bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Atacicept in Combination With Rituximab for Reducing the Signs and Symptoms of Rheumatoid Arthritis: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Pilot Trial
Authors: van Vollenhoven R. F. , Wax S. , Li Y. , Tak P. P. 
Published: July 2015

ObjectiveTo explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re‐treatment.MethodsIn this randomized, double‐blind, placebo‐controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once‐weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs). Secondary end points were the effects on peripheral blood B cells, disease activity biomarkers, and American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) response rates.ResultsEighteen patients were randomized to receive atacicept and 9 to receive placebo. AEs occurred in 17 atacicept‐treated patients (94.4%) and in all 9 placebo‐treated patients (100%). There were no infection‐related serious adverse events. Hypersensitivity and injection site reactions were more common, and more patients withdrew due to AEs, in the atacicept group. Median reductions in Ig levels from baseline to week 32 were greater with atacicept (median change in IgG −31.2%, IgM −60.9%, and IgA −56.4%) than with placebo (median change in IgG −4.4%, IgM −15.9%, and IgA −8.2%). Peripheral B cell numbers remained low in all patients after rituximab‐mediated B cell depletion, limiting comparison of time to recovery between treatment groups. There were no between‐group differences in ACR20, ACR50, and ACR70 response rates.ConclusionIn this exploratory trial, atacicept in combination with rituximab showed no new safety issues. Peripheral B cell counts remained too low to determine whether atacicept delayed B cell re‐expansion following rituximab‐mediated depletion. Despite clear biologic effects, adding atacicept to rituximab in patients with active RA was not associated with clinical benefit.
Brief Report: Intraarticular Sprifermin Not Only Increases Cartilage Thickness, but Also Reduces Cartilage Loss: Location‐Independent Post Hoc Analysis Using Magnetic Resonance Imaging
Authors: Eckstein Felix , Wirth Wolfgang , Guermazi Ali , Maschek Susanne , Aydemir Aida 
Published: July 2015

ObjectiveTo determine whether an anabolic drug (sprifermin) is capable of reducing cartilage loss wherever it occurs in a given knee, using a subject‐specific, location‐independent analysis of cartilage change in patients with knee osteoarthritis (OA).MethodsStudy participants (n = 168; ages ≥40 years, 69% women) had symptomatic femorotibial OA not confined to the medial compartment. Sprifermin (10, 30, or 100 μg) or placebo was injected intraarticularly 3 times over 3 weeks, both after randomization (baseline) and 3 months later. Coronal magnetic resonance images were acquired at baseline and 3, 6, and 12 months after treatment. The femorotibial cartilage of each subject was segmented, and changes in cartilage thickness were computed across 16 subregions. Location‐independent post hoc analysis was used to compute summary scores of negative and positive changes in the subregions, summarized as the total cartilage thinning sum score (ThCTnS) and the total cartilage thickening sum score (ThCTkS), capturing change in either direction in each knee. Ordered values of the magnitude of subject‐specific subregional changes in thickness were determined. The ThCTnS and ThCTkS in each sprifermin dose group at 12 months of followup were compared with the values in the matched placebo groups, using the Wilcoxon‐Mann‐Whitney test.ResultsThe mean ± SD ThCTnS was −591 ± 617 μm (median −360 μm, Q1/Q3 = −820/−200 μm) in patients treated with 100 μg sprifermin (n = 57), and −921 ± 777 μm (median −745 μm, Q1/Q3 = −1,190/−380 μm) in patients given placebo (n = 18). The mean difference in the ThCTnS between the 100‐μg sprifermin group and the placebo group was 331 μm (95% confidence interval [95% CI] 24, 685), a difference that was statistically significant (P = 0.03). The mean difference in the ThCTkS in the 100‐μg sprifermin group compared with the placebo group was 237 μm (95% CI 34, 440), also a statistically significant difference (P = 0.028).ConclusionSprifermin not only increases cartilage thickness, but also reduces cartilage loss. Subject‐specific, location‐independent analysis of both cartilage thinning and thickening represents a sensitive and informative approach for studying the effects of disease‐modifying OA drugs.
Role of Bcl‐3 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis
Authors: Meguro Kazuyuki , Suzuki Kotaro , Hosokawa Junichi , Sanayama Yoshie , Tanaka Shigeru , Furuta Shunsuke , Ikeda Kei , Takatori Hiroaki , Suto Akira , Sakamoto Akemi , Ohara Osamu , Nakajima Hiroshi 
Published: July 2015

ObjectiveWe have previously shown that expression of the Bcl‐3 gene, a member of the IκB family, is down‐regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl‐3 in the pathogenesis of RA.MethodsDNA microarray analysis was used to compare the signal intensity of Bcl‐3 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin‐6 (IL‐6)/STAT‐3 signaling in the induction of Bcl‐3. In addition, we analyzed the gene expression profiles of Bcl‐3–transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl‐3 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl‐3 and Tfh cell–related genes in CD4+ T cells from untreated RA patients.ResultsBcl‐3 levels were significantly higher in RA patients than in healthy controls. IL‐6 induced Bcl‐3 expression in CD4+ T cells in a STAT‐3–dependent manner. Transcriptome analysis revealed that the expression of Bcl‐6, a master regulator of Tfh cell differentiation, was significantly up‐regulated by the enforced Bcl‐3 expression. The enforced Bcl‐3 expression increased, but Bcl‐3 silencing decreased, the numbers of IL‐21–producing Tfh‐like cells. Bcl‐3 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell–related genes CXCR5, inducible costimulator, and achaete‐scute homolog 2.ConclusionBcl‐3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL‐21 production.
Risk Factors for the Rapid Increase in Risk of Acute Coronary Events in Patients With New‐Onset Rheumatoid Arthritis: A Nested Case–Control Study
Authors: Mantel Ängla , Holmqvist Marie , Nyberg Fredrik , Tornling Göran , Frisell Thomas , Alfredsson Lars , Askling Johan 
Published: July 2015

ObjectiveTo investigate risk factors for acute coronary syndrome (ACS) in patients with new‐onset rheumatoid arthritis (RA).MethodsWe performed a nested case–control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density–based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register‐based sources.ResultsWe identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C‐reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease‐modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti–citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk.ConclusionIn this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels.
Asymmetric Total Synthesis of (−)‐Maoecrystal V
Authors: Zhang Wei‐bin , Shao Wen‐bin , Li Fu‐zhuo , Gong Jian‐xian , Yang Zhen 
Published: July 2015

AbstractThe asymmetric total synthesis of (−)‐maoecrystal V, a novel cytotoxic pentacyclic ent‐kaurane diterpene, has been accomplished. Key steps of the current strategy involve an early‐stage semipinacol rearrangement reaction for the construction of the C10 quaternary stereocenter, a rhodium‐catalyzed intramolecular O−H insertion reaction, and a sequential Wessely oxidative dearomatization/intramolecular Diels–Alder reaction to forge the pentacyclic framework of maoecrystal V.
Development of a new procedure for the determination of captopril in pharmaceutical formulations employing chemiluminescence and a multicommuted flow analysis approach
Authors: Lima Manoel J. A. , Fernandes Ridvan N. , Tanaka Auro A. , Reis Boaventura F. 
Published: July 2015

AbstractThis paper describes a new technique for the determination of captopril in pharmaceutical formulations, implemented by employing multicommuted flow analysis. The analytical procedure was based on the reaction between hypochlorite and captopril. The remaining hypochlorite oxidized luminol that generated electromagnetic radiation detected using a homemade luminometer. To the best of our knowledge, this is the first time that this reaction has been exploited for the determination of captopril in pharmaceutical products, offering a clean analytical procedure with minimal reagent usage. The effectiveness of the proposed procedure was confirmed by analyzing a set of pharmaceutical formulations. Application of the paired t‐test showed that there was no significant difference between the data sets at a 95% confidence level. The useful features of the new analytical procedure included a linear response for captopril concentrations in the range 20.0–150.0 µmol/L (r = 0.997), a limit of detection (3σ) of 2.0 µmol/L, a sample throughput of 164 determinations per hour, reagent consumption of 9 µg luminol and 42 µg hypochlorite per determination and generation of 0.63 mL of waste. A relative standard deviation of 1% (n = 6) for a standard solution containing 80 µmol/L captopril was also obtained. Copyright © 2015 John Wiley & Sons, Ltd.
Increased titer and reduced lactate accumulation in recombinant retrovirus production through the down‐regulation of HIF1 and PDK
Authors: Rodrigues A. F. , Guerreiro M. R. , Formas‐Oliveira A. S. , Fernandes P. , Blechert A.‐K. , Genzel Y. , Alves P. M. , Hu W. S. , Coroadinha A. S. 
Published: July 2015

ABSTRACTMany mammalian cell lines used in the manufacturing of biopharmaceuticals exhibit high glycolytic flux predominantly channeled to the production of lactate. The accumulation of lactate in culture reduces cell viability and may also decrease product quality. In this work, we engineered a HEK 293 derived cell line producing a recombinant gene therapy retroviral vector, by down‐regulating hypoxia inducible factor 1 (HIF1) and pyruvate dehydrogenase kinase (PDK). Specific productivity of infectious viral titers could be increased more than 20‐fold for single gene knock‐down (HIF1 or PDK) and more than 30‐fold under combined down‐regulation. Lactate production was reduced up to 4‐fold. However, the reduction in lactate production, alone, was not sufficient to enhance the titer: high‐titer clones also showed significant enrolment of metabolic routes not related to lactate production. Transcriptome analysis indicated activation of biological amines metabolism, detoxification routes, including glutathione metabolism, pentose phosphate pathway, glycogen biosynthesis and amino acid catabolism. The latter were validated by enzyme activity assays and metabolite profiling, respectively. High‐titer clones also presented substantially increased transcript levels of the viral genes expression cassettes. The results herein presented demonstrate the impact of HIF1 and PDK down‐regulation on the production performance of a mammalian cell line, reporting one of the highest fold‐increase in specific productivity of infectious virus titers achieved by metabolic engineering. They additionally highlight the contribution of secondary pathways, beyond those related to lactate production, that can be also explored to pursue improved metabolic status favoring a high‐producing phenotype. Biotechnol. Bioeng. 2016;113: 150–162. © 2015 Wiley Periodicals, Inc.
Demographic patterns of cutaneous T‐cell lymphoma incidence in Texas based on two different cancer registries
Authors: Litvinov Ivan V. , Tetzlaff Michael T. , Rahme Elham , Jennings Michelle A. , Risser David R. , Gangar Pamela , Netchiporouk Elena , Moreau Linda , Prieto Victor G. , Sasseville Denis , Duvic Madeleine 
Published: July 2015

AbstractCutaneous T‐cell lymohomas (CTCLs) are rare, but potentially devastating malignancies, with Mycosis fungoides and Sézary Syndrome being the most common. In our previous study, we identified and described regions of geographic clustering of CTCL cases in Texas by analyzing ~1990 patients using two distinct cancer registries. In the current work, we describe in detail demographic patterns for this malignancy in our study population and apply logistic regression models to analyze the incidence of CTCL by sex, race, age, and clinical stage at the time of diagnosis. Furthermore, using Fisher's exact test, we analyze changes in incidence over time in the identified Houston communities with unusually high CTCL incidence. While CTCL primarily affects Caucasian individuals >55 years old, we confirm that it presents at a younger age and with more advanced disease stages in African‐American and Hispanic individuals. Also, we demonstrate a significant increase in CTCL incidence over time in the identified communities. Spring, Katy, and Houston Memorial areas had high baseline rates. Furthermore, a statistically significant disease surge was observed in these areas after ~2005. This report supplements our initial study documenting the existence of geographic clustering of CTCL cases in Texas and in greater detail describes demographic trends for our patient population. The observed surge in CTCL incidence in the three identified communities further argues that this malignancy may be triggered by one or more external etiologic agents.
CuI and H2O2 Inactivate and FeII Inhibits [Fe]‐Hydrogenase at Very Low Concentrations
Authors: Hidese Ryota , Ataka Kenichi , Bill Eckhard , Shima Seigo 
Published: July 2015

Abstract[Fe]‐Hydrogenase (Hmd) catalyzes reversible hydride transfer from H2. It harbors an iron‐guanylylpyridinol as a cofactor with an FeII that is ligated to one thiolate, two COs, one acyl‐C, one pyridinol‐N, and solvent. Here, we report that CuI and H2O2 inactivate Hmd (half‐maximal rates at 1 μM CuI and 20 μM H2O2) and that FeII inhibits the enzyme with very high affinity (Ki=40 nM). Infrared and EPR studies together with competitive inhibition studies with isocyanide indicated that CuI exerts its inhibitory effect most probably by binding to the active site iron‐thiolate ligand. Using the same methods, it was found that H2O2 binds to the active‐site iron at the solvent‐binding site and oxidizes FeII to FeIII. Also it was shown that FeII reversibly binds away from the active site iron, with binding being competitive to the organic hydride acceptor; this inhibition is specific for FeII and is reminiscent of that for the [FeFe]‐hydrogenase second iron, which specifically interacts with H2.
ChemInform Abstract: Sunlight‐Activated Eu2+/Dy3+ Doped SrAl2O4 Water Resistant Phosphorescent Layer for Optical Displays and Defence Applications.
Authors: Kumar Arun , Kedawat Garima , Kumar Pawan , Dwivedi Jaya , Gupta Bipin Kumar 
Published: July 2015

AbstractA long persistent, transparent, flexible, and water resistant phosphorescent layer of sunlight‐activated green luminescent Sr1‐x‐yAl2O4:Eux 2+/Dyy3+ (x = 0.05—0.3, y = 0.1—0.6) is fabricated via solid state reaction/solution casting of SrCO3, Al2O3, Eu2O3, and Dy2O3 (10% H2/N2 atmosphere, alumina crucible, 1300 °C, 3 h).
ChemInform Abstract: Enhanced Thermoelectric Performance of N‐Type Bi2Se3 Doped with Cu.
Authors: Sun Guolong , Qin Xiaoying , Li Di , Zhang Jian , Ren Baojin , Zou Tianhua , Xin Hongxing , Paschen Silke Buehler , Yan Xinlin 
Published: July 2015

AbstractSingle phase samples of CuxBi2Se3 (x = 0‐0.020) are prepared by melting and vacuum hot pressing stoichiometric amounts of the elements (563 K, 300 MPa, 60 min).
ChemInform Abstract: Synthesis, Crystal Structure and Physical Properties of [Li0.85Fe0.15OH][FeS].
Authors: Zhang Xian , Lai Xiaofang , Yi Na , He Jianqiao , Chen Haijie , Zhang Hui , Lin Jianhua , Huang Fuqiang 
Published: July 2015

AbstractPhase‐pure [Li0.85Fe0.15OH][FeS] is prepared by hydrothermal reaction of Fe, (NH2)2CS, and LiOH (autoclave, 200 °C, 3 d).
ChemInform Abstract: Rh(II)‐Catalyzed Cycloadditions of 1‐Tosyl 1,2,3‐Triazoles with 2H‐Azirines: Switchable Reactivity of Rh‐Azavinylcarbene as [2C]‐ or Aza‐[3C]‐Synthon.
Authors: Wang Yuanhao , Lei Xiaoqiang , Tang Yefeng 
Published: July 2015

AbstractIn some cases it is possible to divert the outcome of the reaction in favor of aminopyrroles and dihydropyrazines, respectively by altering the reaction conditions [e.g. reaction of (XII) and (XV)].
ChemInform Abstract: Intramolecular Aminochalcogenation and Diamination of Alkenes Employing N‐Iodosuccinimide.
Authors: Zhang Jun , Zhang Xuejun , Wu Weijie , Zhang Gengtao , Xu Sheng , Shi Min 
Published: July 2015

AbstractA new NIS‐mediated intramolecular diamination and aminosulfuration of alkenes with N‐alkyl or N‐aryl thioureas is presented.
ChemInform Abstract: A Strategy for Generating Alkyl Radicals from Aliphatic Esters and Lactones via Sequential Hydrolysis and Photoinduced Decarboxylation.
Authors: Saito Hikaru , Kanetake Takayuki , Osaka Kazuyuki , Maeda Kousuke , Morita Toshio , Yoshimi Yasuharu 
Published: July 2015

AbstractAlkyl radicals generated from substrates (I) and (IX) react with acrylonitrile, tert‐dodecanethiol, or 1,4‐dicyanobenzene to afford the corresponding addition, reduction, and substitution products.
ChemInform Abstract: Zinc‐Catalyzed Selective Reduction of Cyclic Imides with Hydrosilanes: Synthesis of ω‐Hydroxylactams.
Authors: Ding Guangni , Lu Bin , Li Yuyuan , Wan Jun , Zhang Zhaoguo , Xie Xiaomin 
Published: July 2015

AbstractThe hydrosilylation shows remarkable regioselectivity for unsymmetrical imides bearing coordinating groups adjacent to the carbonyl.
ChemInform Abstract: Iodobenzene Dichloride Mediated Sequential C—Cl Bond Formation: A Safe, Convenient and Efficient Method for the Direct α,α‐Dichlorination of β‐Dicarbonyl Compounds.
Authors: Duan Xiyan , Zhou Huiyun , Tian Xinlei , Liu Jianwei , Ma Junying 
Published: July 2015

AbstractWhereas the α,α‐dichlorination of β‐dicarbonyl compounds proceeds efficiently, it is not applicable to the corresponding transformation of simple ketones.
ChemInform Abstract: Catalyst‐Free and Metal‐Free Electrophilic Bromoamidation of Unactivated Olefins Using the N‐Bromosuccinimide/Sulfonamide Protocol.
Authors: Yu Wesley Zongrong , Chen Feng , Cheng Yi An , Yeung Ying‐Yeung 
Published: July 2015

AbstractAn efficient and metal catalyst‐free protocol is used for the synthesis of brominated sulfonamides from aromatic, aliphatic, and cycloaliphatic olefins.
ChemInform Abstract: Kinetic Resolution in the [2 + 2] Cycloaddition of Ketenes: An Experimental and Theoretical Study.
Authors: Rulliere Pauline , Carret Sebastien , Milet Anne , Poisson Jean‐Francois 
Published: July 2015

AbstractThe procedure uses the high difference in reactivity and thus allows the access to pure (E) alkenes, often difficult or impossible to isolate from the mixtures or expensive in trade.
ChemInform Abstract: One Pot Domino Reaction Accessing γ‐Nitroesters: Synthesis of GABA Derivatives.
Authors: Naciuk Fabricio F. , Vargas Debora Z. , D'Oca Caroline R. M. , Moro Celso C. , Russowsky Dennis 
Published: July 2015

AbstractVarious γ‐nitroesters are efficiently synthesized by Michael addition of 1,3‐dicarbonyl compounds to nitrostyrenes using Mg‐Al‐hydrotalcite as catalyst.
ChemInform Abstract: Additive‐Free Decarboxylative Coupling of Cinnamic Acid Derivatives in Water: Synthesis of Allyl Amines.
Authors: Park Kyungho , Lee Sunwoo 
Published: July 2015

AbstractThis is the first example of an additive‐free decarboxylative coupling of cinnamic acid derivatives with formaldehyde and amines to give the corresponding allyl amines.
ChemInform Abstract: Organoselenium‐Catalyzed Baeyer—Villiger Oxidation of α,β‐Unsaturated Ketones by Hydrogen Peroxide to Access Vinyl Esters.
Authors: Zhang Xu , Ye Jianqing , Yu Lei , Shi Xinkang , Zhang Ming , Xu Qing , Lautens Mark 
Published: July 2015

AbstractA practical and functional group‐tolerant chemoselective preparation of various (E)‐vinyl esters from readily available (E)‐α,β‐unsaturated ketones is described.
ChemInform Abstract: Synthesis of Sulfonamides via I2‐Mediated Reaction of Sodium Sulfinates with Amines in an Aqueous Medium at Room Temperature.
Authors: Pan Xiaojun , Gao Jian , Liu Juan , Lai Junyi , Jiang Huanfeng , Yuan Gaoqing 
Published: July 2015

AbstractCompared with previous studies, the introduced procedure has the advantages of simplicity, environmentally friendliness, and low costs.
ChemInform Abstract: Platinum‐Catalyzed Asymmetric Ring‐Opening Reactions of Oxabenzonorbornadienes with Phenols.
Authors: Meng Ling , Yang Wen , Pan Xuejing , Tao Meng , Cheng Guo , Wang Sanyong , Zeng Heping , Long Yuhua , Yang Dingqiao 
Published: July 2015

AbstractOptimized conditions A) are elaborated in detail.
ChemInform Abstract: Rhodium‐Catalyzed Dehydrogenative Coupling of Phenylheteroarenes with Alkynes or Alkenes.
Authors: Iitsuka Tomonori , Hirano Koji , Satoh Tetsuya , Miura Masahiro 
Published: July 2015

AbstractThe Rh‐catalyzed alkenylation of 3‐phenylthiophene (I) with alkenes (II) affords (E)‐ortho‐products (IIIa‐g).
ChemInform Abstract: Mild Microwave‐Assisted Synthesis of Dipyrromethanes and Their Analogues.
Authors: Xiong Ruisheng , Borbas K. Eszter 
Published: July 2015

AbstractThe Mannich reaction between pyrroles or indoles and Eschenmoser′s salt (II) forms N‐aminomethylated derivatives with high regioselectivity, which undergo substitution with pyrrole (III) under microwave irradiation, affording the corresponding dipyrromethanes such as (IV) and (VI) and their analogues (VIII).
ChemInform Abstract: RhII‐Catalyzed [3 + 2] Cycloaddition of 2H‐Azirines with N‐Sulfonyl‐1,2,3‐triazoles.
Authors: Zhao Yun‐Zhou , Yang Hai‐Bin , Tang Xiang‐Ying , Shi Min 
Published: July 2015

AbstractThe title reaction affords a series of fully functionalized pyrrole derivatives (III) and (V) via rhodium azavinyl carbene intermediates.
ChemInform Abstract: Visible Light Induced Radical Cyclization of o‐Iodophenylacrylamides: A Concise Synthesis of Indolin‐2‐one.
Authors: Dong Wuheng , Liu Yan , Hu Bei , Ren Kai , Li Yuyuan , Xie Xiaomin , Jiang Yuexiu , Zhang Zhaoguo 
Published: July 2015

AbstractThe reaction proceeds through 5‐exo‐trig radical cyclization.