bluuebunny/crossref_metadata_2025_split huggingface dataset:
What outcomes from pharmacologic treatments are important to people with rheumatoid arthritis? Creating the basis of a patient core set
Authors: Sanderson T. , Morris M. , Calnan M. , Richards P. , Hewlett S. 
Published: April 2010

AbstractObjectiveFunction, patient global assessment, and pain are routinely measured in rheumatoid arthritis (RA) clinical trials. However, other patient‐reported outcomes identified as important to patients in qualitative studies, such as fatigue and quality of life, are commonly not included, and modern treatment regimens may have changed patients' expectations of treatment outcomes. Our objective was to elicit patient priority treatment outcomes for pharmacologic interventions since the common use of anti–tumor necrosis factor (anti‐TNF) therapy, which will form the basis of a core set of patient priorities to complement existing professional core sets.MethodsIn‐depth interviews were conducted with 23 RA patients, purposively sampled for age, sex, medication (anti‐TNF or other disease‐modifying antirheumatic drugs), disease severity, and work status. Grounded theory guided iterative data collection and analysis. Coding of the data was peer reviewed. A patient research partner collaborated in the research design and analysis.ResultsSixty‐three different outcomes important to patients were generated from the interviews. Four major categories of patient outcomes from pharmacologic treatments were developed: “RA under control,” “Doing things,” “Emotional health,” and “Coping with illness.” The core category (or overall theme) was “Minimizing the personal impact of RA.”ConclusionAlthough the routine outcomes of pain, function, and overall well‐being were raised by the patients, they also generated a further 60 important outcomes that they look for from treatment. This difference in perspective may potentially influence treatment decisions. The next step is therefore to use these data to develop a patient core set.
Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients
Authors: Farragher Tracey M. , Plant Darren , Flynn Edward , Eyre Steve , Bunn Diane , Thomson Wendy , Symmons Deborah , Barton Anne 
Published: April 2010

AbstractObjectiveTo investigate whether recently identified rheumatoid arthritis (RA) susceptibility loci are also associated with disease severity, specifically all‐cause and cardiovascular disease (CVD) mortality, in patients with inflammatory polyarthritis (IP).MethodsSubjects with recent‐onset IP were recruited from the Norfolk Arthritis Register. Seventeen RA susceptibility single‐nucleotide polymorphisms (SNPs) were tested using Sequenom MassArray iPLEX chemistry. Vital status was ascertained from central records. The association of SNP allele carriage with mortality risk was assessed using Cox proportional hazards models after adjusting by sex. The mortality risks of those SNP alleles found to be associated were then stratified by baseline anti–citrullinated peptide (anti‐CCP) antibody and shared epitope (SE) status.ResultsAll SNPs were successfully genotyped in 2,324 IP subjects. The presence of 2 copies of the risk allele rs2812378 mapping to the CCL21 gene predicted all‐cause mortality (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.04–1.87), whereas risk allele carriage also predicted increased CVD mortality (HR 1.33, 95% CI 1.01–1.75). The highest mortality risks were seen in anti‐CCP antibody–positive subjects with 2 copies of the CCL21 risk alleles and 2 copies of the SE (all‐cause HR 3.20, 95% CI 1.52–6.72; CVD HR 3.73, 95% CI 1.30–10.72).ConclusionIn this large study, we found that carriage of CCL21 risk alleles was associated with premature mortality in IP independently of anti‐CCP antibody and SE status. Interestingly, CCL21 expression has been reported in atherosclerotic plaques supporting the thesis that the increased CVD mortality in IP patients may be mediated by shared inflammatory mechanisms.
High prevalence of gouty arthritis among the Hmong population in Minnesota
Authors: Portis Andrew J. , Laliberte Mark , Tatman Penny , Moua Maikia , Culhane‐Pera Kathleen , Maalouf Naim M. , Sakhaee Khashayar 
Published: April 2010

AbstractObjectiveThe prevalence of gout is on the rise worldwide, especially among newly industrialized populations. We evaluated the prevalence of gout in the recently established Hmong of Minneapolis/St. Paul (MSP) compared with that in non‐Hmong populations.MethodsThe prevalence of self‐reported gout in the Hmong population was estimated from 2 cross‐sectional community surveys and compared with national data extrapolated from the Third National Health and Nutrition Examination Survey. The prevalence of physician‐diagnosed gout in Hmong and non‐Hmong MSP residents was separately estimated from the diagnosis codes of 11 MSP primary care clinics.ResultsThe prevalence of self‐reported gout among MSP Hmong was 2‐fold higher than in the general US population (6.5% versus 2.9%; P < 0.001). Although women of both groups reported gout at a rate of 1.9%, Hmong men were significantly more likely than their non‐Hmong counterparts to report gout (11.5% versus 4.1%; P < 0.001). Similar results were observed when investigating physician‐diagnosed gout in MSP (2.8% Hmong versus 1.5% non‐Hmong; P < 0.001). No difference was observed between the women of the 2 groups (0.8% versus 0.7%; P = 0.833), whereas Hmong men were more than twice as likely to be diagnosed with gout compared with their non‐Hmong counterparts (6.1% versus 2.5%; P < 0.001). Among Hmong men, advancing age was associated with a considerably higher likelihood of being diagnosed with gout.ConclusionA significant association is observed between Hmong ethnicity and gout, both self‐reported and physician diagnosed. This unique population may provide an opportunity to further our understanding of the pathophysiology of gout.
Development of Diphenylamine‐Linked Bis(imidazoline) Ligands and Their Application in Asymmetric Friedel–Crafts Alkylation of Indole Derivatives with Nitroalkenes
Authors: Liu Han , Du Da‐Ming 
Published: April 2010

AbstractThe new diphenylamine‐linked bis(imidazoline) ligands were prepared through Kelly‐You’s imidazoline formation procedure mediated by Hendrickson’s reagent in good yields. The novel ligands were tested in the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes. In most cases, good yields (up to 97%) and excellent enantioselectivities (up to 98%) can be achieved. The optimized bis(imidazoline) ligand with trans‐diphenyl substitution on the imidazoline ring gave better enantioselectivity than the corresponding bis(oxazoline) ligand.
What kind of science is cosmology?
Authors: Goenner H.F.M. 
Published: April 2010

AbstractIn recent years, by theory and observation cosmology has advanced substantially. Parameters of the concordance or ΛCDM cosmological model are given with unprecedented precision (“precision cosmology”). On the other hand, 95% of the matter content of the universe are of an unknown nature. This awkward situation motivates the present attempt to find cosmology's place among the (exact) natural sciences. Due to its epistemic and methodical particularities, e.g., as a mathematized historical science, cosmology occupies a very special place. After going through some of the highlights of cosmological modeling, the conclusion is reached that knowledge provided by cosmological modeling cannot be as explicative and secure as knowledge gained by laboratory physics.
Winterschlafende Bären, Antibiotika und die Evolution des Ribosoms (Nobel‐Aufsatz)
Authors: Yonath Ada 
Published: April 2010

AbstractDank der hochaufgelösten Strukturen von Ribosomen, der zellulären Maschinen, die den genetischen Code in Proteine übersetzen, konnten zahlreiche ribosomale Aktivitäten und Strukturdetails aufgedeckt und erklärt werden: der Mechanismus der DNA‐Decodierung, der Prozessierungspfad der mRNA, die Bindungsstellen der tRNA im Ribosom, die Position und Eigenschaften des ribosomalen Austrittstunnels der naszierenden Proteine und die Wechselwirkungen des Ribosoms mit nicht‐ribosomalen Faktoren wie den Initiations‐, Freisetzungs‐ und Recyclingfaktoren. Vor allem haben diese Strukturen den Beweis erbracht, dass das Ribosom ein Ribozym ist, dessen aktives Zentrum – d. h. die Stelle, an der die Bildung der Peptidbindungen erfolgt – in einer symmetrischen Region liegt, die in die ansonsten unsymmetrische Ribosomstruktur eingebettet ist. Diese symmetrische Region ist hoch konserviert und enthält bereits alle Komponenten, die für die Bildung der Peptidbindungen und die Polymeraseaktivität des Ribosoms erforderlich sind. Sie könnte daher das Relikt eines Protoribosoms sein, einer dimeren präbiotischen Funktionseinheit, die Peptidbindungen und uncodierte Polypeptidketten bildete. Strukturen von Ribosom‐Antibiotika‐Komplexen haben die Grundlagen für eine klinische Verwendung dieser Antiobiotika geschaffen, Resistenzmechanismen aufgedeckt und Aufschluss darüber gegeben, wie Antibiotika zwischen pathogenen Bakterien und Wirtzellen differenzieren. Damit haben diese Forschungen wertvolle Strukturinformationen für die Verbesserung von Antibiotika und den Entwurf neuartiger Verbindungen, die als Antibiotika dienen könnten, geliefert.
Hibernating Bears, Antibiotics, and the Evolving Ribosome (Nobel Lecture)
Authors: Yonath Ada 
Published: April 2010

AbstractHigh‐resolution structures of ribosomes, the cellular machines that translate the genetic code into proteins, revealed the decoding mechanism, detected the mRNA path, identified the sites of the tRNA molecules in the ribosome, elucidated the position and the nature of the nascent proteins exit tunnel, illuminated the interactions of the ribosome with non‐ribosomal factors, such as the initiation, release and recycling factors. Notably, these structures proved that the ribosome is a ribozyme whose active site, namely where the peptide bonds are being formed, is situated within a universal symmetrical region that is embedded in the otherwise asymmetric ribosome structure. As this symmetrical region is highly conserved and provides the machinery required for peptide bond formation and for ribosome polymerase activity, it may be the remnant of the proto‐ribosome, a dimeric prebiotic machine that formed peptide bonds and non‐coded polypeptide chains. Structures of complexes of ribosomes with antibiotics targeting them revealed the principles allowing for their clinical use, identified resistance mechanisms and showed the structural bases for discriminating pathogenic bacteria from hosts, hence providing valuable structural information for antibiotics improvement and for the design of novel compounds that can serve as antibiotics.
Analyzing the real advantages of bifunctional initiator over monofunctional initiator in free radical polymerization
Authors: Machado Paula F. de M. P. B. , Lona Liliane M. F. 
Published: April 2010

AbstractMonofunctional initiators are extensively used in free radical polymerization. To enhance productivity, a higher temperature is usually used; however, this leads to lower molecular weights. Bifunctional initiators can increase the polymerization rate without decreasing the average molecular weight and this can be desirable. A bifunctional initiator is an important issue to be investigated, and it is of great interest to industries. The objective of this work is to study polymerization reactions with mono‐ and bi‐functional initiators through comprehensive mathematical models. Polystyrene is considered as case study. This work collects and presents some experimental data available in literature for polymerization using two different types of bifunctional initiators. Model prediction showed good agreement with experimental data. It was observed that the initial initiator concentration has a huge impact on the efficiency of initiators with functionality bigger than one and high concentrations of bifunctional initiator make the system behave as if it were a system operating with monofunctional initiator. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Effect of nanofillers as reinforcement agents for lignin composite fibers
Authors: Sevastyanova O. , Qin W. , Kadla J. F. 
Published: April 2010

AbstractBiobased nanocomposites and composite fibers were prepared from organosolv lignin/organoclay mixtures by mechanical mixing and subsequent melt intercalation. Two organically‐modified montmorillonite (MMT) clays with different ammonium cations were used. The effect of organoclay varying from 1 to 10 wt % on the mechanical and thermal properties of the nanocomposites was studied. Thermal analysis revealed an increased in Tg for the nanocomposites as compared with the original organosolv lignin. For both organoclays, lignin intercalation into the silicate layers was observed using X‐ray diffraction (XRD). The intercalated hybrids exhibited a substantial increase in tensile strength and melt processability. In the case of organoclay Cloisite 30B, X‐ray analysis indicates the possibility of complete exfoliation at 1 wt % organoclay loading. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Analysing metals in bottle‐grade poly(ethylene terephthalate) by X‐ray fluorescence spectrometry
Authors: Romão Wanderson , Franco Marcos F. , Bueno Maria Izabel M. S. , Eberlin Marcos N. , De Paoli Marco‐Aurelio 
Published: April 2010

AbstractAfter a rigorous cleaning process, recycled food‐grade poly(ethylene terephthalate) (PET), can be mixed with virgin PET resin in different concentrations and used for packaging of soft drinks. Therefore, it is important to have an experimental method to distinguish the presence of recycled polymer in a batch and to check its “true quality.” One of the issues to be verified is the presence of inorganic contaminants due to the recycling process. X‐ray fluorescence technique is one alternative for this kind of analysis. The results obtained in this work show that bottle‐grade PET samples (PET‐btg) are made either via direct esterification or by a transesterification process. Samples that were subjected to thermo‐mechanical processings (superclean® processing, PET‐btg blends processed in our laboratory and soft drink PET packaging) present Fe Kα emission lines with higher intensities than those presented by virgin bottle‐grade PET. After applying principal component analysis, it can be concluded that Fe is an intrinsic contaminant after the recycling process, furnishing a way to indicate class separations of PET‐btg. A calibration and validation partial least squares model was constructed to predict the weight percent of post‐consumption bottle‐grade PET in commercial PET samples. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Efficacy of traditional and biologic agents in different clinical phenotypes of adult‐onset Still's disease
Authors: Franchini Stefano , Dagna Lorenzo , Salvo Fulvio , Aiello Patrizia , Baldissera Elena , Sabbadini Maria Grazia 
Published: April 2010

AbstractObjectiveTo evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult‐onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease.MethodsForty‐five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed.ResultsOur data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease‐modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid‐resistant or steroid‐dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high‐dose steroids and cyclosporine was administered to successfully control some acute life‐threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients.ConclusionSteroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid‐resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid‐resistant and DMARD‐resistant AOSD.
Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis
Authors: Ercan Altan , Cui Jing , Chatterton Dereck E. W. , Deane Kevin D. , Hazen Melissa M. , Brintnell William , O'Donnell Colin I. , Derber Lezlie A. , Weinblatt Michael E. , Shadick Nancy A. , Bell David A. , Cairns Ewa , Solomon Daniel H. , Holers V. Michael , Rudd Pauline M. , Lee David M. 
Published: April 2010

AbstractObjectiveTo examine the association between aberrant IgG galactosylation and disease parameters in rheumatoid arthritis (RA).MethodsAnalysis of N‐glycan in serum samples from multiple cohorts was performed. The IgG N‐glycan content and the timing of N‐glycan aberrancy relative to disease onset were compared in healthy subjects and in patients with RA. Correlations between aberrant galactosylation and disease activity were assessed in the RA cohorts. The impact of disease activity, sex, age, anti–cyclic citrullinated peptide (anti‐CCP) antibody titer, disease duration, and C‐reactive protein level on aberrant galactosylation was determined using multivariate analysis. The N‐glycan content was also compared between epitope affinity–purified autoantibodies and the remaining IgG repertoire in RA patients.ResultsOur results confirm the aberrant galactosylation of IgG in RA patients as compared with healthy controls (mean ± SD 1.36 ± 0.43 versus 1.01 ± 0.23; P < 0.0001). We observed a significant correlation between levels of aberrant IgG galactosylation and disease activity (Spearman's ρ = 0.37, P < 0.0001). This correlation was higher in women (Spearman's ρ = 0.60, P < 0.0001) than in men (Spearman's ρ = 0.16, P = 0.10). Further, aberrant IgG galactosylation substantially predated the onset of arthritis and the diagnosis of RA (3.5 years) and resided selectively in the anticitrullinated antigen fraction.ConclusionOur findings identify aberrant IgG galactosylation as a dysregulated component of the humoral immune response in RA that begins prior to disease onset, associates with disease activity in a sex‐specific manner, and resides preferentially in autoantibodies.
Aberrant hypertrophy in Smad3‐deficient murine chondrocytes is rescued by restoring transforming growth factor β–activated kinase 1/activating transcription factor 2 signaling: A potential clinical implication for osteoarthritis
Authors: Li Tian‐Fang , Gao Lin , Sheu Tzong‐Jen , Sampson Erik R. , Flick Lisa M. , Konttinen Yrjö T. , Chen Di , Schwarz Edward M. , Zuscik Michael J. , Jonason Jennifer H. , O'Keefe Regis J. 
Published: April 2010

AbstractObjectiveTo investigate the biologic significance of Smad3 in the progression of osteoarthritis (OA), the crosstalk between Smad3 and activating transcription factor 2 (ATF‐2) in the transforming growth factor β (TGFβ) signaling pathway, and the effects of ATF‐2 overexpression and p38 activation in chondrocyte differentiation.MethodsJoint disease in Smad3‐knockout (Smad3−/−) mice was examined by microfocal computed tomography and histologic analysis. Numerous in vitro methods including immunostaining, real‐time polymerase chain reaction, Western blotting, an ATF‐2 DNA‐binding assay, and a p38 kinase activity assay were used to study the various signaling responses and protein interactions underlying the altered chondrocyte phenotype in Smad3−/− mice.ResultsIn Smad3−/− mice, an end‐stage OA phenotype gradually developed. TGFβ‐activated kinase 1 (TAK1)/ATF‐2 signaling was disrupted in Smad3−/− mouse chondrocytes at the level of p38 MAP kinase (MAPK) activation, resulting in reduced ATF‐2 phosphorylation and transcriptional activity. Reintroduction of Smad3 into Smad3−/− cells restored the normal p38 response to TGFβ. Phosphorylated p38 formed a complex with Smad3 by binding to a portion of Smad3 containing both the MAD homology 1 and linker domains. Additionally, Smad3 inhibited the dephosphorylation of p38 by MAPK phosphatase 1 (MKP‐1). Both ATF‐2 overexpression and p38 activation repressed type X collagen expression in wild‐type and Smad3−/− chondrocytes. P38 was detected in articular cartilage and perichondrium; articular and sternal chondrocytes expressed p38 isoforms α, β, and γ, but not δ.ConclusionSmad3 is involved in both the onset and progression of OA. Loss of Smad3 abrogates TAK1/ATF‐2 signaling, most likely by disrupting the Smad3–phosphorylated p38 complex, thereby promoting p38 dephosphorylation and inactivation by MKP‐1. ATF‐2 and p38 activation inhibit chondrocyte hypertrophy. Modulation of p38 isoform activity may provide a new therapeutic approach for OA.
Adjusting for Nonignorable Missingness When Estimating Generalized Additive Models
Authors: Xie Hui 
Published: April 2010

AbstractGeneralized additive models (GAMs) have been widely used for flexible modeling of various types of outcomes. When the outcome in a GAM is subject to missing, practical analyses often assume that missingness is missing at random (MAR). This assumption can be of suspicion when the missingness is not by design. Evaluating the potential effects of alternative nonignorable missing data mechanism on the MAR inference from a GAM can be important but often challenging due to the complicatedness of alternative nonignorable models. We apply the index approach to local sensitivity (Troxel, Ma, and Heitjan (2004). Statistica Sinica 14, 1221–1237) to evaluate the potential changes of the GAM estimates in the neighborhood of the MAR model. The approach avoids fitting any complicated nonignorable GAM. Only MAR estimates are required to calculate the resulting sensitivity index and adjust the GAM estimates to account for nonignorable missingness. Thus the proposed approach is considerably simpler to conduct, as compared with the alternative methods. The simulation study shows that the index provides valid assessment of the local sensitivity of the GAM estimates to nonignorable missingness. We then illustrate the method using a rheumatoid arthritis clinical trial data set.
Enhancing the credibility of complainants in child sexual assault trials: The effect of expert evidence and judicial directions
Authors: Goodman‐Delahunty Jane , Cossins Anne , O'Brien Kate 
Published: April 2010

AbstractThis study investigated the knowledge and misconceptions of jury‐eligible citizens about children's reliability as witnesses and responses to child sexual assault (CSA), and examined the influence of expert evidence and judicial directions in challenging common misconceptions. Community volunteers (N = 130) read one of five versions of a simulated jury trial, and completed a pre‐ and post‐trial questionnaire to provide measures of their knowledge of children's responses to sexual abuse, perceptions of victim credibility, and verdict. Results revealed that endorsement of CSA misconceptions negatively impacted ratings of complainant credibility and verdicts. Judicial directions provided before the child complainant testified enhanced complainant credibility, which in turn predicted guilty verdicts. Comparisons of the effectiveness of two procedural legal mechanisms to manage juror misconceptions and improve knowledge about CSA provide guidance for future researchers investigating ways to increase fairness in cases of CSA. Copyright © 2010 John Wiley & Sons, Ltd.