bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pial synangiosis in patients with moyamoya syndrome and sickle cell anemia: perioperative management and surgical outcome
Authors: Smith Edward R. , McClain Craig D. , Heeney Matthew , Scott R. Michael 
Published: March 2009

Object
Many children with sickle cell anemia (SCA) also have clinical and radiographic findings of an arteriopathy suggestive of moyamoya syndrome. These patients may continue to experience strokes despite optimal medical management. The authors wished to define features of moyamoya syndrome associated with SCA and determine the results of surgical revascularization in these patients at early and late follow-up.

Methods
The authors reviewed the clinical and radiographic records of all patients with moyamoya syndrome and SCA who underwent cerebral revascularization surgery using a standardized surgical procedure—pial synangiosis—from 1985 to 2008.

Results
Twelve patients had SCA and moyamoya syndrome. Six patients were female and 6 were male. The average patient age at surgery was 11.3 years (range 3–22 years). All patients presented with ischemic symptoms, 11 (92%) with previous transient ischemic attacks, and 10 (83%) with completed strokes. Eleven patients (92%) had radiographic evidence of previous stroke at presentation. None presented with hemorrhage. Surgical treatment included pial synangiosis in all patients. Complications included 1 perioperative stroke, 1 wound infection, and 1 perioperative pneumonia. The average length of hospital stay was 5.7 days (including a 24-hour preoperative admission for hydration) and average blood loss was 92.5 ml/hemisphere (in a total of 19 hemispheres). Clinical and radiographic follow-up with an average of 49 months (range 9–144 months) demonstrated no worsening in neurological status in any patient. No clinical or radiographic evidence of new infarcts was observed in any patient at late follow-up, despite disease progression in 13 (68%) of 19 hemispheres.

Conclusions
The clinical and radiographic features of moyamoya syndrome associated with SCA appear comparable to primary moyamoya disease. Successful treatment of these patients requires multidisciplinary care involving hematologists, anesthesiologists, and neurosurgeons. Operative treatment of moyamoya syndrome using pial synangiosis appears to be safe and confers long-lasting protection against further stroke in this population, and provides an alternative for failure of optimal medical therapy in patients. This study underscores the potential merit of screening patients with SCA for moyamoya syndrome.
Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis
Authors: MOURÃO ANA FILIPA , CAETANO-LOPES JOANA , COSTA PAULA , CANHÃO HELENA , SANTOS MARIA JOSÉ , PINTO PATRÍCIA , BRITO IVA , NICOLA PAULO , CAVALEIRO JOÃO , TELES JOSÉ , SOUSA ARTUR , GOMES JOSÉ MELO , BRANCO JAIME , da COSTA JOSÉ TEIXEIRA , PEDRO JOÃO GOMES , de QUEIROZ MÁRIO VIANA , FONSECA JOÃO EURICO 
Published: April 2009

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.
CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis
Authors: SAITO AKIKO , MURO YOSHINAO , SUGIURA KAZUMITSU , IKENO MASASHI , YODA KINYA , TOMITA YASUSHI 
Published: April 2009

Objective.CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases.Methods.Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens.Results.Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O.Conclusion.CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is an ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity.
Safety and Efficacy of the Selective Costimulation Modulator Abatacept in Patients with Rheumatoid Arthritis Receiving Background Methotrexate: A 5-year Extended Phase IIB Study
Authors: WESTHOVENS RENE , KREMER JOEL M. , MORELAND LARRY W. , EMERY PAUL , RUSSELL ANTHONY S. , LI TRACY , ARANDA RICHARD , BECKER JEAN-CLAUDE , QI KEQIN , DOUGADOS MAXIME 
Published: April 2009

Objective.To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis.Methods.Patients were randomized to abatacept 10 or 2 mg/kg or placebo, plus MTX. Patients completing the 1-year, double-blind period entered the longterm extension, where all patients received a fixed dose of abatacept ~10 mg/kg. We describe safety analyses for all patients who received at least 1 dose of abatacept and efficacy analyses for the original ~10 mg/kg abatacept-treated group, over 5 years.Results.Of the 235 abatacept- or placebo-treated patients completing the double-blind period, 219 entered the longterm extension; 130 (59.4%) were continuing at Year 5. No unexpected safety events were observed during the longterm extension compared with the double-blind period. Incidence rates of adverse events (AE) and serious AE were 489.7 and 20.0/100 patient-years in Year 1 versus 374.9 and 18.9/100 patient-years in the cumulative period, respectively. Using exploratory analyses, improvements observed at Year 1 in the 10 mg/kg group were maintained at Year 5, as assessed by ACR responses (ACR20 = 77.1% vs 82.7%; ACR50 = 53.0% vs 65.4%; ACR70 = 28.9% vs 40.4% at Years 1 and 5, respectively) and disease activity (Low Disease Activity State = 48.2% vs 58.5%; Disease Activity Score-28-defined remission = 25.3% vs 45.3% at Years 1 and 5, respectively).Conclusion.Abatacept maintained the efficacy observed at Year 1 over 5 years of treatment, and demonstrated consistent safety and tolerability. These data, along with relatively high retention rates, support the longterm clinical benefit provided by selective T cell costimulation modulation. Clinical trial registry: ClinicalTrials.gov; clinical trial registration number: NCT00254293.
Ethnic Influence on Disease Manifestations and Autoantibodies in Chinese-Descent Patients with Systemic Sclerosis
Authors: LOW ANDREA H.L. , JOHNSON SINDHU R. , LEE PETER 
Published: April 2009

Objective.To investigate ethnic influence on disease manifestations and autoantibody profile in patients of Chinese descent with systemic sclerosis (SSc).Methods.In a retrospective study of a multiethnic SSc cohort followed over a 17-year period, disease manifestations and autoantibody profile of patients of European and Chinese descent were compared.Results.There were 300 patients of European descent and 36 of Chinese descent, with similar proportions of women (81% and 72%, respectively) and patients with diffuse SSc (50% and 56%). Patients of Chinese descent [mean age ± standard deviation (SD) 52 ± 16 yrs; p = 0.05] were diagnosed at an older age compared to patients of European descent (mean ± SD 46 ± 12 yrs). Patients of Chinese descent compared to those of European descent had less frequent joint (69% vs 86%; p = 0.01) and gastrointestinal involvement (78% vs 94%; p = 0.004), but increased prevalence of myositis (17% vs 5%; p = 0.01). Patients of Chinese descent had less frequent digital ulceration (36% vs 55%; p = 0.04), and an absence of renal crisis. The frequency of cardiac and pulmonary involvement was similar in both groups. More patients of Chinese than of European descent were positive for anti-topoisomerase-I (47% vs 27%; p = 0.02), anti-Ro (36% vs 10%; p = 0.001), and anti-U1RNP (17% vs 5%; p = 0.03) antibodies. The observed differences for anti-topoisomerase-I, anti-Ro, and joint and gastrointestinal manifestations persisted in the subgroup analysis of patients matched for sex, disease subtype, and age at diagnosis.Conclusion.Patients of Chinese descent have milder SSc disease with less frequent joint and gastrointestinal manifestations, less severe vasculopathy, but increased prevalence of myositis and certain autoantibodies. Research is needed to identify determinants (genetic, environmental, and cultural factors) of the relationship between ethnicity and disease.
Correlation of Biomarkers of Endothelium Dysfunction and Matrix Remodeling in Patients with Systemic Sclerosis
Authors: BLAISE SOPHIE , MAAS RENKE , TROCME CANDICE , KOM GHAINSOM D. , ROUSTIT MATTHIEU , CARPENTIER PATRICK H. , CRACOWSKI JEAN-LUC 
Published: March 2009

Objective.Systemic sclerosis (SSc) is a multisystem disease characterized by microvascular dysfunction and excessive fibrosis. However, the relationship between these 2 features remains unclear. Endothelial dysfunction can be assessed by quantifying plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase. Matrix remodeling can be assessed by quantifying serum tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Both biomarkers are elevated in patients with SSc. Our objective was to test whether plasma ADMA is correlated with serum TIMP-1.Methods.We enrolled 91 subjects, 39 patients with SSc, 28 patients with primary Raynaud’s phenomenon (RP), and 24 healthy volunteers. Plasma ADMA concentrations were measured by liquid chromatography-tandem mass spectrometry. Serum TIMP-1 concentrations were determined by ELISA.Results.Mean ADMA concentrations were higher in patients with SSc (0.68 μM ± 0.12) than in patients with primary RP or healthy volunteers (respectively, 0.56 μM ± 0.14 and 0.62 μM ± 0.12; p = 0.002). Median serum TIMP-1 concentrations were increased in patients with SSc compared to primary RP and healthy volunteers [12 (9–15), 11 (8–13), and 10 (7–13) nM, respectively; p = 0.05]. In the SSc group, we observed a statistically significant correlation between plasma ADMA and serum TIMP-1 (r = 0.34, p = 0.035).Conclusion.These data are consistent with our hypothesis of an association of endothelial dysfunction and matrix remodeling in scleroderma spectrum disorders.
A Ditopic Ion‐Pair Receptor Based on Stacked Nucleobase Quartets
Authors: van der Wijst Tushar , Fonseca Guerra Célia , Swart Marcel , Bickelhaupt F. Matthias , Lippert Bernhard 
Published: March 2009

AbstractReichen Sie bitte das Salz!Die Ergebnisse hochleistungsfähiger Rechnungen sprechen dafür, dass der Stapelkomplex aus einem Guanin‐ und einem Adeninquartett (G4A4) in wässriger Lösung als wirksamer ditoper Rezeptor für NaCl fungieren kann (siehe Bild; Na+, Cl− gelb, O rot, N blau, C schwarz, H weiß).magnified image
High‐density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
Authors: Namjou Bahram , Sestak Andrea L. , Armstrong Don L. , Zidovetzki Raphael , Kelly Jennifer A. , Jacob Noam , Ciobanu Voicu , Kaufman Kenneth M. , Ojwang Joshua O. , Ziegler Julie , Quismorio Francesco P. , Reiff Andreas , Myones Barry L. , Guthridge Joel M. , Nath Swapan K. , Bruner Gail R. , Mehrian‐Shai Ruth , Silverman Earl , Klein‐Gitelman Marisa , McCurdy Deborah , Wagner‐Weiner Linda , Nocton James J. , Putterman Chaim , Bae Sang‐Cheol , Kim Yun Jung , Petri Michelle , Reveille John D. , Vyse Timothy J. , Gilkeson Gary S. , Kamen Diane L. , Alarcón‐Riquelme Marta E. , Gaffney Patrick M. , Moser Kathy L. , Merrill Joan T. , Scofield R. Hal , James Judith A. , Langefeld Carl D. , Harley John B. , Jacob Chaim O. 
Published: March 2009

AbstractObjectiveSystemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT‐1 and STAT‐4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility.MethodsFifty‐six single‐nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population‐based case–control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated.ResultsWe observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 × 10−25). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4.ConclusionOur findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
On a new goodness‐of‐fit process for families of copulas
Authors: Mesfioui Mhamed , Quessy Jean‐François , Toupin Marie‐Hélène 
Published: March 2009

AbstractA goodness‐of‐fit procedure is proposed for parametric families of copulas. The new test statistics are functionals of an empirical process based on the theoretical and sample versions of Spearman's dependence function. Conditions under which this empirical process converges weakly are seen to hold for many families including the Gaussian, Frank, and generalized Farlie–Gumbel–Morgenstern systems of distributions, as well as the models with singular components described by Durante [Durante (2007) Comptes Rendus Mathématique. Académie des Sciences. Paris, 344, 195–198]. Thanks to a parametric bootstrap method that allows to compute valid P‐values, it is shown empirically that tests based on Cramér–von Mises distances keep their size under the null hypothesis. Simulations attesting the power of the newly proposed tests, comparisons with competing procedures and complete analyses of real hydrological and financial data sets are presented. The Canadian Journal of Statistics 37: 80‐101; 2009 © 2009 Statistical Society of Canada
CD4+ T‐cell‐mediated anti‐tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis
Authors: Zhang Sheng , Bernard Dannie , Khan Waliul I. , Kaplan Mark H. , Bramson Jonathan L. , Wan Yonghong 
Published: March 2009

AbstractPrevious reports have suggested that autoimmune sequelae may be an unavoidable consequence of successful immunization against tumor‐associated antigens, which are typically non‐mutated self‐antigens. Using a melanoma model, we demonstrated that CD4+ T‐cell‐mediated anti‐tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis. Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti‐tumor immunity is mediated via a STAT6 and IL‐4‐dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN‐γ. Our results offer a possibility to elicit specific anti‐tumor responses without triggering unwanted tissue autoimmune diseases.
Reaction of 3,3,5,5‐Tetraphenyl‐1,2,4‐trithiolane with Pt0(bisphosphane)(η2‐nbe) Complexes Bearing Bridged Bisphosphane Ligands with Various Bite Angles
Authors: Weisheit Thomas , Petzold Holm , Görls Helmar , Mloston Grzegorz , Weigand Wolfgang 
Published: March 2009

AbstractA series of Pt0(η2‐nbe) complexes [nbe = norbornene (bicyclo[2.2.1]hept‐2‐ene)] bearing bridged bisphosphane ligands with various bite angles (5a–c) was treated with 3,3,5,5‐tetraphenyl‐1,2,4‐trithiolane (1) at 50 °C in a toluene solution. These reactions resulted in the formation of the appropriate dithiolato complexes 6a–c as well as the η2‐thioketone complexes 7a–c with respect to the 31P{1H} NMR spectroscopic data. All isolated complexes were fully characterized. Kinetic investigations using 31P{1H} NMR spectroscopy revealed first‐order kinetics in 1, pointing to the known cycloreversion of 1 as the initial and rate‐determining step for these reactions. The formation of dithiolato complexes 6a–c suggests 1,3‐dipolar electrocyclization of diphenylthiosulfine (3) to diphenyldithiirane (4) in solution. On the basis of these results a plausible mechanism for the overall reaction is developed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Variational generation of prismatic boundary‐layer meshes for biomedical computing
Authors: Dyedov Volodymyr , Einstein Daniel R. , Jiao Xiangmin , Kuprat Andrew P. , Carson James P. , del Pin Facundo 
Published: March 2009

AbstractBoundary‐layer meshes are important for numerical simulations in computational fluid dynamics, including computational biofluid dynamics of air flow in lungs and blood flow in hearts. Generating boundary‐layer meshes is challenging for complex biological geometries. In this paper, we propose a novel technique for generating prismatic boundary‐layer meshes for such complex geometries. Our method computes a feature size of the geometry, adapts the surface mesh based on the feature size, and then generates the prismatic layers by propagating the triangulated surface using the face‐offsetting method. We derive a new variational method to optimize the prismatic layers to improve the triangle shapes and edge orthogonality of the prismatic elements and also introduce simple and effective measures to guarantee the validity of the mesh. Coupled with a high‐quality tetrahedral mesh generator for the interior of the domain, our method generates high‐quality hybrid meshes for accurate and efficient numerical simulations. We present comparative study to demonstrate the robustness and quality of our method for complex biomedical geometries. Copyright © 2009 John Wiley & Sons, Ltd.
Oral rapamycin reduces tumour burden and vascularization in Lkb1+/− mice
Authors: Robinson James , Lai Cecilia , Martin Alison , Nye Emma , Tomlinson Ian , Silver Andrew 
Published: March 2009

AbstractPatients with Peutz–Jeghers syndrome (PJS) are affected by hamartomatous intestinal polyposis and increased risk of cancers in multiple organs caused by germline mutations in the tumour suppressor gene LKB1. Murine models that recapitulate aspects of PJS have been created. Here we examine the therapeutic effect of rapamycin, a macrolide with anti‐tumourigenic and anti‐angiogenic properties, in reducing tumour incidence in a large cohort of Lkb1+/− mice. To study the influence of early intervention, the animals were dosed with rapamycin from the age of 8 weeks, well before the onset of polyposis. These mice continued to receive the drug, which was well tolerated, throughout their lives. At sacrifice, we observed a reduction in gastric tumour burden in the rapamycin‐treated mice (p = 0.0001) compared with age‐ and sex‐matched controls. Treated animals also have a lower number of polyps per mouse than controls. In the polyps from the treated mice, phosphorylation of ribosomal p70 S6 kinase was maintained, while the phosphorylation of AKT at serine‐473 was elevated, suggesting that mTORC1 function is maintained at this dosage. Despite this, a significant reduction in microvessel density was seen in polyps from the rapamycin‐treated mice compared to those from the control mice (p = 5 × 10−5), suggesting that the anti‐angiogenic effect of rapamycin played a role in polyp reduction. Overall, we demonstrated that prolonged oral administration of rapamycin from an early age is effective in lowering tumour burden in the Lkb1+/− mice without evident side effects. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.