bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Facial Integument of Centrosaurine Ceratopsids: Morphological and Histological Correlates of Novel Skin Structures
Authors: Hieronymus Tobin L. , Witmer Lawrence M. , Tanke Darren H. , Currie Philip J. 
Published: August 2009

AbstractThe horned dinosaur Pachyhinosaurus possesses rugose bony bosses across the skull roof in lieu of the projecting bony horn cores seen in most ceratopsians. This elaboration of typical ceratopsian ornaments provides an opportunity to test hypotheses of ceratopsian facial skin morphology and function. We analyze bone morphology and histology associated with several classes of skin features in extant amniotes using a classification tree analysis. We isolate key osteological and histological correlates for unpreserved skin structures, including both a pattern of pitting and resorption characteristic of muskox (Ovibos) frontal horn boss, and a pattern of metaplastic ossification characteristic of rhinoceros nasal horn boss. We also describe correlates for other skin features, such as epidermal scales and horn sheaths. Dermatocranial elements from centrosaurine ceratopsians are then examined for the same osteological and histological correlates. From this comparison we propose that the rugose bosses that replace horn cores in many centrosaurine dinosaurs, most notably Achelousaurus and Pachyrhinosaurus, were covered by a thick pad of cornified skin derived from the caudodorsal side of the primitive horn sheath comparable to the horny boss of extant muskoxen (Ovibos). We examine extant taxa with skin morphologies similar to Pachyrhinosaurus for consistent adaptive relationships between structure and behavior. We determine that high‐energy headbutting is consistently associated with the acquisition of thick cornified pads, seen in muskoxen as well as helmeted hornbills [Buceros (=Rhinoplax) vigil] and African buffalo (Syncerus). The association of the bony ornaments of Pachyrhinosaurus with risky agonistic behaviors casts doubt on the role of species recognition as a primary selection pressure driving the diversity of all ceratopsian horns. We conclude that social selection (a broad form of intraspecific competition) is a more appropriate explanation for the diversity of centrosaurine ceratopsian ornaments in the Late Cretaceous. Anat Rec, 292:1370–1396, 2009. © 2009 Wiley‐Liss, Inc.
Palaeobiological Implications of the Bone Histology of Pterodaustro guinazui
Authors: Chinsamy Anusuya , Codorniú Laura , Chiappe Luis 
Published: August 2009

AbstractThis study provides a comprehensive investigation of the bone microstructure of multiple bones of the Early Cretaceous filter‐feeder, Pterodaustro guinazui, from the Largacito Formation of Central Argentina. We provide information regarding the bone histology of multiple elements from single skeletons, as well as a variety of bones from different individuals. In addition, we analysed changes in bone microstructure through ontogeny in growth series of several long bones of the taxon. Our investigation of skeletal and ontogenetic variation in Pterodaustro gives insights into the developmental growth dynamics of this unusual ctenochasmatid pterodactyloid from early ontogeny through to adulthood and also provides information pertaining to histological variability within and between bones of individuals. This study also documents the presence of what appears to be medullary bone tissue within the medullary cavity of a large femur of Pterodaustro. This suggests that, like birds, reproductively active female pterosaurs may have deposited a special bone tissue (medullary bone) to cope with the demand of calcium during eggshelling. Our study supports the hypothesis that small Jurassic pterodactyloids took several years to reach adult body size. More specifically, we provide data that suggests that Pterodaustro attained sexual maturity at about 2 years of age, and continued to grow for a further 3–4 years doubling in size before attaining skeletal maturity. Anat Rec, 292:1462–1477, 2009. © 2009 Wiley‐Liss, Inc.
Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents
Authors: Rostom Sherif A. F. , Hassan Ghada S. , El‐Subbagh Hussein I. 
Published: August 2009

AbstractA series of 3,5‐bis(arylidene)‐4‐piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3‐c]pyridines, pyrido[4,3‐d]pyrimidines, and pyrido[3,2‐c]pyridines, carrying an arylidene moiety, and some pyrano[3,2‐c]pyridines, like flavone and coumarin isosteres, were synthesized and screened for their in‐vitro antitumor activity at the National Cancer Institute (NCI, USA). The tested compounds 7, 9, 10, 12, 13, 15, 17, and 19 exhibited a broad spectrum of antitumor activity. Compounds belonging to the pyrazolo[4,3‐c]pyridine series proved to be more active than those of the pyrido[3,2‐c]pyridine and pyrano[3,2‐c]pyridine analogues, in which the monomethoxylated derivatives showed better antitumor activity when compared with their corresponding dimethoxylated congeners. Compound 7 is considered to be the most active member identified in this study with a broad spectrum of activity against 22 different tumor cell lines belonging to the nine subpanels employed, and a particular effectiveness against the breast cancer T‐47D cell line (GI 54.7%). The pyrano[3,2‐c]pyridine heterocyclic system 19 proved to be the most active antitumor agent among the six‐membered fused pyridines, with variable activity against 18 different tumor cell lines, and special activity against the non‐small cell lung cancer Hop‐92 and ovarian cancer OVCAR‐4 cell lines (GI values 63.9 and 48.5%, respectively).
Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort
Authors: Segal Neil A. , Torner James C. , Felson David , Niu Jingbo , Sharma Leena , Lewis Cora E. , Nevitt Michael 
Published: August 2009

AbstractObjectiveTo assess whether knee extensor strength or hamstring:quadriceps (H:Q) ratio predicts risk for incident radiographic tibiofemoral and incident symptomatic whole knee osteoarthritis (OA) in adults ages 50–79 years.MethodsWe followed 1,617 participants (2,519 knees) who, at the baseline visit of the Multicenter Osteoarthritis (MOST) Study, did not have radiographic tibiofemoral OA and 2,078 participants (3,392 knees) who did not have symptomatic whole knee OA (i.e., did not have the combination of radiographic OA and frequent knee symptoms). Isokinetic strength was measured at baseline, and participants were followed for development of incident radiographic tibiofemoral OA, or incident symptomatic whole knee OA at 30 months. Generalized estimating equations accounted for 2 knees per subject, and multivariable models adjusted for age, body mass index (BMI), hip bone mineral density, knee surgery or pain, and physical activity score.ResultsIn the studies of incident radiographic and incident symptomatic knee OA, mean ± SD ages were 62.4 ± 8.0 years and 62.3 ± 8.0 years, respectively, and mean ± SD BMI scores were 30.6 ± 5.8 kg/m2 and 30.2 ± 5.5 kg/m2, respectively. Knee extensor strength and H:Q ratio at baseline significantly differed between men and women. Neither knee extensor strength nor the H:Q ratio was predictive of incident radiographic tibiofemoral OA. Compared with the lowest tertile, the highest tertile of knee extensor strength protected against development of incident symptomatic whole knee OA in both sexes (adjusted odds ratio 0.5–0.6). H:Q ratio was not predictive of incident symptomatic whole knee OA in either sex.ConclusionThigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.
Evaluation of a novel 7‐joint ultrasound score in daily rheumatologic practice: A pilot project
Authors: Backhaus M. , Ohrndorf S. , Kellner H. , Strunk J. , Backhaus T. M. , Hartung W. , Sattler H. , Albrecht K. , Kaufmann J. , Becker K. , Sörensen H. , Meier L. , Burmester G. R. , Schmidt W. A. 
Published: August 2009

AbstractObjectiveTo introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice.MethodsThe ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0–3) by gray‐scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0–27 for GS synovitis, 0–39 for PD synovitis, 0–7 for GS tenosynovitis, 0–21 for PD tenosynovitis, and 0–14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease‐modifying antirheumatic drug (DMARD) and/or tumor necrosis factor α (TNFα) inhibitor therapy 3 and 6 months later. C‐reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti–cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed.ResultsOne hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNFα inhibitors (41%), or TNFα inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (Δ = 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (−32%) and 2.0 (−39%), respectively.ConclusionThe German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.
A phase II, randomized, double‐blind, placebo‐controlled, dose‐ranging study of belimumab in patients with active systemic lupus erythematosus
Authors: Wallace Daniel J. , Stohl William , Furie Richard A. , Lisse Jeffrey R. , McKay James D. , Merrill Joan T. , Petri Michelle A. , Ginzler Ellen M. , Chatham W. Winn , McCune W. Joseph , Fernandez Vivian , Chevrier Marc R. , Zhong Z. John , Freimuth William W. 
Published: August 2009

AbstractObjectiveTo assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE).MethodsPatients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52‐week study. Coprimary end points were the percent change in the SELENA–SLEDAI score at week 24 and the time to first SLE flare.ResultsSignificant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA–SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24–52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer ≥1:80 and/or anti–double‐stranded DNA [anti‐dsDNA] ≥30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA–SLEDAI score (−28.8% versus −14.2%; P = 0.0435), physician's global assessment (−32.7% versus −10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63–71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti‐dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups.ConclusionBelimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.
Do psychological characteristics predict response to exercise and advice for subacute low back pain?
Authors: Smeets Rob J. E. M. , Maher Chris G. , Nicholas Michael K. , Refshauge Kathy M. , Herbert Robert D. 
Published: August 2009

AbstractObjectiveTo determine whether psychological characteristics predict outcome and/or response to physiotherapist‐directed exercise‐ or advice‐based treatment of subacute low back pain.MethodsWe conducted a secondary analysis of a factorial, placebo‐controlled trial (n = 259). The psychological characteristics were catastrophizing, coping, pain self‐efficacy, fear of injury/movement, depression, anxiety, and stress. We used mixed models to predict pain and function outcomes (both scored on a 0–10 scale). The models include a term for treatment group, a term for the psychological characteristic (which tested prediction of outcome), and an interaction term between the treatment group and psychological characteristic (which tested treatment effect modification). To aid the interpretation of the magnitude of the effect modification, we calculated the change in outcome for a 1 SD increase of the baseline score of the putative effect modifier. A ≥1.5‐point change of the outcome of interest per 1 SD change of putative effect modifier was regarded as clinically important.ResultsAll of the psychological characteristics except coping predicted outcome, but none appeared to be important treatment effect modifiers. Only 5 of the 56 tests of treatment modification were statistically significant, and none of the 95% confidence intervals (95% CIs) for the interactions included clinically important effects. For example, a 1 SD higher baseline level of anxiety was associated with a 0.62 (95% CI 0.10, 1.15) additional effect of exercise on function at 52 weeks.ConclusionMost of the psychological characteristics we tested predicted outcome, but none predicted response to physiotherapist‐guided exercise and/or advice.
Frequency and determinants of flare and persistently active disease in systemic lupus erythematosus
Authors: Nikpour Mandana , Urowitz Murray B. , Ibañez Dominique , Gladman Dafna D. 
Published: August 2009

AbstractObjectiveSelection of flare as the primary outcome variable in systemic lupus erythematosus (SLE) clinical trials fails to capture patients with persistently active disease (PAD). We sought to elucidate the frequency and determinants of flare and PAD.MethodsProspectively collected data from the Toronto Lupus Cohort were used to determine the incidence of flare and PAD in 2004 and 2005. Flare was defined as an increase in SLE Disease Activity Index 2000 update (SLEDAI‐2K) score of ≥4 from the previous visit. PAD was defined as a SLEDAI‐2K score of ≥4, excluding serology alone, on ≥2 consecutive visits. Data from 1, 2, and 3 years prior were used to model flare and PAD in 2004. Model properties were tested for prediction of flare and PAD in 2005.ResultsOne‐third of the patients had ≥1 flare, whereas nearly half experienced PAD in a given year. Nearly 60% of the patients had episodes of flare or PAD per year. At least 25% of patients had PAD without achieving the definition of flare. In the best‐fitting model, predictors of PAD in 2004 were SLEDAI‐2K score at the start of the outcome interval and prior cutaneous or musculoskeletal disease activity. This model gave 79% correct prediction of PAD in 2005. In contrast, flare prediction models performed poorly.ConclusionPersistent activity is a common disease state in SLE and should be an outcome variable in SLE clinical trials. Our PAD prediction model may aid prognostication and selection of patients for inclusion in clinical trials.
MicroRNA‐140 is expressed in differentiated human articular chondrocytes and modulates interleukin‐1 responses
Authors: Miyaki Shigeru , Nakasa Tomoyuki , Otsuki Shuhei , Grogan Shawn P. , Higashiyama Reiji , Inoue Atsushi , Kato Yoshio , Sato Tempei , Lotz Martin K. , Asahara Hiroshi 
Published: August 2009

AbstractObjectiveMicroRNA (miRNA) are a class of noncoding small RNAs that act as negative regulators of gene expression. MiRNA exhibit tissue‐specific expression patterns, and changes in their expression may contribute to pathogenesis. The objectives of this study were to identify miRNA expressed in articular chondrocytes, to determine changes in osteoarthritic (OA) cartilage, and to address the function of miRNA‐140 (miR‐140).MethodsTo identify miRNA specifically expressed in chondrocytes, we performed gene expression profiling using miRNA microarrays and quantitative polymerase chain reaction with human articular chondrocytes compared with human mesenchymal stem cells (MSCs). The expression pattern of miR‐140 was monitored during chondrogenic differentiation of human MSCs in pellet cultures and in human articular cartilage from normal and OA knee joints. We tested the effects of interleukin‐1β (IL‐1β) on miR‐140 expression. Double‐stranded miR‐140 (ds–miR‐140) was transfected into chondrocytes to analyze changes in the expression of genes associated with OA.ResultsMicroarray analysis showed that miR‐140 had the largest difference in expression between chondrocytes and MSCs. During chondrogenesis, miR‐140 expression in MSC cultures increased in parallel with the expression of SOX9 and COL2A1. Normal human articular cartilage expressed miR‐140, and this expression was significantly reduced in OA tissue. In vitro treatment of chondrocytes with IL‐1β suppressed miR‐140 expression. Transfection of chondrocytes with ds–miR‐140 down‐regulated IL‐1β–induced ADAMTS5 expression and rescued the IL‐1β–dependent repression of AGGRECAN gene expression.ConclusionThis study shows that miR‐140 has a chondrocyte differentiation–related expression pattern. The reduction in miR‐140 expression in OA cartilage and in response to IL‐1β may contribute to the abnormal gene expression pattern characteristic of OA.
Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody–associated vasculitis
Authors: Abdulahad Wayel H. , Kallenberg Cees G. M. , Limburg Pieter C. , Stegeman Coen A. 
Published: August 2009

AbstractObjectiveNumbers of circulating CD4+ effector memory T cells are proportionally increased in patients with proteinase 3 antineutrophil cytoplasmic antibody–associated vasculitis (AAV) whose disease is in remission and are decreased during active disease, which presumably reflects their migration toward sites of inflammation. Since renal infiltrating cells may appear in urine, we investigated the presence of CD4+ effector memory T cells in urinary sediment as a reflection of renal disease activity in AAV.MethodsCD4+ effector memory (CD45RO+CCR7−CD3+CD4+) T cells were quantitated in the urine and peripheral blood of patients with AAV with renal involvement (n = 33), patients with AAV without renal involvement (n = 18), patients with AAV whose disease was in remission (n = 29), and patients with active disease (n = 22), using 4‐color flow cytometric analysis. Numbers and percentages of urine CD4+ effector memory T cells in 12 patients with AAV with active renal disease were obtained over several weeks of followup during remission induction.ResultsA notable increase in urine CD4+ effector memory T cell numbers was observed in patients with active renal AAV compared with patients whose disease was in remission and patients with active disease without renal involvement. The increase in these cells in the urine of patients with active renal AAV was accompanied by a reciprocal decrease in these cells in peripheral blood. Results from followup analysis showed a clear reduction in urine CD4+ effector memory T cells following treatment. Moreover, a negative correlation was observed between percentages of circulating and urine CD4+ effector memory T cells, consistent with their migration toward sites of inflammation.ConclusionOur findings indicate that the presence of CD4+ effector memory T cells in urine reflects renal involvement in AAV. Flow cytometric analysis of these cells in urine may contribute to assessing renal disease activity in patients with AAV.
Reevaluation of the interaction between HLA–DRB1 shared epitope alleles, PTPN22, and smoking in determining susceptibility to autoantibody‐positive and autoantibody‐negative rheumatoid arthritis in a large UK Caucasian population
Authors: Morgan Ann W. , Thomson Wendy , Martin Stephen G. ,   Yorkshire Early Arthritis Register Consortium, Carter Angela M. ,   UK Rheumatoid Arthritis Genetics Consortium, Erlich Henry A. , Barton Anne , Hocking Lynne , Reid David M. , Harrison Pille , Wordsworth Paul , Steer Sophia , Worthington Jane , Emery Paul , Wilson Anthony G. , Barrett Jennifer H. 
Published: August 2009

AbstractObjectiveTo define interactions between the HLA–DRB1 shared epitope (SE), PTPN22, and smoking in cyclic citrullinated peptide (CCP) antibody– and rheumatoid factor (RF)–positive and –negative rheumatoid arthritis (RA).MethodsData on ∼5,000 RA patients and ∼3,700 healthy controls recruited from 6 centers in the UK were analyzed; not all centers had both genotype data and smoking data available for study. The magnitude of association was assessed in autoantibody‐positive and ‐negative subgroups. The effect of smoking on antibody status among cases was assessed following adjustment for year of birth and center, using Mantel‐Haenszel analysis. Analyses of the combined effects of PTPN22, HLA–DRB1 SE, and smoking were performed using additive and multiplicative models of interaction within a logistic regression framework.ResultsThe combined effects of PTPN22, HLA–DRB1 SE, and smoking were defined, with no evidence of departure from a multiplicative model. Within the case population, all 3 factors were independently associated with the generation of CCP antibodies (odds ratio [OR] 11.1, P < 0.0001), whereas only HLA–DRB1 SE and smoking were independently associated with RF production (OR 4.4, P < 0.0001). There was some evidence of increasing likelihood of antibody positivity with heavier smoking. Finally, we demonstrated that smoking was associated with the generation of both CCP and RF antibodies (OR 1.7, P = 0.0001).ConclusionPTPN22 appears to be primarily associated with anticitrulline autoimmunity, whereas HLA–DRB1 SE is independently associated with RF. This study has confirmed associations of specific gene–environment combinations with a substantially increased risk of developing RA. Further work is needed to determine how these data can be used to inform clinical practice.