tbuckley/cabot-search huggingface dataset:
AB0358 Phenotypes of secondary sarcopenia in patients with rheumatoid arthritis
Authors: R. Yatsyshyn, I. Stoika
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Secondary sarcopenia may be caused by low physical activity, eating disorders, chronic inflammation. In patients with rheumatoid arthritis (RA), sarcopenia co-occurs with osteoporosis as well as obesity and, in most cases, both osteoporosis and obesity co-occur with sarcopenia. Therefore, 3 phenotypes of sarcopenia can be identified: sarco-osteoporosis, sarcopenic obesity, osteosarcopenic obesity. <h3>Objectives</h3> The aim of the research was to study the features of sarcopenia and her phenotypes in patients with RA. There were examined 40 women with stage II-III RA, Rtg stage II-III, functional limitation stage II. The patients average age was 40.7±2.25 years. <h3>Methods</h3> The algorithm for diagnosing phenotypes of sarcopenia recommended by the <sup>European Working Group on Sarcopenia in Older People (2009)</sup> was used. Body mass index was determined. Dynamometry (the measurement of hand-grip strength using handgrip dynamometer) was performed and the evaluation of physical fitness. <b>S</b>erum levels of leptin and creatine phosphokinase MM (CPK MM) fraction were determined. The dual-energy X-ray absorbtiometry DEXA (tocalculate a T-score) was performed <h3>Results</h3> According to the results of laboratory tests and methods of evaluating functional muscle disorders, 87.5% of patients were diagnosed with sarcopenia. The mean values of dynamometry were within 18.3±0.7 kg being significantly lower as compared to healthy individuals – 28.3±0.5 kg. After the evaluation of physical fitness, the average score was 7.9±0.7, while in healthy individuals, it was 11.3±0.4. The mean CPK MM concentration was 175±2.34 U/L, while in healthy individuals, it was 144±3.5 U/L. The average T-score were within the limits (– 1,83±0,17) SD and was significantly lower than in healthy (−0,56±0,10) SD. After conducting studies in 17 patients were diagnosed with osteosarcopenic obesity in 11 – sarco-osteoporosis, 7 – sarcopenic obesity, 5 patients sarcopenia has not been diagnosed. <h3>Conclusions</h3> RA leads to muscle metabolism disorders which result in the development of secondary sarcopenia. Therefore, a high-protein diet, physical exercise, namely aerobic exercise (swimming, cycling) and medical preparations that improve muscle metabolism should be included in therapeutic measures and preparations of calcium. <h3>Disclosure of Interest</h3> None declared
Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide
Authors: Avichai Shimoni, Myriam Labopin, Francesca Lorentino, Maria Teresa Van Lint, Yener Koc, Zafer Gülbas, Johanna Tischer, Benedetto Bruno, Didier Blaise, Pietro Pioltelli, Boris Afanasyev, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Journal: Leukemia (2018)
Sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks in noncirrhotic subjects chronically infected with hepatitis C virus genotype 1: a randomized clinical trial
Authors: H. Pott-Junior, G. Bricks, G. Grandi, J. Figueiredo Senise, A. Castelo Filho
Journal: Clinical Microbiology and Infection (2018)
SAT0353 Geographical differences in psoriatic arthritis: a transatlantic comparison
Authors: S.B. Üreyen, D. Solmaz, G. Kimyon, E.K. Gunal, A. Dogru, O. Bayindir, E. Dalkiliç, C. Ozisler, M. Can, S. Akar, G.Y. Cetin, E.F. Tarhan, S. Yavuz, L. Kilic, O. Kucuksahin, A. Omma, E. Gonullu, F. Yildiz, E.D. Ersozlu, M.A. Tufan, M. Cinar, A. Erden, S. Yilmaz, S. Pehlevan, T. Duruoz, U. Kalyoncu, S.Z. Aydin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The environmental and genetic factors play a crucial role in the pathogenesis of psoriatic arthritis (PsA) which may cause a difference in disease characteristics for patients from different geographical regions. <h3>Objectives</h3> The aim of the study was to explore the disease characteristics, treatment choices and comorbidities in patients with PsA in different countries to see the impact of geographic factors. <h3>Methods</h3> PsArt-ID (Psoriatic Arthritis- International Database) is a prospective, multicentre registry in PsA, which was initially developed in Turkey in 2014, with participation of <sup>Canada since 2015</sup> and Italy since 2017. Patients with PsA are consecutively registered to this registry with the aim of investigating the real-life data. Patient characteristics across Turkey (n=1283) and Canada (n=119) are compared for this analysis. <h3>Results</h3> Canadian patients were older at the time of recruitment (Table). They also were more frequently smokers, had higher duration of education and higher BMI than patients in Turkey. Patients in Canada had more frequent polyarthritis (66.7% vs 39.6%, p&lt;0.001), DIP joint disease (34.2% vs 16%, p&lt;0.001), dactylitis (38.1% vs 29%, p=0.037) nail involvement (55.9% vs 45.7%, p=0.008) and higher number deformed joints (29.3% vs 20.7%, p=0.035) whereas Turkish patients had oligoarthritis more often (37.6% vs 24.8%, p=0.016). For disease activity, tender and swollen joint counts were similar for whereas the skin activity was higher in Turkish patients. There were no major differences between countries regarding treatment choices with similar frequencies of patients on biologic therapies (34.5% vs 30.2%, p=0.339) (figure 1). Although the numbers were very low, there was more frequent cancer in Canada than Turkey (4.3% vs 1.4%, p=0.022) whereas all the other comorbidities were similar. <h3>Conclusions</h3> Geographical differences have impacts on the disease features in PsA, which may be due to genetic, environmental and cultural differences. The treatments are comparable suggesting a similar approach by the physicians. <h3>Disclosure of Interest</h3> None declared
Maintenance Treatment Of Eosinophilic Esophagitis With Swallowed Topical Steroids Alters Disease Course Over A 5-Year Follow-up Period In Adult Patients
Authors: Thomas Greuter, Ekaterina Safroneeva, Christian Bussmann, Luc Biedermann, Stephan R. Vavricka, David A. Katzka, Alain M. Schoepfer, Alex Straumann
Journal: Clinical Gastroenterology and Hepatology (2018)
Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy
Authors: Marvin Gonzalez-Quiroz, Evangelia-Theano Smpokou, Richard J. Silverwood, Armando Camacho, Dorien Faber, Brenda La Rosa Garcia, Amin Oomatia, Michael Hill, Jason Glaser, Jennifer Le Blond, Catharina Wesseling, Aurora Aragon, Liam Smeeth, Neil Pearce, Dorothea Nitsch, Ben Caplin
Journal: Journal of the American Society of Nephrology (2018)

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.
OP0027 Characteristics of cytokines and changes in interleukin-17 levels in the synovial fluid of patients with ankylosing spondylitis on treatment with biologics
Authors: B.S. Koo, S. Jo, E. Kwon, J.H. Shin, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biologic drugs targeting the inflammatory cytokines have been recommended in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Yet, some patients require a change in treatment because an adequate response is not achieved. <h3>Objectives</h3> The current study aimed to evaluate the levels of tumour necrosis factor alpha (TNF-α), interleukin (IL)−17, IL-23, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the joint fluid in patients with AS and RA and identify the important cytokines related with treatment-response. <h3>Methods</h3> Synovial fluid was obtained from 18 patients with AS and 19 with RA who suffered from arthritis of the knee; and the levels of the cytokines were measured. The differences in their levels between patients with AS and RA, and between patients treated with and without biologics (biologics group and non-biologics group) were analysed. <h3>Results</h3> TNF-α and GM-CSF levels in patients with AS were significantly lower than those in patients with RA (figure 1A, both p&lt;0.01); however, IL-17 and IL-23 levels were not significantly different between the two groups. Furthermore, levels of IL-17 were markedly elevated in the biologics group compared with the non-biologics group in AS (figure 1B, p=0.04). However, in RA, there were no significant differences between the non-biologics and biologics group (figure 1C). <h3>Conclusions</h3> In AS, IL-17 in synovial fluid is a good marker of non-response to biologics and may be a good target for non-responders to TNF inhibitor. <h3>Disclosure of Interest</h3> None declared
Heterogeneity of Treatment Effect by Baseline Risk in a Trial of Balanced Crystalloids versus Saline
Authors: Andrew C. McKown, Luis E. Huerta, Todd W. Rice, Matthew W. Semler
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

from patients with non-PH IPF in a cohort study (8).This may be a result of the absence of severe PH in these patients, or because of differences in the mechanisms driving PH in IPF versus PAH.We conclude that nintedanib shows disadvantageous effects in PAH, and future investigations are needed to reveal the precise underlying mechanisms.Moreover, the effect of this agent on pulmonary hemodynamics in patients with IPF and severe accompanying PH should be investigated in future studies.
Response by Beddhu et al to Letters Regarding Article, “Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control”
Authors: Srinivasan Beddhu, Glenn M. Chertow, Alfred K. Cheung, William C. Cushman, Tom Greene, Guo Wei, Robert Boucher, Paul K. Whelton
Journal: Circulation (2018)
Receipt of Guideline-Concordant Care Among Older Women With Stage I–III Breast Cancer: A Population-Based Study
Authors: Traci LeMasters, S. Suresh Madhavan, Usha Sambamoorthi, Hannah W. Hazard-Jenkins, Kimberly M. Kelly, Dustin Long
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: This study examined receipt of guideline-concordant care (GCC) according to evidence-based treatment guidelines and quality measures and specific types of treatment among older women with breast cancer. Patients and Methods: A total of 142,433 patients aged ≥66 years diagnosed with stage I–III breast cancer between 2007 and 2011 were identified in the SEER-Medicare linked database. Algorithms considering cancer characteristics and the appropriate course of care as per guidelines versus actual care received determined receipt of GCC. Multivariable logistic regression estimated the likelihood of GCC and specific types of treatment for women aged ≥75 versus 66 to 74 years. Results: Overall, 39.7% of patients received GCC. Patients diagnosed at stage II or III, with certain preexisting conditions, and of nonwhite race were less likely to receive GCC. Patients with hormone-negative tumors, higher grade tumors, and greater access to oncology care resources were more likely to receive GCC. Patients aged ≥75 years were approximately 40% less likely to receive GCC or adjuvant endocrine therapy, 78% less likely to have any surgery, 61% less likely to have chemotherapy, and about half as likely to have radiation therapy than those aged 66 to 74 years. Conclusions: Fewer than half of older women with breast cancer received GCC, with the lowest rates observed among the oldest age groups, racial/ethnic minorities, and women with later-stage cancers. However, patients with more aggressive tumor characteristics and greater access to oncology resources were more likely to receive GCC. Considering that older women have the highest incidence of breast cancer and that many are diagnosed at stages requiring more aggressive treatment, efforts to increase rates of earlier stage diagnosis and the development of less toxic treatments could help improve GCC and survival while preserving quality of life.
Uptick in Autism
Authors: Bridget Kuehn
Journal: JAMA (2018)

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AB0161 Interleukin-37: a therapeutic for lupus nephritis in mrl-faslpr mice
Authors: L. Ding, X. Hong, Z. Huang, D. Liu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a serious and noticed autoimmune disease, and lupus nephritis (LN) as one of its major complications without effective treatment. IL-37 has been identified as a natural inhibitor of innate immunity. Although increasing evidence shown that serum IL-37 correlated with SLEDAI and nephritis activity, However, it is still unclear that the therapeutic effect of IL-37 on lupus mice <i>in vivo</i>. <h3>Objectives</h3> This study aims to determine the inhibitory effect of IL-37 in lupus mice and lupus nephritis <i>in vivo</i>, and to expose the IL-37 related mechanisms of cell and molecules that inhibits the inflammmation in lupus nephritis. <h3>Methods</h3> MRL-Fas<sup>lpr</sup> mice with mild and advanced disease were treated with lentiviral vector pLVX-IL-37b. The protein levels of IL-37b in serum and tissue, IL-17, IL-6, IL-10 and TGFβ-3 produced by cell culture from spleen and kidney of mice were measured by ELISA, the relative mRNA expression of these cytokines in PBMCs was detected by RT-PCR, and the frequency of Th17 and Treg cells in splenocyte were determined by FACS. <h3>Results</h3> Our results show that IL-37 was highly effective in prolonging survival, alleviating the pathologic characteristics of lupus nephritis (LN) in MRL-Fas<sup>lpr</sup> mice by reducing the autoimmune complex deposition such as IgM, IgG and C3, decreasing the production of Inflammatory cytokines such as IL-17, IL-6 and promoting the anti-inflammatory cytokines IL-1 0and TGFβ-3. We also found that IL-37 protect lupus mice from LN associated with increasing the frequency of Treg cells and reducing the frequency of Th17 cells. <h3>Conclusions</h3> These results indicate the protective action of IL-37 in LN, and strengthen the support for IL-37 as a new target for therapy of SLE. <h3>Disclosure of Interest</h3> None declared
Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a
Authors: Xiaoru Xin, Mengying Wu, Qiuyu Meng, Chen Wang, Yanan Lu, Yuxin Yang, Xiaonan Li, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Jiao Li, Song Jia, Dongdong Lu
Journal: Molecular Cancer (2018)

Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer. Moreover, HULC accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, HULC increasesthe expression of P62 via decreasing mature miR15a. On the other hand, excessive HULC increases the expression of LC3 on the level of transcription and then activates LC3 through Sirt1 (a deacetylase). Notably, HULC enhanced the interplay between LC3 and ATG3. Furthermore, HULC also increases the expression of becline-1(autophagy related gene). Therefore, HULC increases the cellular autophagy by increasing LC3II dependent on Sirt1.Noteworthy, excessive HULC reduces the expression of PTEN, β-catenin and enhances the expression of SAPK/JUNK, PKM2, CDK2, NOTCH1, C-Jun in liver cancer cells. Of significance, our observations also revealed that HULC inhibited PTEN through ubiquitin–proteasome system mediated by autophagy-P62.Ultimately,HULC activates AKT-PI3K-mTOR pathway through inhibiting PTEN in human liver cancer cells. This study elucidates a novel mechanism that lncRNA HULC produces a vital function during hepatocarcinogenesis.
A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing
Authors: Huihui Sun, Fanfan Li, Jie Liu, Fayu Yang, Zhenhai Zeng, Xiujuan Lv, Mengjun Tu, Yeqing Liu, Xianglian Ge, Changbao Liu, Junzhao Zhao, Zongduan Zhang, Jia Qu, Zongming Song, Feng Gu
Journal: Molecular Therapy (2018)

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome. Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome.
AB0014 Genetic influence of different measure for tumour necrosis factor inhibitors response in rheumatoid arthritis
Authors: S. Bang, Y. Park, K. Kim, Y.B. Joo, S.-K. Cho, C.-B. Choi, Y.-K. Sung, T.-H. Kim, J.-B. Jun, D.-H. Yoo, H.-S. Lee, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The genetic studies of tumour necrosis factor inhibitors (TNFi) response in patients with rheumatoid arthritis (RA) have largely relied on the changes in complex disease scores as a measure of treatment response. It is expected that genetic architecture of such complex score is heterogeneous and not very suitable for pharmacogenetic studies. <h3>Objectives</h3> We aimed to select the most optimal phenotype for TNFi response using heritability estimates using genome-wide association studies (GWAS) in the Korean population. <h3>Methods</h3> Disease Activity Scores based on 28 joint counts (DAS28) and Clinical Disease Activity Index (CDAI) were assessed at baseline, and after 6 months in 370 Korean RA patients who started TNFi due to moderate or high disease activity. Genotypes were generated on the Illumina HumanOmni2.5Exome array (2.5 million variants) in TNFi-treated Korean patients with RA. We estimated heritability using a linear mixed-modelling approach (GCTA) for the TNFi drug-response phenotype ΔDAS28, ΔCDAI and its separate components, such as Δ swollen joint count (SJC), Δ tender joint count (TJC), Δ erythrocyte sedimentation rate (ESR), Δ visual-analogue scale of general health (VAS-GH) and Δ provider global assessment of disease activity (PrGA). Furthermore, a multivariate GWAS approach was implemented, analysing separate DAS28 and CDAI components simultaneously <h3>Results</h3> The highest heritability estimates were found for ΔPrGA (h<sup>2</sup>=0.76) and ΔTJC (h<sup>2</sup>=0.73); lower heritability was found for ΔDAS28 (h<sup>2</sup>=0.32) with estimates for ΔESR (h<sup>2</sup>=0.66), ΔSJC (h<sup>2</sup>=0.62), ΔCDAI (h<sup>2</sup>=0.60) and ΔVAS-GH (h<sup>2</sup>=0.53) (all p-value&lt;0.005). <h3>Conclusions</h3> Our results indicate that multiple SNPs together explain a substantial portion of the variation in change in provider global assessment of disease activity in TNFi-treated patients with RA. In conclusion, optimal phenotype based on heritability suggests the use of changes in clinical disease activity index (CDAI) including provider global assessment than DAS28 in pharmacogenetic study. <h3>Disclosure of Interest</h3> None declared