bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a Novel Radiographic Scoring System for Calcinosis Affecting the Hands of Patients With Systemic Sclerosis
Authors: Chung Lorinda , Valenzuela Antonia , Fiorentino David , Stevens Kathryn , Li Shufeng , Harris Jonathan , Hutchinson Charles , Assassi Shervin , Beretta Lorenzo , Lakshminarayanan Santhanam , Rodriguez‐Reyna Tatiana S. , Denton Christopher P. , Taillefer Rebecca G. , Herrick Ariane L. , Baron Murray ,   for the Scleroderma Clinical Trials Consortium Calcinosis Working Group
Published: August 2014

ObjectiveThere are currently no validated outcome measures to assess calcinosis severity in systemic sclerosis (SSc; scleroderma). We sought to develop and validate a novel radiographic scoring system for calcinosis affecting the hands of SSc patients for potential use in future clinical trials.MethodsFollowing a 1‐hour teleconference training session, 12 investigators (8 rheumatologists, 1 dermatologist, and 3 radiologists) scored 12 hand radiographs in random order using 2 scoring systems (termed “simple” and “complex”) and re‐scored 2 randomly assigned radiographs after a minimum of 24 hours. Interrater and intrarater reliability were assessed using a weighted kappa coefficient for the simple system (κ), and an intraclass correlation coefficient (ICC) for the complex system (ICC <0.4 for poor, 0.4–0.7 for moderate, and >0.7 for excellent).ResultsMean time to complete the complex scoring system was significantly longer than the simple scoring system (4.0 versus 0.4 minutes; P < 0.0001). Overall interrater reliability for the simple scoring system was poor (κ = 0.39, 95% confidence interval [95% CI] 0.1–0.52) but improved if dichotomized as mild/moderate versus severe (κ = 0.51, 95% CI 0.26–0.7). Interrater reliability was excellent for the complex scoring system (ICC 0.89, 95% CI 0.86–0.92). Intrarater reliability was moderate for the simple scoring system (κ = 0.67, 95% CI 0.37–0.96) but almost perfect for the complex scoring system (ICC 0.93, 95% CI 0.89–0.97).ConclusionWe developed a novel radiographic scoring system that accounts for the area coverage, density, and anatomic location of calcinosis affecting the hands in patients with SSc. This scoring system is feasible with excellent reliability and should undergo further validation testing for use in clinical trials.
Dimethyl Sulfoxide Participating in Copper(I) Iodide‐Catalyzed Cascade Oxidation/Formylation Reactions: The Synthesis of α‐Formylpyrroles from 2,3‐Dihydro‐1H‐pyrroles
Authors: Qian Jingjing , Zhang Zhiguo , Liu Qingfeng , Liu Tongxin , Zhang Guisheng 
Published: August 2014

AbstractAn efficient copper‐catalyzed tandem oxidation/α‐formylation reaction of 2,3‐dihydro‐1H‐pyrroles in an oxygen atmosphere has been developed. The new reaction is conducted in dimethyl sulfoxide (DMSO), which serves as both the carbonyl carbon source and solvent, in the presence of trifluoroacetic acid to directly generate structurally diverse α‐formylpyrrole derivatives in one pot in moderate to good yields. Sensitive aldehyde groups remain intact in the presence of an oxidant, trifluoroacetic acid and a transition metal salt. A possible mechanism is presented.magnified image
Cobalt‐Catalyzed Cross‐Coupling of Organozinc Halides with Bromoalkynes
Authors: Corpet Martin , Bai Xian‐Zhou , Gosmini Corinne 
Published: August 2014

AbstractThe cobalt‐catalyzed cross‐coupling of organozinc bromides is described. In the case of arylzinc reagents, the same cobalt catalyst, CoBr2(phen), can be used for both the synthesis of the organozinc species and the cross‐coupling reaction. In the case of alkylzinc halides, which allow access to dialkylalkynes, the method used for the preparation of the organozinc species has a significant impact on the yields.magnified image
Silver‐Catalyzed Transformation of Propargylic Amine N‐Oxides to Enones and Acyloxy Ketones via Isoxazolinium Intermediates
Authors: Cui Jian‐Fang , Kung Karen Ka‐Yan , Ko Hok‐Ming , Hui Tsz‐Wai , Wong Man‐Kin 
Published: August 2014

AbstractA novel silver‐catalyzed transformation of propargylic amine N‐oxides with switchable product profiles has been developed. A diversity of enones with excellent E/Z ratios (up to >20:1) were obtained when the reactions were conducted in aprotic solvents. In contrast, 3‐chlorobenzoxymethyl ketones and α‐(3‐chloro)‐benzoxy enones were obtained by using protic solvents. Mechanistic studies suggested that in situ generated isoxazolinium ions are the key intermediates involved in these novel silver‐catalyzed reaction pathways. Applications on the chemoselective modification of cysteine‐containing peptides in aqueous medium have also been achieved.magnified image
Salivary cortisol and α‐amylase responses to repeated bouts of downhill running
Authors: Mckune Andrew J. , Bach Christopher W. , Semple Stuart J. , Dyer Barry J. 
Published: August 2014

ObjectivesTo determine the hypothalamic‐pituitary‐adrenal (HPA) axis and sympathoadrenal (SA) system response to repeated bouts of downhill running.MethodsEleven active but untrained males (age: 19.7 ± 0.4 y; VO2peak 47.8 ± 3.6 ml/kg/min) performed two 60 min bouts of downhill running (−13.5% gradient), separated by 14 days, at a speed eliciting 75% of their VO2peak on a level grade. Saliva samples were collected before (baseline), after, and every hour for 12 h and every 24 h for 6 days after each run. Salivary cortisol and α‐amylase levels were measured as markers of the HPA axis and SA response, respectively. Results were analyzed using repeated measures ANOVA (12 h period: 2 × 14; 24 h intervals 2 × 7, P ≤ 0.05) with Tukey post‐hoc tests where appropriate. Paired samples t‐tests were used to compare collapsed data vs. baseline measurements.ResultsThere were no significant group × time interactions for cortisol or α‐amylase for the hourly samples up to 12 h after each run, nor for the 24 h samples up to 6 days later. The 24 h samples for α‐amylase showed a significant group effect between runs (Run 1: 69.77 ± 7.68 vs. Run 2: 92.19 ± 7.67 U/ml; P = 0.04). Significant time effects were measured for both cortisol (decreased 2 h to 12 h post‐run) and α‐amylase (elevated immediately after, 1 h and 2 h post‐run) (P < 0.001).ConclusionThe 24 h period group effect for salivary α‐amylase suggested an adaptation in the sympathoadrenal system that may alter the systemic inflammatory response to exercise‐induced muscle damage but may also reflect enhanced mucosal immunity. Am. J. Hum. Biol. 26:850–855, 2014. © 2014 Wiley Periodicals, Inc.
Synthese und Reaktion der ersten 1,2‐Oxaphosphetankomplexe
Authors: Kyri Andreas Wolfgang , Nesterov Vitaly , Schnakenburg Gregor , Streubel Rainer 
Published: August 2014

AbstractWährend PV‐1,2‐Oxaphosphetane von der Wittig‐Reaktion her geläufig sind, waren die PIII‐Analoga bisher unbekannt. Wir präsentieren hier die Synthese und Reaktionen der ersten 1,2‐Oxaphosphetankomplexe, die durch Reaktion des Phosphinidenoidkomplexes [Li(12‐Krone‐4)(Lsgm)][(OC)5W{(Me3Si)2HC‐PCl}] mit unterschiedlichen Epoxiden erhalten wurden. Die Titelverbindungen sind in Toluol bis ca. 100 °C stabil, bevor eine unselektive Zersetzung eintritt. Die säureinduzierte Ringerweiterung mit Benzonitril führt zur selektiven Bildung des ersten Komplexes mit einem 1,3,4‐Oxazaphosphacyclohex‐2‐en‐Liganden.
Cell‐Mediated Assembly of Phototherapeutics
Authors: Smith Weston J. , Oien Nathan P. , Hughes Robert M. , Marvin Christina M. , Rodgers Zachary L. , Lee Junghyun , Lawrence David S. 
Published: August 2014

AbstractLight‐activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light‐sensitive prodrugs are typically converted to their active forms using short‐wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte‐mediated assembly of long‐wavelength‐sensitive phototherapeutics. The activating wavelength of the constructs is readily preassigned by using fluorophores with the desired excitation wavelength λex. Drug release from the erythrocyte carrier was confirmed by standard analytical tools and by the expected biological consequences of the liberated drugs in cell culture: methotrexate, binding to intracellular dihydrofolate reductase; colchicine, inhibition of microtubule polymerization; dexamethasone, induced nuclear migration of the glucocorticoid receptor.
Incorporation of high oil content in polyvinyl acetate nanoparticles produced by batch miniemulsion polymerization stabilized with a polymeric stabilizer
Authors: Steinmacher Fernanda Regina , Araújo Pedro Henrique Hermes , Sayer Claudia 
Published: August 2014

ABSTRACTNanoparticles (NPs) have been widely applied in the biomedical area. In order to satisfy the requirements for biomedical applications, sodium lauril sulfate (SLS) and hexadecane, widely used as anionic surfactant and co‐stabilizer, were successfully replaced by biocompatible compounds, in order to obtain poly(vinyl acetate) (PVAc) NPs via miniemulsion polymerization. The incorporation of high oil content in PVAc NPs was investigated, using different poly(vinyl alcohol) (PVOH) concentrations as polymeric surfactant. Besides the polymeric surfactant, lecithin and Miglyol 812, a triacylglycerol of saturated fatty acids obtained from coconut oil, were used as surfactant and co‐stabilizer, respectively. A high Miglyol 812 content was incorporated in the PVAc NPs and the morphology was investigated by TEM. The influence of PVOH concentration on the droplet nucleation mechanism and final morphology of PVAc NPs was evaluated. High PVOH concentration favored micellar particle nucleation. According to the TEM images, hemispheres nanoparticles were obtained. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41365.
Association of FCGR3A and FCGR3B Copy Number Variations With Systemic Lupus Erythematosus and Rheumatoid Arthritis in Taiwanese Patients
Authors: Chen Ji‐Yih , Wang Chin‐Man , Chang Su‐Wei , Cheng Ching‐Hui , Wu Yeong‐Jian Jan , Lin Jing‐Chi , Yang Bing , Ho Huei‐Huang , Wu Jianming 
Published: August 2014

ObjectiveTo determine whether copy number variations (CNVs) in FCGR3A and FCGR3B are associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese individuals.MethodsFCGR3A and FCGR3B CNV genotypes were determined in 846 patients with SLE, 948 patients with RA, and 1,420 healthy control subjects, using custom TaqMan CNV assays. The FCGR3A and FCGR3B CNV genotypes were compared between healthy control subjects and patients and among patients stratified according to clinical characteristics.ResultsA low (<2) FCGR3A copy number was significantly associated with SLE (for <2 copies versus 2 copies, P = 5.06 × 10−4, false discovery rate–corrected P [PFDR] = 0.001, odds ratio [OR] 3.26, 95% confidence interval [95% CI] 1.68−6.35) and RA (for <2 copies versus 2 copies, P = 5.83 × 10−4, PFDR = 0.0012, OR 2.82, 95% CI 1.56−5.1). A low FCGR3B copy number was also significantly associated with SLE (for <2 copies versus 2 copies, P = 0.0032, PFDR = 0.0032, OR 1.59, 95% CI 1.17−2.18). Notably, a high (>2) FCGR3A copy number was also associated with SLE (for >2 copies versus 2 copies, P = 0.003, PFDR = 0.0061, OR 1.6, 95% CI 1.17−2.18). Additionally, the FCGR3A low copy number genotype was significantly enriched in subsets of patients with SLE (those with ulcer, arthritis, rash, discoid rash, photosensitivity, nephritis, leukopenia, thrombocytopenia, depressed complement levels, and autoantibody positivity) and patients with RA (those positive for rheumatoid factor) compared with healthy control subjects. The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti–double‐stranded DNA antibody positivity compared with control subjects. However, FCGR3B CNVs were not associated with RA susceptibility (for <2 copy numbers versus 2 copy numbers, P = 0.3584, OR 1.15, 95% CI 0.85–1.55) and clinical characteristics.ConclusionIn Taiwanese individuals, a low FCGR3A copy number is a common risk factor for SLE and RA, while a low FCGR3B copy number confers a risk of SLE but not RA.
Redox‐Mediated Angiogenesis in the Hypoxic Joint of Inflammatory Arthritis
Authors: Biniecka Monika , Connolly Mary , Gao Wei , Ng Chin T. , Balogh Emese , Gogarty Martina , Santos Lelani , Murphy Evelyn , Brayden David , Veale Douglas J. , Fearon Ursula 
Published: August 2014

ObjectiveInflammatory arthritis is associated with joint inflammation, synovial tissue proliferation, and degradation of articular cartilage and bone. Angiogenesis is an early and fundamental component of synovial inflammation. Oxygen metabolism is recognized as an important mediator of joint vascular remodeling. The aim of this study was to determine whether in vivo synovial hypoxia (tissue PO2 [tPO2]) and tumor necrosis factor (TNF) blocking therapy alter synovial vascular expression of NADPH oxidase (NOX) and how this action regulates angiogenic mechanisms.MethodsNOX‐2 protein and messenger RNA expression was examined in patients with inflammatory arthritis before and after receiving TNF inhibitor (TNFi) therapy and in mice with collagen‐induced arthritis (CIA). Proangiogenic processes were assessed in human microvascular endothelial cells (HMVECs) following culture with NOX‐2 activators (TNFα and 4‐hydroxynonenal), small interfering RNA (siRNA) for NOX, and the inhibitor diphenyleneiodonium (DPI) under conditions of normoxia or 3% hypoxia.ResultsWe demonstrated significantly increased NOX‐2 expression in the joints of patients with inflammatory arthritis and the joints of mice with CIA as compared to controls. NOX‐2 expression was higher in patients with synovial tPO2 levels <3% than in those with tPO2 levels >3% (P < 0.05), and correlated with in vivo macroscopic/microscopic measures of angiogenesis, such as vascularity and levels of vascular endothelial growth factor, angiopoietin 2, factor VIII, neural cell adhesion molecule, and α‐smooth muscle actin (P < 0.05 for all). A decrease in NOX‐2 expression was paralleled by an increase in in vivo tPO2levels only in those patients who were defined as TNFi responders. In vitro NOX‐2 activators and 3% hypoxia significantly promoted HMVEC migration, angiogenic tube formation, and secretion of proangiogenic mediators, effects that were blocked by siRNA for NOX‐2 or the NOX‐2 inhibitor DPI.ConclusionWe demonstrated that hypoxia activates NOX‐2 protein expression, and NOX‐2–induced oxidative stress may be an initiating factor in driving angiogenesis.
Transcriptome‐Wide Analysis of Messenger RNA Decay in Normal and Osteoarthritic Human Articular Chondrocytes
Authors: Tew Simon R. , McDermott Benjamin T. , Fentem Rory B. , Peffers Mandy J. , Clegg Peter D. 
Published: August 2014

ObjectiveMessenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome‐wide posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes.MethodsHuman articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels in samples were confirmed using quantitative reverse transcription–polymerase chain reaction.ResultsExamination of total mRNA expression levels demonstrated significant differences in the expression of transcripts between normal and OA chondrocytes. Interestingly, almost no difference was observed in total mRNA expression between chondrocytes from intact OA cartilage and those from fibrillated OA cartilage. Decay analysis revealed a set of rapidly turned over transcripts associated with transcriptional control and programmed cell death that were common to all chondrocytes and contained binding sites for abundant cartilage microRNAs. Many transcripts exhibited altered mRNA half‐lives in human OA chondrocytes compared to normal cells. Specific transcripts whose decay rates were altered were generally less stable in these pathologic cells. Examination of selected genes in chondrocytes from young and old healthy horses did not identify any change in mRNA turnover.ConclusionThis is the first investigation into the “posttranscriptome” of the chondrocyte. It identifies a set of short‐lived chondrocyte mRNAs likely to be highly responsive to altered transcriptional input as well as mRNAs whose decay rates are affected in OA chondrocytes.
Comparison of Outcomes in Adults With Pediatric‐Onset Morphea and Those With Adult‐Onset Morphea: A Cross‐Sectional Study From the Morphea in Adults and Children Cohort
Authors: Condie Daniel , Grabell Daniel , Jacobe Heidi 
Published: August 2014

ObjectiveFew studies have examined outcomes in adults with pediatric‐onset morphea. The objective of the present study was to compare clinical outcomes and health‐related quality of life (HRQOL) in adults with onset of morphea in childhood to those in patients with adult onset of morphea.MethodsParticipants in the study were drawn from the Morphea in Adults and Children cohort and included 68 adults with pediatric‐onset morphea and 234 patients with adult‐onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical examination findings, and HRQOL questionnaires.ResultsAdults with pediatric‐onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric‐onset disease were less likely to have active disease. Among patients with active disease, those with pediatric‐onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric‐onset disease had higher severity of disease damage when measured by the physician's global assessment of damage, but had similar levels of disease damage when measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric‐onset disease had more favorable HRQOL scores for all measures, all of which were statistically significantly different from those in patients with adult‐onset morphea.ConclusionAdults with pediatric‐onset morphea differ from patients with adult‐onset disease with respect to disease subtype, severity of disease activity and damage, and levels of HRQOL.
Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus
Authors: Fleischer Sarah J. , Giesecke Claudia , Mei Henrik E. , Lipsky Peter E. , Daridon Capucine , Dörner Thomas 
Published: August 2014

ObjectiveSystemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk.MethodsB cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/plasma cells, and Syk induction by cytokines were determined.ResultsSyk expression was higher in CD27+ memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27− B cells with bright expression of Syk (Syk++) was found in SLE patients. CD27−Syk++ B cells showed enhanced basal expression of p‐Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27−Syk+ B cells. CD27−Syk++ B cells were CD38− as well as CD19++, CD20++, and mainly CD21−, with decreased ABCB1 transporter activity. In contrast to CD27−Syk+ B cells, CD27−Syk++ B cells exhibited enhanced differentiation into CD27++ IgG‐secreting cells and expressed somatically mutated BCR gene rearrangements. Syk++ B cells were inducible in vitro by stimulation with interferon‐γ, lipopolysaccharide, or tumor necrosis factor α.ConclusionSLE patients exhibit an increased frequency of hitherto unknown CD27−Syk++ memory‐like B cells, indicating that intracellular Syk density could distinguish CD27− memory B cells from truly naive B cell subsets. Furthermore, the CD27−Syk++ subset is a candidate for a source of increased plasma cells in SLE.
Necessary and Sufficient Near‐Optimal Conditions for Mean‐Field Singular Stochastic Controls
Authors: Li Ruijing , Liu Bin 
Published: August 2014

AbstractWe consider the near‐optimal control problems for mean‐field singular stochastic systems, where the control domain is non‐convex. By virtue of Ekeland's principle and some estimates on the state and adjoint processes, necessary and sufficient conditions for near‐optimality are established in the mean‐field framework. As an application, an example is presented to demonstrate the results.
Blocking endocytotic mechanisms to improve heterologous protein titers in Saccharomyces cerevisiae
Authors: Rodríguez‐Limas William A. , Tannenbaum Victoria , Tyo Keith E. J. 
Published: August 2014

ABSTRACTSaccharomyces cerevisiae is a useful platform for protein production of biopharmaceuticals and industrial enzymes. To date, substantial effort has focused on alleviating several bottlenecks in expression and the secretory pathway. Recently, it has been shown that highly active endocytosis could decrease the overall protein titer in the supernatant. In this study, we block endocytosis and trafficking to the vacuole using a modified TEV Protease‐Mediated Induction of Protein Instability (mTIPI) system to disrupt the endocytotic and vacuolar complexes. We report that conditional knock‐down of endocytosis gene Rvs161 improved the concentration of α‐amylase in supernatant of S. cerevisiae cultures by 63.7% compared to controls. By adaptive evolution, we obtained knock‐down mutants in Rvs161 and End3 genes with 2‐fold and 3‐fold α‐amylase concentrations compared to controls that were not evolved. Our study demonstrates that genetic blocking of endocytotic mechanisms can improve heterologous protein production in S. cerevisiae. This result is likely generalizable to other eukaryotic secretion hosts. Biotechnol. Bioeng. 2015;112: 376–385. © 2014 Wiley Periodicals, Inc.
Essential‐Oil Diversity of Salvia tomentosaMill. in Greece
Authors: Hanlidou Effie , Karousou Regina , Lazari Diamanto 
Published: August 2014

AbstractSalvia tomentosa essential oils from Greece were studied for the first time here. The oils from five populations growing in Mediterranean pine forests on the island of Thassos (northern Aegean Sea) and from 14 populations situated in deciduous forests in Thrace (northeastern Greek mainland) were investigated. Their essential‐oil contents ranged from 1.1 to 3.3% (v/w, based on the dry weight of the plant material). The populations from Thassos had high contents of α‐pinene (18.0±2.9%), 1,8‐cineole (14.7±3.0%), cis‐thujone (14.0±6.9%), and borneol (12.8±2.2%) and smaller amounts of camphene, camphor, and β‐pinene, whereas the populations from Thrace showed high α‐pinene (16.7±4.0%), β‐pinene (22.8±4.5%), camphor (18.3±4.3%), and camphene (10.3±2.4%) contents, much lower 1,8‐cineole and borneol amounts, while cis‐thujone was completely lacking. The comparison of the present results with published data showed that oils having cis‐thujone as one of the main compounds were reported for the first time here. Multivariate statistical analyses indicate that the observed essential‐oil variation was related to geographical and environmental factors.