bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of construction and demolition wastes as mineral fillers in hybrid wood–polymer composites
Authors: Keskisaari Anna , Butylina Svetlana , Kärki Timo 
Published: January 2016

ABSTRACTThe recycling of construction materials has been the subject of much research in past years. In this study, the use of construction and demolition wastes (CDWs) as mineral fillers in hybrid wood–polymer composites was studied. Two types of waste materials were used as fillers in the composites: (1) a mixture consisting of waste mineral wool (MW) and plasterboard (PB) and (2) mixed CDWs. The performance of the composites was evaluated from their mechanical properties and water‐absorption behavior. We found in the study that the addition of mineral fillers decreased the flexural strength and modulus values of the wood–polypropylene (PP) composites. On the other hand, the exchange of part of the wood with a mineral filler resulted in an increase in the impact strength of the composite. The composite manufactured with the combination of MW and PB had the lowest water absorption. The decrease in wood loading resulted in improved dimensional stability in the hybrid wood–mineral filler–PP composites. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43412.
Newly Identified BRAF Mutation in Rheumatoid Arthritis
Authors: Arnoux Fanny , Fina Frederic , Lambert Nathalie , Balandraud Nathalie , Martin Marielle , Ouafik L'Houcine , Kanaan Sami B. , Roudier Jean , Auger Isabelle 
Published: January 2016

ObjectiveRheumatoid arthritis (RA)–associated autoantibodies include those directed at the kinase site of BRAF (v‐Raf murine sarcoma viral oncogene homolog B1), a serine–threonine kinase involved in the MAPK signaling pathway. To understand anti‐BRAF immunization, we sought to identify BRAF mutations in the peripheral blood lymphocytes (PBLs) of patients with RA.MethodsWe first cloned the major BRAF region known for mutations in the pCR2.1 vector, using genomic DNA from the PBLs of 8 RA patients. For each patient, 100 clones were sequenced. In 5 of 8 patients, we detected a new BRAF mutation in 1 clone. The frequency of this new mutation was evaluated by droplet digital polymerase chain reaction in PBLs from RA patients and controls. To test whether p.Val600Ala influences the kinase activity of BRAF, we developed an in vitro assay based on phosphorylation of MEK‐1, a major BRAF substrate.ResultsA BRAF mutation, p.Val600Ala, was identified in 1 of 8,000 PBLs and 1 of 6,000 T lymphocytes from RA patients and in 1 of 12,500 PBLs and 1 of 12,500 T lymphocytes from controls. The BRAF p.Val600Ala mutation was not correlated with the presence of anti‐BRAF autoantibodies. The p.Val600Ala mutation activated phosphorylation of MEK‐1 in vitro.ConclusionMost RA patients have a p.Val600Ala mutation in the BRAF gene. This mutation activates the kinase activity of BRAF. The p.Val600Ala mutation could activate the MAPK pathway, leading to the activation of T lymphocytes.
Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations
Authors: Yih Chen Ji , Ling Wu Yee , Yin Mok Mo , Jan Wu Yeong‐Jian , Lintner Katherine E. , Wang Chin‐Man , Chung Erwin K. , Yang Yan , Zhou Bi , Wang Huanyu , Yu Denise J. H. C. , Alhomosh Alaaedin , Jones Karla , Spencer Charles H. , Nagaraja Haikady N. , Lung Lau Yu , Lau Chak‐Sing , Yung Yu C. 
Published: January 2016

Objective Human complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in systemic lupus erythematosus (SLE), and to compare the basis of race‐specific C4A deficiency between East Asians and individuals of European descent.Methods The East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4‐Long and C4‐Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency.Results In East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4‐Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 × 10−7) and C4B (OR 2.53, P = 2.5 × 10−5). Patients with low serum complement levels had high frequencies of anti–double‐stranded DNA antibodies (OR 4.96, P = 9.7 × 10−17), hemolytic anemia (OR 3.89, P = 3.6 × 10−10), and renal disease (OR 2.18, P = 8.5 × 10−6). The monomodular‐Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA–DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4‐Long and C4‐Short genes, encoding C4B1 and C4B96, which was linked to HLA–DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96.ConclusionC4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations.
Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumatoid Arthritis
Authors: Plant Darren , Webster Amy , Nair Nisha , Oliver James , Smith Samantha L. , Eyre Steven , Hyrich Kimme L. , Wilson Anthony G. , Morgan Ann W. , Isaacs John D. , Worthington Jane , Barton Anne 
Published: January 2016

ObjectiveBiologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA.MethodsAn epigenome‐wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis‐acting single‐nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients.ResultsFive positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10−8 and cg26401028, P = 1.69 × 10−8). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10−7 and P = 1.05 × 10−6, respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204).ConclusionWe identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low‐density lipoprotein receptor–related protein 1. Additional replication experiments in independent sample collections are now needed.
Interferon‐γ, but Not Interleukin‐4, Suppresses Experimental Polymyositis
Authors: Yoshihashi‐Nakazato Yoko , Kawahata Kimito , Kimura Naoki , Miyasaka Nobuyuki , Kohsaka Hitoshi 
Published: January 2016

ObjectiveC protein–induced myositis (CIM) is a mouse model of polymyositis in which activated antigen‐specific CD8+ T cells injure the muscles. Animal models of autoimmunity that have been examined in the past for the effects of the type 1 cytokine interferon‐γ (IFNγ) and the type 2 cytokine interleukin‐4 (IL‐4) are all mediated by pathogenic CD4+ T cells. In those models, the disruption of IFNγ leads to up‐regulation of IL‐17A, exacerbating the disease with neutrophil infiltration into sites of inflammation. This study was undertaken to investigate the roles of IFNγ and IL‐4, as well as IL‐17A in the absence of IFNγ, in CD8+ T cell–mediated CIM.MethodsIFNγ−/− mice, anti–IL‐17A antibody–treated IFNγ−/− mice, IFNγ−/−IL‐17A−/− mice, IL‐4−/− mice, and wild‐type C57BL/6 mice were immunized with skeletal muscle C protein fragments to induce CIM. Muscle tissue specimens were examined histologically.ResultsIFNγ−/− mice developed myositis at a higher incidence and with greater severity than wild‐type mice. Unlike wild‐type mice, IFNγ−/− mice had infiltration of neutrophils into the endomysial sites of the affected muscles. IFNγ−/− mice treated with anti–IL‐17A antibodies and IFNγ−/−IL‐17A−/− mice developed myositis with an incidence and severity comparable to those in IFNγ−/− mice and showed neutrophil infiltration similar to that in IFNγ−/− mice. IL‐4−/− mice developed CIM comparable to that in wild‐type mice.ConclusionOur findings indicate that IFNγ, but not IL‐4, plays a suppressive role in the development of CIM. Unlike in CD4+ T cell–mediated autoimmune disease models, IFNγ prevents factors other than IL‐17A from exacerbating myositis and neutrophil infiltration in CD8+ T cell–mediated CIM.
Brief Report: Association of Rheumatoid Factor and Anti–Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan‐European Registry Analysis
Authors: Gottenberg J. E. , Courvoisier D. S. , Hernandez M. V. , Iannone F. , Lie E. , Canhão H. , Pavelka K. , Hetland M. L. , Turesson C. , Mariette X. , Finckh A. 
Published: January 2016

ObjectiveTo investigate the role of rheumatoid factor (RF) status and anti–citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA).MethodsWe conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR‐DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM‐RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated.ResultsWe identified 2,942 patients with available data on RA‐associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease‐ and treatment‐related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69–0.90], P < 0.001 and HR 0.78 [95% CI 0.68–0.90], P < 0.001, respectively), compared to RF‐negative and ACPA‐negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61–0.84) and 0.74 (95% CI 0.62–0.88), respectively (both P < 0.001).ConclusionOur results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.
Histone Demethylation and Toll‐like Receptor 8–Dependent Cross‐Talk in Monocytes Promotes Transdifferentiation of Fibroblasts in Systemic Sclerosis Via Fra‐2
Authors: Ciechomska Marzena , O'Reilly Steven , Przyborski Stefan , Oakley Fiona , Bogunia‐Kubik Katarzyna , van Laar Jacob M. 
Published: January 2016

ObjectiveTo investigate whether epigenetic changes can modulate monocytes to produce tissue inhibitor of metalloproteinases 1 (TIMP‐1) via Fra‐2 (an activator protein 1 [AP‐1] family member), a novel downstream mediator that promotes fibrogenesis.MethodsAP‐1 transcription factors and TIMP‐1 expression were measured in monocytes from systemic sclerosis (SSc) patients and healthy controls. Involvement of Fra‐2 in the regulation of TIMP‐1 following treatment with Toll‐like receptor 8 (TLR‐8) agonist was investigated using a luciferase activity assay and chromatin immunoprecipitation (ChIP) analysis. Expression of TIMP‐1 and Fra‐2 was determined in response to TLR‐8 treatment and to different histone modifications, including 3′‐deazaneplanocin (DZNep) and apicidin. Fibroblasts from healthy controls were cocultured with DZNep plus TLR‐8–treated healthy control monocytes.ResultsUp‐regulation of Fra‐2 was detected in bleomycin‐challenged mice and in skin biopsy samples from SSc patients. Enhanced expression of Fra‐2 and TIMP‐1 was correlated in SSc monocytes (P = 0.021). The expression of Fra‐1 was significantly reduced (P = 0.037) in SSc monocytes. Inhibiting AP‐1 activity reduced TIMP‐1 production in TLR‐8–stimulated monocytes from healthy controls and SSc patients. ChIP experiments revealed binding of Fra‐2 to the TIMP‐1 promoter. Stimulation with DZNep plus TLR‐8 enhanced Fra‐2 and TIMP‐1 expression in healthy control monocytes, whereas TLR‐8 plus apicidin repressed Fra‐2 and TIMP‐1 expression. Finally, healthy control monocytes treated with DZNep plus TLR‐8 induced strong production of α‐smooth muscle actin in dermal fibroblasts, which was inhibited by TIMP‐1–blocking antibody.ConclusionThese data demonstrate a novel role of histone demethylation induced by DZNep on Fra‐2–mediated TIMP‐1 production by monocytes in the presence of TLR‐8 agonist. This consequently orchestrates the transdifferentiation of fibroblasts, a key event in the pathogenesis of SSc.
Cγ1 Deficiency Exacerbates Collagen‐Induced Arthritis
Authors: Strait Richard T. , Thornton Sherry , Finkelman Fred D. 
Published: January 2016

ObjectiveIgG antibodies protect by aggregating pathogens and activating complement and stimulatory Fcγ receptors (FcγR). Although IgG1 accounts for a large percentage of murine serum antibodies, it poorly activates complement, binds more avidly to inhibitory FcγRIIb than to stimulatory FcγRIII, and has a relatively low aggregating ability. We previously demonstrated that IgG1 protects against complement‐ and FcγR‐independent renal disease by inhibiting immune complex obstruction of glomerular capillaries. The purpose of this study was to determine whether IgG1 also protects against the complement‐ and FcγR‐dependent disorder, collagen‐induced arthritis (CIA).MethodsCIA was induced by injecting mice with type II collagen (CII) (active model) or with IgG2a and IgG2b anti‐CII monoclonal antibodies (ArthritoMab) (passive model). Arthritis severity was assessed, and CII‐specific IgG was titered.ResultsCγ1‐deficient C57BL/6 mice lack IgG1 (IgG1−/−); in these mice, arthritis developed at a higher frequency and was more severe compared with IgG1+/+ mice in the active model. Disease was FcγRIII‐ and C3‐dependent in both the IgG+/+ and IgG−/− mouse strains and was not influenced by interleukin‐4 receptor α in either strain. CII‐specific IgG2a/c titers were considerably higher in IgG1−/− than in IgG1+/+ mice and correlated with CIA incidence and severity. IgG1+/+ mice that developed CIA had higher CII‐specific IgG1 and IgG2a/c levels than did those without CIA. CII‐inoculated BALB/c IgG1+/+ and IgG1−/− mice had much lower CII‐specific IgG2a/c titers than did C57BL/6 mice and failed to develop CIA but developed passive CIA when given ArthritoMab.ConclusionThe absence of a functional Cγ1 gene indirectly promotes the development of CIA, likely through increased production of IgG2a/c, an isotype that strongly activates complement and stimulatory FcγR.
Frequency of Axial Spondyloarthritis Diagnosis Among Patients Seen by US Rheumatologists for Evaluation of Chronic Back Pain
Authors: Deodhar Atul , Mease Philip J. , Reveille John D. , Curtis Jeffrey R. , Chen Su , Malhotra Kailash , Pangan Aileen L. 
Published: January 2016

ObjectiveTo determine the proportion of patients with axial spondyloarthritis (SpA) among those with chronic back pain and ≥1 of 3 SpA features in the US.MethodsThe study was conducted at rheumatology practices in the US. Patients were required to have chronic back pain for ≥3 months beginning at <45 years of age, no prior SpA diagnosis, and ≥1 of the following 3 SpA features: HLA–B27 positivity, current inflammatory back pain, and magnetic resonance imaging (MRI) or radiographic evidence of sacroiliitis. Medical history and physical examination findings, pelvic radiographs, MRIs of sacroiliac joints, C‐reactive protein (CRP) level, and HLA–B27 status were obtained. Investigators were asked if a clinical diagnosis of axial SpA could be made based on the results. Data were also analyzed separately to determine if patients fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA and/or modified New York criteria for ankylosing spondylitis (AS).ResultsA total of 751 patients were enrolled (46% were existing patients in rheumatology practices, 40% were new referrals, and 14% were self referred). Among patients with available data, 319 of 697 (46%) were diagnosed as having axial SpA by the investigator, and 348 of 744 (47%) fulfilled the ASAS criteria, of whom 238 were classified as having nonradiographic axial SpA and 108 as having AS; 2 had missing data. Using investigator's clinical diagnosis as the gold standard, the specificity and sensitivity of the ASAS criteria were 79% and 81%, respectively.ConclusionOur findings indicate that among patients with chronic back pain for ≥3 months beginning at ages younger than 45 years, the presence of ≥1 of 3 SpA features is an effective way to identify those with possible axial SpA.
Observability Under Sampling for Nonlinear Systems
Authors: Ammar Sabeur , Massaoud Majid , Vivalda Jean‐Claude 
Published: January 2016

AbstractA previous article has investigated the problem of the preservation of the observability under sampling in the framework of compact manifolds. A natural generalization of the cited result would be to extend it to the systems globally Lipschitzian defined on non compact manifolds. A simple representative of this class of systems is constituted by the set of bilinear systems, for this particular class of systems the preservation of the property of observability has been shown in a previous work. In this paper, we deal with the preservation of the observability under sampling for globally Lipschitzian systems defined on Rn.
H∞ Control for Continuous‐Time Mean‐Field Stochastic Systems
Authors: Ma Limin , Zhang Tianliang , Zhang Weihai 
Published: January 2016

AbstractAn H∞‐type control is considered for mean‐field stochastic differential equations (SDEs) in this paper. A stochastic bounded real lemma (SBRL) is proved for mean‐field stochastic continuous‐time systems with state‐ and disturbance‐dependent noise. Based on SBRL, a sufficient condition is given for the existence of a stabilizing H∞ controller in terms of coupled nonlinear matrix inequalities.
Optical analysis of RE3+ (RE = Pr3+, Er3+ and Nd3+):cadmium lead boro tellurite glasses
Authors: Giridhar P. , Bhushana Reddy M. , Neelima G. , Ramanaiah R. , Nagamuni Reddy K. , Sahadeva Reddy V. , Sudhakar Reddy B. 
Published: January 2016

AbstractThis article reports on the optical characterization of Pr3+‐, Er3+‐ and Nd3+‐doped cadmium lead boro tellurite (CLBT) glasses prepared using the melt quenching method. The visible–near infrared (Vis–NIR) absorption spectra of these glasses were analyzed systematically. On measuring the NIR emission spectra of Er3+:CLBT glasses, a broad emission band centered at 1536 nm (4I13/2 → 4I15/2) was observed, as were three NIR emission bands at 900 nm (4F3/2 → 4I9/2), 1069 nm (4F3/2 → 4I11/2) and 1338 nm (4F3/2 → 4I13/2) from Nd3+:CLBT glasses and an NIR emission band at 1334 nm (1G4 → 3H5) from Pr3+:CLBT glasses at an excitation wavelength (λex) of 514.5 nm (Ar+ laser). Copyright © 2016 John Wiley & Sons, Ltd.
Pretreatment lymphopenia is an easily detectable predictive and prognostic marker in patients with metastatic esophagus squamous cell carcinoma receiving first‐line chemotherapy
Authors: Kou Furong , Lu Zhihao , Li Jian , Zhang Xiaotian , Lu Ming , Zhou Jun , Wang Xicheng , Gong Jifang , Gao Jing , Li Jie , Li Yan , Shen Lin 
Published: January 2016

AbstractTo explore the influence of pretreatment lymphopenia on the toxicity and efficacy of first‐line chemotherapy in patients with metastatic esophagus squamous cell carcinoma (ESCC). In total, 215 patients were included in this retrospective study. Correlations between pretreatment lymphopenia (lymphocyte count <1 × 109/L) and the occurrence of toxicity and the efficacy of first‐line palliative chemotherapy were investigated. Pretreatment lymphopenia was found in 19.1% of the patients. The overall response rate (ORR) was 35.5% (65 of 183 patients). Patients with pretreatment lymphopenia had a lower ORR to chemotherapy compared with those without lymphopenia (22.2% vs. 38.8%, respectively; P = 0.045). Furthermore, the patients with pretreatment lymphopenia have higher grade 3–4 hematological toxicity than that of patients without pretreatment lymphopenia (19 of 41 patients, 46.3% vs. 54 of 174 patients, 31.0%; P = 0.048). Pretreatment lymphopenia was not correlated with grade 3–4 nonhematological toxicity. Multivariate analysis showed that pretreatment lymphopenia is an independent prognostic factor. Patients with pretreatment lymphopenia had a significantly shorter overall survival time than those without lymphopenia (8.2 months vs. 12.7 months; P = 0.020). This study shows that pretreatment lymphopenia is a good prognostic factor as well as a predictive factor for tumor response and chemotherapy‐related hematological toxicity in metastatic ESCC.