48/104 (45.7%) and 78/137 (56.9%) respectively. 77.9% of our patients had education of high school or less. RAID average score was detected as 6.72 (1.98). In female patients RAID disease activity was significantly higher than in men [RAID 6.8 (2.0) vs. 5.9 (1.6), p=0.038]. There was no significant difference among RF, CCP positive patients and auto antibody-negative patients in terms of RAID disease activity. [RAID for RF + vs -; 6.75 (2.05) vs 6.68 (1.86), p=0.82, RAID for CCP + vs -; 6.74 (1.96) vs 6.98 (1.82), p=0.52]. RAID disease activity measurements were correlated moderately acute phase reactants, it was very weak. In table, it is grouped by level of education and re-evaluated. In those with an education higher than college, rising parameters were seen in good level of correlation. [RAID vs Pain, r =0.65, p&lt;0.005; RAID vs PGA, r =0.68, p&lt;0.005]. <h3>Conclusions</h3> RAID has low correlation with other composite index such as DAS-28 score. RAID also has moderate correlation with pain, fatigue ad PGA VAS. On the other hand, patient with high education level had better perception for those patient reported composite index. RAID can be used confidently in these selected cases. <h3>Disclosure of Interest</h3> None declared
Absorption of Subcuatneously Implanted Pellets of Diethylstilbestrol in Men
Authors: Michael B. Shimkin, Leo Zon
Journal: JNCI Journal of the National Cancer Institute (1943)

Absorption of Subcuatneously Implanted Pellets of Diethylstilbestrol in Men Michael B. Shimkin, Michael B. Shimkin passed assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Leo Zon Leo Zon passed assistant surgeon (R) Research Laboratory, Tumor Clinic, Marine Hosptial, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 367–370, https://doi.org/10.1093/jnci/3.4.367 Published: 01 February 1943
Identification of extant vertebrate Myxine glutinosa VWF: evolutionary conservation of primary hemostasis
Authors: Marianne A. Grant, David L. Beeler, Katherine C. Spokes, Junmei Chen, Harita Dharaneeswaran, Tracey E. Sciuto, Ann M. Dvorak, Gianluca Interlandi, José A. Lopez, William C. Aird
Journal: Blood (2017)
AB0528 Patient activation and the factors affecting it in primary sjÖgren's syndrome
Authors: ST Souter, B Hargreaves, KL Hackett, W-F Ng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Increased patient activation has been associated with reduced costs of treatment<sup>1</sup> and improved patient outcomes<sup>2</sup>. The effect of primary Sjögren9s syndrome (pSS) on patient activation however has not been established. <h3>Objectives</h3> This study aims to identify how activated patients with pSS are, and to ascertain whether factors such as ESSPRI score, EULAR dryness score and self-reported quality of life influence this. <h3>Methods</h3> Patient activation in 170 pSS patients was assessed using the 13-item Patient Activation Measure (PAM-13). A PAM-13 score from 0–100 was obtained using the PAM-13 Scoring Spreadsheet, which also gave a corresponding activation level ranging from 1–4. Descriptive statistics of the PAM-13 scores was performed, and frequency analysis of the corresponding activation level. Demographic, clinical and self-reported measures such as age, gender, ESSPRI score and EQ5D-3L score were linked to each patients9 PAM-13 scores. Spearman9s correlation analysis was performed to assess the relationship between the continuous variables and PAM-13 score, and Fisher9s exact test was used to assess the relationship between activation level and the categorical variables. <h3>Results</h3> The mean PAM-13 score of the 170 patients studied was 59.5 (SD 13.5). 17.6% of patients were in level 1 of activation, 26.5% in level 2, 40.0% in level 3, and 15.9% in level 4. The mean age of the sample was 59.6 (SD 13.1), and 83.5% were female. EQ5D-3L score had the strongest correlation with increased PAM score (r<sub>s</sub> 0.405, p 0.000). Increasing self-reported pain in the ESSPRI questionnaire was correlated with a decreasing PAM score (r<sub>s</sub> -0.355, p 0.000), as was increasing ESSPRI score (r<sub>s</sub> -0.337, p 0.000). Increasing abnormal fatigue (r<sub>s</sub> -0.189, p 0.016) and EULAR dryness (r<sub>s</sub> -0.190, p 0.013) score were only weakly correlated with a decrease in PAM-13 score. Decreases in patients self-reported mobility (p 0.000), self-care (p 0.002), and ability to perform daily activities (p 0.018) were also associated with differences in activation score. <h3>Conclusions</h3> Factors such as a patients self-reported health and pain have a moderate correlation with activation in pSS patients, while dryness and fatigue are only weakly correlated with changes in activation. This should be considered in the future when devising treatment plans and clinical trials. <h3>References</h3> Hibbard JH, Greene J, Overton V. Patients With Lower Activation Associated With Higher Costs; Delivery Systems Should Know Their Patients9 9Scores9. Health Affairs. 2013;32(2):216–222. Hibbard JH, Greene J, Shi Y, Mittler J, Scanlon D. Taking the Long View: How Well Do Patient Activation Scores Predict Outcomes Four Years Later? Medical Care Research and Review. 2015;72(3):324–337. <h3>Disclosure of Interest</h3> None declared
Nucleic Acid-Based Theranostics for Tackling Alzheimer's Disease
Authors: Madhuri Chakravarthy, Suxiang Chen, Peter R Dodd, Rakesh N Veedu
Journal: Theranostics (2017)

Nucleic acid-based technologies have received significant interest in recent years as novel theranostic strategies for various diseases. The approval by the United States Food and Drug Administration (FDA) of Nusinersen, an antisense oligonucleotide drug, for the treatment of spinal muscular dystrophy highlights the potential of nucleic acids to treat neurological diseases, including Alzheimer's disease (AD). AD is a devastating neurodegenerative disease characterized by progressive impairment of cognitive function and behavior. It is the most common form of dementia; it affects more than 20% of people over 65 years of age and leads to death 7-15 years after diagnosis. Intervention with novel agents addressing the underlying molecular causes is critical. Here we provide a comprehensive review on recent developments in nucleic acid-based theranostic strategies to diagnose and treat AD.
Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease
Authors: Graham F. Brady, Raymond Kwan, Peter J. Ulintz, Phirum Nguyen, Shirin Bassirian, Venkatesha Basrur, Alexey I. Nesvizhskii, Rohit Loomba, M. Bishr Omary
Journal: Hepatology (2017)

Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial, but twin and familial studies indicate significant heritability, which is not fully explained by currently known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina‐associated proteins predispose to NAFLD and used a candidate gene‐sequencing approach to test for variants in 10 nuclear lamina‐related genes in a cohort of 37 twin and sibling pairs: 21 individuals with and 53 without NAFLD. Twelve heterozygous sequence variants were identified in four lamina‐related genes ( ZMPSTE24 , TMPO , SREBF1 , SREBF2 ). The majority of NAFLD patients (&gt;90%) had at least one variant compared to &lt;40% of controls ( P &lt; 0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (&gt;80% versus &lt;25%; P &lt; 0.0001). Presence of a lamina variant segregated with NAFLD independently of the PNPLA3 I148M polymorphism. Several variants were found in TMPO , which encodes the lamina‐associated polypeptide‐2 (LAP2) that has not been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin–LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin‐binding protein p62/SQSTM1. Conclusion: Several variants in nuclear lamina‐related genes were identified in a cohort of twins and siblings with NAFLD; one such variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents an association of TMPO /LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD. (H epatology 2018;67:1710‐1725).
AB0082 Alkaline phosphatase elicits prophylactic and therapeutic effects in arthritic rats
Authors: DMSH Chandrupatla, CFM Molthoff, E Elshof, W Ritsema, M Verlaan, R Vos, A Hammond, AA Lammertsma, CJ van der Laken, R Brands, G Jansen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Alkaline phosphatase (AP) functions as a gate-keeper of the innate immune system [1] by detoxifying inflammation triggering moieties (ITMs). As an ectophosphatase, AP thus acts extracellularly by dephosphorylating ITMs that originate and are released from endogenous sources, e.g. by converting ADP and ATP nucleotides into adenosine to establish a key signalling anti-inflammatory effect. Consequently, AP activity prevents the production of pro-inflammatory cytokines by activated leucocytes and their downstream effects. Due to its broad mechanism of action, AP may potentially serve as an attractive therapeutic moiety in chronic inflammatory disorders, including rheumatoid arthritis (RA). <h3>Objectives</h3> To examine the anti-arthritic effects of prophylactic and therapeutic AP interventions in arthritic rats. <h3>Methods</h3> Wistar rats were immunized twice with methylated bovine serum albumin (mBSA), followed by local arthritis induction (intra-articular (i.a.) mBSA injection with 3 repeated injections) in the right knee (arthritic knee) with the contralateral left knee serving as internal control [2]. Interventions were performed using 200 μg human recombinant placental AP, administered subcutaneously, either before i.a. mBSA injections (2x, every 3 days, 2 rats/group; <i>prophylactic</i> setting) or after arthritis induction (4x, every 3 days, 4 rats/group; <i>therapeutic</i> setting). After <i>ex vivo</i> tissue distribution, knees were excised, fixed, decalcified and paraffin-embedded. Knee sections were examined for synovial macrophage infiltration by immunohistochemistry with ED1 (∼CD68) and ED2 (∼CD163) macrophage specific antibodies. Results were compared with untreated arthritic rats and arthritic rats receiving MTX therapy (1 mg/kg, intraperitoneally, 4x, every 3 days, 4 rats/group). <h3>Results</h3> Prophylactic and therapeutic schedules of AP treatment were well tolerated and reduced knee swelling comparable with MTX treatment. Following AP prophylactic intervention, synovial macrophage infiltration in the arthritic knees was reduced 4-fold (ED1) and 6-fold (ED2) when compared with affected knees of untreated arthritic rats, approaching macrophage counts in contralateral (non-arthritic) knees of AP treated rats. Therapeutic AP interventions resulted in 3.5-fold lower synovial infiltration of both ED1 and ED2 macrophages in arthritic knees, comparable with effects of MTX treatment. <h3>Conclusions</h3> AP, both as prophylactic and as therapeutic intervention, demonstrated favourable anti-arthritic efficacy in a rat model of arthritis. These studies warrant further preclinical and clinical evaluation as a putative novel therapeutic entity for arthritis. <h3>References</h3> Pike AF et al, Biochim Biophys Acta (2013);1832:2044–2056. Chandrupatla DM et al, Biomed Res Int. (2015), 509295. <h3>Disclosure of Interest</h3> None declared
FRI0258 Long-term prognosisofpatients with systemic lupus erythematosus-associated pulmonary arterial hypertension: cstar-pah cohort study
Authors: J Qian, M Li, X Zhang, Q Wang, J Zhao, Z Tian, X Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> SLE-associated pulmonary arterial hypertension (PAH) is common in Asian countries, and the clinical outcome of patients with SLE-associated PAH is dramatically impaired. <h3>Objectives</h3> This study aimed to identify the long-term clinical outcomes and prognostic factors of patients with SLE-associated PAH confirmed by right heart catheterization (RHC). <h3>Methods</h3> A multicenter cohort of SLE-associated PAH was established. Baseline and follow-up records were collected. The primary endpoint was death from any cause. The secondary experimental end point was treatment goal achievement (TGA), defined as an integrated outcome. <h3>Results</h3> Among the 310 patients enrolled from 14 PAH centers, the median follow-up was 24.0 months. The 1-, 3- and 5-year survival rates were 92.1%, 84.8% and 72.9%, respectively. The 1-, 3- and 5-year TGA rates were 31.5%, 53.6% and 62.7%, respectively.Serositis, 6MWD &gt;380 m and CI ≥2.5 L/min×m<sup>2</sup> were identified as independent prognostic factors of TGA. TGA within 5 years was identified as a factor associated with survival in patients with SLE-associated PAH (Figure 1). <h3>Conclusions</h3> TGA was associated with the long-term survival, which supports and provides evidence to the treat-to-target strategy in SLE-associated PAH. Early diagnosis, intervention and heart function preservation are priorities for better long-term outcomes. <h3>References</h3> Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137:376–87. Chung L, Liu J, Parsons L, Hassoun PM, McGoon M, Badesch DB, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138:1383–94. Condliffe R, Kiely DG, Peacock AJ, Corris PA, Gibbs JS, Vrapi F, et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med. 2009;179:151–7. <h3>Disclosure of Interest</h3> None declared
SAT0381 Correlation between three different methods to assess dermal thickness in systemic sclerosis patients with different patterns of nailfold microangiopathy
Authors: B Ruaro, A Sulli, E Alessandri, S Paolino, M Ghio, AC Trombetta, C Pizzorni, V Tomatis, M Cutolo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized by the increase of dermal thickness (DT) (1). The modified Rodnan skin score (mRss) is the validated method to evaluate the severity of skin impairment (2,3). Several studies have reported the capability of high frequency skin ultrasound (US) to reflect the overall severity of the skin damage in SSc patients (4–5). The plicometer skin test (PST) is another method to evaluated cutaneous involvement in SSc patients (6). <h3>Objectives</h3> The aim of this study was to identify possible correlations between US, mRss and PST to evaluate DT in SSc patients with different patterns of nailfold microangiopathy. <h3>Methods</h3> Sixty-three SSc patients (mean age 64±11SD years, mean disease duration 7±6 years, 43 lcSSc and 20 dcSSc) and 63 sex and age matched healthy subjects were enrolled after written informed consent. All subjects were assessed by mRss, US and PST to evaluate the DT in the seventeen skin areas of the body usually evaluated by mRss (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet) (1–6). Nailfold videocapillaroscopy (NVC) was used to assess the proper pattern of microangiopathy and to calculate the microangiopathy evolution score (MES) (7–8). Statistical evaluation was performed by non-parametric tests. <h3>Results</h3> As expected, the group of SSc patients had a statistically significant higher DT, as evaluated by the three methods, at level of all areas when compared to the control group (p=0.0001). All methods demonstrated a progressively higher DT in patients with "Early", vs. "Active" and vs "Late" pattern of nailfold microangiopathy (p&lt;0.005), and a positive correlation was observed with MES (r=0.71 p&lt;0.001). A positive correlation was observed in SSc patients between the three method to evaluate DT (PST vs mRss r=0.98, p&lt;0.0001; PST vs US r=0.53, p&lt;0.0001; US vs mRss r=0.53, p&lt;0.0001). <h3>Conclusions</h3> This study demonstrates a relationship between different methods to assess DT (US, mRss and PST) in SSc patients and a relationship between skin damage and microangiopathy impairment. <h3>References</h3> Moore TL, et al. Rheumatology 2003;42:1559–63. Sulli A, et al. Ann Rheum Dis. 2014;69:1140–3. Kaldas M, et al. Rheumatology 2009;48:1143–6. Hesselstrand R, et al. Rheumatology 2008;47:84–7. Kaloudi O, et al. Ann Rheum Dis. 2010;69:1140–3. Parodi MN, et al. Br JRheumatol. 1997;36:244–50. Sulli A, et al. Ann Rheum Dis 2008;67:885–7. Cutolo et al. J Rheumatol 2000; 27;155.60. <h3>Disclosure of Interest</h3> None declared
Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration–Approved Drugs
Authors: Nathan P. Coussens, John C. Braisted, Tyler Peryea, G. Sitta Sittampalam, Anton Simeonov, Matthew D. Hall
Journal: Pharmacological Reviews (2017)

High-throughput screening (HTS) of small-molecule libraries accelerates the discovery of chemical leads to serve as starting points for probe or therapeutic development. With this approach, thousands of unique small molecules, representing a diverse chemical space, can be rapidly evaluated by biologically and physiologically relevant assays. The origins of numerous United States Food and Drug Administration–approved cancer drugs are linked to HTS, which emphasizes the value in this methodology. The National Institutes of Health Molecular Libraries Program made HTS accessible to the public sector, enabling the development of chemical probes and drug-repurposing initiatives. In this work, the impact of HTS in the field of oncology is considered among both private and public sectors. Examples are given for the discovery and development of approved cancer drugs. The importance of target validation is discussed, and common assay approaches for screening are reviewed. A rigorous examination of the PubChem database demonstrates that public screening centers are contributing to early-stage drug discovery in oncology by focusing on new targets and developing chemical probes. Several case studies highlight the value of different screening strategies and the potential for drug repurposing.
AB0720 Characteristics of tunisien spondyloarthritis patients with hip disease
Authors: K Maatallah, F Essafi, I Mahmoud, K Ben Abdelghani, O Saidane, W Hamdi, MM Kchir, R Tekaya, L Abdelmoula
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> spondyloarthritis (SpA) is characterized by inflammation of spine and sacroiliac joints. Hip involvement is the most frequent extra spinal arthritic manifestation of SpA and may lead to a worse functional outcome. <h3>Objectives</h3> The objective of this study was to assess clinical, biological and radiological characteristics of SpA patients with hip disease. <h3>Methods</h3> This is a transversal multicenter study, including SpAs patients (satisfying ASAS criteria2009) with hip disease Demographic, clinical, radiographic, and laboratory data were collected and analyzed. Radiographic forms of hip disease were assessed according to Netter classification (early, condensing, destructive, combined and synostosante forms). Radiographic severity was assessed by the modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) and BASRI (Bath Ankylosing Spondylitis Radiologic Index). <h3>Results</h3> ninety four patients were evaluated (77men). The mean age was 41.53±11.97 years. The median age at disease onset was 26.23±10.29 years.The mean diagnostic delay was 6.48 years. 46% of patients were smoker. HLA B27 was positive in 50% of cases. A peripheral joint involvement was found in 33% of cases. Extra-articular manifestation was seen in 57% of patients: osteoporosis (16 patients), uveitis (15 patients), psoraisis (10 patients), chronic inflammatory bowel disease (12 patients). 78 patients had bilateral hip involvement and 147 hips were evaluated. The median BASDAI and BASFI scores were respectively 5,4 and 5,5. The mean index of severity for osteoarthritis for the hip (ISH) was 12.24 (±6.84). Patients had an early form of hip disease in 22% of cases, Condensing form in 3% of cases, combined forms in 22% of cases and destructive form in 53% of cases. BASRI-hip score was 1 in 24%, 2 in 49%, 3 in 19% and 4 in 8% of hips. Sacoiliac joint grade was 2 in 17%, 3 in 37% and 4 in 46% of cases. The mean mSASSS score was 15.34±16.22. TNF inhibitors were indicated in 49% of patients (infliximab 23, Adalimumab 7 and Etanercept 18).31 patients received csDMARDs and 46 NSAID. <h3>Conclusions</h3> Our finding confirm previous observation that clinical and radiological hip involvement is associated with a more severe disease with a high activity and pronounced functional impairments. <h3>Disclosure of Interest</h3> None declared