bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Targeted Fungal and Mycobacterial Infections in Patients Taking Tumor Necrosis Factor Inhibitors
Authors: Salt Elizabeth , Wiggins Amanda T. , Rayens Mary Kay , Huaman Moises A. , Mannino David , Schwieterman Philip , Merkley Scott A. , Jones Allison R. , Crofford Leslie J. 
Published: October 2015

ObjectiveTo identify predictors of the receipt of medical care, including the receipt of pre‐drug screening, for diagnostically targeted fungal or mycobacterial infections among patients prescribed a tumor necrosis factor inhibitor (TNFi).MethodsWe conducted a case–control study using deidentified patient health claims information from a data set representing a commercially insured US population of 15 million patients annually from January 1, 2007 to December 31, 2009. Descriptive statistics as well as a 2‐sample t‐test, chi‐square test of association, Fisher's exact test, and multivariate logistic regression were used for data analysis.ResultsA total of 30,772 patients received a TNFi during the study period. Of these, 158 patients (0.51%) developed targeted fungal and/or mycobacterial infections (cases). The median number of infections per case was 1.0 (interquartile range 1.0–2.0). Tuberculosis was diagnosed in 61% of cases, followed by histoplasmosis in 60%, nontuberculous mycobacterial infections in 11%, coccidioidomycosis in 10%, unspecified fungal infection in 8%, blastomycosis in 4%, cryptococcal infection in 3%, and pneumocystosis in 2%. Compared to controls (n = 474), a higher proportion of cases were prescribed prednisone (55% versus 37%; P < 0.001). Patients who were prescribed prednisone during the study period were twice as likely as those not taking prednisone to seek medical care attributable to a targeted fungal or mycobacterial infection (odds ratio 2.03; P < 0.001).ConclusionDevelopment of a targeted fungal or mycobacterial infection among patients taking a TNFi is rare. Concomitant use of prednisone predicted development of such infections.
VX‐509 (Decernotinib), an Oral Selective JAK‐3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis
Authors: Genovese Mark C. , van Vollenhoven Ronald F. , Pacheco‐Tena César , Zhang Yanqiong , Kinnman Nils 
Published: October 2015

ObjectiveTo assess the efficacy and safety of decernotinib (VX‐509), an oral selective inhibitor of JAK‐3, in patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.MethodsIn this 24‐week, double‐blind, randomized phase IIb study, 358 patients with active RA received either placebo (n = 71) or VX‐509 at dosages of 100 mg/day (n = 71), 150 mg/day (n = 72), 200 mg/day (n = 72), or 100 mg twice daily (n = 72). Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and change from baseline in the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP).ResultsAt week 12, the ACR20 response rates were 46.5%, 66.7%, 56.9%, and 68.1% in the groups receiving VX‐509 at dosages of 100 mg/day, 150 mg/day, 200 mg/day, and 100 mg twice daily, respectively, and 18.3% in the placebo group (P < 0.001 for all comparisons). At week 12, the mean change from baseline in the DAS28‐CRP was significantly greater in each VX‐509 group compared with the placebo group (P < 0.001). Improvements were maintained at week 24, as shown by the ACR20, ACR50, and ACR70 response rates and mean change from baseline in the DAS28‐CRP. The most common adverse event in the VX‐509 group was headache (8.7%), and elevated levels of transaminases, lipoproteins, and creatinine were observed.ConclusionVX‐509 significantly improved the signs and symptoms of RA at weeks 12 and 24 compared with the placebo group when it was administered in combination with methotrexate. Safety signals included infection and increases in liver transaminase and lipid levels.
Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis–Associated Genetic and Environmental Factors
Authors: Wei Peng , Yang Yang , Guo Xinjian , Hei Nainan , Lai Syeling , Assassi Shervin , Liu Mengyuan , Tan Filemon , Zhou Xiaodong 
Published: October 2015

ObjectiveSystemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc‐associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time‐course and dose‐response experiments.MethodsA total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole‐genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta‐analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype‐based longitudinal association test on regions that included the loci identified.ResultsThe single‐nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time‐course and/or dose‐response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta‐analysis. Results of the haplotype‐based analysis validated the association signals.ConclusionOur findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica‐induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome‐wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.
Antifibrotic, Antioxidant, and Immunomodulatory Effects of Mesenchymal Stem Cells in HOCl‐Induced Systemic Sclerosis
Authors: Maria Alexandre T. J. , Toupet Karine , Bony Claire , Pirot Nelly , Vozenin Marie‐Catherine , Petit Benoît , Roger Pascal , Batteux Frédéric , Le Quellec Alain , Jorgensen Christian , Noël Danièle , Guilpain Philippe 
Published: October 2015

ObjectiveSystemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis‐related mortality. Absence of efficient treatments has prompted the development of novel therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal cells appear to be one of the most attractive options. The purpose of this study was to use the murine model of hypochlorite‐induced SSc to investigate the systemic effects of MSCs on the main features of the diffuse form of the disease: skin and lung fibrosis, autoimmunity, and oxidative status.MethodsWe compared the effects of different doses of MSCs (2.5 × 105, 5 × 105, and 106) infused at different time points. Skin thickness was assessed during the experiment. At the time of euthanasia, biologic parameters were quantified in blood and tissues (by enzyme‐linked immunosorbent assay, quantitative reverse transcription–polymerase chain reaction, assessment of collagen content). Assessments of histology and immunostaining were also performed.ResultsA lower expression of markers of fibrosis (Col1, Col3, Tgfb1, and aSma) was observed in both skin and lung following MSC infusion, which was consistent with histologic improvement and was inversely proportional to the injected dose. Importantly, sera from treated mice exhibited lower levels of anti–Scl‐70 autoantibodies and enhanced antioxidant capacity, confirming the systemic effect of MSCs. Of interest, MSC administration was efficient in both the preventive and the curative approach. We further provide evidence that MSCs exerted an antifibrotic role by normalizing extracellular matrix remodeling parameters as well as reducing proinflammatory cytokine levels and increasing antioxidant defenses.ConclusionThe results of this study demonstrate the beneficial and systemic effects of MSC administration in the HOCl murine model of diffuse SSc, which is a promising finding from a clinical perspective.
Salt tolerant chromatography provides salt tolerance and a better selectivity for protein monomer separations
Authors: Yoshimoto Noriko , Itoh Daisuke , Isakari Yu , Podgornik Ales , Yamamoto Shuichi 
Published: October 2015

AbstractSalt tolerant chromatography (STC) is an attractive method as buffer exchange during protein purification processes can be skipped; however, the retention and separation mechanism of such STC are still not fully understood. We carried out linear gradient elution (LGE) experiments of bovine serum albumin (BSA) including its dimer form by using poly‐amine ligand STC. The peak salt concentration IR was measured as a function of normalized gradient slope GH, and the number of binding sites B was determined. The separation performance of monomer and dimer was much higher for STC. The IR values of BSA monomer and dimer for STC were much higher (IR > 0.5M) than those for conventional IEC. The IR values of arginine‐Cl gradient decreased markedly compared to those of NaCl gradient whereas they did not change for conventional IEC. This might be due to combined effects of electrostatic and hydrophobic interaction to the retention of proteins in STC. Adding polyethylene glycol (PEG) into the mobile phase of IEC also increased the retention (salt tolerance) and the resolution of BSA monomer and dimer. Higher viscosity and low solubility of proteins due to PEG were disadvantages of this method. STC with poly‐amine ligand might be also suited for the continuous flow‐through separation of monomer.
Dual utilization of NADPH and NADH cofactors enhances xylitol production in engineered Saccharomyces cerevisiae
Authors: Jo Jung‐Hyun , Oh Sun‐Young , Lee Hyeun‐Soo , Park Yong‐Cheol , Seo Jin‐Ho 
Published: October 2015

AbstractXylitol, a natural sweetener, can be produced by hydrogenation of xylose in hemicelluloses. In microbial processes, utilization of only NADPH cofactor limited commercialization of xylitol biosynthesis. To overcome this drawback, Saccharomyces cerevisiae D452‐2 was engineered to express two types of xylose reductase (XR) with either NADPH‐dependence or NADH‐preference. Engineered S. cerevisiae DWM expressing both the XRs exhibited higher xylitol productivity than the yeast strain expressing NADPH‐dependent XR only (DWW) in both batch and glucose‐limited fed‐batch cultures. Furthermore, the coexpression of S. cerevisiae ZWF1 and ACS1 genes in the DWM strain increased intracellular concentrations of NADPH and NADH and improved maximum xylitol productivity by 17%, relative to that for the DWM strain. Finally, the optimized fed‐batch fermentation of S. cerevisiae DWM‐ZWF1‐ACS1 resulted in 196.2 g/L xylitol concentration, 4.27 g/L h productivity and almost the theoretical yield. Expression of the two types of XR utilizing both NADPH and NADH is a promising strategy to meet the industrial demands for microbial xylitol production.
MDM4 SNP34091 (rs4245739) and its effect on breast‐, colon‐, lung‐, and prostate cancer risk
Authors: Gansmo Liv B. , Romundstad Pål , Birkeland Einar , Hveem Kristian , Vatten Lars , Knappskog Stian , Lønning Per Eystein 
Published: October 2015

AbstractThe MDM4 protein plays an important part in the negative regulation of the tumor suppressor p53 through its interaction with MDM2. In line with this, MDM4 amplification has been observed in several tumor forms. A polymorphism (rs4245739 A>C; SNP34091) in the MDM4 3′ untranslated region has been reported to create a target site for hsa‐miR‐191, resulting in decreased MDM4 mRNA levels. In this population‐based case–control study, we examined the potential association between MDM4 SNP34091, alone and in combination with the MDM2 SNP309T>G (rs2279744), and the risk of breast‐, colon‐, lung‐, and prostate cancer in Norway. SNP34091 was genotyped in 7,079 cancer patients as well as in 3,747 gender‐ and age‐matched healthy controls. MDM4 SNP34091C was not associated with risk for any of the tumor forms examined, except for a marginally significant association with reduced risk for breast cancer in a recessive model (OR = 0.77: 95% CI = 0.59–0.99). Stratifying according to MDM2 SNP309 status, we observed a reduced risk for breast cancer related to MDM4 SNP34091CC among individuals harboring the MDM2 SNP309GG genotype (OR = 0.41; 95% CI = 0.21–0.82). We conclude, MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung‐, colon‐ or prostate cancer.
The interplay of emotions, elaboration, and ambivalence on attitude–behavior consistency
Authors: Jiang Hongyan , Liang Jianping , Wang Haizhong , Sun Peizhen 
Published: October 2015

AbstractPrevious research on the relationship between attitudinal ambivalence and behavioral prediction mainly focused on the cognitive perspective. This paper introduces the simultaneous roles played by emotions (positive or negative) and elaboration. We find that both emotions and elaboration could moderate the effect of attitudinal ambivalence on attitude–behavior consistency. Furthermore, positive and negative emotions have different psychological mechanisms: positive emotions influence attitude–behavior consistency directly; negative emotions influence attitude–behavior consistency indirectly through elaboration. This article also discusses the theory contribution, marketing implication, and avenues for future research. Copyright © 2016 John Wiley & Sons, Ltd.
Relationship between Surface Roughness, Internal Crystal Perfection, and Crystal Growth Rate
Authors: Galbraith Shaun C. , Flood Adrian E. , Rugmai Supagorn , Chirawatkul Prae 
Published: October 2015

AbstractPotential mechanisms affecting growth rate dispersion (GRD) are investigated. Previous studies have identified surface roughness and internal lattice perfection as key mechanisms which are both evaluated with respect to GRD. Crystal growth of potassium dihydrogen phosphate was studied in two solvent mixtures, water and water‐ethanol. The surface roughness was analyzed by atomic force microscopy and the internal crystal perfection by X‐ray diffraction using a synchrotron source. The crystals grown at higher supersaturation have more pronounced and more frequent surface irregularities, supporting previous findings on a feedback mechanism between surface roughness and growth rate. No significant relationship was found between internal crystal perfection and growth rate, however, this is likely due to the size of the crystals analyzed herein and not the absence of any such mechanism in small crystals.
Oligomerization of n‐Butenes in a Two‐Phase Reaction System with Homogeneous Ni/Al‐Catalysts
Authors: Behr Arno , Bayrak Zeynep , Samli Güner , Yildiz Dilbar , Peitz Stefan , Stochniol Guido 
Published: October 2015

AbstractThe oligomerization of n‐butenes in a two‐phase catalyst system consisting of a Lewis acidic ionic liquid (IL) and a nonpolar phase is described. A highly active catalyst system with NiCl2(PMe3)2 was investigated, resulting in 91 % dimers with N‐methylpyrrole as a buffer. The reaction was found to be dependent on the molar ratio of the IL to the catalyst. Additionally, the influence of the Lewis acid was investigated and AlCl3 was determined as the most suitable for activating the nickel complex. The concentration of AlCl3 played an important role in achieving high catalyst activity and dimer selectivity. Several reactions with different pyrrole derivatives demonstrated that the use of a buffer with low steric hindrance was also important with regard to increased dimer selectivity.
Isoprene Polymerization on Iron Nanoparticles Confined in Carbon Nanotubes
Authors: Li Xiaojian , Zhang Liping , Tan Reasmey P. , Fazzini Pier‐Francesco , Hungria Teresa , Durand Jérôme , Lachaize Sébastien , Sun Wen‐Hua , Respaud Marc , Soulantica Katerina , Serp Philippe 
Published: October 2015

AbstractThe confinement of air‐protected metallic magnetic nanoparticles in the inner cavity of carbon nanotubes (CNTs) should offer an interesting perspective for biomedical applications or for controlling CNT alignment in composites. Because the direct confinement of polymer‐precoated nanoparticles in CNTs could be restricted by diffusion limitations, we developed a process based on: 1) the confinement of iron nanoparticles surface‐modified with an iron polymerization catalyst in the cavity of CNTs and 2) the polymerization of isoprene on the confined nanoparticles. The resulting material consists in CNT‐confined iron nanoparticles coated with a polyisoprene air barrier. This approach constitutes a proof of concept for the development of smart materials for use in medicine or composites.
Oxidation of a P−C Bond under Mild Conditions
Authors: Ilić Gordana , Gaguly Rakesh , Petković Milena , Vidović Dragoslav 
Published: October 2015

AbstractThe reactivity of phosphenium dication [(Ph3P)2C‐P‐NiPr2]2+, 12+, towards pyridine N‐oxide (O‐py) has been investigated. The resulting oxophosphonium dication [(Ph3P)2C(NiPr2)P(O)(O‐py)]2+, 22+, was surprisingly stabilized by a less nucleophilic O‐py ligand instead of pyridine (py). This compound was then identified as an analogue of the elusive Criegee intermediate as it underwent oxygen insertion into the P−C bond through a mechanism usually observed for Baeyer–Villiger oxidations. This oxygen insertion appears to be the first example of a Baeyer–Villiger oxidation involving O‐py.
Incremental computations over strongly distributed databases
Authors: Ravve Elena V. 
Published: October 2015

SummaryThis contribution deals with systematic exploitation of logical reduction techniques to big distributed data handling. The particular applications are views and parallel updates over large‐scale distributed databases as well as handling of queries over different generations of databases. Logical reduction techniques come in two favors. The first one: the syntactically defined translation schemes, which describe transformations of database schemes. They give rise to two induced maps, translations and transductions. Transductions describe the induced transformation of database instances and the translations describe the induced transformations of queries. The second one: Feferman‐Vaught reductions, which are applied in situations of distributed databases. The reduction describes how the queries over a distributed database can be computed from queries over the components and queries over the index set. Combination and development of these techniques allow us to introduce the notion of strongly distributed databases. For such databases, we extend and generalize the known propagation techniques. The method allows unification of the distributed and parallel computation and communication as well as significant reduction of the communication load. The proposed general approach may be easily adopted to other distributed objects and their integration into large‐scale systems. Copyright © 2015 John Wiley & Sons, Ltd.
A Low‐Intensity Mindfulness‐Based Intervention for Mood Symptoms in People with Early Psychosis: Development and Pilot Evaluation
Authors: Tong Alan Chun Yat , Lin Jessie Jing Xia , Cheung Veronica Yuen Ki , Lau Nicole Ka Man , Chang Wing Chung , Chan Sherry Kit Wa , Hui Christy Lai Ming , Lee Edwin Ho Ming , Chen Eric Yu Hai 
Published: October 2015

BackgroundDepressive and anxiety symptoms are common in people suffering from early psychosis. Growing evidence shows that mindfulness‐based intervention is an effective option in handling depression and anxiety disorders. Current article aims to provide documentation on the development and pilot study, before a RCT of larger scale, evaluating the acceptability and potential effects of a 7‐week mindfulness‐based intervention programme (MBI‐p).MethodMBI‐p was developed over nine months in 2014. A total of 14 people with early psychosis were recruited to three pilot trials of MBI‐p. Eleven of them completed the programme and were interviewed. Eight of them were measured quantitatively at baseline and post‐intervention on clinical symptoms, depression and anxiety levels, quality of life and mindfulness.ResultsMixed qualitative and quantitative results supported MBI‐p as an acceptable and feasible intervention. Significant statistical improvements were found in depression levels, mental quality of life, general psychopathology and ability to observe emotions and act with awareness. Qualitative comments suggested that the intervention was safe, enjoyable and had a positive impact on mood symptoms. In summary, these results provide a promising pilot support for a potentially effective and cost‐efficient treatment option for people with early psychosis. Copyright © 2015 John Wiley & Sons, Ltd.Key Practitioner Message

Depressive and anxiety symptoms are common in people with early psychosis but long received little attention.
A low‐intensity mindfulness‐based intervention targeting depression and anxiety symptoms among people with early psychosis was developed and pilot tested.
It is feasible and acceptable to use mindfulness‐based intervention as a complementary treatment for psychosis.
Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction
Authors: Sanders‐van Wijk S. , van Empel V. , Davarzani N. , Maeder M. T. , Handschin R. , Pfisterer M. E. , Brunner‐La Rocca H. P. ,   for the TIME‐CHF investigators
Published: October 2015

AbstractAimsThe aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF.Methods and resultsA total of 458 HFrEF (LVEF ≤40%) and 112 HFpEF (LVEF ≥50%) patients aged ≥60 years with NYHA class ≥II from TIME‐CHF were included. Endpoints are 18‐month overall and HF hospitalization‐free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor‐like 1 [ST2; 37.6 (28.5–54.7) vs. 35.7 (25.6–52.2), P = 0.02], high sensitivity C‐reactive protein (hsCRP; 8.54 (3.39–25.86) vs. 6.66 (2.42–15.39), P = 0.01), and cystatin‐C [1.94 (1.57–2.37) vs. 1.75 (1.39–2.12), P = 0.01]. In contrast, HFrEF patients exhibited higher NT‐proBNP [2142 (1473–4294) vs. 4202 (2239–7411), P < 0.001], high sensitivity troponin T [hsTnT; 27.7 (16.8–48.0) vs. 32.4 (19.2–59.0), P = 0.03], and haemoglobin [124 (110–135) vs. 134 (122–145), P < 0.001]. In addition to these clinical characteristics, NT‐proBNP, haemoglobin, cystatin‐C, hsTnT, and ST2 improved the area under the curve from 0.86 (0.82–0.89) to 0.91 (0.87–0.94; P < 0.001) for discriminating HFpEF from HFrEF. There were no significant interactions between HFpEF and HFrEF when considering the prognostic value of the investigated biomarkers (P > 0.10 for both endpoints), except for cystatin‐C which had less prognostic impact in HFpEF (P < 0.01).ConclusionBiomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin‐C, and for NT‐proBNP in the NT‐proBNP‐guided study arm only, both of which had less prognostic value in HFpEF.Trial registrationISRCTN43596477