bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics of Children With Juvenile Dermatomyositis: The Childhood Arthritis and Rheumatology Research Alliance Registry
Authors: Robinson Angela Byun , Hoeltzel Mark F. , Wahezi Dawn M. , Becker Mara L. , Kessler Elizabeth A. , Schmeling Heinrike , Carrasco Ruy , Huber Adam M. , Feldman Brian M. , Reed Ann M. ,   the Juvenile Myositis CARRA Subgroup, for the CARRA Registry Investigators
Published: August 2013

ObjectiveTo investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry.MethodsSubjects meeting the modified Bohan and Peter criteria for definite juvenile DM were analyzed from the cross‐sectional Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between 2010 and 2012 from 55 US pediatric rheumatology centers. Demographics, disease characteristics, diagnostic assessments, and medication exposure data were collected at enrollment.ResultsA total of 384 subjects met the criteria for analysis. At enrollment, the median Childhood Myositis Assessment Scale score was 51 (interquartile range [IQR] 46–52), the median Childhood Health Assessment Questionnaire score was 0 (IQR 0–0.5), and the median physician and subject global assessment scores were 1 (IQR 0–2) and 1 (IQR 0–3), respectively, out of a maximum of 10. Of the diagnostic assessments, magnetic resonance imaging was more likely than electromyography or muscle biopsy to show abnormalities. A total of 329 subjects had ≥2 diagnostic studies performed, and >34% of these subjects reported ≥1 negative study. Ninety‐five percent had been treated with corticosteroids and 92% with methotrexate, suggesting that these medications were almost universally prescribed for juvenile DM in the US.ConclusionIn 2 years, the ongoing CARRA Registry has collected clinical data on 384 children with juvenile DM and has the potential to become one of the largest juvenile DM cohorts in the world. More research is needed about prognostic factors in juvenile DM, and differences in therapy based on manifestations of disease need to be explored by practitioners. This registry provides the infrastructure needed to advance clinical and translational research and represents a major step toward improving outcomes of children with juvenile DM.
Complementary and Alternative Medicine Use in African Americans With Rheumatoid Arthritis
Authors: Tamhane Ashutosh , McGwin Gerald , Redden David T. , Hughes Laura B. , Brown Elizabeth E. , Westfall Andrew O. , Conn Doyt L. , Jonas Beth L. , Smith Edwin A. , Brasington Richard D. , Moreland Larry W. , Bridges S. Louis , Callahan Leigh F. 
Published: August 2013

ObjectiveRacial/ethnic differences with regard to complementary and alternative medicine (CAM) use have been reported in the US. However, specific details of CAM use by African Americans with rheumatoid arthritis (RA) are lacking.MethodsData were collected from African Americans with RA enrolled in a multicenter registry regarding the use of CAM, including food supplements, topical applications, activities, and alternative care providers. Factors associated with CAM use by sex and disease duration were assessed using t‐test, Wilcoxon's rank sum test, chi‐square test, and logistic regression analyses.ResultsOf the 855 participants, 85% were women and mean age at enrollment was 54 years. Overall, ever using any of the CAM treatments, activities, and providers was 95%, 98%, and 51%, respectively (median of 3 for number of treatments, median of 5 for activities, and median of 1 for providers). Those with longer disease duration (>2 years) were significantly more likely (odds ratio ≥2.0, P < 0.05) to use raisins soaked in vodka/gin, to take fish oils, or to drink alcoholic beverages for RA treatment than those with early disease. As compared to men, women were significantly (P < 0.05) more likely to pray/attend church, write in a journal, and use biofeedback, but were less likely to smoke tobacco or topically apply household oils for treatment of RA.ConclusionCAM use was highly prevalent in this cohort, even in individuals with early disease. Health care providers need to be aware of CAM use as some treatments may potentially have interactions with conventional medicines. This could be important within this cohort of African Americans, where racial disparities are known to affect access to conventional care.
Deletion of the Transforming Growth Factor β Receptor Type II Gene in Articular Chondrocytes Leads to a Progressive Osteoarthritis‐like Phenotype in Mice
Authors: Shen Jie , Li Jia , Wang Baoli , Jin Hongting , Wang Meina , Zhang Yejia , Yang Yunzhi , Im Hee‐Jeong , O'Keefe Regis , Chen Di 
Published: August 2013

ObjectiveWhile transforming growth factor β (TGFβ) signaling plays a critical role in chondrocyte metabolism, the TGFβ signaling pathways and target genes involved in cartilage homeostasis and the development of osteoarthritis (OA) remain unclear. Using an in vitro cell culture method and an in vivo mouse genetic approach, we undertook this study to investigate TGFβ signaling in chondrocytes and to determine whether Mmp13 and Adamts5 are critical downstream target genes of TGFβ signaling.MethodsTGFβ receptor type II (TGFβRII)–conditional knockout (KO) (TGFβRIICol2ER) mice were generated by breeding TGFβRIIflox/flox mice with Col2‐CreER–transgenic mice. Histologic, histomorphometric, and gene expression analyses were performed. In vitro TGFβ signaling studies were performed using chondrogenic rat chondrosarcoma cells. To determine whether Mmp13 and Adamts5 are critical downstream target genes of TGFβ signaling, TGFβRII/matrix metalloproteinase 13 (MMP‐13)– and TGFβRII/ADAMTS‐5–double‐KO mice were generated and analyzed.ResultsInhibition of TGFβ signaling (deletion of the Tgfbr2 gene in chondrocytes) resulted in up‐regulation of Runx2, Mmp13, and Adamts5 expression in articular cartilage tissue and progressive OA development in TGFβRIICol2ER mice. Deletion of the Mmp13 or Adamts5 gene significantly ameliorated the OA‐like phenotype induced by the loss of TGFβ signaling. Treatment of TGFβRIICol2ER mice with an MMP‐13 inhibitor also slowed OA progression.ConclusionMmp13 and Adamts5 are critical downstream target genes involved in the TGFβ signaling pathway during the development of OA.
Local Synovial Engagement of Angiogenic TIE‐2 Is Associated With the Development of Persistent Erosive Rheumatoid Arthritis in Patients With Early Arthritis
Authors: van de Sande Marleen G. H. , de Launay Daphne , de Hair Maria J. H. , García Samuel , van de Sande Gijs P. M. , Wijbrandts Carla A. , Gerlag Danielle M. , Reedquist Kris A. , Tak Paul P. 
Published: August 2013

ObjectiveTo examine the role of vascular endothelial growth factor (VEGF) and angiopoietin signaling in the diagnosis and disease outcome of patients with early arthritis.MethodsFifty patients with early arthritis (disease duration <1 year) who had not been treated with disease‐modifying antirheumatic drugs (DMARDs) were monitored prospectively and were classified at baseline and after 2 years as having undifferentiated arthritis (UA), rheumatoid arthritis (RA), or spondyloarthritis (SpA). All patients underwent arthroscopic synovial biopsy at baseline. Synovial expression of VEGF, VEGF receptor, angiopoietin 1 (Ang‐1), Ang‐2, TIE‐2, and activated p–TIE‐2 was evaluated by immunohistochemistry. Serum levels of VEGF, Ang‐1, and Ang‐2 were measured by enzyme‐linked immunosorbent assay. Secreted products of macrophages stimulated with Ang‐1 and Ang‐2 were measured using a multiplex system.ResultsExpression of Ang‐1 was comparable between the patients with RA at baseline and patients with UA who fulfilled the criteria for RA over time (UA/RA), and it was significantly higher in patients with RA (P < 0.05) or UA/RA (P < 0.005) than in patients with SpA. TIE‐2 and p–TIE‐2 were more highly expressed in patients with RA (P < 0.005) or UA/RA (P < 0.05) than in patients with SpA. Ang‐1 significantly enhanced the tumor necrosis factor–dependent macrophage production of cytokines and chemokines that are known to be elevated in the synovial fluid of patients with early RA. In RA, relative TIE‐2 activation predicted the development of erosive disease (R2 = 0.35, P < 0.05).ConclusionLocal engagement of synovial TIE‐2 is observed during the earliest phases of RA, suggesting that TIE‐2 signaling may contribute to disease development and progression or may indicate an attempt to protect against these processes. Early therapeutic targeting of TIE‐2 signaling may be useful in improving outcome in arthritis.
Role of Fms‐like Tyrosine Kinase 3 Ligand as a Potential Biologic Marker of Lymphoma in Primary Sjögren's Syndrome
Authors: Tobón Gabriel J. , Saraux Alain , Gottenberg Jacques‐Eric , Quartuccio Luca , Fabris Martina , Seror Raphaèle , Devauchelle‐Pensec Valérie , Morel Jacques , Rist Stéphanie , Mariette Xavier , De Vita Salvatore , Youinou Pierre , Pers Jacques‐Olivier 
Published: August 2013

ObjectivePatients with primary Sjögren's syndrome (SS) are at greater risk of developing lymphoma. This study was undertaken to evaluate whether the Fms‐like tyrosine kinase 3 ligand (Flt‐3L) might be associated with lymphoma in primary SS.MethodsSerum levels of Flt‐3L were measured in 369 patients with primary SS from the French Assessment of Systemic Signs and Evolution of Sjögren's Syndrome study cohort and in 10 patients with primary SS at the time of lymphoma diagnosis in an Italian cohort. Associations between increased levels of Flt‐3L and a history of lymphoma, history of previously diagnosed criteria related to a high risk of lymphoma, and greater extent of disease activity were evaluated.ResultsAmong patients with primary SS, higher levels of Flt‐3L were significantly associated with a history of lymphoma (P = 0.0001). Previous markers for risk of lymphoma development, such as presence of purpura, low levels of C4, presence of lymphocytopenia, low levels of IgM, high levels of β2‐microglobulin, and a higher primary SS disease activity score, were all associated with higher levels of Flt‐3L. The levels of Flt‐3L were also increased in serum obtained from patients with primary SS at the time of lymphoma diagnosis. Furthermore, the Flt‐3L levels were elevated in the serum of 6 patients up to 94 months (mean 46 months) prior to the diagnosis of lymphoma. Receiver operating characteristic curve analysis showed that an Flt‐3L level of 175 pg/ml was the ideal cutoff value for demonstrating an association with lymphoma (specificity 97.5%, sensitivity 44%, negative predictive value 97%).ConclusionFlt‐3L is associated with lymphoma in primary SS, and constitutes a good biologic marker. Higher levels of this cytokine are present several years before the diagnosis of lymphoma, and may be useful as a predictive marker of lymphoproliferative disorders in primary SS.
The Peroxisome Proliferator–Activated Receptor γ Agonist Pioglitazone Preserves Bone Microarchitecture in Experimental Arthritis by Reducing the Interleukin‐17–Dependent Osteoclastogenic Pathway
Authors: Koufany Meriem , Chappard Daniel , Netter Patrick , Bastien Claire , Weryha Georges , Jouzeau Jean‐Yves , Moulin David 
Published: August 2013

ObjectiveTo investigate the effect of pioglitazone on inflammation‐induced bone loss and changes in bone microarchitecture in rats with adjuvant‐induced arthritis (AIA), focusing on the contribution of interleukin‐17 (IL‐17) and the balance of RANKL and osteoprotegerin (OPG).MethodsMale Lewis rats sensitized with Freund's complete adjuvant were treated orally for 21 days with 30 mg/kg/day of pioglitazone or vehicle. Arthritis severity was evaluated by clinical and histologic examination. Bone mineral density (BMD) was assessed by dual x‐ray absorptiometry. The therapeutic effect of pioglitazone on changes of the bone architecture was determined by micro–computed tomography (micro‐CT). Levels of RANKL, OPG, and IL‐17 were determined by serum immunoassay and by synovial tissue immunohistochemistry. Messenger RNA for IL‐17 and retinoic acid receptor–related orphan nuclear receptor γt (RORγt) was evaluated by quantitative reverse transcription–polymerase chain reaction and IL‐17 promoter activity by gene‐reporter assay.ResultsMicro‐CT analysis revealed that pioglitazone treatment reduced arthritis severity and bone erosion scores and increased BMD in comparison to vehicle treatment. Cortical bone thickness was preserved, although the major beneficial effect of pioglitazone was on indices of the trabeculae, especially trabecular separation. Pioglitazone reduced the ratio of RANKL to OPG, in both the serum and the inflamed synovium. Circulating levels of IL‐17 were significantly reduced by pioglitazone treatment, as were the percentages of IL‐17–positive cells, mainly polymorphonuclear cells, in the inflamed synovium. Induction of IL‐17 was strictly dependent on the binding of RORγt to IL‐17 promoter, and lentiviral overexpression of peroxisome proliferator–activated receptor γ (PPARγ) reduced the expression of RORγt.ConclusionPioglitazone decreased the level of inflammatory bone destruction and protected the bone microarchitecture in rats with AIA by controlling the circulating and local expression of IL‐17, with a subsequent decrease in the RANKL‐to‐OPG ratio. Along with the inhibition of RORγt expression after PPARγ overexpression, these findings provide evidence of the major contribution of reduced IL‐17/RANKL‐dependent osteoclastogenesis.
Sulforaphane Represses Matrix‐Degrading Proteases and Protects Cartilage From Destruction In Vitro and In Vivo
Authors: Davidson Rose K. , Jupp Orla , de Ferrars Rachel , Kay Colin D. , Culley Kirsty L. , Norton Rosemary , Driscoll Clare , Vincent Tonia L. , Donell Simon T. , Bao Yongping , Clark Ian M. 
Published: August 2013

ObjectiveSulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis.MethodsGene expression, histone acetylation, and signaling of the transcription factors NF‐E2–related factor 2 (Nrf2) and NF‐κB were examined in vitro. The bovine nasal cartilage explant model and the destabilization of the medial meniscus (DMM) model of osteoarthritis in the mouse were used to assess chondroprotection at the tissue and whole‐animal levels.ResultsSFN inhibited cytokine‐induced metalloproteinase expression in primary human articular chondrocytes and in fibroblast‐like synovial cells. SFN acted independently of Nrf2 and histone deacetylase activity to regulate metalloproteinase expression in human articular chondrocytes but did mediate prolonged activation of JNK and p38 MAPK. SFN attenuated NF‐κB signaling at least through inhibition of DNA binding in human articular chondrocytes, with decreased expression of several NF‐κB–dependent genes. Compared with cytokines alone, SFN (10 μM) abrogated cytokine‐induced destruction of bovine nasal cartilage at both the proteoglycan and collagen breakdown levels. An SFN‐rich diet (3 μmoles/day SFN versus control chow) decreased the arthritis score in the DMM model of osteoarthritis in the mouse, with a concurrent block of early DMM‐induced gene expression changes.ConclusionSFN inhibits the expression of key metalloproteinases implicated in osteoarthritis, independently of Nrf2, and blocks inflammation at the level of NF‐κB to protect against cartilage destruction in vitro and in vivo.
A Novel p53/microRNA‐22/Cyr61 Axis in Synovial Cells Regulates Inflammation in Rheumatoid Arthritis
Authors: Lin Jinpiao , Huo Rongfen , Xiao Lianbo , Zhu Xianjin , Xie Jun , Sun Songtao , He Yong , Zhang Jie , Sun Yue , Zhou Zhou , Wu Pinru , Shen Baihua , Li Dangsheng , Li Ningli 
Published: August 2013

ObjectiveWe previously showed that Cyr61 acts to promote fibroblast‐like synoviocyte (FLS) proliferation and Th17 cell differentiation, suggesting that Cyr61 plays an important role in mediating the joint inflammation and damage in rheumatoid arthritis (RA). The aim of this study was to investigate whether Cyr61 expression is regulated at the posttranscription level, and if so, how this regulation connects to other etiologic factors in RA.MethodsExpression of microRNA‐22 (miR‐22) in synovial tissue was detected by real‐time polymerase chain reaction (PCR) using miRNA‐specific TaqMan MGB probes. MicroRNA‐22 promoter activity was analyzed using a Dual‐Luciferase Reporter Assay. Cytokine expression was measured by enzyme‐linked immunosorbent assay, and the expression of other factors was measured by real‐time PCR or Western blotting.ResultsMicroRNA‐22 directly targeted the 3′‐untranslated region of Cyr61 messenger RNA and inhibited Cyr61 expression. Expression of miR‐22 was down‐regulated and was negatively correlated with Cyr61 expression in RA synovial tissue. Furthermore, wild‐type p53 activated miR‐22 transcription by binding to the promoter region of the miR‐22 gene, while the mutant forms of p53 frequently found in RA synovial tissue were shown to have lost the ability to activate miR‐22 expression. As a result, miR‐22 was down‐regulated, contributing to the overexpression of Cyr61 in RA FLS.ConclusionOur results not only reveal a novel mechanism whereby p53 is involved in the posttranscriptional regulation of Cyr61 expression via miRNA‐22, but also provide a molecular explanation for the role of somatic mutations of p53, which are frequently observed in RA synovial tissue, in the etiology of this autoimmune disease.
Chronic Kidney Disease and the Risk of Incident Gout Among Middle‐Aged Men: A Seven‐Year Prospective Observational Study
Authors: Krishnan Eswar 
Published: August 2013

ObjectiveThe kidney is the major organ that facilitates excretion of urate in humans. Surprisingly, few studies have assessed whether a reduced glomerular filtration rate (GFR) and/or kidney damage is associated with a higher incidence of gout, and this study was undertaken to address this question.MethodsData from a 7‐year followup of patients enrolled in the Multiple Risk Factor Intervention Trial, a primary prevention trial for cardiovascular disease among 12,866 men ages 35–57 years, were used for the present investigation. Presence of gout was determined by the study physicians from the original trial. Chronic kidney disease was defined using criteria similar to those proposed by the National Kidney Foundation. The Cox proportional hazards regression model was used to assess the association between gout and chronic kidney disease, after accounting for the effects of potential confounders.ResultsOverall, there were 722 cases of physician‐ diagnosed incident gout over 76,602 person‐years of followup. The standardized incidence ratio of gout among those with chronic kidney disease was 1,217 (95% confidence interval [95% CI] 1,191–1,244). The adjusted hazard ratio (HR) among those with chronic kidney disease was 1.61 (95% CI 1.60–1.61). Each standard deviation decline in the estimated GFR was associated with an HR of 1.43 (95% CI 1.35–1.51). Including the serum urate level, as well as the urate–chronic kidney disease interaction term, as variables in the second analysis did not attenuate the HR. Proteinuria and hematuria, two markers of kidney damage, were associated with an elevated risk of gout independent of the estimated GFR.ConclusionChronic kidney disease manifesting as reduced glomerular function or as presence of blood or protein in the urine increases the risk of incident gout.
Stabilization of the Triphosphallyl Ligand η3‐P3{P(O)H} at Iridium via Alkaline Activation of P4
Authors: Mirabello Vincenzo , Caporali Maria , Gonsalvi Luca , Manca Gabriele , Ienco Andrea , Peruzzini Maurizio 
Published: August 2013

AbstractThe selective functionalization of the polyphosphorus moiety Ph2PCH2PPh2PPPP present as a tetrahapto‐ligand in complex [Ir(dppm)(Ph2PCH2PPh2PPPP)]+ (1, dppm=Ph2PCH2PPh2) was obtained by reaction of 1 with water under basic conditions at room temperature. The formation of the new triphosphaallyl moiety η3‐P3{P(O)H} was determined in solution by NMR spectroscopy, and confirmed in the solid state by a single‐crystal X‐ray structure of the stable product [Ir(κ2‐dppm)(κ1‐dppm)(η3‐P3{P(O)H})] (2). In solution, 2 has a fluxional behavior attributable to the four P atoms belonging to the tetraphosphorus moiety in 1 and exhibits a chemical exchange process involving the two PPh2 moieties of the same bidentate ligand, as determined by 1D and 2D NMR spectroscopy experiments carried out at variable temperature. The mechanism of the reaction was investigated at the DFT level, which suggested a selective attack of an in‐situ generated OH− anion on one of the non‐coordinated phosphorus atoms of the P4 moiety. The reaction then evolves through an acid‐assisted tautomerization, which leads to the final compound 2. Bonding analysis pointed out that the new unsubstituted P3‐unit in the η3‐P3{P(O)H} moiety behaves as a triphosphallyl ligand.
Long‐term biomass yields of giant reed, mimosa and switchgrass in Alabama
Authors: Ping Huang , Bransby David I. , van Santen Edzard 
Published: August 2013

AbstractThe US Department of Energy conducted two studies to estimate the potential of cellulosic biomass crops for production of biofuels on a national scale. However, limited long‐term experimental information is available to support the resultant yield projections. The objectives of this research were: (i) to determine long‐term (>10 years) biomass yields and soil impacts of switchgrass (Panicum virgatum L.), giant reed (Arundo donax L.) and mimosa (Albizia julibrissin Durazz.) in Alabama; and (ii) to establish relationships between precipitation and yields of these perennial biomass crops, and yields of cotton, maize, and soybean. Mimosa and giant reed received no fertilizer and were harvested once each year while switchgrass received 84 kg ha–1 of N fertilizer annually, and was harvested twice each year. Cotton, maize, and soybean were managed according to traditional practices for these crops in this region. Average annual biomass yields of mimosa, giant reed, and switchgrass were 40.1, 35.5 and 23.5 kg ha–1 over 16‐, 11‐ and 22‐year periods, respectively, with corresponding estimated annual N accumulation in aboveground biomass of 388, 372 and 163 kg ha–1. Yields of maize, cotton and soybean decreased sharply with decreasing precipitation, but there was no corresponding decrease in yield of the three perennial biomass crops. Changes in the yields of the biomass crops with age were also relatively small. Analysis of topsoil samples suggested considerably less removal of P, K, Ca, and Mg than was estimated from yield and concentrations of these elements in the biomass that was actually removed. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd
Spectrofluorimetric determination of aluminum ions via complexation with luteolin in absolute ethanol
Authors: Sun Jinyu , Wu You , Xiao Dan , Lin Xia , Li Hui 
Published: August 2013

ABSTRACTAn optimized and validated spectrofluorimetric method has been developed for the rapid determination of aluminum in absolute ethanol. The method is based on the chelation of aluminum and luteolin which results in a complex exhibiting an intense emission signal. The characterization of Al–luteolin complex was studied using ultraviolet–visible spectrometry, infrared spectrometry, fluorescence and mass spectrometry. The complex stoichiometry ratio of aluminum:luteolin was 1:2. The fluorescence of the complex was monitored at an emission wavelength of 545 nm with excitation at 518 nm. The linear concentration range was 6.5 × 10‐7 to 4.0 × 10‐5 M with a correlation coefficient of r = 0.998. The detection limit was 5.0 × 10‐7 M. The method was appropriately validated and yielded relative standard deviations of < 2.3% (n = 5), which was considered acceptable. The method was successfully applied in the determination of aluminum in river water, skin care products and pharmaceutical samples. Copyright © 2013 John Wiley & Sons, Ltd.