bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome‐wide association analysis
Authors: Hinks Anne , Barton Anne , Shephard Neil , Eyre Steve , Bowes John , Cargill Michele , Wang Eric , Ke Xiayi ,   British Society of Paediatric and Adolescent Rheumatology Study Group, Kennedy Giulia C. , John Sally , Worthington Jane , Thomson Wendy 
Published: December 2008

AbstractObjectiveJuvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well‐established genetic factors known to contribute to JIA susceptibility, HLA and PTPN22, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA.MethodsA genome‐wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single‐nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort (n = 2,024). In one region in which association was confirmed, fine‐mapping was performed (654 cases and 1,847 controls).ResultsOf the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the HLA region, while the second strongest association was with a SNP within the VTCN1 gene. Fine‐mapping of that gene was performed, and 10 SNPs were found to be associated with JIA.ConclusionThis study is the first to successfully apply a SNP‐based genome‐wide association approach to the investigation of JIA. The replicated association with markers in the VTCN1 gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood.
CTLA‐4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice
Authors: Kolar Paula , Knieke Karin , Hegel J. Kolja E. , Quandt Dagmar , Burmester Gerd‐R. , Hoff Holger , Brunner‐Weinzierl Monika C. 
Published: December 2008

AbstractObjectiveCD4+CD25+ regulatory T cells (known as Treg cells) suppress unwanted and autoreactive T cell responses. Treg cells express the costimulatory molecule CTLA‐4 intracellularly, but the mechanisms by which Treg cells exploit CTLA‐4 signaling remain unclear. The present study was undertaken to investigate the role of CTLA‐4 in controlling the homeostasis and suppressive function of Treg cells.MethodsMurine Treg cells were analyzed by flow cytometry for coexpression of CTLA‐4 and typical Treg cell–expressed molecules, and the influence of CTLA‐4 on T cell proliferation, suppression, and apoptosis was investigated by in vitro assays. To analyze the importance of CTLA‐4 in Treg cell–mediated suppression in vivo, wild‐type Treg cells were transferred into CTLA‐4–deficient mice displaying lymphoproliferation, and survival was monitored over time.ResultsA strong correlation between expression of forkhead box P3 and ex vivo expression of CTLA‐4 in Treg cells was observed. Inhibition of CTLA‐4 signaling in Treg cells during in vitro stimulation increased cell cycling and led to enhanced activation‐induced cell death (AICD), which was mediated by CD95/CD95 ligand–induced activation of caspases. Blockade of CTLA‐4 signaling resulted in impairment of the suppressive capacity of Treg cells. Despite these effects, high amounts of Treg cells persisted in CTLA‐4–deficient mice. Results of transfer experiments in CTLA‐4–deficient mice showed that the mice had a significantly prolonged lifespan when CTLA‐4–competent Treg cells were injected.ConclusionExpression of CTLA‐4 on Treg cells serves to control T cell proliferation, to confer resistance against AICD, and to maintain the suppressive function of Treg cells.
The combination of the biomarkers urinary C‐terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy
Authors: Jansen Nathalie W. D. , Roosendaal Goris , Lundin Björn , Heijnen Lily , Mauser‐Bunschoten Evelien , Bijlsma Johannes W. J. , Theobald Matthias , Lafeber Floris P. J. G. 
Published: December 2008

AbstractObjectiveHemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers.MethodsBlood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C‐terminal telopeptide of type I collagen (CTX‐I), urinary CTX‐II, serum CTX‐I, serum CTX‐II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS‐846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy.ResultsUrinary CTX‐II, serum C1,2C, and serum CS‐846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX‐II, serum COMP, and serum CS‐846. Bone‐specific markers (urinary/serum CTX‐I and serum C1,2C) did not correlate with specific bone‐related items of the Pettersson score (osteoporosis and erosions).ConclusionThese results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX‐II, serum COMP, and serum CS‐846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage.
Patient‐reported outcomes in a randomized trial comparing four different treatment strategies in recent‐onset rheumatoid arthritis
Authors: van der Kooij S. M. , de Vries‐Bouwstra J. K. , Goekoop‐Ruiterman Y. P. M. , Ewals J. A. P. M. , Han K. H. , Hazes J. M. W. , Kerstens P. J. S. M. , Peeters A. J. , van Zeben D. , Breedveld F. C. , Huizinga T. W. J. , Dijkmans B. A. C. , Allaart C. F. 
Published: December 2008

AbstractObjectiveTo investigate the effectiveness of 4 different treatment strategies for recent‐onset rheumatoid arthritis (RA) on 2‐year patient‐reported outcomes, including functioning and quality of life.MethodsA total of 508 patients with recent‐onset RA were randomly assigned to 1) sequential monotherapy, 2) step‐up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high‐dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF‐36), and scores for pain, global health, and disease activity measured on a 100‐mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years.ResultsAfter 2 years, all patient‐reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF‐36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF‐36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4).ConclusionAll 4 DAS‐driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self‐assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient‐reported measures.
Development and testing of a decision board to help clinicians present treatment options to lupus nephritis patients in Brazil
Authors: De Abreu Mirhelen Mendes , Gafni Amiran , Ferraz Marcos Bosi 
Published: December 2008

AbstractObjectiveDecision boards (DBs) help clinicians present options and include patients in the decision‐making process. Our objective was to describe the steps to develop a DB to support shared decision making and assess reliability and construct validity.MethodsSystemic lupus erythematosus (SLE) scenarios were designed with the support of experts for disease severity, potential side effects, and outcomes. The DB comprised clinical information, 2 different treatment options (oral and intravenous), a description of the potential to control SLE within 5 years, and a list of potential side effects. Patients selected what they thought would be the 3 worst side effects and were informed of the probability that these would occur. We presented the DB to 172 patients who were asked to select and justify 1 treatment option. Reliability was assessed by kappa statistics. Construct validity was tested by an a priori hypothesis, analyzing the correlation between treatment decision and side effects selected, self‐assessment score, educational level, and clinical aspects.ResultsPatients favored oral medication, and side effects most often listed were iatrogenic cancer (44.2%), hair loss (21.6%), and severe infection (19.1%). Justifications were risk (48.9%), practicality (36.6%), effectiveness (12.2%), and risk‐benefit tradeoff (2.3%). Reliability was similar to that found in the test phase (κ = 0.689, P < 0.001). Validity was tested by prediction of treatment decision based on the undesirable side effects selected (P = 0.047). DB content was clear and easy for all patients to understand (P = 0.05). Immunosuppressive drugs influenced patient decisions (P = 0.006).ConclusionDB is a reliable and valid instrument to assess SLE patient preference.
How to evaluate and improve the reliability of power Doppler ultrasonography for assessing enthesitis in spondylarthritis
Authors: D'agostino Maria Antonietta , Aegerter Philippe , Jousse‐Joulin Sandrine , Chary‐Valckenaere Isabelle , Lecoq Bertrand , Gaudin Philippe , Brault Isabelle , Schmitz Jérôme , Dehaut François‐Xavier , Le Parc Jean‐marie , Breban Maxime , Landais Paul 
Published: December 2008

AbstractObjectiveTo evaluate and improve the reliability of power Doppler ultrasonography (PDUS) for detecting and scoring enthesitis in patients with spondylarthitis, using a 3‐step procedure.MethodsIn the first step, we evaluated the reliability of 5 sonographers by bilaterally scanning 5 entheses twice in 5 patients. In the second step, starting from disagreements observed during the first step, we established consensus guidelines. The sonographers' implementation was further evaluated in 2 reliability exercises: one on 60 PDUS enthesitis images and the other by scanning 5 new patients. In the third step, we performed a final reliability evaluation of 5 additional patients after 1 year. Kappa coefficients (κ) as well as variance component analysis (VCA) and generalizability theory (GT) were used to assess reliability.ResultsThe initial intra‐ and interobserver reliability were poor, especially for detecting and scoring Doppler signal. VCA and GT showed that most variability was accounted for by interaction between sonographer and enthesis. Implementation of consensus guidelines was associated with a significant improvement in Doppler reliability between the first and second steps (mean interobserver κ increased from 0.13 to 0.51 for binary Doppler scoring in patients; P < 0.005), which persisted in the third step (mean interobserver κ = 0.57). The high GT coefficients reached in the last steps supported such improvement.ConclusionThe 3‐step procedure used in this study to standardize PDUS technique was associated with a significant improvement in interobserver reliability for detecting enthesitis in spondylarthritis patients. Such an approach can be useful to standardize PDUS assessment of musculoskeletal disorders.
Effectiveness of treatment of calcific tendinitis of the shoulder by disodium EDTA
Authors: Cacchio Angelo , De Blasis Elisabetta , Desiati Piergiorgio , Spacca Giorgio , Santilli Valter , De Paulis Fosco 
Published: December 2008

AbstractObjectiveTo evaluate the effectiveness of disodium EDTA administration in the treatment of calcific tendinitis of the shoulder.MethodsEighty patients with radiographically verified calcific tendinitis of the shoulder were enrolled between September 2001 and October 2003. Patients were randomly assigned to either a study group (n = 40) or a control group (n = 40). Pain and functional level were evaluated before and after treatment and at 1‐year followup. Radiographic modifications in calcifications were evaluated before and after treatment. Disodium EDTA was administered through single needle mesotherapy and 15 minutes of pulsed‐mode 1 MHz‐ultrasound.ResultsThe study group displayed improvement in all of the parameters analyzed after treatment and at the 1‐year followup. Calcifications disappeared completely in 62.5% of the patients in the study group and partially in 22.5%; calcifications partially disappeared in only 15% of the patients in the control group, and none displayed a complete disappearance.ConclusionOur results suggest that the use of disodium EDTA for the management of calcific tendinitis of the shoulder is safe and effective, leading to a significant reduction in pain, improvement in shoulder function, and disappearance of calcifications after 4 weeks, without adverse effects.
(Mis)understanding in patient‐health care provider communication about total knee replacement
Authors: Street Richard L. , Richardson Marsha N. , Cox Vanessa , Suarez‐Almazor Maria E. 
Published: December 2008

AbstractObjectiveTo examine whether communication factors affect health care provider and patient agreement on the need for, risks of, and benefits of joint replacement, and also whether degree of agreement predicts patient satisfaction and intent to follow treatment recommendations.MethodsHealth care providers (n = 27) and patients (n = 74) with severe osteoarthritis (OA) were recruited from clinics in Houston, Texas. Patients completed a baseline survey prior to the consultation. After the visit, patients and providers completed measures of the severity of the patient's OA, the expected benefits of total knee replacement (TKR), and concern about surgical complications. Patients also completed satisfaction and intent to adhere measures. Provider communication and patient participation were measured by patient self‐report and by observers' codings of audiorecordings of the consultations.ResultsProvider‐patient agreement was modest to poor regarding severity of the patient's OA and the expected benefits and risks of TKR. Providers and patients were more aligned on the patient's OA severity when providers used more partnership building but spent less time simply giving information. Differences between providers' and patients' concerns about surgery were greater when patients were less participatory, African American, or expressed lower trust in their doctors. Patient satisfaction and intent to adhere were predicted by provider‐patient agreement on the benefits of TKR.ConclusionPatients and providers often differ in their beliefs about the need for, risks of, and benefits of TKR, and these differences can affect patient satisfaction and commitment to treatment. Facilitating active patient participation might contribute to greater physician–patient agreement on the patient's concerns about OA and surgical interventions.
Bio‐Inspired Silicification on Patterned Surfaces Generated by Microcontact Printing and Layer‐by‐Layer Self‐Assembly
Authors: Yang Sung Ho , Choi Insung S. 
Published: December 2008

AbstractMicropatterns of silica were generated under biocompatible conditions by a combination of microcontact printing (μCP), layer‐by‐layer (LbL) self‐assembly, and biomimetic silicification. Quaternary amine‐containing poly(diallyl dimethyl ammonium chloride) induced polycondensation of silicic acid, resulting in spatioselective formation of silica micropatterns. Scale bar: 10 μm.magnified image
The onset of autism: patterns of symptom emergence in the first years of life
Authors: Ozonoff Sally , Heung Kelly , Byrd Robert , Hansen Robin , Hertz‐Picciotto Irva 
Published: December 2008

AbstractPrevious conceptualizations of autism have suggested that symptoms are evident either early in the first year of life or later in the second year, after a loss of previously acquired skills. New research suggests, however, that these two patterns do not capture all the different ways autism can emerge. For example, some children show a developmental plateau marked by failure to progress, while other children display mixed features, with both early delays and later losses evident. This article reviews the literature on autism onset, discusses problems with the traditional ways in which onset has been conceptualized, and provides recommendations for future research. We suggest that onset is better thought of as a dimensional process rather than dichotomous categories.
Evidence that the pattern of visuomotor sequence learning is altered in children with autism
Authors: Gidley Larson Jennifer C. , Mostofsky Stewart H. 
Published: December 2008

AbstractMotor deficits are commonly reported in autism, with one of the most consistent findings being impaired execution of skilled movements and gestures. Given the developmental nature of autism, it is possible that deficits in motor/procedural learning contribute to impaired acquisition of motor skills. Thus, careful examination of mechanisms underlying learning and memory may be critical to understanding the neural basis of autism. A previous study reported impaired motor learning in children with high‐functioning autism (HFA); however, it is unclear whether the observed deficits in motor learning are due, in part, to impaired motor execution and whether these deficits are specific to autism. In order to examine these questions, 153 children (52 with HFA, 39 with attention‐deficit/hyperactivity disorder (ADHD) and 62 typically developing (TD) children) participated in two independent experiments using a Rotary Pursuit task, with change in performance across blocks as a measure of learning. For both tasks, children with HFA demonstrated significantly less change in performance than did TD children, even when differences in motor execution were minimized. Differences in learning were not seen between ADHD and TD groups on either experiment. Analyses of the pattern of findings revealed that compared with both ADHD and TD children, children with HFA showed a similar degree of improvement in performance; however, they showed significantly less decrement in performance when presented with an alternate (“interference”) pattern. The findings suggest that mechanisms underlying acquisition of novel movement patterns may differ in children with autism. These findings may help explain impaired skill development in children with autism and help to guide approaches for helping children learn novel motor, social and communicative skills.
Enhanced Cellular Uptake and Cytotoxicity Studies of Organometallic Bioconjugates of the NLS Peptide in Hep G2 Cells
Authors: Noor Fozia , Kinscherf Ralf , Bonaterra Gabriel A. , Walczak Steffen , Wölfl Stefan , Metzler‐Nolte Nils 
Published: December 2008

AbstractSpace invaders: Organometallic fragments such as the ferrocenyl group (shown in red in the picture) help to enhance cellular entry of NLS peptides. Eventually, these nontoxic conjugates find their way to the cellular nucleus as shown by fluorescence microscopy studies in this work.magnified imageIntracellular delivery to biomolecular targets is still a major challenge in molecular and cell biology. We recently found that attaching an organometallic group, namely the cobaltocenium cation, to the SV 40 large T antigen nuclear localisation signal (NLS) greatly enhances cellular uptake of the conjugate (Noor et al., Angew. Chem. Int. Ed. 2005, 45, 2429). In addition, nuclear localisation of the conjugate was observed. In this work, we present a thorough investigation of this novel cellular delivery system with respect to the nature of the metal complex and the peptide sequence. A number of ferrocene ((FeII), neutral metal complex) and cobaltocenium ((CoIII), cationic metal complex) bioconjugates with both the NLS wild‐type sequence PKKKRKV and a scrambled sequence (NLSscr, KKVKPKR) were prepared by solid‐phase peptide synthesis (SPPS). Cellular and nuclear uptake of these bioconjugates was studied by fluorescence microscopy on living Hep G2 cells. In addition, cytotoxicity screening on the conjugates was carried out, as the toxic effects of several simple metallocenes have been noted previously. Rapid cellular uptake as well as nuclear localisation was observed for the metal–NLS conjugates, but not for any dipeptide controls, the metal–NLSscr conjugates or any metal‐free conjugates. It thus appears that the presence of a metallocene, but not its charge, and the correct NLS sequence is essential for cellular uptake. Fluorescence microscopy co‐localisation studies did not reveal a significant endosomal entrapment of the conjugates. The metallocene not only provides a hydrophobic handle for membrane translocation but also facilitates the localisation and distribution of the conjugate in the cytoplasm. The NLS peptide on the other hand is responsible for the nuclear localisation of the bioconjugate. Finally, none of the conjugates were found to be toxic up to the highest concentrations that was tested (1 mM) against the Hep G2 cells that were used in this study. In conclusion, this work supports metallocene–NLS bioconjugates, in particular with the very robust cobaltocenium group, as a simple but potent, nontoxic system for cellular uptake and nuclear delivery. Concurrently, our finding is relevant to the still‐unresolved question of cytotoxicity of metallocenes because it excludes binding and/or damage to the DNA as a mechanism of metallocene cytotoxicity. This finding is confirmed by a combined yeast cytotoxicity/genotoxicity assay, which also shows very little toxic effects for all organometal–NLS conjugates that were tested.