bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Occupation, Sick Leave, and Disability Pension Due to Knee and Hip Osteoarthritis From a Sex Perspective
Authors: Hubertsson Jenny , Turkiewicz Aleksandra , Petersson Ingemar F. , Englund Martin 
Published: April 2016

ObjectiveTo investigate the association between occupation and risk for sick leave or disability pension due to knee or hip osteoarthritis (OA) from a sex perspective.MethodsWe conducted a population‐based study including residents ages 40–70 years in the Skåne region, Sweden (2007) and working in the included job sectors (n = 165,179). We retrieved data on cause‐specific sick leave and disability pension (2007–2012) and linked to individual information on occupation and education (2007). Occupations were classified into job sectors. We calculated sex‐specific, age‐adjusted odds ratios (ORs) of sick leave and disability pension due to OA in traditionally female‐dominated job sectors (health care, child care, and cleaning) and traditionally male‐dominated job sectors (construction, farming, metal work, or transportation) compared to business and administration.ResultsOf all eligible subjects, 2,445 had sick leave or disability pension due to knee or hip OA. Adjusted for age, the risk of sick leave due to knee OA was increased for women working in health care, with an OR of 3.3 (95% confidence interval [95% CI] 2.6–4.2), child care OR 2.9 (95% CI 2.2–3.8), and cleaning OR 3.0 (95% CI 2.2–4.1), as was the risk for disability pension. The risk was increased also for persons working in occupations with higher educational requirements. The risk was similarly increased in male‐dominated sectors. In female‐dominated job sectors the risk of sick leave and disability pension due to knee OA, but not hip OA, was higher than that for other musculoskeletal diseases.ConclusionTraditionally female‐dominated occupational sectors are associated with an increased risk of sick leave and disability pension due to knee OA.
Use of Rituximab in Systemic Lupus Erythematosus: A Single Center Experience Over 14 Years
Authors: Aguiar R. , Araújo C. , Martins‐Coelho G. , Isenberg D. 
Published: April 2016

ObjectiveTo describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or whose disease is refractory to standard immunosuppressive therapy, treated at a single center.MethodsThis was a retrospective analysis of all patients with SLE treated with RTX at 1 center between June 2000 and December 2013. The clinical outcome was assessed by determining British Isles Lupus Assessment Group (BILAG) scores and anti–double‐stranded DNA (anti‐dsDNA) and C3 levels before and 6 months after RTX treatment. For safety analysis, adverse events and deaths were recorded.ResultsOf a total of 115 patients, 93.9% were female, the mean ± SD age at diagnosis was 26.39 ± 11.90 years, and the mean ± SD disease duration at first RTX treatment was 91.96 ± 84.80 months. A BILAG score variation of −11.26 ± 11.38 (P < 0.001) was recorded 6 months after the first RTX treatment; 40% of patients had a complete response and 27% had a partial response; in 36.5% of patients, C3 levels increased more than 25%, and in 33.5% anti‐dsDNA levels decreased more than 50%. Depletion of CD19+ cells was achieved in 94.0% of patients. Hypogammaglobulinemia was detected in 14.9% of patients, with significant reduction for IgM (P < 0.001) and IgG (P = 0.001) levels. Severe infections, infusion‐related reactions, and hypersensitivity reactions occurred in 7%, 3.5%, and 2.6% of patients, respectively. Of the 115 patients, 62 patients had repeated RTX treatments, with an average number of 1.95 ± 1.17 cycles per patient and a mean ± SD interval between infusions of 21.44 ± 20.11 months. At the end of followup, 11 patients were deceased; 6 had cardiovascular events.ConclusionRTX treatment was effective in decreasing disease activity, with a low incidence of adverse effects.
Altered Blood–Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach
Authors: Gulati Gaurav , Jones Jordan T. , Lee Gregory , Altaye Mekibib , Beebe Dean W. , Meyers‐Eaton Jamie , Wiley Kasha , Brunner Hermine I. , DiFrancesco Mark W. 
Published: April 2016

ObjectiveTo evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood–brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile‐onset systemic lupus erythematosus (SLE).MethodsIn this cross‐sectional, case–control study, capillary permeability was measured as a marker of blood–brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion‐weighted brain MRI. Regional gray matter volume was measured by voxel‐based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood–brain barrier integrity among juvenile SLE patients.ResultsFormal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all).ConclusionThere is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood–brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood–brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.
Risk of Cardiovascular Morbidity in Patients With Psoriatic Arthritis: A Meta‐Analysis of Observational Studies
Authors: Polachek Ari , Touma Zahi , Anderson Melanie , Eder Lihi 
Published: April 2016

ObjectiveTo assess the magnitude of risk of cardiovascular and cerebrovascular morbidity in patients with psoriatic arthritis (PsA) compared with the general population through a systematic review and meta‐analysis of observational studies.MethodsWe searched the Medline, Embase, and Cochrane databases, as well as abstracts archives from rheumatology conferences. Observational studies that included a PsA diagnosis, cardiovascular or cerebrovascular outcomes, and a comparison group of individuals without psoriasis and rheumatic diseases and were case–control, cross‐sectional, or cohort studies, were assessed by 2 researchers. We calculated weighted pooled summary estimates of the maximally adjusted effect size estimates for cardiovascular and cerebrovascular diseases using the random‐effects model, and tested for heterogeneity using the I2 statistic.ResultsEleven studies, comprising 32,973 patients with PsA, met the inclusion criteria. There was a 43% increased risk of cardiovascular diseases in patients with PsA compared with the general population (pooled odds ratio [OR] 1.43 [95% confidence interval (95% CI) 1.24–1.66]). The risk of incident cardiovascular events was increased by 55% (pooled OR 1.22–1.96). Morbidity risks for myocardial infarction, cerebrovascular diseases, and heart failure were increased by 68%, 22%, and 31%, respectively (pooled OR 1.68 [95% CI 1.31–2.15], pooled OR 1.22 [95% CI 1.05–1.41], and pooled OR 1.31 [95% CI 1.11–1.55], respectively). We identified significant heterogeneity in all main analyses (P < 0.001).ConclusionCardiovascular and cerebrovascular morbidity are increased by 43% and 22%, respectively, in patients with PsA compared with the general population.
Thinking Like a Chemist: Intuition in Thermoelectric Materials
Authors: Zeier Wolfgang G. , Zevalkink Alex , Gibbs Zachary M. , Hautier Geoffroy , Kanatzidis Mercouri G. , Snyder G. Jeffrey 
Published: April 2016

AbstractThe coupled transport properties required to create an efficient thermoelectric material necessitates a thorough understanding of the relationship between the chemistry and physics in a solid. We approach thermoelectric material design using the chemical intuition provided by molecular orbital diagrams, tight binding theory, and a classic understanding of bond strength. Concepts such as electronegativity, band width, orbital overlap, bond energy, and bond length are used to explain trends in electronic properties such as the magnitude and temperature dependence of band gap, carrier effective mass, and band degeneracy and convergence. The lattice thermal conductivity is discussed in relation to the crystal structure and bond strength, with emphasis on the importance of bond length. We provide an overview of how symmetry and bonding strength affect electron and phonon transport in solids, and how altering these properties may be used in strategies to improve thermoelectric performance.
Value of Formalin Fixation for the Prolonged Preservation of Rodent Myocardial Microanatomical Organization: Evidence by MR Diffusion Tensor Imaging
Authors: Giannakidis Archontis , Gullberg Grant T. , Pennell Dudley J. , Firmin David N. 
Published: April 2016

ABSTRACTPrevious ex vivo diffusion tensor imaging (DTI) studies on formalin‐fixed myocardial tissue assumed that, after some initial changes in the first 48 hr since the start of fixation, DTI parameters remain stable over time. Prolonged preservation of cardiac tissue in formalin prior to imaging has been seen many times in the DTI literature as it is considered orderly. Our objective is to define the effects of the prolonged cardiac tissue exposure to formalin on tissue microanatomical organization, as this is assessed by DTI parameters. DTI experiments were conducted on eight excised rodent hearts that were fixed by immersion in formalin. The samples were randomly divided into two equinumerous groups corresponding to shorter (∼2 weeks) and more prolonged (∼6–8 weeks) durations of tissue exposure to formalin prior to imaging. We found that when the duration of cardiac tissue exposure to formalin before imaging increased, water diffusion became less restricted, helix angle (HA) histograms flattened out and exhibited heavier tails (even though the classic HA transmural variation was preserved), and a significant loss of inter‐voxel primary diffusion orientation integrity was introduced. The prolonged preservation of cardiac tissue in formalin profoundly affected its microstructural organization, as this was assessed by DTI parameters. The accurate interpretation of diffusivity profiles necessitates awareness of the pitfalls of prolonged cardiac tissue exposure duration to formalin. The acquired knowledge works to the advantage of a proper experimental design of DTI studies of fixed hearts. Anat Rec, 299:878–887, 2016. © 2016 Wiley Periodicals, Inc.
Brief Report: Whole‐Exome Sequencing for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis
Authors: Mak Angel C. Y. , Tang Paul L. F. , Cleveland Clare , Smith Melanie H. , Kari Connolly M. , Katsumoto Tamiko R. , Wolters Paul J. , Kwok Pui‐Yan , Criswell Lindsey A. 
Published: April 2016

ObjectiveScleroderma is a genetically complex autoimmune disease with substantial phenotypic heterogeneity. Previous genome‐wide association studies have identified common genetic variants associated with disease risk, but these studies are not designed to capture rare or potential causal variants. Our goal was to identify rare as well as common genetic variants in patients with diffuse cutaneous systemic sclerosis (dcSSc) through whole‐exome sequencing (WES) in order to identify potential causal variants.MethodsWe generated WES data for 32 dcSSc patients with or without interstitial lung disease (ILD) and for 17 healthy “in‐house” controls. Variants were annotated and filtered by quality, minor allele frequency, and deleterious effects on gene function. We applied a gene burden test to identify novel dcSSc and dcSSc‐associated ILD candidate genes that were enriched with deleterious variants in cases compared to in‐house controls as well as controls from the 1000 Genomes Project (n = 130).ResultsWe identified 70 genes that were enriched with deleterious variants in dcSSc patients. Two of them (BANK1 and TERT) were in pathways previously implicated in SSc or ILD pathogenesis or known susceptibility loci. Newly identified genes (COL4A3, COL4A4, COL5A2, COL13A1, and COL22A1) were significantly enriched in the extracellular matrix–related pathway, which is relevant to the fibrotic features of dcSSc, and in the DNA repair pathway (XRCC4).ConclusionThis study demonstrates the value of WES for the identification of novel gene variants and pathways that may contribute to scleroderma risk and/or severity. The candidate genes we discovered are potential targets for in‐depth functional studies.
MicroRNA‐130b Ameliorates Murine Lupus Nephritis Through Targeting the Type I Interferon Pathway on Renal Mesangial Cells
Authors: Han Xiao , Wang Yan , Zhang Xiaoyan , Qin Yuting , Qu Bo , Wu Lingling , Ma Jianyang , Zhou Zhenyuan , Qian Jie , Dai Min , Tang Yuanjia , Chan Edward K. L. , Harley John B. , Zhou Shiyu , Shen Nan 
Published: April 2016

ObjectiveType I interferon (IFN) is a critical pathogenic factor during the progression of lupus nephritis (LN). Although microRNAs (miRNAs) have been shown to control the IFN response in immune cells in LN, the role of miRNAs in resident renal cells remains unclear. We undertook this study to investigate the role of microRNA‐130b (miR‐130b) in the IFN pathway in renal cells as well as its therapeutic effect in LN.MethodsKidney tissues from patients and (NZB × NZW)F1 lupus‐prone mice were collected for detecting miR‐130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR‐130b in the IFN pathway. We overexpressed miR‐130b by administering miR‐130b agomir in a mouse model of IFNα‐accelerated LN to test its therapeutic efficacy.ResultsDown‐regulated miR‐130b expression was observed in kidney tissues from patients and lupus‐prone mice. Further analysis showed that underexpression of miR‐130b correlated negatively with abnormal activation of the IFN response in LN patients. In vitro, overexpressing miR‐130b suppressed signaling downstream from the type I IFN pathway in RMCs by targeting IFN regulatory factor 1 (IRF‐1). The opposite effect was observed when endogenous miR‐130b expression was inhibited. The inverse correlation between IRF1 and miR‐130b levels was detected in renal biopsy samples from LN patients. More importantly, in vivo administration of miR‐130b agomir reduced IFNα‐accelerated progression of LN, with decreased proteinuria, lower levels of immune complex deposition, and lack of glomerular lesions.ConclusionMicroRNA‐130b is a novel negative regulator of the type I IFN pathway in renal cells. Overexpression of miR‐130b in vivo ameliorates IFNα‐accelerated LN, providing potential novel strategies for therapeutic intervention in LN.
Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross‐Disease Meta‐Analysis of Genome‐Wide Association Studies
Authors: López‐Isac Elena , Martín Jose‐Ezequiel , Assassi Shervin , Simeón Carmen P. , Carreira Patricia , Ortego‐Centeno Norberto , Freire Mayka , Beltrán Emma , Narváez Javier , Alegre‐Sancho Juan J. ,   the Spanish Scleroderma Group, Fernández‐Gutiérrez Benjamín , Balsa Alejandro , Ortiz Ana M. , González‐Gay Miguel A. , Beretta Lorenzo , Santaniello Alessandro , Bellocchi Chiara , Lunardi Claudio , Moroncini Gianluca , Gabrielli Armando , Witte Torsten , Hunzelmann Nicolas , Distler Jörg H. W. , Riekemasten Gabriella , van der Helm‐van Mil Annette H. , de Vries‐Bouwstra Jeska , Magro‐Checa Cesar , Voskuyl Alexandre E. , Vonk Madelon C. , Molberg Øyvind , Merriman Tony , Hesselstrand Roger , Nordin Annika , Padyukov Leonid , Herrick Ariane , Eyre Steve , Koeleman Bobby P. C. , Denton Christopher P. , Fonseca Carmen , Radstake Timothy R. D. J. , Worthington Jane , Mayes Maureen D. , Martín Javier 
Published: April 2016

ObjectiveSystemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome‐wide association (meta‐GWAS) strategy.MethodsThe study was designed as a meta‐analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same‐direction and opposite‐direction allelic effects. The top single‐nucleotide polymorphisms were followed up in independent SSc and RA case–control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.ResultsThis cross‐disease meta‐analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 10−6) that also showed evidence of association in the disease‐specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow‐up analyses of the putatively new SSc–RA loci identified IRF4 as a shared risk factor for these 2 diseases (Pcombined = 3.29 × 10−12). Analysis of the biologic relevance of the known SSc–RA shared loci identified the type I interferon and interleukin‐12 signaling pathways as the main common etiologic factors.ConclusionThis study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross‐disease GWAS meta‐analysis strategy in the identification of common risk loci.
Interleukin‐23–Dependent γ/δ T Cells Produce Interleukin‐17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice
Authors: Reinhardt Annika , Yevsa Tetyana , Worbs Tim , Lienenklaus Stefan , Sandrock Inga , Oberdörfer Linda , Korn Thomas , Weiss Siegfried , Förster Reinhold , Prinz Immo 
Published: April 2016

ObjectiveThe spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin‐23 (IL‐23) is involved in the pathogenesis of SpA by acting on IL‐23 receptor (IL‐23R) expressed on enthesis‐resident lymphocytes. Upon IL‐23 binding, CD3+CD4−CD8− tissue‐resident lymphocytes secrete IL‐17A and IL‐22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis‐resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis.MethodsWe used 2‐photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd‐H2BeGFP, Rorc‐GFP, and IL‐23R‐eGFP mice. To analyze entheseal γ/δ T cells in IL‐23−induced inflammation, Tcrd‐H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL‐23 minicircle DNA was performed for overexpression of IL‐23 and induction of inflammation. Light‐sheet fluorescence microscopy was used to visualize arthritic inflammation.ResultsActivated Vγ6+CD27− γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor−related orphan nuclear receptor γt (RORγt)+IL‐23R+ enthesis‐resident lymphocytes. Fetal thymus−dependent γ/δ T cells were the main source of IL‐17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body.ConclusionEntheseal γ/δ T cells are derived from fetal thymus and are maintained as self‐renewing tissue‐resident cells. As main IL‐17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL‐23−induced local inflammation.
Prion‐like Aggregation of Mitochondrial Antiviral Signaling Protein in Lupus Patients Is Associated With Increased Levels of Type I Interferon
Authors: Shao Wen‐Hai , Shu Daniel H. , Zhen Yuxuan , Hilliard Brendan , Priest Stephen O. , Cesaroni Matteo , Ting Jenny P.‐Y. , Cohen Philip L. 
Published: April 2016

ObjectiveIncreased levels of type I interferon (IFN) and type I IFN–regulated genes are found in patients with systemic lupus erythematosus (SLE) and may be central to its pathogenesis. Mitochondrial antiviral signaling protein (MAVS) is a key regulator of type I IFN that undergoes a dramatic prion‐like aggregation and self propagates the activation signal from viral RNA to amplify downstream IFN production. We undertook this study to determine whether such MAVS aggregates might play a role in the sustained increased production of type I IFN in SLE.MethodsPeripheral blood mononuclear cells were isolated and mitochondrial extracts were prepared. MAVS aggregation was detected by semidenatured agarose gel electrophoresis and confirmed by immunofluorescence staining. MAVS‐associated signaling proteins were analyzed by Western blotting. MAVS aggregation–associated gene expression signature was analyzed by microarray.ResultsIn blood cells from 22 of 67 SLE patients, essentially all MAVS was in a high molecular weight aggregated form. None of 6 rheumatoid arthritis patients and only 3 of 33 healthy controls had abnormal MAVS. Compared to MAVS aggregate–negative patients, MAVS aggregate–positive SLE patients had significantly higher serum levels of IFNβ and significantly increased levels of autoantibodies against Sm and U1 RNP. Gene array data revealed a characteristic gene expression pattern in these patients, with altered expression of genes involved in IFN signaling and membrane trafficking.ConclusionPersistent MAVS aggregates may lead to increased type I IFN production and result in unmitigated signals leading to autoimmunity.