bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flexible, Multifunctional, Magnetically Actuated Nanocomposite Films
Authors: Sotiriou Georgios A. , Blattmann Christoph O. , Pratsinis Sotiris E. 
Published: August 2012

AbstractFiller nanoparticles greatly enhance the performance of polymers and minimize filler content in the resulting nanocomposites. At the same time, they challenge the manufacturing of such nanocomposites by filler agglomeration and non‐uniform spatial distribution. Here, multifunctional nanocomposite films are made by capitalizing on flame‐synthesis of ceramic or metal filler nanoparticles followed by rapid, in situ deposition on sacrificial substrates, resulting in a filler film with controlled porosity. The polymer is then spin‐coated on the porous film that retained its stochastic but uniform structure, resulting in nanocomposites with homogeneous filler distribution and high filler‐loading. By sequential repetition of this procedure, sophisticated, multilayer, free‐standing, plasmonic‐ (Ag‐Fe2O3) and phosphorescent‐superparamagnetic (Y2O3:Eu3+‐ Fe2O3) actuators are made by precisely tuning the polymer thickness between each functional nanostructured layer. These actuators are quite flexible, have fast response times, and exhibit superior superparamagnetism due to their high filler content and homogeneous spatial distribution.
Bottom‐Up Tailoring of Plasmonic Nanopeapods Making Use of the Periodical Topography of Carbon Nanocoil Templates
Authors: Qin Yong , Vogelgesang Ralf , Eßlinger Moritz , Sigle Wilfried , van Aken Peter , Moutanabbir Oussama , Knez Mato 
Published: August 2012

AbstractAu nanoparticle chains embedded in helical Al2O3 nanotubes (“nanopeapods”) are synthesized by annealing carbon nanocoils coated with Au by sputtering and Al2O3 by atomic layer deposition. Regular spacing between nanoparticles with a sharp size distribution is achieved by fragmentation of the Au coating in agreement with the pitch of the nanocoils arising from three‐dimensional periodical topography of the carbon nanocoil templates. A strong plasmonic resonance behavior of the fabricated nanopeapods manifests itself in confocal laser scanning microscopy by a clear polarization contrast at red wavelengths, which is absent in the blue. Numerical simulations confirm an incisive resonance enhancement for longitudinal polarization and suggest the nanopeapods as promising candidates for highly efficient, ultrathin waveguides. The waveguiding properties of the nanopeapods are investigated by electron energy‐loss spectroscopy and energy‐filtered TEM imaging.
Mouse models of frontotemporal dementia
Authors: Roberson Erik D. 
Published: August 2012

AbstractThe pace of discovery in frontotemporal dementia (FTD) has accelerated dramatically with the discovery of new genetic causes and pathological substrates of the disease. MAPT/tau, GRN/progranulin, and C9ORF72 have emerged as common FTD genes, and TARDBP/TDP‐43, VCP, FUS, and CHMP2B have been identified as less common genetic causes. TDP‐43 and FUS have joined tau as common neuropathological substrates of the disease. Mouse models provide an important tool for understanding the role of these molecules in FTD pathogenesis. Here, we review recent progress with mouse models based on tau, TDP‐43, progranulin, VCP, and CHMP2B. We also consider future prospects for FTD models, including developing new models to address unanswered questions. There are also opportunities for capitalizing on conservation of the salience network, which is selectively vulnerable in FTD, and the availability of FTD‐related behavioral paradigms to analyze mouse models of the disease. Ann Neurol ANN NEUROL 2012;72:837–849
Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: Drug‐specific comparisons in the Swedish Biologics Register
Authors: Simard Julia F. , Neovius Martin , Askling Johan ,   for the ARTIS Study Group
Published: August 2012

AbstractObjectiveTo determine whether the differences in the modes of action and safety profiles of individual tumor necrosis factor inhibitors (TNFi) translate into differential mortality risks, as investigated in etanercept, infliximab, and adalimumab.MethodsData on patients with rheumatoid arthritis (RA) identified in the Swedish Biologics Register (Anti‐Rheumatic Therapy in Sweden [ARTIS]) in whom first‐ever treatment with a biologic agent (etanercept [n = 2,686], infliximab [n = 2,027], or adalimumab [n = 1,609]) was initiated between 2003 and 2008 were linked to national Swedish registers to get information on deaths from any cause, demographic features, RA characteristics, comorbid conditions, and concurrent treatment at the start of TNFi treatment. Hazard ratios (HRs) were modeled using multivariable adjusted and weighted Cox models.ResultsDuring 19,118 person‐years of followup, 211 patients died (3.3%; 1.1 deaths per 100 person‐years); 85% of the deaths occurred among patients who had been exposed to only one TNFi. We found no statistically significant difference in overall mortality rates across the exposure groups, regardless of adjustment and modeling approach (for infliximab versus etanercept, HR 1.1 [95% confidence interval (95% CI) 0.7–1.7], and for adalimumab versus etanercept, HR 1.3 [95% CI 0.9–2.0]).ConclusionOverall, we noted no statistically significant difference in mortality rates between the 3 TNF inhibitors under study. Further studies need to examine whether certain subsets of patients are at increased risk of death with specific TNFi.
A preliminary disease severity score for juvenile systemic sclerosis
Authors: La Torre Francesco , Martini Giorgia , Russo Ricardo , Katsicas Maria Marta , Corona Fabrizia , Calcagno Giuseppina , Falcini Fernanda , Vittadello Fabio , Zulian Francesco 
Published: August 2012

AbstractObjectiveTo develop a preliminary disease severity score for juvenile systemic sclerosis (SSc).MethodsWe conducted an evidence‐ and consensus‐based study that included the following 5 phases: 1) prospective collection of data regarding the demographic and clinical characteristics of patients with diffuse juvenile SSc who were followed up for at least 4 years or until death; 2) blinded evaluation of the disease course profiles of these patients by experts in juvenile SSc, so that patient profiles with a defined clinical course could be used as the gold standard for the score validation phase; 3) definition of candidate severity indices to be included in potential scores; 4) selection of the pediatric severity score with the best statistical performance, as determined by its ability to classify individual patients as having improvement or worsening of disease compared with baseline values or the previous evaluation; 5) validation of the efficiency of the selected score in patients with a mild, moderate, or severe disease course and comparison with the Medsger severity score for adults with SSc.ResultsThirty‐five patients classified as having a mild (n = 17), moderate (n = 10), or severe (n = 8) disease course entered the study. The selected pediatric SSc score, defined as the Juvenile Systemic Sclerosis Severity Score (J4S), included indices of 9 organ systems each scored on a scale of 0–4. To weight the importance of the involvement of different organ systems, a coefficient of severity was introduced. Compared with the modified Medsger severity score, the J4S performed significantly better in detecting change in severity, both in patients with a moderate disease course (0.89 versus 0.52) and in patients with a severe disease course (0.82 versus 0.75).ConclusionThe J4S is a valid instrument to assess disease severity in juvenile SSc.
Brief Report: Association of HLA–DRB1*0101/*0405 with susceptibility to anti–melanoma differentiation–associated gene 5 antibody–positive dermatomyositis in the Japanese population
Authors: Gono Takahisa , Kawaguchi Yasushi , Kuwana Masataka , Sugiura Tomoko , Furuya Takefumi , Takagi Kae , Ichida Hisae , Katsumata Yasuhiro , Hanaoka Masanori , Ota Yuko , Yamanaka Hisashi 
Published: August 2012

AbstractObjectiveThe complication of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) is associated with anti–aminoacyl–transfer RNA synthetase (anti‐aaRS) antibody or anti–melanoma differentiation–associated gene 5 (anti–MDA‐5) antibody positivity. Anti–MDA‐5 antibody is associated with clinically amyopathic DM and fatal outcome due to rapidly progressive ILD in Asian populations. The association between genetic factors and anti–MDA‐5 antibody–positive DM is unclear. This study was undertaken to investigate the HLA–DRB1 genotype in patients with anti–MDA‐5 antibody–positive DM.MethodsWe examined genetic differences among 17 patients with anti–MDA‐5 antibody–positive DM, 33 patients with anti‐aaRS antibody–positive PM/DM, 33 patients with PM/DM without anti‐aaRS antibody or ILD, and 265 healthy controls.ResultsThe frequencies of HLA–DRB1*0101 and DRB1*0405 were 29% and 71%, respectively, in patients with anti–MDA‐5 antibody–positive DM, which were higher than the frequencies in healthy controls (10% and 25%, respectively). Among the 17 patients with anti–MDA‐5 antibody–positive DM, 16 (94%) harbored either the DRB1*0101 or DRB1*0405 allele. The combined frequency of the DRB1*0101 allele and the DRB1*0405 allele was significantly higher in patients with anti–MDA‐5 antibody–positive DM than in patients with PM/DM without anti‐aaRS antibody or ILD, with an odds ratio (OR) of 42.7 (95% confidence interval [95% CI] 4.9–370.2) (P = 1.1 × 10−5), or in patients with anti‐aaRS antibody–positive PM/DM (OR 13.3 [95% CI 1.6–112.6], P = 4.5 × 10−3).ConclusionOur findings indicate that HLA–DRB1*0101/*0405 is associated with susceptibility to anti–MDA‐5 antibody–positive DM in the Japanese population.
Macrophage activation syndrome in children with systemic lupus erythematosus and children with juvenile idiopathic arthritis
Authors: Bennett Tellen D. , Fluchel Mark , Hersh Aimee O. , Hayward Kristen N. , Hersh Adam L. , Brogan Thomas V. , Srivastava Rajendu , Stone Bryan L. , Korgenski E. Kent , Mundorff Michael B. , Casper T. Charles , Bratton Susan L. 
Published: August 2012

AbstractObjectiveTo describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA).MethodsWe performed a retrospective cohort study using data recorded in the Pediatric Health Information System (PHIS) database from October 1, 2006 to September 30, 2010. Participants had International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality (for the index admission). Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use.ResultsA total of 121 children at 28 children's hospitals met the inclusion criteria, including 19 children with SLE and 102 children with JIA. The index admission mortality rate was 7% (8 of 121 patients). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had a similar mortality rate (6% versus 11%, respectively; exact P = 0.6). More patients with SLE than those with JIA received ICU care (63% versus 27%; P = 0.002), received mechanical ventilation (53% versus 21%; P = 0.003), and had cardiovascular dysfunction (47% versus 23% received inotrope/vasopressor therapy; P = 0.02). Children with SLE and those with JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil, and more children with JIA received interleukin‐1 antagonists.ConclusionOrgan system dysfunction is common in children with rheumatic diseases complicated by MAS, and more organ system support is required in children with underlying SLE than in children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease.
Brief Report: Enrichment of associations in genes with fibrosis, apoptosis, and innate immunity functions with cardiac manifestations of neonatal lupus
Authors: Ramos Paula S. , Marion Miranda C. , Langefeld Carl D. ,   the International Consortium on Systemic Lupus Erythematosus Genetics, Buyon Jill P. , Clancy Robert M. 
Published: August 2012

AbstractObjectiveThe proposed pathogenesis of the cardiac manifestations of neonatal lupus (cardiac‐NL) involves maternal autoantibodies to the RNPs SSA/Ro and SSB/La, enhanced by as‐yet‐unknown factors that likely involve dysregulation of both inflammatory and fibrotic fetal responses. This study was designed to improve the power to detect specific associations in genes with candidate biologic functions.MethodsUsing data from our genome‐wide association study of 116 Caucasian children with cardiac‐NL and 3,351 Caucasian controls, we tested for enrichment of single‐nucleotide polymorphism (SNP) associations in genes with candidate biologic functions related to fibrosis, immune function, apoptosis, T cell function, cell infiltration, innate immune cell function, interferon, Toll‐like receptors, and calcium channels. After linkage disequilibrium pruning and exclusion of the extended HLA region, a total of 15,103 SNPs in 3,068 genes remained.ResultsA highly significant enrichment of P values was observed for genes related to fibrosis (P = 2.27 × 10−9), apoptosis (P = 7.67 × 10−7), and innate immune cell (P = 2.53 × 10−6), immune (P = 5.01 × 10−4), T cell (P = 2.23 × 10−4), and interferon functions (P = 1.64 × 10−3). The most significant non‐HLA associations included the sialyltransferase gene ST8SIA2 (rs1487982; odds ratio 2.20 [95% confidence interval 1.52–3.19], P = 3.37 × 10−5), the integrin gene ITGA1 (rs2432143; odds ratio 2.31 [95% confidence interval 1.54–3.45], P = 4.54 × 10−5), and the complement regulator gene CSMD1 (rs7002001; odds ratio 2.41 [95% confidence interval 1.57–3.72], P = 6.33 × 10−5).ConclusionThis study identified novel candidate genes associated with cardiac‐NL and highlights the value of studying this cohort for advancing knowledge regarding the genetic etiology of this syndrome. Identification of causal alleles is expected to provide critical insight into the molecular mechanisms responsible for linking maternal autoantibodies to cardiac scarring in these fetuses/neonates.
Aggrecanase cleavage in juvenile idiopathic arthritis patients is minimally detected in the aggrecan interglobular domain but robust at the aggrecan C‐terminus
Authors: Struglics André , Lohmander L. Stefan , Last Karena , Akikusa Jonathan , Allen Roger , Fosang Amanda J. 
Published: August 2012

AbstractObjectiveTo investigate aggrecan degradation in juvenile idiopathic arthritis (JIA).MethodsThe pattern and abundance of aggrecan fragments in synovial fluid (SF) aspirates from JIA patients were analyzed and compared with aggrecan fragments in SF from patients with other arthritides, children with knee injury, and a knee‐healthy reference group. Concentrations of sulfated glycosaminoglycan (sGAG) in SF were measured by Alcian blue precipitation assay. Aggrecan fragments were purified by dissociative CsCl density‐gradient centrifugation, deglycosylated, and analyzed by Western blot using antibodies specific for either aggrecanase‐derived ARGS, SELE, and KEEE neoepitopes or the aggrecan G3 domain.ResultsThe concentration of sGAG in SF from patients with JIA was significantly lower compared with that in SF from patients with osteoarthritis (OA) (P < 0.001), patients with juvenile knee injury (P = 0.006), and knee‐healthy controls (P = 0.022). Western blot analysis revealed KEEE, SELE, and G3 fragments generated by aggrecanase cleavage in the chondroitin sulfate–rich region of aggrecan in patients with JIA. The pattern of aggrecan fragments in JIA patients was not identical to that in pooled OA SF, although there were notable similarities. Surprisingly, aggrecanase‐derived ARGS fragments were barely detectable in JIA SF, in marked contrast to levels in OA SF.ConclusionAggrecanases appear to cleave minimally in the interglobular domain of aggrecan in JIA patients despite robust levels of cleavage in the chondroitin sulfate–rich region. These results suggest that in JIA, unlike other arthritides, aggrecanase cleavage in the aggrecan interglobular domain might not be a major pathogenic event.
Distribution of CYP2C9*13 allele in the Chinese Han and the long‐range haplotype containing CYP2C9*13 and CYP2C19*2
Authors: Si Dayong , Wang Juan , Zhang Yifan , Zhong Dafang , Zhou Hui 
Published: August 2012

ABSTRACTCytochrome P450 2C9 (CYP2C9) and CYP2C19, located in tandem on chromosome 10q23–24, are known as genetically polymorphic. CYP2C9*13 is an important CYP2C9 variant in Asian populations, and is correlated with the reduced plasma clearance of some clinically important drugs. In this research, the allele frequency of CYP2C9*13 was determined to be 0.42% (95% CI of 0.17% to 0.86%) in 839 Chinese Han, male subjects. All detected subjects with CYP2C9*13 carry the CYP2C19*2 allele, too. Sequencing results infer the CYP2C9*13 haplotype, which contains eight linked SNPs, originates from the CYP2C9*1B haplotype group. CYP2C9*1B has been reported to be linked with CYP2C19*2. These indicate a long‐range haplotype containing the CYP2C9*13 and CYP2C19*2 mutation, which means most CYP2C9*13 carriers will carry the CYP2C19*2 allele and the six SNPs of the CYP2C9*1B haplotype group, and may have more reduced intrinsic clearance of drugs such as phenytoin, tolbutamide and chlorpropamide that are metabolized by both CYP2C9 and CYP2C19. Copyright © 2012 John Wiley & Sons, Ltd.
Current status of drug screening and disease modelling in human pluripotent stem cells
Authors: Rajamohan Divya , Matsa Elena , Kalra Spandan , Crutchley James , Patel Asha , George Vinoj , Denning Chris 
Published: August 2012

AbstractThe emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overcome to fully realise the potential of hPSCs. Details are provided for all disease‐specific human induced pluripotent stem cell lines spanning a dozen dysfunctional organ systems. Phenotype and pharmacology have been examined in only 17 of 63 lines, primarily those that model neurological and cardiac conditions. Drug screening is most advanced in hPSC‐cardiomyocytes. Responses for almost 60 agents include examples of how careful tests in hPSC‐cardiomyocytes have improved on existing in vitro assays, and how these cells have been integrated into high throughput imaging and electrophysiology industrial platforms. Such successes will provide an incentive to overcome bottlenecks in hPSC technology such as improving cell maturity and industrial scalability whilst reducing cost.
Cumulative disease progression models for cross‐sectional data: A review and comparison
Authors: Hainke Katrin , Rahnenführer Jörg , Fried Roland 
Published: August 2012

A better understanding of disease progression is beneficial for early diagnosis and appropriate individual therapy. Many different approaches for statistical modelling of cumulative disease progression have been proposed in the literature, including simple path models up to complex restricted Bayesian networks. Important fields of application are diseases such as cancer and HIV. Tumour progression is measured by means of chromosome aberrations, whereas people infected with HIV develop drug resistances because of genetic changes of the HI‐virus. These two very different diseases have typical courses of disease progression, which can be modelled partly by consecutive and partly by independent steps.This paper gives an overview of the different progression models and points out their advantages and drawbacks. Different models are compared via simulations to analyse how they work if some of their assumptions are violated. In a simulation study, we evaluate how models perform in terms of fitting induced multivariate probability distributions and topological relationships. We often find that the true model class used for generating data is outperformed by either a less or a more complex model class. The more flexible conjunctive Bayesian networks can be used to fit oncogenetic trees, whereas mixtures of oncogenetic trees with three tree components can be well fitted by mixture models with only two tree components.
Proline dehydrogenase (oxidase) in cancer
Authors: Liu Wei , Phang James M. 
Published: August 2012

AbstractProline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the proline degradative pathway, plays a special role in tumorigenesis and tumor development. Proline metabolism catalyzed by PRODH/POX is closely linked with the tricarboxylic acid (TCA) cycle and urea cycle. The proline cycle formed by the interconversion of proline and Δ1‐pyrroline‐5‐carboxylate (P5C) between mitochondria and cytosol interlocks with pentose phosphate pathway. Importantly, by catalyzing proline to P5C, PRODH/POX donates electrons into the electron transport chain to generate ROS or ATP. In earlier studies, we found that PRODH/POX functions as a tumor suppressor to initiate apoptosis, inhibit tumor growth, and block the cell cycle, all by ROS signaling. It also suppresses hypoxia inducible factor signaling by increasing α‐ketoglutarate. During tumor progression, PRODH/POX is under the control of various tumor‐associated factors, such as tumor suppressor p53, inflammatory factor peroxisome proliferator‐activated receptor gamma (PPARγ), onco‐miRNA miR‐23b*, and oncogenic transcription factor c‐MYC. Recent studies revealed the two‐sided features of PRODH/POX‐mediated regulation. Under metabolic stress such as oxygen and glucose deprivation, PRODH/POX can be induced to serve as a tumor survival factor through ATP production or ROS‐induced autophagy. The paradoxical roles of PRODH/POX can be understood considering the temporal and spatial context of the tumor. Further studies will provide additional insights into this protein and on its metabolic effects in tumors, which may lead to new therapeutic strategies. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Evaluation of density and distribution of CART‐immunoreactive structures in gastrointestinal tract of hypertensive rats
Authors: Kasacka Irena , Piotrowska Żaneta 
Published: August 2012

AbstractThe prevalence of CART (cocaine‐ and amphetamine‐regulated transcript) throughout the organism, multiplicity of functions fulfilled by that peptide, and the collected evidence confirming CART contribution to blood pressure regulation prompted us to undertake the research aiming to identify, localize, and assess changes in CART‐immunopositive structures of the gastrointestinal tract (GI tract) of rats with renovascular hypertension. The two‐kidney one‐clip model of arterial hypertension was used to evaluate the location and density of CART‐containing structures in the stomach (cardia, fundus, and pylorus), duodenum, jejunum, ileum, and colon of hypertensive rats. The study was carried out on the GI tract of 20 rats. Ten rats were subjected to the renal artery clipping procedure and after a 6‐week period each of them developed stable hypertension. An immunohistochemical localization of CART was performed on paraffin GI tract sections from all the study animals. CART was detected in the extensive population of neurons, particularly within the myenteric plexuses all along the GI tract, and also in neuroendocrine cells, being especially numerous in the stomach and a few in the small intestine. The hypertension significantly increased the density of CART‐positive structures in the rat GI tract. The differences between the hypertensive rats and the control animals concerned not only the density of CART‐immunoreactive structures but also the staining intensity. As this study provides novel findings, we are planning further molecular examinations to better understand the impact of hypertension on the functioning and activity of CART in the GI tract. © 2012 International Union of Biochemistry and Molecular Biology, Inc.