bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consistency of Knee Pain and Risk of Knee Replacement: The Multicenter Osteoarthritis Study
Authors: WISE BARTON L. , FELSON DAVID T. , CLANCY MARGARET , NIU JINGBO , NEOGI TUHINA , LANE NANCY E. , HIETPAS JEAN , CURTIS JEFFREY R. , BRADLEY LAURENCE A. , TORNER JAMES C. , ZHANG YUQING 
Published: April 2011

Objective.To examine whether the consistency or persistence of knee pain, in addition to its severity, predicts incident total knee replacement (TKR).Methods.The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of persons aged 50 to 79 years with symptomatic knee osteoarthritis or at high risk of disease. Subjects were queried about the presence of knee pain on most days of the previous 30 days (i.e., frequent knee pain; FKP) at 2 timepoints: a telephone screen followed by a clinic visit (median separation 4 weeks). We defined a knee as having “consistent pain” if the subject answered positively to the FKP question at both timepoints, “inconsistent pain” if FKP was positive at only one timepoint, or as “no FKP” if negative at both. We examined the association between consistent FKP and risk of TKR using multiple binomial regression with generalized estimating equations.Results.In 3026 persons (mean age 63 yrs, mean body mass index 30.4), 2979 knees (50%) had no FKP at baseline, 1279 knees (21.5%) had inconsistent FKP, and 1696 knees (28.5%) had consistent FKP. Risk of TKR over 30 months was 0.8%, 2.6%, and 8.8% for knees with no, inconsistent, and consistent FKP, respectively. Relative risks of TKR over 30 months were 1.2 (95% CI 0.6–2.3) and 2.3 (95% CI 1.2–4.4) for knees with inconsistent and consistent FKP, compared with those without FKP. This association was consistent across each level of pain severity on the Western Ontario and McMaster Universities Osteoarthritis Index.Conclusion.Consistency of frequent knee pain is associated with an increased risk of TKR independently of knee pain severity.
Incidence and Risk Factors for Serious Infection in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors: A Report from the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety
Authors: KOMANO YUKIKO , TANAKA MICHI , NANKI TOSHIHIRO , KOIKE RYUJI , SAKAI RYOKO , KAMEDA HIDETO , NAKAJIMA ATSUO , SAITO KAZUYOSHI , TAKENO MITSUHIRO , ATSUMI TATSUYA , TOHMA SHIGETO , ITO SATOSHI , TAMURA NAOTO , FUJII TAKAO , SAWADA TETSUJI , IDA HIROAKI , HASHIRAMOTO AKIRA , KOIKE TAKAO , ISHIGATSUBO YOSHIAKI , EGUCHI KATSUMI , TANAKA YOSHIYA , TAKEUCHI TSUTOMU , MIYASAKA NOBUYUKI , HARIGAI MASAYOSHI 
Published: April 2011

Objective.To compare tumor necrosis factor-α (TNF-α) inhibitors to nonbiological disease-modifying antirheumatic drugs (DMARD) for the risk of serious infection in Japanese patients with rheumatoid arthritis (RA).Methods.Serious infections occurring within the first year of the observation period were examined using the records for patients recruited to the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety (REAL), a hospital-based prospective cohort of patients with RA. The analysis included 1144 patients, 646 of whom were treated with either infliximab or etanercept [exposed group: 592.4 patient-years (PY)]. The remaining 498 patients received nonbiological DMARD with no biologics (unexposed group: 454.7 PY).Results.In the unexposed group, the incidence rate for all serious adverse events (SAE) was 9.02/100 PY and for serious infections, 2.64/100 PY. In the exposed group, SAE occurred in 16.04/100 PY and serious infections in 6.42/100 PY. The crude incidence rate ratio comparing serious infections in the exposed group with the unexposed group was 2.43 (95% CI 1.27–4.65), a significant increase. A multivariate analysis revealed that the use of TNF inhibitors is a significant independent risk factor for serious infection (relative risk 2.37, 95% CI 1.11–5.05, p = 0.026).Conclusion.Our study has provided the first epidemiological data on Japanese patients with RA for the safety of TNF inhibitors compared to nonbiological DMARD for up to 1 year of treatment. Anti-TNF therapy was associated with a significantly increased risk for serious infections, compared to treatment with nonbiological DMARD.
Prevalence of Thyroid Autoimmunity in Patients with Spondyloarthropathies
Authors: PELUSO ROSARIO , LUPOLI GELSY ARIANNA , DEL PUENTE ANTONIO , IERVOLINO SALVATORE , BRUNER VINCENZO , LUPOLI ROBERTA , DI MINNO MATTEO NICOLA DARIO , FOGLIA FRANCESCA , SCARPA RAFFAELE , LUPOLI GIOVANNI 
Published: April 2011

Objective.To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto’s thyroiditis (HT) in a group of patients with spondyloarthritis (SpA).Methods.We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated.Results.Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05).Conclusion.Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.
Heterotopic Ossification of the Temporomandibular Joint in Juvenile Idiopathic Arthritis
Authors: RINGOLD SARAH , THAPA MAHESH , SHAW ELIZABETH A. , WALLACE CAROL A. 
Published: April 2011

Objective.To describe the clinical, laboratory, pathologic, and radiographic imaging characteristics of a series of children with juvenile idiopathic arthritis (JIA) and radiographic imaging evidence of heterotopic ossification of their temporomandibular joint (TMJ).Methods.Children were identified through search of an administrative database of imaging results at Seattle Children’s Hospital. Retrospective chart review was performed to collect data on each patient’s clinical and laboratory characteristics, systemic therapies, timing and number of TMJ intraarticular corticosteroid injections (IAS), TMJ symptoms, and TMJ findings on physician examination. TMJ imaging studies for which heterotopic ossifications were reported were reviewed. Pathology specimens were reviewed for the 2 children who underwent synovial biopsy of their TMJ.Results.Twelve children were identified. The average duration between onset of JIA and detection of heterotopic ossification of TMJ on an imaging study was 36 months (range 19–94). Half the children had abnormal mouth-opening for age when the calcifications were first detected. In each case, the heterotopic ossification was first detected by computed tomography scan, and in 11 of the cases they were associated with synovial pannus formation as documented on an imaging study. Two children underwent synovial biopsy, which revealed reactive parosteal osteochondromatosis in one case and findings consistent with an intraarticular rheumatoid nodule in the other.Conclusion.Heterotopic ossifications of the TMJ may be seen in children with JIA and are associated with particularly severe TMJ arthritis, joint destruction, and pannus formation. Pathology from these joints suggests that the heterotopic ossification may result from multiple pathological processes.
Cutting Edge: PHLPP Regulates the Development, Function, and Molecular Signaling Pathways of Regulatory T Cells
Authors: Patterson Scott J. , Han Jonathan M. , Garcia Rosa , Assi Kiran , Gao Tianyan , O’Neill Audrey , Newton Alexandra C. , Levings Megan K. 
Published: April 2011

Abstract
Regulatory T cells (Tregs) have a reduced capacity to activate the PI3K/Akt pathway downstream of the TCR, and the resulting low activity of Akt is necessary for their development and function. The molecular basis for the failure of Tregs to activate Akt efficiently, however, remains unknown. We show that PH-domain leucine-rich-repeat protein phosphatase (PHLPP), which dephosphorylates Akt, is upregulated in Tregs, thus suppressing Akt activation. Tregs expressed higher levels of PHLPP than those of conventional T cells, and knockdown of PHLPP1 restored TCR-mediated activation of Akt in Tregs. Consistent with their high Akt activity, the suppressive capacity of Tregs from PHLPP1−/− mice was significantly reduced. Moreover, the development of induced Tregs was impaired in PHLPP1−/− mice. The increased level of Akt’s negative regulator, PHLPP, provides a novel mechanism used by T cells to control the Akt pathway and the first evidence, to our knowledge, for a molecular mechanism underlying the functionally essential reduction of Akt activity in Tregs.
TLR4 Signaling via MyD88 and TRIF Differentially Shape the CD4+ T Cell Response to Porphyromonas gingivalis Hemagglutinin B
Authors: Gaddis Dalia E. , Michalek Suzanne M. , Katz Jannet 
Published: April 2011

Abstract
Recombinant hemagglutinin B (rHagB), a virulence factor of the periodontal pathogen Porphyromonas gingivalis, has been shown to induce protective immunity against bacterial infection. Furthermore, we have demonstrated that rHagB is a TLR4 agonist for dendritic cells. However, it is not known how rHagB dendritic cell stimulation affects the activation and differentiation of T cells. Therefore, we undertook the present study to examine the role of TLR4 signaling in shaping the CD4+ T cell response following immunization of mice with rHagB. Immunization with this Ag resulted in the induction of specific CD4+ T cells and Ab responses. In TLR4−/− and MyD88−/− but not Toll/IL-1R domain-containing adapter inducing IFN-β–deficient (TRIFLps2) mice, there was an increase in the Th2 CD4+ T cell subset, a decrease in the Th1 subset, and higher serum IgG1/IgG2 levels of HagB-specific Abs compared with those in wild-type mice. These finding were accompanied by increased GATA-3 and Foxp3 expression and a decrease in the activation of CD4+ T cells isolated from TLR4−/− and MyD88−/− mice. Interestingly, TLR4−/− CD4+ T cells showed an increase in IL-2/STAT5 signaling. Whereas TRIF deficiency had minimal effects on the CD4+ T cell response, it resulted in increased IFN-γ and IL-17 production by memory CD4+ T cells. To our knowledge, these results demonstrate for the first time that TLR4 signaling, via the downstream MyD88 and TRIF molecules, exerts a differential regulation on the CD4+ T cell response to HagB Ag. The gained insight from the present work will aid in designing better therapeutic strategies against P. gingivalis infection.
HLA-A*7401–Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703
Authors: Matthews Philippa C. , Adland Emily , Listgarten Jennifer , Leslie Alasdair , Mkhwanazi Nompumelelo , Carlson Jonathan M. , Harndahl Mikkel , Stryhn Anette , Payne Rebecca P. , Ogwu Anthony , Huang Kuan-Hsiang Gary , Frater John , Paioni Paolo , Kloverpris Henrik , Jooste Pieter , Goedhals Dominique , van Vuuren Cloete , Steyn Dewald , Riddell Lynn , Chen Fabian , Luzzi Graz , Balachandran Thambiah , Ndung’u Thumbi , Buus Søren , Carrington Mary , Shapiro Roger , Heckerman David , Goulder Philip J. R. 
Published: April 2011

Abstract
The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of &gt;2100 C-clade–infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401–restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401–restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703.
Colonic Eosinophilic Inflammation in Experimental Colitis Is Mediated by Ly6Chigh CCR2+ Inflammatory Monocyte/Macrophage-Derived CCL11
Authors: Waddell Amanda , Ahrens Richard , Steinbrecher Kris , Donovan Burke , Rothenberg Marc E. , Munitz Ariel , Hogan Simon P. 
Published: April 2011

AbstractRecent genome-wide association studies of pediatric inflammatory bowel disease have implicated the 17q12 loci, which contains the eosinophil-specific chemokine gene CCL11, with early-onset inflammatory bowel disease susceptibility. In the current study, we employed a murine model of experimental colitis to define the molecular pathways that regulate CCL11 expression in the chronic intestinal inflammation and pathophysiology of experimental colitis. Bone marrow chimera experiments showed that hematopoietic cell-derived CCL11 is sufficient for CCL11-mediated colonic eosinophilic inflammation. We show that dextran sodium sulfate (DSS) treatment promotes the recruitment of F4/80+CD11b+CCR2+Ly6Chigh inflammatory monocytes into the colon. F4/80+CD11b+CCR2+Ly6Chigh monocytes express CCL11, and their recruitment positively correlated with colonic eosinophilic inflammation. Phenotypic analysis of purified Ly6Chigh intestinal inflammatory macrophages revealed that these cells express both M1- and M2-associated genes, including Il6, Ccl4, Cxcl2, Arg1, Chi3l3, Ccl11, and Il10, respectively. Attenuation of DSS-induced F4/80+CD11b+CCR2+Ly6Chigh monocyte recruitment to the colon in CCR2−/− mice was associated with decreased colonic CCL11 expression, eosinophilic inflammation, and DSS-induced histopathology. These studies identify a mechanism for DSS-induced colonic eosinophilia mediated by Ly6ChighCCR2+ inflammatory monocyte/macrophage-derived CCL11.
Crowe Type I and II Ddh Managed by Large Diameter Metal-on-Metal Total Hip Arthroplasty
Authors: Yalcin Nadir , Kilicarslan Kasim , Cicek Hakan , Kayaalp Cetin , Yildirim Hasan 
Published: April 2011

Large bearing metal-on-metal (MOM) total hip arthroplasty (THA) may offer advantages relating to stability and range of motion in patients with Crowe Type I and II developmental dysplasia of the hip (DDH). The purpose of this study was to provide an analysis of the clinical and radiological results of MOM THA in this context and compare the results with a cohort of patients treated with metal-on-polyethylene (MOP) bearing surfaces. 75 hips in 65 patients were treated with cementless MOM THA using large femoral heads (36–56 mm). The mean age of the patients was 47.4 years (29 to 59) and 54 were female. A group of 47 hips (41 patients) treated with conventional THA (screwed cup-polyethylene insert-28mm head) was used for comparison. The study group was followed up for a mean of 62.1 months (32 to 76). No difference was found between the two groups in relation to improvement in Harris hip score (HHS) (43.1 to 90.3 points in the study group, 42.6 to 89.5 points in the control group, p>0.05). Although the preoperative range of motion in all planes were similar in both groups, the large head group demonstrated greater motion in all planes postoperatively, which was significant (all p=0.001). Additionally, there was a significant difference between groups in relation to the necessity for acetabular structural graft (8% and 31.9%, respectively; p=0.001). No major complications or adverse reactions to metal debris (ARMD) were observed in the study group. The results of large head MOM THA in young and active patients with DDH are similar to conventional THA at early follow-up, but the former offers the advantages of secure acetabular fixation without screws, greater range of motion, and lower risk of dislocation.
Optimization of the microstructure of porous composite cathodes in solid oxide fuel cells
Authors: Farhad Siamak , Hamdullahpur Feridun 
Published: April 2011

AbstractA comprehensive micromodel to predict the electrochemical performance of porous composite LSM‐YSZ cathodes in solid oxide fuel cells (SOFCs) is developed. The random packing sphere model is used to estimate the cathode microstructural properties required for the micromodel. The micromodel developed takes into account the complex interdependency among the mass transport, electron and ion transports, and the electrochemical reaction, and can be used for optimization of the microstructure of porous LSM‐YSZ composite cathodes. It is shown that the electrochemical performance of these cathodes depends on the microstructural variables of the cathode porosity, thickness, particle size ratio, and size and volume fraction of LSM particles. The effect of these microstructural variables on the cathode total resistance, as the objective function to achieve the optimum microstructure for the cathode, is studied through computer simulation. The results indicated that for a LSM‐YSZ cathode operated at the average temperature of 1073.15 K, bulk oxygen partial pressure of 0.21 atm, and total current density of 5000 Am−2, and constrained to the minimum value of 1 μm for the size of LSM particles and 0.25 for the cathode porosity, the optimum microstructure is obtained at the particle size ratio of unity, LSM particle size of 1 μm and volume fraction of 0.413, porosity of 0.25, and thickness of 60 μm. The cathode total resistance corresponding to the cathode optimized is estimated to be 0.291 Ω cm2. © 2011 American Institute of Chemical Engineers AIChE J, 2012
Adaptation of simple molecular networks to time‐dependent stimulus
Authors: Chang Xiao , Liu Dengyu , Liu Zengrong , Chen Luonan , Wang Ruiqi 
Published: April 2011

AbstractAdaptation is the ability by which signaling systems reset themselves after responding to a stimulus. Incoherent feedforward loops and negative feedback loops are the only two types of three‐node topologies showing adaptation to constant stimuli. In this study, adaptation of these two types of topologies to time‐dependent stimuli are discussed. Through analytical calculation and numerical simulations, it is found that they may show adaptation when the pulse duration and internal are properly assigned. In particular, for incoherent feedforward loops, two kind of models, i.e., logic approximation piecewise‐linear equations and Hill‐type equations are considered. When adaptation to time‐dependent stimulus is considered, analytical solutions for logic approximation piecewise‐linear equations and numerical simulation for Hill‐type equations are in substantial agreement. The study on adaptation to time‐dependent stimulus could serve as a manual providing different possible solutions to develop intelligent therapeutic strategies and to build biological circuits with specified functions.Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Carbohydrate–Protein Interactions: A 3D View by NMR
Authors: Roldós Virginia , Cañada F. Javier , Jiménez‐Barbero Jesús 
Published: April 2011

AbstractThis review focuses on the application of NMR methods for understanding, at the molecular and atomic levels, the diverse mechanisms by which sugar molecules are recognised by the binding sites of lectins, antibodies and enzymes. Given the intrinsic chemical natures of sugars and their flexibility, it is well established that NMR parameters should be complemented by computational methods in attempts to unravel the structural and conformational features of the molecular recognition process unambiguously. We therefore aim here to describe new and significant advances in the knowledge of carbohydrate–protein interactions, obtained by employing state‐of‐the‐art NMR and molecular modelling. We have not attempted to prepare an exhaustive review but have tried to focus on describing the key aspects that should be considered when tackling a problem within this research topic.
Stereochemistry and Mechanism of the Brønsted Acid Catalyzed Intramolecular Hydrofunctionalization of an Unactivated Cyclic Alkene
Authors: McKinney Brooner Rachel E. , Widenhoefer Ross A. 
Published: April 2011

AbstractThrough employment of deuterium‐labeled substrates, the triflic acid catalyzed intramolecular exo addition of the XH(D) (X=N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the CC bond of a pendant cyclohexene moiety was found to occur, in each case, with exclusive formation (≥90 %) of the anti‐addition product without loss or scrambling of deuterium as determined by 1H and 2H NMR spectroscopy and mass spectrometry analysis. Kinetic analysis of the triflic‐acid‐catalyzed intramolecular hydroamination of N‐(2‐cyclohex‐2′‐enyl‐2,2‐diphenylethyl)‐p‐toluenesulfonamide (1 a) established the second‐order rate law: rate=k2[HOTf][1a] and the activation parameters ΔH≠=(9.7±0.5) kcal mol−1 and ΔS≠=(−35±5) cal K−1 mol−1. An inverse α‐secondary kinetic isotope effect of kD/kH=(1.15±0.03) was observed upon deuteration of the C2′ position of 1 a, consistent with partial CN bond formation in the highest energy transition state of catalytic hydroamination. The results of these studies were consistent with a mechanism for the intramolecular hydroamination of 1 a involving concerted, intermolecular proton transfer from an N‐protonated sulfonamide to the alkenyl C3′ position of 1 a coupled with intramolecular anti addition of the pendant sulfonamide nitrogen atom to the alkenyl C2′ position.