bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Serious Infection in Juvenile Idiopathic Arthritis Patients Associated With Tumor Necrosis Factor Inhibitors and Disease Activity in the German Biologics in Pediatric Rheumatology Registry
Authors: Becker Ingrid , Horneff Gerd 
Published: July 2016

ObjectiveTo examine the effects of tumor necrosis factor inhibitors on the risk for serious infections and other influencing factors in a registry.MethodsPatients exposed for the first time to etanercept, adalimumab, or methotrexate and serious infections were identified in the German Biologic Registry for Pediatric Rheumatology (BIKER) registry. Serious infection rates per 1,000 observation‐years and relative risks were calculated. Cox regression identified risk factors and provided hazard ratios (HRs) for occurrence of infections.ResultsA total of 3,350 patients with 5,919 observation‐years fulfilled the inclusion criteria for the study. The first biologic agents were etanercept (1,720 cases) and adalimumab (177 cases). A total of 1,453 patients were treated with methotrexate and no biologic agent. In total, 28 serious infections were reported in 26 patients (4.7 per 1,000 patient‐years), 5 with methotrexate (1.6 per 1,000 patient‐years), 21 with etanercept (8.1 per 1,000 patient‐years), and 2 with adalimumab (9.7 per 1,000 patient‐years). Significant univariate risk factors for infection were therapy with biologic agents, disease duration before therapy start, corticosteroid medication, nonbiologic premedications, higher clinical Juvenile Arthritis Disease Activity Score including maximal 10 joints (cJADAS10) at therapy start, and higher mean cJADAS10 during therapy. In multivariate Cox regression, only biologic therapy and cJADAS10 at therapy start remained significant. Risk for infection was increased by etanercept (univariate HR 6.0 [95% confidence interval (95% CI) 2.0–17.5]) or adalimumab (HR 7.3 [95% CI 1.3–40.0]) compared to methotrexate as well as by an elevated cJADAS10 at therapy start (HR 1.1 [95% CI 1.0–1.2] per unit increase).ConclusionThe total rate of serious infections reported in the BIKER registry seems low. Treatment with etanercept or adalimumab increases the risk for serious infection slightly, compared to methotrexate. Disease activity expressed by cJADAS10 appears to be an independent risk factor.
Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti–Interferon‐Inducible Protein 16 Antibodies
Authors: McMahan Zsuzsanna H. , Wigley Frederick M. , Casciola‐Rosen Livia 
Published: July 2016

ObjectiveTo evaluate whether scleroderma patients who are double‐positive for anti–interferon‐inducible protein 16 (anti–IFI‐16) antibodies and anticentromere (anti‐CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti‐CENP antibodies alone.MethodsSera from 165 scleroderma patients who tested positive for anti‐CENP antibodies upon clinical evaluation were reassayed for both anti‐CENP and anti–IFI‐16 antibodies using enzyme‐linked immunosorbent assay testing. Patients who were positive for anti‐CENP antibodies alone were then compared to patients who were double‐positive for both anti–IFI‐16 and anti‐CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double‐positive antibody status was examined using chi‐square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates.ResultsOf the 165 anti–CENP antibody positive patients, 21 (12.7%) also had anti–IFI‐16 antibodies. Patients who were double‐positive for anti‐CENP and anti‐IFI‐16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double‐positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1–11.1]; P = 0.03).ConclusionScleroderma patients who are double‐positive for antibodies recognizing CENP and IFI‐16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti‐CENP and anti–IFI‐16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma.
Incidence of Chronic Persistent Rheumatoid Arthritis and the Impact of Smoking: A Historical Twin Cohort Study
Authors: Svendsen Anders J. , Junker Peter , Houen Gunnar , Kyvik Kirsten O. , Nielsen Christian , Skytthe Axel , Holst René 
Published: July 2016

ObjectiveTo assess the incidence of chronic persistent rheumatoid arthritis (RA) in a population‐based cohort of twins and to determine the impact of smoking.MethodsIn a historical cohort study on twins born in 1920 to 1982, we identified 157 cases of RA among 45,280 responders (response rate 80%). Information on smoking was obtained by questionnaire and interview. A mixed‐effects Poisson regression model was used to estimate incidence rate ratios with age, sex, smoking duration, and smoking intensity as covariates. We used the SplitLexis procedure in the Epi R package to study a possible effect of period or cohort in addition to age on the variation of the incidence.ResultsThe annual incidence of chronic persistent RA was 18.8 per 100,000 person‐years, ages 15–73 years (females 25.2, males 12.0), increasing with age to a maximum at age 60 years in females and age 70 years in males. The incidence rate ratio among ever‐smoking patients was 1.96 (95% confidence interval [95% CI] 1.43–3.76), 1.93 (95% CI 1.00–3.7) after 30 pack‐years, and 1.034 (P < 0.001) per year of smoking, implying a doubling of risk after 20 years regardless of sex and smoking intensity. We did not detect significant period or cohort effects.ConclusionThe incidence of chronic persistent RA is lower than the incidence figures reported in inception cohorts. Smoking duration, but not intensity, doubled the risk of RA after 20 years of smoking in both sexes.
Developing Electronic Health Record Algorithms That Accurately Identify Patients With Systemic Lupus Erythematosus
Authors: Barnado April , Casey Carolyn , Carroll Robert J. , Wheless Lee , Denny Joshua C. , Crofford Leslie J. 
Published: July 2016

ObjectiveTo study systemic lupus erythematosus (SLE) in the electronic health record (EHR), we must accurately identify patients with SLE. Our objective was to develop and validate novel EHR algorithms that use International Classification of Diseases, Ninth Revision (ICD‐9), Clinical Modification codes, laboratory testing, and medications to identify SLE patients.MethodsWe used Vanderbilt's Synthetic Derivative, a de‐identified version of the EHR, with 2.5 million subjects. We selected all individuals with at least 1 SLE ICD‐9 code (710.0), yielding 5,959 individuals. To create a training set, 200 subjects were randomly selected for chart review. A subject was defined as a case if diagnosed with SLE by a rheumatologist, nephrologist, or dermatologist. Positive predictive values (PPVs) and sensitivity were calculated for combinations of code counts of the SLE ICD‐9 code, a positive antinuclear antibody (ANA), ever use of medications, and a keyword of “lupus” in the problem list. The algorithms with the highest PPV were each internally validated using a random set of 100 individuals from the remaining 5,759 subjects.ResultsThe algorithm with the highest PPV at 95% in the training set and 91% in the validation set was 3 or more counts of the SLE ICD‐9 code, ANA positive (≥1:40), and ever use of both disease‐modifying antirheumatic drugs and steroids, while excluding individuals with systemic sclerosis and dermatomyositis ICD‐9 codes.ConclusionWe developed and validated the first EHR algorithm that incorporates laboratory values and medications with the SLE ICD‐9 code to identify patients with SLE accurately.
Annulation of Alkynyl Aryl Ethers with Allyl Pivalates To Give 2,3‐Bismethylenechromanes through Double C−H Bond Cleavage
Authors: Minami Yasunori , Sakai Megumi , Anami Tomohiro , Hiyama Tamejiro 
Published: July 2016

AbstractThe treatment of silylethynyloxyarenes with allylic pivalates in the presence of a palladium catalyst led to efficient C−H bond cleavage in both substrates and a novel annulation reaction to give 2,3‐bismethylenechromanes. When ortho‐allylated silylethynyloxybenzenes were used as the substrates, the same products were obtained. This result shows that site‐selective intramolecular hydrovinylation is involved in the annulation reaction. The synthetic utility of the products was demonstrated by the construction of condensed polycycles.
Operando Synchrotron X‐ray Powder Diffraction and Modulated‐Excitation Infrared Spectroscopy Elucidate the CO2 Promotion on a Commercial Methanol Synthesis Catalyst
Authors: Martin Oliver , Mondelli Cecilia , Cervellino Antonio , Ferri Davide , Curulla‐Ferré Daniel , Pérez‐Ramírez Javier 
Published: July 2016

AbstractOptimal amounts of CO2 are added to syngas to boost the methanol synthesis rate on Cu‐ZnO‐Al2O3 in the industrial process. The reason for CO2 promotion is not sufficiently understood at the particle level due to the catalyst complexity and the high demands of characterization under true reaction conditions. Herein, we applied operando synchrotron X‐ray powder diffraction and modulated‐excitation infrared spectroscopy on a commercial catalyst to gain insights into its morphology and surface chemistry. These studies unveiled that Cu and ZnO agglomerate and ZnO particles flatten under CO/H2 and/or CO2/H2. Under the optimal CO/CO2/H2 mixture, sintering is prevented and ZnO crystals adopt an elongated shape due to the minimal presence of the H2O byproduct, enhancing the water‐gas shift activity and thus the methanol production. Our results provide a rationale to the CO2 promotion emphasizing the importance of advanced analytical methods to establish structure–performance relations in heterogeneous catalysis.
Kinetic Resolution of 2H‐Azirines by Asymmetric Imine Amidation
Authors: Hu Haipeng , Liu Yangbin , Lin Lili , Zhang Yuheng , Liu Xiaohua , Feng Xiaoming 
Published: July 2016

AbstractHighly efficient kinetic resolution of 2H‐azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N′‐dioxide/ScIII complex, thus providing a promising method to obtain the enantioenriched 2H‐azirine derivatives and protecting‐group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H‐azirines were stereospecifically transformed into an unprotected aziridine and α‐amino ketone.
Triiodide‐Mediated δ‐Amination of Secondary C−H Bonds
Authors: Wappes Ethan A. , Fosu Stacy C. , Chopko Trevor C. , Nagib David A. 
Published: July 2016

AbstractThe Cδ−H amination of unactivated, secondary C−H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I3−)‐mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I2) as I3−, this approach precludes undesired I2‐mediated decomposition which can otherwise limit synthetic utility to only weak C(sp3)−H bonds. The mechanism of this triiodide‐mediated cyclization of unbiased, secondary C(sp3)−H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates.
Brief Report: CXCL10 Is a Possible Biomarker for the Development of Psoriatic Arthritis Among Patients With Psoriasis
Authors: Abji Fatima , Pollock Remy A. , Liang Kun , Chandran Vinod , Gladman Dafna D. 
Published: July 2016

ObjectiveBiomarkers that can predict the development of psoriatic arthritis (PsA) in patients with psoriasis would be useful in clinical practice. The aim of this study was to assess whether CXCL10 could be a predictive biomarker of PsA prior to its onset.MethodsPsoriasis patients without arthritis were followed up prospectively and assessed annually for development of PsA by a rheumatologist. Patients in whom PsA developed were designated as converters, while those in whom PsA did not develop were termed nonconverters. Baseline serum concentrations of CXCL10 were measured by Luminex assay in 46 converters and 45 nonconverters.ResultsThe level of CXCL10 was significantly higher in converters (median 493 pg/ml [interquartile range (IQR) 356–984]) than in nonconverters (median 371 pg/ml [IQR 263–578]; P = 0.005). In contrast, C‐reactive protein (CRP) levels were not significantly different between converters and nonconverters at baseline. CXCL10 was associated with conversion status after adjustment for age, sex, duration of psoriasis, and duration of follow‐up (odds ratio 1.3, 95% confidence interval 1.1–1.5, P = 0.004). In a subset of converters, the CXCL10 level was significantly higher at baseline (median 927.4 pg/ml [IQR 547.6–1,243]) than after PsA diagnosis (491.5 pg/ml [IQR 323.2–607]; P < 0.0001), while CRP levels were lower at baseline (26.6 μg/ml [IQR 16.37–62.75]) than after PsA diagnosis (36.1 μg/ml [IQR 14.74–101.7]; P = 0.003). CXCL10 gene expression was increased 17.3‐fold in synovial fluid (SF) compared with blood from PsA patients (P = 0.01) and 44.3‐fold in the SF of PsA patients compared with the SF of patients with gout (P = 0.001).ConclusionCXCL10 may be involved in PsA pathogenesis and is a candidate predictive biomarker for PsA in patients with psoriasis.
A Phase IIb Study of ABT‐494, a Selective JAK‐1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–Tumor Necrosis Factor Therapy
Authors: Kremer Joel M. , Emery Paul , Camp Heidi S. , Friedman Alan , Wang Li , Othman Ahmed A. , Khan Nasser , Pangan Aileen L. , Jungerwirth Steven , Keystone Edward C. 
Published: July 2016

ObjectiveTo compare the efficacy and safety of ABT‐494, a novel selective JAK‐1 inhibitor, with placebo in patients with moderate‐to‐severe rheumatoid arthritis (RA) and an inadequate response or intolerance to at least 1 anti–tumor necrosis factor (anti‐TNF) agent.MethodsIn this 12‐week, double‐blind, placebo‐controlled, dose‐ranging study, 276 RA patients receiving a stable dose of methotrexate (MTX) who had previously received treatment with at least 1 anti‐TNF agent were randomized equally to receive immediate‐release ABT‐494 at 3, 6, 12, or 18 mg twice daily or matching placebo twice daily. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 12.ResultsAt week 12, significantly more patients receiving ABT‐494 (53–71%) than those receiving placebo (34%) achieved an ACR20 response (by nonresponder imputation analysis) (P < 0.05), with a dose‐response relationship among all ABT‐494 doses (P < 0.001). ACR50 and ACR70 response rates were significantly higher in those receiving ABT‐494 (36–42% and 22–26%, respectively) than in those receiving placebo (16% and 4%, respectively). Changes from baseline in the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) were significantly greater for all doses of ABT‐494 than for placebo (P ≤ 0.01). Onset of action of ABT‐494 was rapid, with significant differences from placebo at week 2 both in ACR20 response rate (for 12 and 18 mg) and in change in the DAS28‐CRP (P < 0.001 for 6–18 mg). The most frequent adverse events (AEs) were headache, nausea, upper respiratory tract infection, and urinary tract infection. Infection rates were higher at higher doses of ABT‐494, but no infections were serious. No deaths were reported among those receiving ABT‐494.ConclusionIn patients with an inadequate response or intolerance to anti‐TNF agents, ABT‐494 added to MTX showed rapid, dose‐dependent improvements in RA signs and symptoms, with safety and tolerability similar to those of other drugs of this class. No new AEs were identified.
New Ruthenium Complexes Based on Tetradentate Bipyridine Ligands for Catalytic Hydrogenation of Esters
Authors: Wang Fangyuan , Tan Xuefeng , Lv Hui , Zhang Xumu 
Published: July 2016

AbstractNew bipyridinemethanamine‐containing tetradentate ligands and their corresponding ruthenium complexes have been synthesized. The synthesized complexes performed well in the hydrogenation of a variety of esters with high efficiency (TON up to 9700) giving alcohols in good yields.
Amino‐substituted para‐Benzoquinones as Potential Herbicides
Authors: Nain‐Perez Amalyn , Barbosa Luiz C. A. , Picanço Marcelo C. , Giberti Samuele , Forlani Giuseppe 
Published: July 2016

Although quinones present a large array of biological activities, a few studies on the herbicidal potential of 2,5‐bis(alkyl/arylamino)‐1,4‐benzoquinones have been reported to date. In this work, starting from benzoquinone, 13 2,5‐bis(alkyl/arylamino)‐1,4‐benzoquinones were prepared in 46 – 93% yield. The products were fully characterized by spectroscopic analyses and their phytotoxicity against Cucumis sativus and Sorghum bicolor seedlings was investigated. At 100 ppm, compounds caused 10 – 88% growth inhibition of the dicotyledonous species, whereas the monocotyledon was less affected. Most compounds exerted little inhibitory effect on a cyanobacterial model strain. However, at 100 μm, compounds 8 – 10 caused about 50% inhibition of algal growth, and compounds 1 and 2 reduced cell viability in the 1 – 10 μm range. The ability of benzoquinone derivatives to interfere with the light‐driven ferricyanide reduction by isolated spinach chloroplasts was evaluated. Some substances showed a moderate effect as uncouplers, but no relationship was found between this property and their biological activity, indicating that the herbicidal effect is not associated with the inhibition of the photosynthetic electron transport chain. Phytotoxic compounds were not toxic to insects, strengthening the possibility that they may serve as lead for the development of eco‐friendly herbicides.
Absorption and Oxidation of Nitrogen Oxide in Ionic Liquids
Authors: Kunov‐Kruse Andreas J. , Thomassen Peter L. , Riisager Anders , Mossin Susanne , Fehrmann Rasmus 
Published: July 2016

AbstractA new strategy for capturing nitrogen oxide, NO, from the gas phase is presented. Dilute NO gas is removed from the gas phase by ionic liquids under ambient conditions. The nitrate anion of the ionic liquid catalyzes the oxidation of NO to nitric acid by atmospheric oxygen in the presence of water. The nitric acid is absorbed in the ionic liquid up to approximately one mole HNO3 per mole of the ionic liquid due to the formation of hydrogen bonds. The nitric acid can be desorbed by heating, thereby regenerating the ionic liquid with excellent reproducibility. Here, time‐resolved in‐situ spectroscopic investigations of the reaction and products are presented. The procedure reveals a new vision for removing the pollutant NO by absorption into a non‐volatile liquid and converting it into a useful bulk chemical, that is, HNO3.
Modified Guanines as Constituents of Smart Ligands for Nucleic Acid Quadruplexes
Authors: Durec Matúš , Zaccaria Francesco , Fonseca Guerra Célia , Marek Radek 
Published: July 2016

AbstractRepetitive guanine‐rich nucleic acid sequences play a crucial role in maintaining genome stability and the cell life cycle and represent potential targets for regulatory drugs. Recently, it has been demonstrated that guanine‐based ligands with a porphyrin core can be used as markers of G‐quadruplex assemblies in cell tissues. Herein, model systems of guanine‐based ligands are explored by DFT methods. The energies of formation of modified guanine tetrads and those of modified tetrads stacked on the top of natural guanine tetrads have been calculated. The interaction energy has been decomposed into contributions from hydrogen bonding, stacking, and ion coordination and a twist–rise potential energy scan has been performed to find the individual local minima. Energy decomposition analysis reveals the impact of various substituents (F, Cl, Br, I, Me, NMe2) on individual energy terms. In addition, cooperative reinforcement in forming the modified and stacked tetrads, as well as the frontier orbitals participating in the hydrogen‐bonding framework involving the HOMO–LUMO gap between the occupied σHOMO on the proton‐accepting C=O and =N− groups and unoccupied σLUMO on the N−H groups, has been studied. The investigated systems are demonstrated to have a potential in ligand development, mainly due to stacking enhancement compared with natural guanine, which is used as a reference.
Direct Structural Identification of Gas Induced Gate‐Opening Coupled with Commensurate Adsorption in a Microporous Metal–Organic Framework
Authors: Banerjee Debasis , Wang Hao , Plonka Anna M. , Emge Thomas J. , Parise John B. , Li Jing 
Published: July 2016

AbstractGate‐opening is a unique and interesting phenomenon commonly observed in flexible porous frameworks, where the pore characteristics and/or crystal structures change in response to external stimuli such as adding or removing guest molecules. For gate‐opening that is induced by gas adsorption, the pore‐opening pressure often varies for different adsorbate molecules and, thus, can be applied to selectively separate a gas mixture. The detailed understanding of this phenomenon is of fundamental importance to the design of industrially applicable gas‐selective sorbents, which remains under investigated due to the lack of direct structural evidence for such systems. We report a mechanistic study of gas‐induced gate‐opening process of a microporous metal–organic framework, [Mn(ina)2] (ina=isonicotinate) associated with commensurate adsorption, by a combination of several analytical techniques including single crystal X‐ray diffraction, in situ powder X‐ray diffraction coupled with differential scanning calorimetry (XRD‐DSC), and gas adsorption–desorption methods. Our study reveals that the pronounced and reversible gate opening/closing phenomena observed in [Mn(ina)2] are coupled with a structural transition that involves rotation of the organic linker molecules as a result of interaction of the framework with adsorbed gas molecules including carbon dioxide and propane. The onset pressure to open the gate correlates with the extent of such interaction.
Trangmolins A–F with an Unprecedented Structural Plasticity of the Rings A and B: New Insight into Limonoid Biosynthesis
Authors: Li Wanshan , Shen Li , Bruhn Torsten , Pedpradab Patchara , Wu Jun , Bringmann Gerhard 
Published: July 2016

AbstractThe absolute stereostructures of trangmolins A–F (1–6), limonoids with three new and one known topologies of the rings A and B, were unambiguously determined by NMR spectroscopic investigations, single‐crystal XRD analysis, and quantum‐chemical electronic circular dichroism calculations. Compounds 1–3 contain a hexahydro‐1H‐inden‐4‐one motif, compound 4 comprises a hexahydro‐2,6‐methanobenzofuran‐7‐one cage, and compound 5 consists of a hexahydro‐2H‐2,8‐epoxychromene scaffold. The C1−C30 linkage in 1–3 and the C3−C30 connection in 4 form two unprecedented types of ring A/B‐fused carbobicyclic cores: viii and ix. The oxidative cleavage of the C2−C3 bond in 5 and heterocyclization in 4 and 5 constitute the unprecedented tricyclic 6/6/5 ring A/B1/B2‐ and 6/5/6 ring A1A2/B‐fused topologies, respectively, which are uncovered, for the first time, in the construction of limonoid architectures. The diverse cyclization patterns of 1–6 reveal an unparalleled structural plasticity of rings A and B in limonoid biosynthesis.