bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual magnetic resonance imaging and radiographic features of knee osteoarthritis in subjects with unilateral knee pain: The Health, Aging, and Body Composition Study
Authors: Javaid M. K. , Kiran A. , Guermazi A. , Kwoh C. K. , Zaim S. , Carbone L. , Harris T. , McCulloch C. E. , Arden N. K. , Lane N. E. , Felson D. , Nevitt M. ,   Health ABC Study
Published: June 2012

AbstractObjectiveStrong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms.MethodsThe study population included 283 individuals ages 70–79 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight‐related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole‐Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within‐person case–control design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features.ResultsIn conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade ≥1) (odds ratio 3.20 [95% confidence interval 1.79–5.71]) and MRI features (any cartilage defect scored ≥2) (odds ratio 3.67 [95% confidence interval 1.49–9.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best‐performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade ≥2 (P = 0.42).ConclusionIn persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.
Porphyromonas gingivalis and disease‐related autoantibodies in individuals at increased risk of rheumatoid arthritis
Authors: Mikuls Ted R. , Thiele Geoffrey M. , Deane Kevin D. , Payne Jeffrey B. , O'Dell James R. , Yu Fang , Sayles Harlan , Weisman Michael H. , Gregersen Peter K. , Buckner Jane H. , Keating Richard M. , Derber Lezlie A. , Robinson William H. , Holers V. Michael , Norris Jill M. 
Published: June 2012

AbstractObjectiveTo examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA).MethodsStudy participants included the following: 1) a cohort enriched in subjects with HLA–DR4 and 2) subjects at risk of RA by virtue of having a first‐degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti–citrullinated protein antibody (ACPA; by second‐generation anti–cyclic citrullinated peptide antibody enzyme‐linked immunosorbent assay [ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n = 113) if they had ≥1 RA‐related autoantibody; individuals were further categorized as high risk (n = 38) if they had ACPA or positive findings ≥2 assays for RF. Autoantibody‐negative individuals (n = 171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression.ResultsAnti–P gingivalis concentrations were higher in high‐risk (P = 0.011) and autoantibody positive group (P = 0.010) than in the autoantibody negative group. There were no group differences in anti–P intermedia or anti–F nucleatum concentrations. After multivariable adjustment, anti–P gingivalis concentrations (but not anti–P intermedia or anti–F nucleatum) were significantly associated with autoantibody‐positive and high‐risk status (P < 0.05).ConclusionImmunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA‐related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.
Identification of microRNA‐31 as a novel regulator contributing to impaired interleukin‐2 production in T cells from patients with systemic lupus erythematosus
Authors: Fan Wei , Liang Dong , Tang Yuanjia , Qu Bo , Cui Huijuan , Luo Xiaobing , Huang Xinfang , Chen Shunle , Higgs Brandon W. , Jallal Bahija , Yao Yihong , Harley John B. , Shen Nan 
Published: June 2012

AbstractObjectiveMicroRNAs (miRNAs) function to fine‐tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin‐2 (IL‐2)–related signaling pathways in systemic lupus erythematosus (SLE). The miR‐31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR‐31 in IL‐2 defects in lupus T cells.MethodsExpression levels of miR‐31 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR‐31. NF‐AT nuclear translocation and expression were quantitatively measured using an ImageStream cytometer. Bioinformatics analysis, small interfering RNA (siRNA) knockdown, and Western blotting were performed to validate miR‐31 targets and effects.ResultsThe expression of miR‐31 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL‐2. Overexpression of miR‐31 in T cells increased the production of IL‐2 by altering NF‐AT nuclear expression and IL2 promoter activity, while knockdown of endogenous miR‐31 reduced IL‐2 production. RhoA expression was directly repressed by miR‐31 in T cells. Of note, siRNA‐mediated knockdown of RhoA enhanced IL2 promoter activity and, consequently, up‐regulated IL‐2 production. RhoA expression was consistently up‐regulated and negatively correlated with the levels of miR‐31 in lupus T cells. Manipulation of miR‐31 expression in lupus T cells restored the expression of IL‐2 at both the messenger RNA and protein levels.ConclusionMicroRNA‐31 is a novel enhancer of IL‐2 production during T cell activation. Dysregulation of miR‐31 and its target, RhoA, could be a novel molecular mechanism underlying the IL‐2 deficiency in patients with SLE.
B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells
Authors: Berggren Olof , Hagberg Niklas , Weber Gert , Alm Gunnar V. , Rönnblom Lars , Eloranta Maija‐Leena 
Published: June 2012

AbstractObjectiveThe type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFNα produced by plasmacytoid dendritic cells (PDCs) stimulates several B cell functions, including autoantibody production. However, not much is known about how B cells influence PDC function. The aim of this study was to investigate the regulatory effect of B cells on IFNα production by PDCs.MethodsPDCs and B cells isolated from peripheral blood mononuclear cells from healthy blood donors were stimulated with RNA‐containing immune complexes (ICs) consisting of U1 small nuclear RNP and SLE IgG, herpes simplex virus, or oligonucleotide (ODN) 2216, alone or in cocultures. IFNα, several other cytokines, and PDC‐ or B cell–associated surface molecules were analyzed using immunoassays or flow cytometry.ResultsB cells enhanced IFNα production by PDCs up to 47‐fold, and the effect was most pronounced for PDCs stimulated with RNA‐containing ICs. Anti‐CD31 antibody reduced RNA‐containing IC–induced IFNα production by 80% but had no effect on IFNα production when ODN 2216 was used as an inducer. Supernatants from ODN 2216–stimulated B cells promoted IFNα production by PDCs, while supernatants from RNA‐containing IC–stimulated B cells did not.ConclusionOur results showed that a novel function of B cells is enhancement of type I IFN production by PDCs. Because B cells are activated by type I IFN, this PDC–B cell cross‐talk might be of fundamental importance in the etiopathogenesis of SLE and contribute to long‐term immune activation in SLE and other systemic rheumatic diseases.
Relationship between inflammation, bone destruction, and osteoproliferation in the HLA–B27/human β2‐microglobulin–transgenic rat model of spondylarthritis
Authors: van Duivenvoorde Leonie M. , Dorris Martha L. , Satumtira Nimman , van Tok Melissa N. , Redlich Kurt , Tak Paul P. , Taurog Joel D. , Baeten Dominique L. 
Published: June 2012

AbstractObjectiveInhibition of inflammation and destruction, but not of osteoproliferation, in patients with spondylarthritis (SpA) treated with anti–tumor necrosis factor raises the question of how these three processes are interrelated. This study was undertaken to analyze this relationship in a rat model of SpA.MethodsHistologic spine and joint samples from HLA–B27/human β2‐microglobulin (hβ2m)–transgenic rats were analyzed for signs of spondylitis and destructive arthritis and semiquantitatively scored as showing mild, moderate, or severe inflammation.ResultsIn rats exhibiting spondylitis, mildly inflamed sections displayed lymphocyte infiltration in connective tissue adjacent to the junction of the anulus fibrosus and vertebral bone but not at the enthesis. Moderately inflamed tissue samples contained osteoclasts eroding bone outside the cartilage end plate. In sections from rats with severe inflammation, the cartilage end plate and underlying bone marrow were also affected. End‐stage disease was characterized by complete destruction of the intervertebral disc and vertebrae, with ongoing infiltration. Osteoproliferation was not observed in samples from rats with no or mild inflammation, but was present at the edge of the vertebrae in sections with moderate inflammation and persisted during severe inflammation and end‐stage destruction. Osteoproliferation occurred at the border of inflammation, at a distance from bone destruction. A strong correlation between the extent of inflammation, destruction, and osteoproliferation was observed. Sections from rats with arthritis displayed a similar pattern of synovial inflammation associated with bone destruction, and simultaneous but topographically distinct osteoproliferation starting from the periosteum.ConclusionSpA in B27/hβ2m–transgenic rats is characterized by destructive inflammatory pannus tissue rather than by enthesitis or osteitis. Destruction and osteoproliferation occur simultaneously but at distinct sites in joints with moderate to severe inflammation.
Modulation of STAT‐3 in rheumatoid synovial T cells suppresses Th17 differentiation and increases the proportion of Treg cells
Authors: Ju Ji Hyeon , Heo Yu‐Jung , Cho Mi‐La , Jhun Joo‐Yeon , Park Jin‐Sil , Lee Seon‐Yeong , Oh Hye‐Jwa , Moon Su‐Jin , Kwok Seung‐Ki , Park Kyung‐Su , Park Sung‐Hwan , Kim Ho‐Youn 
Published: June 2012

AbstractObjectiveTo investigate the impact of STAT‐3–mediated regulation on Th17 differentiation in patients with rheumatoid arthritis (RA).MethodsCD4+ T cells isolated from peripheral blood (PB) and synovial fluid (SF) were stimulated to differentiate into Th17 cells or Treg cells. The activity of STAT‐3 was knocked down by transfecting CD4+ T cells with small interfering RNA (siRNA). After 3 days in culture, the proportions of Th17 cells and Treg cells were measured by flow cytometry, and the production of interleukin‐17 (IL‐17) was measured by reverse transcriptase–polymerase chain reaction and enzyme‐linked immunosorbent assay.ResultsThe levels of IL‐17, IL‐6, IL‐23, IL‐1, and tumor necrosis factor α were significantly higher in RA SF and synovial tissue than in SF and synovial tissue from osteoarthritis patients. In RA synovial tissue, the expression of STAT‐3 increased in proportion to the severity of synovitis, as shown by stromal cellularity, intimal hyperplasia, and inflammatory infiltration. The degree of Th17 differentiation was highest in RA SF, followed by RA PB, and lowest in normal subjects. In CD4+ T cells, transfection with STAT‐3 siRNA prevented Th17 differentiation of mononuclear cells from RA PB and SF but increased the proportion of Treg cells. In contrast, inhibition of STAT‐5, the transcription factor for Treg cells, increased the proportion of Th17 cells and reduced that of Treg cells.ConclusionOur findings indicate that modulation of STAT‐3 in CD4+ T cells affects the differentiation of Th17 cells and Treg cells in patients with RA. This role of STAT‐3 in RA synovial T cells may provide a new therapeutic target for the management of RA.
Dkk‐1 promotes angiogenic responses and cartilage matrix proteinase secretion in synovial fibroblasts from osteoarthritic joints
Authors: Weng Lin‐Hsiu , Ko Jih‐Yang , Wang Ching‐Jen , Sun Yi‐Chih , Wang Feng‐Sheng 
Published: June 2012

AbstractObjectiveSynovial hypervascularity is a prominent pathologic feature in osteoarthritic (OA) joints. Wnt inhibitor Dkk‐1 contributes to joint remodeling. We undertook this study to investigate whether Dkk‐1 regulates cartilage destruction activities in OA synovial fibroblasts.MethodsSynovial tissues were harvested from knees of patients with OA and from injured knees of non‐OA patients who underwent arthroscopy. Expression of Dkk‐1, angiogenic factors (stromal cell–derived factor 1 and colony‐stimulating factor 1), and cartilage proteinases (ADAMTS‐5 and matrix metalloproteinase 3 [MMP‐3]) as well as vascularity in synovium and synovial fluid were quantified using enzyme‐linked immunosorbent assay, reverse transcription–polymerase chain reaction, and histomorphometry. Synovial fibroblasts were treated with interleukin‐1β (IL‐1β), anti–Dkk‐1 antibody, and RNA interference to characterize their angiogenic activity. Rats with OA knees were administered Dkk‐1 antisense oligonucleotide to verify synovial angiogenesis and cartilage integrity.ResultsOA synovium exhibited increased vascularity and expression of angiogenic factors and proteinases in association with up‐regulated Dkk‐1 levels. Neutralizing Dkk‐1 reduced the inhibitory effects of OA synovial fluid on aggrecan expression in chondrocyte cultures. IL‐1β induction of Dkk‐1 increased expression of hypoxia‐inducible factor 1α (HIF‐1α), angiogenic factors, ADAMTS‐5, and MMP‐3 in synovial fibroblasts and promoted angiogenesis in vascular endothelial cells. Knockdown of HIF‐1α decreased Dkk‐1 enhancement of angiogenic factor expression. Stabilization of glycogen synthase kinase 3β phosphorylated at Ser9, β‐catenin, T cell factor 4, and ERK signaling attenuated Dkk‐1 up‐regulation of angiogenic factor and proteinase expression in synovial fibroblasts. In vivo, Dkk‐1 interference reduced the expression of angiogenic factors and proteinases and ameliorated synovial vascularity and cartilage deterioration in knees of rats with OA.ConclusionDkk‐1 promoted angiogenic and cartilage degradation activities in synovial fibroblasts, which accelerated synovial angiogenesis and cartilage destruction. Dkk‐1 blockade has therapeutic potential for reducing OA‐induced synovitis and joint deterioration.
Anatomical Sciences Education Vol. 5, Issue 4, 2012 Cover Image
Authors: Ang Eng‐Tat , Sugand Kapil , Hartman Mikael , Seow Choon‐Sheong , Bay Boon‐Huat , Abrahams Peter 
Published: July 2012

AbstractA group of first year medical students at the Yong Loo Lin School of Medicine of the National University of Singapore study anatomy in the Anatomy Museum at this institution. Using an anatomical model, students discuss the extraocular muscles with their lecturers Drs. Boon‐Huat Bay (center) and Eng‐Tat Ang (third from left). In this issue of ASE, Dr. Ang and his colleagues review the past, present, and future of anatomy education in Singapore's three medical schools.
ε‐Optimal Value and Approximate Multidimensional Dual Dynamic Programming
Authors: Nowakowski A. 
Published: June 2012

AbstractThis paper develops an approximate dual dynamic programming for an ε− optimal multidimensional control problem governed by first order hyperbolic equations. The problem considered is of the Dieudonne‐Rashevsky type and contains as a particular case class‐qualified deposit and Capital theory problems. It is proven that each Lipschitz continuous function satisfying the dual Hamilton‐Jacobi inequality can be used to define an ε‐optimal value.
Iterative Learning Control for Nonlinear Systems: A Bounded‐Error Algorithm
Authors: Delchev Kamen 
Published: June 2012

AbstractThis paper presents a nonlinear iterative learning control (NILC) for nonlinear time‐varying systems. An algorithm of a new strategy for the NILC implementation is proposed. This algorithm ensures that trajectory‐tracking errors of the proposed NILC, when implemented, are bounded by a given error norm bound. A special feature of the algorithm is that the trial‐time interval is finite but not fixed as it is for the other iterative learning algorithms. A sufficient condition for convergence and robustness of the bounded‐error learning procedure is derived. With respect to the bounded‐error and standard learning processes applied to a virtual robot, simulation results are presented in order to verify maximal tracking errors, convergence and applicability of the proposed learning control.
Loop‐Shaping and Easy Tuning of Fractional‐Order Proportional Integral Controllers for Position Servo Systems
Authors: Lino P. , Maione G. 
Published: June 2012

AbstractThis paper develops simple formulas directly relating performance specifications to control parameters of fractional‐order proportional integral (PI) controllers for position servo systems. With the proposed controller settings, the open‐loop frequency response achieves a good phase margin, that remains constant in a wide range around the crossover frequency. Consequently, the tuning results in high stability robustness to gain variations in the loop. Moreover, the fractional order integration also leads to limited overshoot and short settling time. Laboratory experiments confirm simulation results.
Einsatz von technischen Textilien für den mobilen Hochwasserschutz
Authors: Heinlein Kai , Wagner Rosemarie 
Published: July 2012

AbstractDer Einsatz von technischen Textilien für den mobilen Hochwasserschutz eignet sich hervorragend, vor allem wenn eine geringe Vorwarnzeit im notfallmäßigen Hochwasserfall besteht. In diesem Beitrag werden die Grundlagen des textilen Hochbaus (textile Überdachungen von Stadien und Schwimmhallen) auf die Entwicklung wassergefüllter Schutzsysteme als Alternative zu Sandsacksystemen übertragen. Es wird gezeigt, dass die Untersuchungen zum Materialverhalten von beschichteten Geweben und das typische Vorgehen bei Membrankonstruktionen in der Architektur, wie Formfindung, statische Berechnung und Zuschnitt für die Auslegung von mobilen Hochwasserschutzsystemen angewendet werden können. Im Folgenden wird dargestellt, wie diese methodische Vorgehensweise ein geeignetes Werkzeug für die Planung von zwei ausgewählten Hochwasserschutzsystemen ist und auf die speziellen Anforderungen angepasst wird. Es wird die Formfindung von Membranhüllen unter hydrostatischer Belastung näher beschrieben und eine statische Analyse eines solchen Systems veranschaulicht. Die Vorgehensweise zur Simulation solcher Probleme anhand eines tragwerksplanerischen Computerprogramms, durch Erweiterung der Randbedingungen mit dem Einsatz von Zusatztools, wird vorgestellt. Die Richtigkeit der Vorgehensweise wird durch experimentelle Verifizierung der Simulationsergebnisse sichergestellt.Mobile flood protection by use of technical textilesThe use of technical textiles for mobile flood protection is excel, especially if there is a short warning time in case of emergency flood events. This paper describes the transmission of textile building construction basics (textile roofs of stadiums and swimming pools) to the development of water‐filled protection systems as an alternative to sand bag systems. It is shown that the investigations of material behavior of coated fabrics and the typical approach of membrane structures in architecture, such as form‐finding, structural analysis and cutting pattern can be used to develop mobile flood protection systems. The following article manifests how this methodological approach is a suitable tool for the design of two selected flood control systems and is adapted to the specific requirements. The requirements and the selection of applicable materials, technical textiles in particular, are discussed. It describes the form finding of membrane shells under hydrostatic stress and illustrates in detail a static analysis of such a system. The procedure of the simulation of such problems by means of a supporting structure planning computer program will be presented by expanding the boundary conditions with the use of additional tools. The correctness of the procedure is ensured by experimental verification of the simulation results.
Neurodevelopmental outcomes following prenatal exposure to serotonin reuptake inhibitor antidepressants: A “social teratogen” or moderator of developmental risk?
Authors: Hanley Gillian E. , Oberlander Tim F. 
Published: June 2012

AbstractUnderstanding how prenatal serotonin reuptake inhibitors (SRIs) influence early brain development can provide critical clues to how early life experience programs developing neural systems that might contribute to risks for illness across the life span. To date, no gross SRI‐related neuroteratogenic effects have been identified, but evidence of subtle functional behavioral disturbances associated with fetal SRI exposure are emerging. Although some outcomes reflect a “main effect” for the SRI exposure, childhood development beyond infancy appears typical or continues to be influenced by life with a mother with a mood disturbance. Research shows that not all infants and children are equally affected; thus appreciating the effects of prenatal and postnatal maternal mental illness and of genetic variations that influence early serotonin signaling offers critical new insights into factors that contribute to developmental risk, plasticity, and resiliency in children with prenatal SRI exposure. Such a developmental perspective should lead us to understand what heightens or lessens neurodevelopmental vulnerability, thereby optimizing maternal pharmacotherapy and identifying who benefits and is least likely to experience neurobehavioral disturbances. Birth Defects Research (Part A) 94:651–659, 2012. © 2012 Wiley Periodicals, Inc.