bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Patient‐Reported Outcomes Measurement Information System Short Forms for Use in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Jones Jordan T. , Carle Adam C. , Wootton Janet , Liberio Brianna , Lee Jiha , Schanberg Laura E. , Ying Jun , Morgan DeWitt Esi , Brunner Hermine I. 
Published: April 2016

ObjectiveTo validate the pediatric Patient‐Reported Outcomes Measurement Information System short forms (PROMIS‐SFs) in childhood‐onset systemic lupus erythematosus (SLE) in a clinical setting.MethodsAt 3 study visits, childhood‐onset SLE patients completed the PROMIS‐SFs (anger, anxiety, depressive symptoms, fatigue, physical function‐mobility, physical function‐upper extremity, pain interference, and peer relationships) using the PROMIS assessment center, and health‐related quality of life (HRQoL) legacy measures (Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters [SMILEY], and visual analog scales [VAS] of pain and well‐being). Physicians rated childhood‐onset SLE activity on a VAS and completed the Systemic Lupus Erythematosus Disease Activity Index 2000. Using a global rating scale of change (GRC) between study visits, physicians rated change of childhood‐onset SLE activity (GRC‐MD1: better/same/worse) and change of patient overall health (GRC‐MD2: better/same/worse). Questionnaire scores were compared in support of validity and responsiveness to change (external standards: GRC‐MD1, GRC‐MD2).ResultsIn this population‐based cohort (n = 100) with a mean age of 15.8 years (range 10–20 years), the PROMIS‐SFs were completed in less than 5 minutes in a clinical setting. The PROMIS‐SF scores correlated at least moderately (Pearson's r ≥ 0.5) with those of legacy HRQoL measures, except for the SMILEY. Measures of childhood‐onset SLE activity did not correlate with the PROMIS‐SFs. Responsiveness to change of the PROMIS‐SFs was supported by path, mixed‐model, and correlation analyses.ConclusionTo assess HRQoL in childhood‐onset SLE, the PROMIS‐SFs demonstrated feasibility, internal consistency, construct validity, and responsiveness to change in a clinical setting.
Muropeptides in Pseudomonas aeruginosa and their Role as Elicitors of β‐Lactam‐Antibiotic Resistance
Authors: Lee Mijoon , Dhar Supurna , De Benedetti Stefania , Hesek Dusan , Boggess Bill , Blázquez Blas , Mathee Kalai , Mobashery Shahriar 
Published: April 2016

AbstractMuropeptides are a group of bacterial natural products generated from the cell wall in the course of its turnover. These compounds are cell‐wall recycling intermediates and are also involved in signaling within the bacterium. However, the identity of these signaling molecules remains elusive. The identification and characterization of 20 muropeptides from Pseudomonas aeruginosa is described. The least abundant of these metabolites is present at 100 and the most abundant at 55,000 molecules per bacterium. Analysis of these muropeptides under conditions of induction of resistance to a β‐lactam antibiotic identified two signaling muropeptides (N‐acetylglucosamine‐1,6‐anhydro‐N‐acetylmuramyl pentapeptide and 1,6‐anhydro‐N‐acetylmuramyl pentapeptide). Authentic synthetic samples of these metabolites were shown to activate expression of β‐lactamase in the absence of any β‐lactam antibiotic, thus indicating that they serve as chemical signals in this complex biochemical pathway.
Von komplexen Naturstoffen zu synthetisch leicht zugänglichen Mimetika mithilfe von computergestütztem De‐novo‐Design
Authors: Friedrich Lukas , Rodrigues Tiago , Neuhaus Claudia S. , Schneider Petra , Schneider Gisbert 
Published: April 2016

AbstractDiese Konzeptstudie präsentiert einen neuen Ansatz für den Entwurf Naturstoff‐inspirierter chemischer Verbindungen mit gewünschten pharmakologischen Eigenschaften. Wir stellen hier das computergestützte De‐novo‐Design von synthetisch zugänglichen Mimetika des strukturell komplexen, pflanzlichen Sesquiterpens (−)‐Englerin A vor. Wir synthetisierten leitstrukturähnliche Verbindungen ausgehend von käuflich verfügbaren Grundbausteinen und testeten diese auf ihre Aktivität gegen mehrere mit einem Computerprogramm vorhergesagte makromolekulare Targets. Sowohl die Designvorlage (−)‐Englerin A als auch deren niedermolekularen Mimetika zeigten nanomolare Bindungsaffinitäten und blockierten den Kalziumkanal TRPM8 (transient receptor potential melastatin 8) in einem zellbasiertem Assay. Die mit dem Computerverfahren erhaltene neuartige Leitstruktur besitzt keine ersichtliche Targetpromiskuität oder Frequent‐Hitter‐Eigenschaften.
Formation and Redox Interconversion of Niobium Methylidene and Methylidyne Complexes
Authors: Searles Keith , Smith Kyle T. , Kurogi Takashi , Chen Chun‐Hsing , Carroll Patrick J. , Mindiola Daniel J. 
Published: April 2016

AbstractThe niobium methylidene [{(Ar′O)2Nb}2(μ2‐Cl)2(μ2‐CH2)] (2) can be cleanly prepared via thermolysis or photolysis of [(Ar′O)2Nb(CH3)2Cl] (1) (OAr′=2,6‐bis(diphenylmethyl)‐4‐tert‐butylphenoxide). Reduction of 2 with two equivalents of KC8 results in formation of the first niobium methylidyne [K][{(Ar′O)2Nb}2(μ2‐CH)(μ2‐H)(μ2‐Cl)] (3) via a binuclear α‐hydrogen elimination. Oxidation of 3 with two equiv of ClCPh3 reforms 2. In addition to solid state X‐ray analysis, all these complexes were elucidated via multinuclear NMR experiments and isotopic labelling studies, including a crossover experiment, support the notion for a radical mechanism as well as a binuclear α‐hydrogen abstraction pathway being operative in the formation of 2 from 1.
Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel–Crafts‐Type 1,4‐Addition
Authors: Yoshida Keisuke , Itatsu Yukihiro , Fujino Yuta , Inoue Hiroki , Takao Ken‐ichi 
Published: April 2016

AbstractThe highly enantioselective organocatalytic construction of spiroindanes containing an all‐carbon quaternary stereocenter by intramolecular Friedel–Crafts‐type 1,4‐addition is described. The reaction was catalyzed by a cinchonidine‐based primary amine and accelerated by water and p‐bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (−)‐cannabispirenones A and B.
Iridium‐Catalyzed Enantioselective Hydroalkynylation of Enamides for the Synthesis of Homopropargyl Amides
Authors: Bai Xiao‐Yan , Wang Zi‐Xuan , Li Bi‐Jie 
Published: April 2016

AbstractReported is an iridium‐catalyzed asymmetric hydroalkynylation of enamides with terminal alkynes. The reaction occurs regioselectively at the β‐position of an enamide to produce homopropargyl amides. Good to high enantioselectivity was observed with an iridium complex ligated by a chiral bis(phosphine) ligand. This method provides a straightforward route to synthesize chiral homopropargyl amides with a stereocenter β to the amide.
Selenium‐Enriched Nickel Selenide Nanosheets as a Robust Electrocatalyst for Hydrogen Generation
Authors: Wang Fengmei , Li Yuanchang , Shifa Tofik Ahmed , Liu Kaili , Wang Feng , Wang Zhenxing , Xu Peng , Wang Qisheng , He Jun 
Published: April 2016

AbstractTo address the urgent need for clean and sustainable energy, the rapid development of hydrogen‐based technologies has started to revolutionize the use of earth‐abundant noble‐metal‐free catalysts for the hydrogen evolution reaction (HER). Like the active sites of hydrogenases, the cation sites of pyrite‐type transition‐metal dichalcogenides have been suggested to be active in the HER. Herein, we synthesized electrodes based on a Se‐enriched NiSe2 nanosheet array and explored the relationship between the anion sites and the improved hydrogen evolution activity through theoretical and experimental studies. The free energy for atomic hydrogen adsorption is much lower on the Se sites (0.13 eV) than on the Ni sites (0.87 eV). Notably, this electrode benefits from remarkable kinetic properties, with a small overpotential of 117 mV at 10 mA cm−2, a low Tafel slope of 32 mV per decade, and excellent stability. Control experiments showed that the efficient conversion of H+ into H2 is due to the presence of an excess of selenium in the NiSe2 nanosheet surface.
SNF5 is Involved in Suppression of Hepatocellular Carcinoma Progression via TGF‐Beta 1 Signaling
Authors: Sun Hongmiao , Zhong Xinping , Wang Chunyu , Wang Shengli , Lin Lin , Zou Renlong , Wu Yi , Sun Ning , Sun Ge , Wen Tao , Chi Zhi‐Hong , Zhao Yue 
Published: April 2016

ABSTRACTSNF5 (SMARCB1/INI1/BAF47), a core subunit of SWI/SNF complex, has been reported to modulate cell proliferation and apoptosis. Genetic evidence has suggested that SNF5 participates in tumor suppression. However, the detailed biological function and underlying mechanisms of SNF5 in hepatocellular carcinoma (HCC) progression remain unclear. Here, SNF5 expression reduction in HCC tissues compared with the adjacent non‐cancerous tissues has been demonstrated. Importantly, the results showed that reduced SNF5 expression has a strong correlation with worse overall survival of HCC patients. The data demonstrated that knockdown of SNF5 significantly promoted cell growth and migration in Hep3B and HCCLM3 cell lines. Interestingly, it was found that SNF5 suppressed transforming growth factor‐β1 (TGF‐β1) expression, and SNF5 mRNA expression was negatively correlated with TGF‐β1 in HCC tissues. Furthermore, depletion of SNF5 attenuated the sensitivity of HCC cells to sorafenib. Thus, the data suggested that SNF5 may participate in HCC suppression, and reduced expression of SNF5 correlates with the poor differentiation and prognosis of HCC, indicating that SNF5 might be an important prognostic biomarker and promising therapeutic target for HCC. Anat Rec, 299:869–877, 2016. © 2016 Wiley Periodicals, Inc.
Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study
Authors: Cutolo Maurizio , Herrick Ariane L. , Distler Oliver , Becker Mike O. , Beltran Emma , Carpentier Patrick , Ferri Clodoveo , Inanç Murat , Vlachoyiannopoulos Panayiotis , Chadha‐Boreham Harbajan , Cottreel Emmanuelle , Pfister Thomas , Rosenberg Daniel , Torres Juan V. , Smith Vanessa ,   on behalf of the CAP Study Investigators
Published: April 2016

ObjectiveTo identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc).MethodsIn this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses.ResultsOf the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756).ConclusionThis international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.
New Perspectives in Rheumatology: Avoiding Antimalarial Toxicity
Authors: Rosenbaum James T. , Mount George R. , Youssef Jameel , Lin Phoebe 
Published: April 2016

This report inaugurates New Perspectives in Rheumatology, a series of authoritative articles that focus on recent scientific and clinical developments and their potential to reshape rheumatology practice. Anticipated topics include the implementation of new guidelines and emerging information from clinical and translational research.
Richard J. Bucala, MD, PhDEditor‐in‐ChiefRobert Terkeltaub, MDCo‐Editor and Review Article Editor
Epigenetic Reprogramming in Naive CD4+ T Cells Favoring T Cell Activation and Non‐Th1 Effector T Cell Immune Response as an Early Event in Lupus Flares
Authors: Coit Patrick , Dozmorov Mikhail G. , Merrill Joan T. , McCune W. Joseph , Maksimowicz‐McKinnon Kathleen , Wren Jonathan D. , Sawalha Amr H. 
Published: April 2016

ObjectiveSystemic lupus erythematosus (SLE) is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus; however, early T cell events triggering disease flares are incompletely understood. This study was undertaken to examine DNA methylation in naive CD4+ T cells from lupus patients to determine if epigenetic remodeling in CD4+ T cells is an early event in lupus flares.MethodsA total of 74 lupus patients with an SLE Disease Activity Index score of 0–18 were included. Naive CD4+ T cells were isolated from peripheral blood samples, and DNA was extracted for genome‐wide methylation assessment. RNA was also extracted from a subset of patients to determine the relationship between epigenetic changes and transcription activity using RNA sequencing and microRNA arrays.ResultsWe demonstrated that naive CD4+ T cells in lupus undergo an epigenetic proinflammatory shift, implicating effector T cell responses in lupus flare. This epigenetic landscape change occurs without changes in expression of the corresponding genes, poises naive CD4+ T cells for Th2, Th17, and follicular helper T cell immune responses, and opposes inhibitory transforming growth factor β signaling. Bioinformatics analyses indicate that the epigenetic modulator EZH2 might play an important role in shifting the epigenetic landscape, with increased disease activity in lupus naive CD4+ T cells. Further, the expression of microRNA‐26a, which is sensitive to glucose availability and targets EZH2, was negatively correlated with disease activity in lupus patients.ConclusionAn epigenetic landscape shift in naive CD4+ T cells that favors T cell activation and non‐Th1 immune responses predates transcription activity and correlates with lupus activity. A role for EZH2 dysregulation in triggering lupus flares warrants further investigation.
A Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis
Authors: Rovin Brad H. , van Vollenhoven Ronald F. , Aranow Cynthia , Wagner Carrie , Gordon Robert , Zhuang Yanli , Belkowski Stanley , Hsu Benjamin 
Published: April 2016

ObjectiveTo assess the efficacy and safety of sirukumab, an anti–interleukin‐6 monoclonal antibody, for the treatment of patients with active lupus nephritis (LN).MethodsPatients with class III or class IV LN (as determined by renal biopsy within 14 months of randomization) who had persistent proteinuria (>0.5 gm/day) despite receiving immunosuppressive therapy and who were being treated with stable doses of a renin‐angiotensin system blocker were randomized (5:1) to receive treatment with sirukumab at a dose of 10 mg/kg intravenously (n = 21) or placebo (n = 4) every 4 weeks through week 24. The primary end point was the percent reduction in proteinuria (measured as the protein‐to‐creatinine [P:C] ratio in a 12‐hour urine collection) from baseline to week 24.ResultsTwenty‐five patients were enrolled, of whom 19 (76.0%) completed treatment through week 24 and 6 (24.0%) discontinued the study agent early, with 5 of the 6 discontinuing due to adverse events. At week 24, the median percent change in proteinuria from baseline to week 24 in sirukumab‐treated patients was 0.0% (95% confidence interval −61.8, 39.6). In contrast, the 4 placebo‐treated patients showed an increase in proteinuria (median percent reduction −43.3%) at week 24. Of note, a subset of 5 sirukumab‐treated patients had ≥50% improvement in their P:C ratio through week 28. In the sirukumab group, 47.6% of patients experienced ≥1 serious adverse event through week 40; most were infection‐related. No deaths or malignancies occurred. No serious adverse events were observed in the 4 placebo‐treated patients.ConclusionThis proof‐of‐concept study did not demonstrate the anticipated efficacy nor did it demonstrate an acceptable safety profile for sirukumab treatment in this population of patients with active LN receiving concomitant immunosuppressive treatment.
Semiquantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium
Authors: Collins Jamie E. , Losina Elena , Nevitt Michael C. , Roemer Frank W. , Guermazi Ali , Lynch John A. , Katz Jeffrey N. , Kent Kwoh C. , Kraus Virginia B. , Hunter David J. 
Published: April 2016

ObjectiveTo determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild‐to‐moderate osteoarthritis (OA).MethodsWe undertook a nested case–control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa‐synovitis, and effusion‐synovitis.ResultsThe most parsimonious model included changes in cartilage thickness and surface area, effusion‐synovitis, Hoffa‐synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8‐fold (95% confidence interval [95% CI] 1.3–5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4‐fold (95% CI 1.3–4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2‐fold (95% CI 1.3–3.8) greater odds of being a case. Worsening effusion‐synovitis and Hoffa‐synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively).ConclusionTwenty‐four–month changes in cartilage thickness, cartilage surface area, effusion‐synovitis, Hoffa‐synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease‐modifying interventions for knee OA.
Functional Interaction of the Ankylosing Spondylitis–Associated Endoplasmic Reticulum Aminopeptidase 2 With the HLA–B*27 Peptidome in Human Cells
Authors: Martín‐Esteban Adrian , Guasp Pablo , Barnea Eilon , Admon Arie , López de Castro José A. 
Published: April 2016

ObjectiveTo determine the influence of endoplasmic reticulum aminopeptidase 2 (ERAP‐2) expression on the HLA–B*27 peptidome in live cells.MethodsUsing immunoaffinity chromatography and acid extraction, HLA–B*27:05–bound peptides were isolated from 2 ERAP‐2–negative lymphoblastoid cell lines and 1 ERAP‐2–positive lymphoblastoid cell line expressing functionally indistinguishable ERAP‐1 variants. More than 2,000–4,000 B*27:05 ligands were identified from each cell line, and their relative abundance was established by quantitative tandem mass spectrometry and MaxQuant‐based peptide analyses. Pairwise comparisons were used to determine the structural features of peptides whose relative abundance was dependent on the presence of ERAP‐2. Synthetic peptide digestions were performed with recombinant ERAP‐1 and ERAP‐2. Peptide affinity was estimated with standard algorithms.ResultsThe B*27:05 peptidome from ERAP‐2–positive cells showed 3–4% fewer peptides with N‐terminal basic residues than did the peptidome from ERAP‐2–negative cells. Among the shared peptides, those most abundant in the presence of ERAP‐2 included more nonamers, fewer decamers, and fewer N‐terminal basic residues than the peptides predominant in ERAP‐2–negative cells. These ERAP‐2–dependent changes did not alter the global affinity of the B*27:05 peptidome.ConclusionERAP‐2 significantly influences the B*27:05‐bound peptidome by destroying some ligands and decreasing the abundance of many more ligands with N‐terminal basic residues, while increasing the abundance of nonamers. The former effects are best explained by direct ERAP‐2 trimming. The effects on peptide length might be attributed to ERAP‐2–induced activation of ERAP‐1 trimming. These data support the notion of a peptide‐mediated mechanism as the basis for the association of ERAP‐2 with ankylosing spondylitis. Analogous effects on other major histocompatibility complex class I peptidomes might explain the involvement of ERAP‐2 in HLA–B27–negative spondyloarthritis.
Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis
Authors: England Bryant R. , Sokolove Jeremy , Robinson William H. , Thiele Geoffrey M. , Ganti Apar K. , Sayles Harlan , Michaud Kaleb , Caplan Liron , Davis Lisa A. , Cannon Grant W. , Sauer Brian , Singh Namrata , Blair Solow E. , Reimold Andreas M. , Kerr Gail S. , Schwab Pascale , Baker Josh F. , Mikuls Ted R. 
Published: April 2016

ObjectiveTo examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA).MethodsMale participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead‐based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing‐risks regression.ResultsAmong 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient‐years of follow‐up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti–cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08–1.85) and lung cancer (SHR 1.86, 95% CI 1.57–2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2‐fold increased risk of overall cancer mortality (P = 0.039) and a 6‐fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed.ConclusionSerum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.