bluuebunny/crossref_metadata_2025_split huggingface dataset:
Declined neural efficiency in cognitively stable human immunodeficiency virus patients
Authors: Ernst Thomas , Yakupov Renat , Nakama Helenna , Crocket Grace , Cole Michael , Watters Michael , Ricardo‐Dukelow Mary Lynn , Chang Linda 
Published: March 2009

AbstractObjectiveTo determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)–infected and in HIV‐seronegative control (SN) participants over a 1‐year period.MethodsFunctional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations.ResultsOver 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1‐year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate).InterpretationBecause fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. Ann Neurol 2009;65:316–325
Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review
Authors: Tanamas Stephanie , Hanna Fahad S. , Cicuttini Flavia M. , Wluka Anita E. , Berry Patricia , Urquhart Donna M. 
Published: March 2009

AbstractObjectiveTo systematically review the evidence for a relationship between malalignment of the knee joint and progression and/or development of knee osteoarthritis (OA).MethodsElectronic searches of Medline, EMBase, and CINAHL were performed up to July 2008 using medical subject headings and free‐text words. We included radiographic or magnetic resonance imaging (MRI) studies that met a set of predefined criteria. Two independent reviewers extracted the data and assessed the methodologic quality of the selected studies. Due to both heterogeneity and a limited number of studies, the results were summarized using a best evidence synthesis.ResultsFourteen studies met our inclusion criteria and 8 were considered high quality. We found limited evidence for an association between knee malalignment and incident knee OA, because only 1 cohort study examined this relationship. However, there was strong evidence based on 4 high‐quality cohort studies that knee malalignment is an independent risk factor for progression of radiographic knee OA. This finding was further supported by 2 high‐quality MRI cohort studies that found a relationship between varus and valgus alignment and structural progression of knee OA.ConclusionMalalignment of the knee joint was found to be an independent risk factor for the progression of knee OA. Given the paucity of investigation into the relationship between knee malalignment and risk of incident OA, further high‐quality cohort studies are needed, and these may have important implications for the prevention of knee OA.
Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus
Authors: Webb Ryan , Wren Jonathan D. , Jeffries Matlock , Kelly Jennifer A. , Kaufman Kenneth M. , Tang Yuhong , Frank Mark Barton , Merrill Joan , Kimberly Robert P. , Edberg Jeffrey C. , Ramsey‐Goldman Rosalind , Petri Michelle , Reveille John D. , Alarcón Graciela S. , Vilá Luis M. , Alarcón‐Riquelme Marta E. , James Judith A. , Vyse Timothy J. , Moser Kathy L. , Gaffney Patrick M. , Gilkeson Gary S. , Harley John B. , Sawalha Amr H. 
Published: March 2009

AbstractObjectiveBoth genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl‐CpG–binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus‐associated MECP2 haplotype.MethodsWe genotyped 18 single‐nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus‐associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus‐associated MECP2 risk haplotype.ResultsWe confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 × 10−11). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease‐associated MECP2 haplotype; most (∼81%) were up‐regulated. Genes that were up‐regulated had significantly more CpG islands in their promoter regions compared with genes that were down‐regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up‐regulated genes are regulated by interferon. The disease‐risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1.ConclusionPolymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.
Defining incident radiographic hip osteoarthritis for epidemiologic studies in women
Authors: Arden Nigel K. , Lane Nancy E. , Parimi Neeta , Javaid Kassim M. , Lui Li‐Yung , Hochberg Marc C. , Nevitt Michael 
Published: March 2009

AbstractObjectiveTo evaluate definitions of radiographic hip osteoarthritis (RHOA) for use in longitudinal epidemiologic studies of disease incidence in women.MethodsWe studied 5,839 women from the Study of Osteoporotic Fractures who had had serial pelvic radiographs obtained (mean of 8.3 years apart) and who were followed up (mean followup 7.1 years from the time of the second radiograph) for evaluation of clinical outcomes. Definitions of RHOA were assessed for construct validity (association with symptoms and signs at the time of the second radiograph) and predictive validity (association with total hip replacement [THR] and signs and symptoms a mean of 7.1 years later). Odds ratios (ORs) and 95% confidence intervals were calculated to assess the strength of association using logistic regression.ResultsThe cumulative incidence of RHOA ranged from 2.2% to 11.7%. All definitions displayed significant construct validity; the most consistent was found for composite definitions that required the concurrent presence of 2 or more individual radiographic features and definitions based on stringent criteria for joint space narrowing. All definitions except minimum joint space ≤2.5 mm displayed consistent predictive validity. Composite definitions had the strongest associations with THR (OR 10.5–18.5) and hip pain (OR 2.6–2.9). The hips identified as having OA by each definition varied, with especially small overlap between findings using definitions based on osteophytes and those using definitions based on joint space narrowing alone.ConclusionMost definitions of incident RHOA display good construct and predictive validity. Composite definitions have the best overall performance, and definitions requiring the presence of both osteophytes (in particular, femoral osteophytes) and joint space narrowing would be recommended for most epidemiologic and genetic studies.
Quantitative heritability of anti–citrullinated protein antibody–positive and anti–citrullinated protein antibody–negative rheumatoid arthritis
Authors: van der Woude Diane , Houwing‐Duistermaat Jeanine J. , Toes René E. M. , Huizinga Tom W. J. , Thomson Wendy , Worthington Jane , van der Helm‐van Mil Annette H. M. , de Vries René R. P. 
Published: March 2009

AbstractObjectiveThe majority of genetic risk factors for rheumatoid arthritis (RA) are associated with anti–citrullinated protein antibody (ACPA)–positive RA, while far fewer genetic risk factors have been identified for ACPA‐negative RA. This study was undertaken to quantify the contribution of genetic risk factors in general, and of the predisposing HLA–DRB1 shared epitope (SE) alleles in particular, to the ACPA‐positive and ACPA‐negative subsets of RA, by computing their heritability and assessing the contribution of the HLA SE alleles.MethodsOne hundred forty‐eight RA twin pairs, in which at least 1 twin of each pair had RA, were tested for ACPAs and typed for HLA–DRB1 genotypes. Heritability was assessed in a logistic regression model including a bivariate, normally distributed random effect, representing the contribution of unobserved genetic factors to RA susceptibility, with the correlation of the random effects fixed according to twin zygosity. The contribution of the HLA SE alleles to genetic variance was assessed using a similar model, except that estimates were based on genotype‐specific population prevalences.ResultsThe heritability of RA among the twin pairs was 66% (95% confidence interval [95% CI] 44–75%). For ACPA‐positive RA, the heritability was 68% (95% CI 55–79%), and for ACPA‐negative RA it was 66% (95% CI 21–82%). Presence of the HLA SE alleles explained 18% (95% CI 16–19%) of the genetic variance of ACPA‐positive RA but only 2.4% (95% CI 1.6–10%) of the genetic variance of ACPA‐negative RA.ConclusionThe heritability of ACPA‐positive RA is comparable with that of ACPA‐negative RA. These data indicate that genetic predisposition plays an important role in the pathogenesis of ACPA‐negative RA, for which most individual genetic risk factors remain to be identified.
Notochordal intervertebral disc cells: Sensitivity to nutrient deprivation
Authors: Guehring Thorsten , Wilde Geoff , Sumner Matthew , Grünhagen Thijs , Karney Graeme B. , Tirlapur Uday K. , Urban Jill P. G. 
Published: March 2009

AbstractObjectiveThe nucleus pulposus (NP) of the intervertebral disc develops from the notochord. Humans and other species in which notochordal cells (NCs) disappear to be replaced by chondrocyte‐like mature NP cells (MNPCs) frequently develop disc degeneration, unlike other species that retain NCs. The reasons for NC disappearance are unknown. In humans, the change in cell phenotype (to MNPCs) coincides with changes that decrease nutrient supply to the avascular disc. We undertook this study to test the hypothesis that the consequent nutrient stress could be associated with NC disappearance.MethodsWe measured cell densities and metabolic rates in 3‐dimensional cultures of porcine NCs and bovine MNPCs, and we determined survival rates under conditions of nutrient deprivation. We used scanning electron microscopy to examine end plate porosity of discs with NCs and those with MNPCs. Nutrient–metabolite profiles and cell viability were calculated as a function of cell density and disc size in a consumption/diffusion mathematical model.ResultsNCs were more active metabolically and more susceptible to nutrient deprivation than were MNPCs. Hypoxia increased rates of glycolysis in NCs but not in MNPCs. Higher end plate porosity in discs with NCs suggested greater nutrient supply in keeping with higher nutritional demands. Mathematical simulations and experiments using an analog disc diffusion chamber indicated that a fall in nutrient concentrations resulting from increased diffusion distance during growth and/or a fall in blood supply through end plate changes could instigate NC disappearance.ConclusionNCs demand more energy and are less resistant to nutritional stress than MNPCs, which may shed light on the fate of NCs in humans. This provides important information about prospective NC tissue engineering approaches.
HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination
Authors: Ball Robert , Shadomy Sean V. , Meyer Abbie , Huber Brigitte T. , Leffell Mary S. , Zachary Andrea , Belotto Michael , Hilton Eileen , Bryant‐Genevier Marthe , Schriefer Martin E. , Miller Frederick W. , Braun M. Miles 
Published: March 2009

AbstractObjectiveTo investigate whether persons with treatment‐resistant Lyme arthritis–associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen.MethodsPersons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA–DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed.ResultsTwenty‐seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment‐resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3‐2.1), 1.6 (95% CI 0.5–4.4), and 1.75 (95% CI 0.6–5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5–5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2–2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1–0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%).ConclusionTreatment‐resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases.
Inflation of Type I error rate in multiple regression when independent variables are measured with error
Authors: Brunner Jerry , Austin Peter C. 
Published: March 2009

AbstractWhen independent variables are measured with error, ordinary least squares regression can yield parameter estimates that are biased and inconsistent. This article documents an inflation of Type I error rate that can also occur. In addition to analytic results, a large‐scale Monte Carlo study shows unacceptably high Type I error rates under circumstances that could easily be encountered in practice. A set of smaller‐scale simulations indicate that the problem applies to various types of regression and various types of measurement error. The Canadian Journal of Statistics 37: 33‐46; 2009 © 2009 Statistical Society of Canada
New aspects of Bregman divergence in regression and classification with parametric and nonparametric estimation
Authors: Zhang Chunming , Jiang Yuan , Shang Zuofeng 
Published: March 2009

AbstractIn statistical learning, regression and classification concern different types of the output variables, and the predictive accuracy is quantified by different loss functions. This article explores new aspects of Bregman divergence (BD), a notion which unifies nearly all of the commonly used loss functions in regression and classification. The authors investigate the duality between BD and its generating function. They further establish, under the framework of BD, asymptotic consistency and normality of parametric and nonparametric regression estimators, derive the lower bound of their asymptotic covariance matrices, and demonstrate the role that parametric and nonparametric regression estimation play in the performance of classification procedures and related machine learning techniques. These theoretical results and new numerical evidence show that the choice of loss function affects estimation procedures, whereas has an asymptotically relatively negligible impact on classification performance. Applications of BD to statistical model building and selection with non‐Gaussian responses are also illustrated. The Canadian Journal of Statistics 37: 119‐139; 2009 © 2009 Statistical Society of Canada
Production of phytosterol esters from soybean oil deodorizer distillates
Authors: Torres Carlos F. , Fornari Tiziana , Torrelo Guzmán , Señoráns F. Javier , Reglero Guillermo 
Published: March 2009

AbstractEnzymatic esterification and supercritical fluid extraction was used to produce phytosterol esters from soybean oil deodorizer distillates. The raw material was first subjected to a two‐step enzymatic reaction; the product obtained mainly comprised fatty acid ethyl esters, tocopherols and phytosterol esters, together with minor amounts of squalene, free fatty acids, free sterols and triacylglycerols. The phytosterol esters were then purified from this mixture using supercritical carbon dioxide. Experimental extractions were carried out in an isothermal countercurrent column (without reflux), with pressures ranging from 200 to 280 bar, temperatures of 45–55 °C and solvent‐to‐feed ratios from 15 to 35 kg/kg. Using these extraction conditions, the fatty acid esters were completely extracted and, thus, the fractionation of tocopherols and phytosterol esters was studied. At 250 bar, 55 °C and a solvent‐to‐feed ratio of 35, the phytosterol esters were concentrated in the raffinate up to 82.4 wt‐% with satisfactory yield (72%).
Effect of Thymus haussknechtii and Origanum acutidens essential oils on the stability of cow milk butter
Authors: Dagdemir Elif , Cakmakci Songul , Gundogdu Engin 
Published: March 2009

AbstractThe aim of this study was to investigate the effects of different essential oils (from Thymus haussknechtii Velen and Origanum acutidens Hand.‐Mazz. Letswaart; endemic species in Turkey) on butter stability. These essential oils were added to butter at two concentrations (0.1 and 0.2 wt‐%). The antioxidant activities of the essential oils were compared with control samples (without antioxidant) and containing butylated hydroxytoluene (BHT). All samples were stored at 4 ± 1 °C for 90 days and their peroxide values (PV), thiobarbituric acid (TBA) values, % titratable acidity and some microbiological properties were analyzed. As a result, the lowest PV and TBA values were determined in the samples containing BHT and 0.2% essential oils; however, TBA and PV were at the highest levels in the control samples during storage. The amount of 0.2% of essential oils exhibited strong antioxidant activity, which was almost equal to that of BHT. T. haussknechtii essential oil showed a stronger antioxidant effect as compared to O. acutidens. None of the essential oils showed remarkable antifungal activity. However, the antimicrobial activity of O. acutidens on coliform bacteria was found to be higher than that of T. haussknechtii. Sensory analysis of the butter showed that the samples containing 0.2% essential oils had lower flavor scores than those with 0.1% essential oils. The present results indicate that these essential oils can be considered as an alternative source of natural antioxidants in the manufacture of butter.
Cytochrome P450 2E1 and head and neck cancer: Interaction with genetic and environmental risk factors
Authors: Ruwali Munindra , Khan Anwar Jamal , Shah Parag P. , Singh Arvind Pratap , Pant Mohan C. , Parmar Devendra 
Published: March 2009

AbstractThe present case‐control study investigates the association of polymorphisms in cytochrome P450 2E1 (CYP2E1), involved in the metabolism of tobacco carcinogens and alcohol, with Head and Neck Squamous Cell Carcinoma (HNSCC). In addition, the interaction of CYP2E1 (CYP2E1*5B and CYP2E1*6) with other genetic factors (null genotype of glutathione‐S‐Transferase M1, GSTM1, X‐Ray Repair Cross Complementing Group I, XRCC1 (Arg194Trp), and environmental risk factors such as alcohol and tobacco in modifying HNSCC risk were investigated. Genotypes were determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay in a total of 350 male cases of HNSCC and an equal number of healthy male controls. Statistical analysis showed a significant increase in HNSCC risk in cases with variant genotypes of CYP2E1*5B (RsaI) (O.R. 3.44; 95% C.I. 1.45–8.14) and CYP2E1*6 (DraI) (O.R. 1.76; 95% C.I. 1.28–2.41). Haplotype analysis revealed that haplotype T‐A was associated with a greater than 10‐fold increase in risk for HNSCC. Our data also revealed a several fold increase in HNSCC risk in cases carrying a combination of variant genotypes of CYP2E1 with the null genotype of GSTM1 or XRCC1 variant genotypes. Alcohol or tobacco use (both smoking and chewing) were also found to interact with variant genotypes of CYP2E1 in significantly enhancing HNSCC risk. This increase in risk associated with an interaction of CYP2E1 genotypes with GSTM1 or XRCC1 or with tobacco and alcohol use demonstrates the importance of gene–gene and gene–environment interactions in the development of HNSCC. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.
Case‐control association testing in the presence of unknown relationships
Authors: Choi Yoonha , Wijsman Ellen M. , Weir Bruce S. 
Published: March 2009

AbstractGenome‐wide association studies result in inflated false‐positive results when unrecognized cryptic relatedness exists. A number of methods have been proposed for testing association between markers and disease with a correction for known pedigree‐based relationships. However, in most case‐control studies, relationships are generally unknown, yet the design is predicated on the assumption of at least ancestral relatedness among cases. Here, we focus on adjusting cryptic relatedness when the genealogy of the sample is unknown, particularly in the context of samples from isolated populations where cryptic relatedness may be problematic. We estimate cryptic relatedness using maximum‐likelihood methods and use a corrected χ2test with estimated kinship coefficients for testing in the context of unknown cryptic relatedness. Estimated kinship coefficients characterize precisely the relatedness between truly related people, but are biased for unrelated pairs. The proposed test substantially reduces spurious positive results, producing a uniform null distribution ofP‐values. Especially with missing pedigree information, estimated kinship coefficients can still be used to correct non‐independence among individuals. The corrected test was applied to real data sets from genetic isolates and created a distribution ofP‐value that was close to uniform. Thus, the proposed test corrects the non‐uniform distribution ofP‐values obtained with the uncorrected test and illustrates the advantage of the approach on real data.Genet. Epidemiol. 33:668–678, 2009. © 2009 Wiley‐Liss, Inc.