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  • Authors: Nancy Spencer-Cavaliere; Danielle Peers;

    The inclusion of able-bodied athletes within disability sport, a phenomenon known as reverse integration, has sparked significant debate within adapted physical activity. Although researchers and practitioners have taken up positions for or against reverse integration, there is a lack of supporting research on the experiences of athletes who already play in such settings. In this study, we explore how competitive female athletes who have a disability experience reverse integration in Canadian wheelchair basketball. Athletic identity was used as the initial conceptual framework to guide semistructured interviews with nine participants. The results suggest that participation in this context contributed to positive athletic identities. Interviews also pointed to the unexpected theme of “what’s the difference?” that this sporting context provided a space for the questioning and creative negotiation of the categories of disability and able-bodiedness. Methodologically, this paper also explores the possibilities and challenges of inter- worldview and insider-outsider research collaboration.

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    Authors: Marwan O. Jalambo; Basil Kanoa; Mohammed S. Ellulu; Smaher Younis; +1 Authors
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ New Insights in Obes...arrow_drop_down
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  • Authors: P.F. Medina; A. Rad; S. Gottfried; E. Matouk; +3 Authors
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    Authors: Suphamai Bunnapradist; Kamyar Kalantar-Zadeh;

    Well-designed randomized, placebo-controlled clinical tri-als are critical for assessing the safety and effectivenessof immunosuppressive therapy (1). However pivotal im-munosuppressive trials have generally had relatively shortfollow-up: from 6 months in the case of MMF to 2 years inthe case of belatacept. Despite the estimated half-life ofmore than a decade for a kidney transplant, the long-termimpact of immunosuppressive therapy is largely unknown.Furthermore, surrogate markers and composite endpointsare often used but their association with long-term out-comes is uncertain. As the main focus of organ transplanthasshiftedtolong-termgraftandpatientsurvival,weneedlonger term follow-up studies.In this issue of AJT, Cortazar et al. compared the long-term outcomes in kidney recipients who received and didnot receive mTOR inhibitor containing regimens at Sem-melweis University in Hungary (2). Despite the limitationsnoted by the authors, this study raises concern about long-term sequelae of immunosuppression and also illustratesthe fact that we currently do not have long-term studies onmTOR inhibitors.This observational cohort study included 993 primarilyEasternEuropeanCaucasianswhosemediantimeatstudyentry was 72 months posttransplant with a median follow-up of 37 months. One hundred and one received mTORinhibitor containing regimens. We do not have details onwhat proportion of the mTOR inhibitor use was

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    Europe PubMed Central
    Other literature type . 2011
    Data sources: PubMed Central
    https://pubmed.ncbi.nlm.nih.go...
    Other literature type . 2011
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      Europe PubMed Central
      Other literature type . 2011
      Data sources: PubMed Central
      https://pubmed.ncbi.nlm.nih.go...
      Other literature type . 2011
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    Authors: Swagatika Das; Umashankar Das; Ponniah Selvakumar; Rajendra K. Sharma; +9 Authors

    AbstractA series of 3,5‐bis(benzylidene)‐4‐piperidones 3 were converted into the corresponding 3,5‐bis(benzylidene)‐1‐phosphono‐4‐piperidones 5 via diethyl esters 4. The analogues in series 4 and 5 displayed marked growth inhibitory properties toward human Molt 4/C8 and CEM T‐lymphocytes as well as murine leukemia L1210 cells. In general, the N‐phosphono compounds 5, which are more hydrophilic than the analogues in series 3 and 4, were the most potent cluster of cytotoxins, and, in particular, 3,5‐bis‐(2‐nitrobenzylidene)‐1‐phosphono‐4‐piperidone 5 g had an average IC50 value of 34 nM toward the two T‐lymphocyte cell lines. Four of the compounds displayed potent cytotoxicity toward a panel of nearly 60 human tumor cell lines, and nanomolar IC50 values were observed in a number of cases. The mode of action of 5 g includes the induction of apoptosis and inhibition of cellular respiration. Most of the members of series 4 as well as several analogues in series 5 are potent multi‐drug resistance (MDR) reverting compounds. Various correlations were noted between certain molecular features of series 4 and 5 and cytotoxic properties, affording some guidelines in expanding this study.

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    Europe PubMed Central
    Other literature type . 2009
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    ChemMedChem
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      Other literature type . 2009
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    Authors: Stephanie Heinrich; Carina Patrizia Derrer; Azra Lari; Karsten Weis; +1 Authors

    The transport of messenger RNAs (mRNAs) from the nucleus to cytoplasm is an essential step in the gene expression program of all eukaryotes. Recent technological advances in the areas of RNA‐labeling, microscopy, and sequencing are leading to novel insights about mRNA biogenesis and export. This includes quantitative single molecule imaging (SMI) of RNA molecules in live cells, which is providing knowledge of the spatial and temporal dynamics of the export process. As this information becomes available, it leads to new questions, the reinterpretation of previous findings, and revised models of mRNA export. In this review, we will briefly highlight some of these recent findings and discuss how live cell SMI approaches may be used to further our current understanding of mRNA export and gene expression.

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    Europe PubMed Central
    Other literature type . 2017
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Europe PubMed Central
      Other literature type . 2017
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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    Authors: Anna Taczanowska; Anke Schwandt; Shazhan Amed; Péter Tóth-Heyn; +4 Authors

    Children with type 1 diabetes (T1D) are at much higher risk of developing celiac disease (CD) than the general population. The aim of the study was to assess the prevalence and differences in clinical presentation of CD in T1D in different regions of the world.This study is based on the Better control in Pediatric and Adolescent diabeteS: Working to crEate cEnTers of Reference (SWEET) database. There were 57 375 patients included in the study, aged ≤18 years from 54 SWEET centers. Only centers with screening for celiac disease were included. Regression models adjusted for age, diabetes duration, and gender and a fixed effect in the models for region was used. Diabetes duration, age at diabetes onset, and sex were presented as unadjusted results.CD was present in 2652 subjects (4.5%), with different prevalence among regions: from 1.9% in Asia/Middle East to 6.9% in Australia/New Zealand. CD was observed more often among females. Comparing children with and without CD, characteristics for those with CD were younger age at diabetes onset (6.3 [3.3; 9.8] vs 8.1 [4.6; 11.3], P 0.001) and had longer diabetes duration (6.4 [3.6; 9.8] vs 4.8 [2.1; 8.2], P 0.001). Further, they had lower glycosylated hemoglobin (HbA1c) in Europe and North America/Canada; lower body mass index (BMI)-SD score (BMI-SDS) in southern Europe, North America, and Canada; In most regions daily insulin dose was lower, height-SDS was lower, and the percentage of insulin pump users was higher in children with T1D and CD.The prevalence and the anthropometric and metabolic consequences of CD in children with T1D differ around the world.背景: 1型糖尿病(T1D)儿童患乳糜泻(CD)的风险比普通人群高得多。该研究旨在评估CD在世界不同地区T1D中的患病率和临床表现的差异。 方法: 这项研究基于“致力于更好控制儿童和青少年糖尿病:注册参考中心” (SWEET)数据库。这项研究包括了来自54个中心的57375名年龄≤ 18岁的患者。有乳糜泻筛查的中心被纳入其中。回归模型根据年龄、糖尿病病程和性别进行了校正,模型中对地区的影响是固定的。糖尿病病程、发病年龄和性别展示的是未校正的结果。 结果: 2652名受试者(4.5%)存在CD,不同地区的患病率不同:从亚洲/中东的1.9%到澳大利亚/新西兰的6.9%。CD多见于女性。CD组与非CD组相比,发病年龄小(6.3 [3.3; 9.8] vs 8.1 岁[4.6; 11.3],P0.001),病程长(6.4 [3.6; 9.8] vs 4.8 [2.1;8.2]年,P0.001)。此外,此外,欧洲和北美/加拿大的糖化血红蛋白(HbA1c)较低,南欧、北美和加拿大的体重指数(BMI)SD评分(BMI-SDS)较低,在大多数地区T1D和CD儿童的胰岛素每日剂量较低,身高-SDS较低,使用胰岛素泵的比例较高。 结论: CD在T1D儿童中的患病率、人口学和代谢指标在世界各地都不同。.

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    Authors: Biruk A. Feyissa; Muhammad Arshad; Margaret Y. Gruber; Susanne E. Kohalmi; +1 Authors

    AbstractBackgroundDevelopingMedicago sativaL. (alfalfa) cultivars tolerant to drought is critical for the crop’s sustainable production. miR156 regulates various plant biological functions by silencing SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors.ResultsTo understand the mechanism of miR156-modulated drought stress tolerance in alfalfa we used genotypes with altered expression levels of miR156, miR156-regulatedSPL13, andDIHYDROFLAVONOL-4-REDUCTASE(DFR) regulatingWD40–1. Previously we reported the involvement of miR156 in drought tolerance, but the mechanism and downstream genes involved in this process were not fully studied. Here we illustrate the interplay between miR156/SPL13 and WD40–1/DFR to regulate drought stress by coordinating gene expression with metabolite and physiological strategies. Low to moderate levels of miR156 overexpression suppressedSPL13and increasedWD40–1to fine-tuneDFRexpression for enhanced anthocyanin biosynthesis. This, in combination with other accumulated stress mitigating metabolites and physiological responses, improved drought tolerance. We also demonstrated that SPL13 binds in vivo to theDFRpromoter to regulate its expression.ConclusionsTaken together, our results reveal that moderate relative miR156 transcript levels are sufficient to enhance drought resilience in alfalfa by silencingSPL13and increasingWD40–1expression, whereas higher miR156 overexpression results in drought susceptibility.

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    Europe PubMed Central
    Article . 2019
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    BMC Plant Biology
    Article . 2019
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      Article . 2019
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      Article . 2019
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    Authors: Carl D. Langefeld; Hannah C. Ainsworth; Deborah S. Cunninghame Graham; Jennifer A. Kelly; +104 Authors

    Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10−8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE. Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeld et al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ SZTE Publicatio Repo...arrow_drop_down
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    NARCIS
    Article . 2017
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    Europe PubMed Central
    Article . 2017
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    Article . 2017
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    Authors: Cortés-Vicente, Elena; Rojas-Garcia, Ricard; Diaz-Manera, Jordi; Querol, Luis; +12 Authors

    ObjectiveTo evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. MethodsThis retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan-Meier methods and survival analyses were undertaken using Cox proportional-hazards models. ResultsTwenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m(2)/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m(2)/4 weeks). Mean follow-up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan-Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log-rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7-2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9-91.8, P = 0.059). InterpretationThis study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG. I. Illa received research support from the Fondo de Investigacion en Salud, Instituto de Salud Carlos III, Ministry of Health (Spain), FIS PI16/01440 (Fondos FEDER). E. Cortes-Vicente was supported by a FIS grant (CM16/00096) from Fondo de Investigacion en Salud, Instituto de Salud Carlos III, Ministry of Health (Spain) and Fondo Social Europeo.

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  • Authors: Nancy Spencer-Cavaliere; Danielle Peers;

    The inclusion of able-bodied athletes within disability sport, a phenomenon known as reverse integration, has sparked significant debate within adapted physical activity. Although researchers and practitioners have taken up positions for or against reverse integration, there is a lack of supporting research on the experiences of athletes who already play in such settings. In this study, we explore how competitive female athletes who have a disability experience reverse integration in Canadian wheelchair basketball. Athletic identity was used as the initial conceptual framework to guide semistructured interviews with nine participants. The results suggest that participation in this context contributed to positive athletic identities. Interviews also pointed to the unexpected theme of “what’s the difference?” that this sporting context provided a space for the questioning and creative negotiation of the categories of disability and able-bodiedness. Methodologically, this paper also explores the possibilities and challenges of inter- worldview and insider-outsider research collaboration.

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    Authors: Marwan O. Jalambo; Basil Kanoa; Mohammed S. Ellulu; Smaher Younis; +1 Authors
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