bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Insights Into the Brain, Braincase, and Ear Region of Tyrannosaurs (Dinosauria, Theropoda), with Implications for Sensory Organization and Behavior
Authors: Witmer Lawrence M. , Ridgely Ryan C. 
Published: August 2009

AbstractThe braincase region of tyrannosaurs was investigated to provide insights on anatomical attributes relevant to inferences of sensory biology and behavior. CT scanning focused on three specimens of Tyrannosaurus rex, a juvenile Gorgosaurus, and the controversial Cleveland skull (CMNH 7541). Analysis shows that the cerebral hemispheres were enlarged, but conflicting information on the optic lobes suggests that brain conformation was not fully avian. Previous estimates of olfactory bulb size for T. rex were much too large, but even the corrected sizes are relatively larger than other theropods, suggesting that odor detection was indeed of particular importance to tyrannosaurs. The inner ears show a number of coelurosaurian traits, such as elongate and rounded and rostral, lateral semicircular canals, and incipient twisting of the common crus, which we interpret to be related to enhanced reflexes coordinating rapid eye and head movements. The cochlea is elongate, which, coupled with the finding of extensive tympanic pneumaticity, supports the inference of behavioral emphasis of low‐frequency sounds. Three main groups of sinuses pneumatized the braincase, and there are a number of perhaps systematically relevant differences. Orientation of the endosseous labyrinth reveals that alert head postures of T. rex and Gorgosaurus were somewhat depressed below the horizontal, but the Cleveland skull had a very strongly down‐turned posture. It is concluded that tyrannosaur sensory biology is consistent with their predatory coelurosaurian heritage, with emphasis on relatively quick, coordinated eye and head movements, and probably sensitive low‐frequency hearing; tyrannosaurs apomorphically enhanced their olfactory apparatus. The taxonomic status of the Cleveland skull remains unresolved. Anat Rec, 292:1266–1296, 2009. © 2009 Wiley‐Liss, Inc.
A Life Table for Psittacosaurus lujiatunensis: Initial Insights Into Ornithischian Dinosaur Population Biology
Authors: Erickson Gregory M. , Makovicky Peter J. , Inouye Brian D. , Zhou Chang‐Fu , Gao Ke‐Qin 
Published: August 2009

AbstractVery little is known about nonavian dinosaur population biology. Multi‐individual sampling and longevity estimation using growth line counts can be used to construct life tables—the foundation for population analyses in ecology. Here we have determined the size and age distribution for a sample consisting of 80 individuals of the small ornithischian, Psittacosaurus lujiatunensis from the early Cretaceous Yixian Formation of China. Their ages ranged from less than a year to eleven years and the distribution was strongly right‐skewed. This is consistent with taphonomic interpretations that these animals derive from a catastrophic death assemblage. The static life table analysis revealed the same general pattern of survivorship as tyrannosaurs including increased attrition before the attainment of full adult size. This may reflect increased physiological demands and/or predation exposure associated with reproduction. Collectively these findings suggest that most nonavian dinosaurs may have had a similar life history strategy. Anat Rec, 292:1514–1521, 2009. © 2009 Wiley‐Liss, Inc.
Novel evidence‐based systemic lupus erythematosus responder index
Authors: Furie Richard A. , Petri Michelle A. , Wallace Daniel J. , Ginzler Ellen M. , Merrill Joan T. , Stohl William , Chatham W. Winn , Strand Vibeke , Weinstein Arthur , Chevrier Marc R. , Zhong Z. John , Freimuth William W. 
Published: August 2009

AbstractObjectiveTo describe a new systemic lupus erythematosus (SLE) responder index (SRI) based on a belimumab phase II SLE trial and demonstrate its potential utility in SLE clinical trials.MethodsData from a randomized, double‐blind, placebo‐controlled study in 449 patients of 3 doses of belimumab (1, 4, 10 mg/kg) or placebo plus standard of care therapy (SOC) over a 56‐week period were analyzed. The Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG) SLE disease activity instruments, the Short Form 36 health survey, and biomarker analyses were used to create a novel SRI. Response to treatment in a subset of 321 serologically active SLE patients (antinuclear antibodies ≥1:80 and/or anti–double‐stranded DNA antibodies ≥30 IU/ml) at baseline was retrospectively evaluated using the SRI.ResultsSRI response is defined as 1) a ≥4‐point reduction in SELENA–SLEDAI score, 2) no new BILAG A or no more than 1 new BILAG B domain score, and 3) no deterioration from baseline in the physician's global assessment by ≥0.3 points. In serologically active patients, the addition of belimumab to SOC resulted in a response in 46% of patients at week 52 compared with 29% of the placebo patients (P = 0.006). SRI responses were independent of baseline autoantibody subtype.ConclusionThis evidence‐based evaluation of a large randomized, placebo‐controlled trial in SLE resulted in the ability to define a robust responder index based on improvement in disease activity without worsening the overall condition or the development of significant disease activity in new organ systems.
Liver X receptor agonism promotes articular inflammation in murine collagen‐induced arthritis
Authors: Asquith Darren L. , Miller Ashley M. , Hueber Axel J. , McKinnon Heather J. , Sattar Naveed , Graham Gerry J. , McInnes Iain B. 
Published: August 2009

AbstractObjectiveLiver X receptors (LXRs) have previously been implicated in the regulation of inflammation and have, in general, been ascribed an antiinflammatory role. This study was therefore undertaken to explore the biologic mechanisms of LXRs in vivo and in vitro in an experimental inflammatory arthritis model.MethodsMale DBA/1 mice were immunized with type II collagen and treated from an early or established stage of arthritis with 2 different concentrations of the LXR agonists T1317 and GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis, histologic examination of the joints, and analysis of serum cytokine and antibody levels. In vitro, primary human monocytes and T cells were cultured in the presence of GW3965 or T1317, and the concentrations of proinflammatory cytokines were measured by multiplex assay.ResultsContrary to expectations, LXR agonism with the use of 2 discrete, specific molecular entities led to substantial exacerbation of articular inflammation and cartilage destruction in this murine collagen‐induced arthritis model. This was associated ex vivo with elevated cytokine expression, with enhanced Th1 and Th17 cellular responses, and with elevated collagen‐specific autoantibody production. In vitro, LXR agonists, in concert with lipopolysaccharide, promoted cytokine and chemokine release from human monocytes, and similar effects were observed in a T cell–macrophage coculture model that closely recapitulates the pathways that drive synovial cytokine release.ConclusionSince LXRs are present in rheumatoid arthritis (RA) synovium, these results suggest that LXR‐mediated pathways could exacerbate the chronic inflammatory response typical of RA.
Reliability and validity of the university of california, los angeles scleroderma clinical trial consortium gastrointestinal tract instrument
Authors: Khanna Dinesh , Hays Ron D. , Maranian Paul , Seibold James R. , Impens Ann , Mayes Maureen D. , Clements Philip J. , Getzug Terri , Fathi Nihal , Bechtel Amber , Furst Daniel E. 
Published: August 2009

AbstractObjectiveTo refine the previously developed scleroderma (systemic sclerosis [SSc]) gastrointestinal tract (GIT) instrument (SSC‐GIT 1.0).MethodsWe administered the SSC‐GIT 1.0 and the Short Form 36 to 152 patients with SSc; 1 item was added to the SSC‐GIT 1.0 to assess rectal incontinence. In addition, subjects completed a rating of the severity of their GIT involvement (from very mild to very severe). Evaluation of psychometric properties included internal consistency reliability, test–retest reliability (mean time interval 1.1 weeks), and multitrait scaling analysis.ResultsStudy participants were mostly women (84%) and white (81%); 55% had diffuse SSc. Self‐rated severity of GIT involvement ranged from no symptoms to very mild (39%), mild (21%), moderate (31%), and severe/very severe (9%). Of an initial 53 items in the SSC‐GIT 1.0, 19 items were excluded, leaving a 34‐item revised instrument (the University of California, Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 [UCLA SCTC GIT 2.0]). Analyses supported 7 multi‐item scales: reflux, distention/bloating, diarrhea, fecal soilage, constipation, emotional well‐being, and social functioning. Test–retest reliability estimates were ≥0.68 and coefficient alphas were ≥0.67. Participants who rated their GIT disease as mild had lower scores on a 0–3 scale on all 7 scales. Symptom scales were also able to discriminate subjects with corresponding clinical GIT diagnoses. The Total GIT Score, developed by averaging 6 of 7 scales (excluding constipation), was reliable and provided greater discrimination between mild, moderate, and severe self‐rated GIT involvement than individual scales.ConclusionThis study provides support for the reliability and validity of the UCLA SCTC GIT 2.0, an improvement over the SSC‐GIT 1.0, and supports a Total GIT Score in SSc patients with GIT.
Rheumatoid arthritis does not share most of the newly identified systemic lupus erythematosus genetic factors
Authors: Suarez‐Gestal Marian , Calaza Manuel , Dieguez‐Gonzalez Rebeca , Perez‐Pampin Eva , Pablos Jose Luis , Navarro Federico , Narvaez Javier , Marenco Jose Luis , Herrero‐Beaumont Gabriel , Fernandez‐Gutierrez Benjamin , Lamas Jose Ramon , de la Serna Arturo Rodriguez , Ortiz Ana Maria , Carreño Luis , Cañete Juan D. , Caliz Rafael , Blanco Francisco J. , Balsa Alejandro , Gomez‐Reino Juan J. , Gonzalez Antonio 
Published: August 2009

AbstractObjectiveRheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) share some genetic factors such as HLA, PTPN22, STAT4, and 6q23. The aim of this study was to determine whether 9 other SLE genetic factors are also implicated in RA susceptibility.MethodsA characteristic single‐nucleotide polymorphism (SNP) in each of 9 genetic factors, ITGAM (rs1143679), C8orf13–BLK (rs13277113), TYK2 (rs2304256), 1q25.1 (rs10798269), PXK (rs6445975), KIAA1542 (rs4963128), MECP2 (rs17435), BANK1 (rs17266594), and LY9 (rs509749), was studied in 1,635 patients with RA and 1,906 control subjects from Spain. The rs7574865 SNP in STAT4 was also included. Analyses were conducted globally and after stratification by sex and clinical features (anti–cyclic citrullinated peptide and rheumatoid factor, shared epitope, rheumatoid nodules, radiographic changes, sicca syndrome, and pneumonitis).ResultsNo association was observed between RA and any of the 9 newly identified SLE genetic factors. A meta‐analysis using previous data was consistent with these results. In addition, there were no significant differences between individuals with and those without each of the clinical features analyzed, except the frequency of the minor allele in the C8orf13–BLK locus that was decreased in patients with sicca syndrome (14.6% versus 22.4% in controls; P = 0.003).ConclusionNone of the 9 recently identified SLE risk factors showed association with RA. Therefore, common genetic factors affecting the pathogenesis of these 2 disorders seem to be limited, revealing that the genetic component contributes to the different expression of these diseases.
Defective phosphorylation of interleukin‐18 receptor β causes impaired natural killer cell function in systemic‐onset juvenile idiopathic arthritis
Authors: de Jager Wilco , Vastert Sebastiaan J. , Beekman Jeffrey M. , Wulffraat Nico M. , Kuis Wietse , Coffer Paul J. , Prakken Berent J. 
Published: August 2009

AbstractObjectiveSystemic‐onset juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by arthritis and systemic features. Its pathogenesis is still largely unknown. It is characterized immunologically by natural killer (NK) cell dysfunction and cytokine signatures that predominantly feature interleukin‐1 (IL‐1), IL‐6, and IL‐18. Since IL‐18 can drive NK cell function, we examined how the high plasma levels of this cytokine are related to the documented NK cell failure in these patients.MethodsThe phenotype and function of NK cells from 10 healthy control subjects, 15 patients with polyarticular JIA, and 15 patients with systemic‐onset JIA were characterized by staining and functional assays in vitro. IL‐18 ligand binding was visualized by fluorescence microscopy. Phosphorylation of several MAP kinases and the IL‐18 receptor β (IL‐18Rβ) were visualized by Western blotting.ResultsIL‐18 from the plasma of systemic‐onset JIA patients stimulated the activation of NK cells from healthy controls and bound its cognate receptor. However, NK cells from systemic‐onset JIA patients failed to up‐regulate cell‐mediated killing molecules, such as perforin and interferon‐γ, after IL‐18 stimulation. Furthermore, treatment with IL‐18 did not induce the phosphorylation of receptor‐activated MAP kinases in NK cells. Alternate activation of NK cells by IL‐12 induced NK cell cytotoxicity. We observed no additive effect of IL‐18 in combination with IL‐12 in systemic‐onset JIA patients. Immunoprecipitation of IL‐18Rβ showed that NK cells from systemic‐onset JIA could not phosphorylate this receptor after IL‐18 stimulation.ConclusionThe mechanism of the impaired NK cell function in systemic‐onset JIA involves a defect in IL‐18Rβ phosphorylation. This observation has major implications for the understanding and, ultimately, the treatment of systemic‐onset JIA.
ADAM‐8 isolated from human osteoarthritic chondrocytes cleaves fibronectin at Ala271
Authors: Zack Marc D. , Malfait Anne‐Marie , Skepner Adam P. , Yates Matthew P. , Griggs David W. , Hall Troii , Hills Robert L. , Alston James T. , Nemirovskiy Olga V. , Radabaugh Melissa R. , Leone Joseph W. , Arner Elizabeth C. , Tortorella Micky D. 
Published: August 2009

AbstractObjectiveFibronectin fragments are thought to play a critical role in the initiation and progression of cartilage degradation in arthritis. In a recent study, fibronectin neoepitopes resulting from cleavage of intact fibronectin at the Ala271/Val272 scissile bond, generating an ∼30‐kd fragment with the new C‐terminus VRAA271 and an ∼50–85‐kd fragment with the new N‐terminus 272VYQP, were identified in osteoarthritis (OA) cartilage. The present study was undertaken to isolate the enzymes responsible for this cleavage from human OA chondrocytes.MethodsFibronectin‐degrading activity in human OA chondrocyte–conditioned medium (OACCM) was purified using conventional chromatography. A fluorescent peptide was developed based on the fibronectin scissile bond 269RAA↓Val272, and this peptide was used to track fibronectinase activity during purification. Western blotting with antibodies that detect the fibronectin neoepitopes VRAA271 and 272VYQP was used to confirm cleavage of intact fibronectin by the enzymatically active fractions. Mass spectrometry was used to identify the proteins found in the fibronectinase‐enriched fractions, with further confirmation by Western blotting. In addition, a recombinant enzyme identified by mass spectrometry was tested by Western blotting and dimethylmethylene blue assay for its ability to produce fibronectin neoepitopes in OA cartilage.ResultsPurification of OACCM by chromatography resulted in isolation of a fibronectin‐degrading enzyme, and mass spectrometry identified ADAM‐8 as the fibronectinase present in these preparations. Furthermore, treatment of OA cartilage with recombinant human ADAM‐8 promoted cartilage catabolism.ConclusionThe results of this study identify ADAM‐8 as a fibronectinase in human OA chondrocytes. Because ADAM‐8 is capable of producing the fibronectin neoepitopes VRAA271 and 272VYQP in human OA cartilage, this enzyme may be an important mediator of cartilage catabolism.
Calcification of articular cartilage in human osteoarthritis
Authors: Fuerst M. , Bertrand J. , Lammers L. , Dreier R. , Echtermeyer F. , Nitschke Y. , Rutsch F. , Schäfer F. K. W. , Niggemeyer O. , Steinhagen J. , Lohmann C. H. , Pap T. , Rüther W. 
Published: August 2009

AbstractObjectiveHypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy.MethodsOne hundred twenty patients with end‐stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x‐ray radiography, digital‐contact radiography (DCR), field‐emission scanning electron microscopy (FE‐SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro.ResultsDCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE‐SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix.ConclusionThese results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.
Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: Data from a single US institution
Authors: Burgos Paula I. , Perkins Elizabeth L. , Pons‐Estel Guillermo J. , Kendrick Scott A. , Liu Jigna M. , Kendrick William T. , Cook William J. , Julian Bruce A. , Alarcón Graciela S. , Kew Clifton E. 
Published: August 2009

AbstractObjectiveTo determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation.MethodsThe archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time‐to‐event data were examined by univariable and multivariable Cox proportional hazards regression analyses.ResultsTwo hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30‐year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time‐to‐event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29–16.65) and death (HR 2.47, 95% CI 0.91–6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09–5.60 and HR 2.72, 95% CI 1.55–4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys.ConclusionAfrican American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patient's survival.
Long‐term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis
Authors: Giannini E. H. , Ilowite N. T. , Lovell D. J. , Wallace C. A. , Rabinovich C. E. , Reiff A. , Higgins G. , Gottlieb B. , Singer N. G. ,   Pediatric Rheumatology Collaborative Study Group, Chon Y. , Lin S.‐L. , Baumgartner S. W. 
Published: August 2009

AbstractObjectiveThis study was undertaken to evaluate the long‐term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA).MethodsPatients ages 2–18 years with rheumatoid factor (RF)–positive or RF‐negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (≥10 mg/m2/week [∼0.3 mg/kg/week], maximum dosage 1 mg/kg/week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open‐label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician's global assessment of disease activity and the pediatric total joint assessment.ResultsA total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure‐adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient‐years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient‐years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician's global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study.ConclusionThese data confirm the findings of other long‐term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication.