bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations
Authors: Sánchez Elena , Rasmussen Astrid , Riba Laura , Acevedo‐Vasquez Eduardo , Kelly Jennifer A. , Langefeld Carl D. , Williams Adrianne H. , Ziegler Julie T. , Comeau Mary E. , Marion Miranda C. , García‐De La Torre Ignacio , Maradiaga‐Ceceña Marco A. , Cardiel Mario H. , Esquivel‐Valerio Jorge A. , Rodriguez‐Amado Jacqueline , Moctezuma José Francisco , Miranda Pedro , Perandones Carlos E. , Castel Cecilia , Laborde Hugo A. , Alba Paula , Musuruana Jorge L. , Goecke I. Annelise , Anaya Juan‐Manuel , Kaufman Kenneth M. , Adler Adam , Glenn Stuart B. , Brown Elizabeth E. , Alarcón Graciela S. , Kimberly Robert P. , Edberg Jeffrey C. , Vilá Luis M. , Criswell Lindsey A. , Gilkeson Gary S. , Niewold Timothy B. , Martín Javier , Vyse Timothy J. , Boackle Susan A. , Ramsey‐Goldman Rosalind , Scofield R. Hal , Petri Michelle , Merrill Joan T. , Reveille John D. , Tsao Betty P. , Orozco Lorena , Baca Vicente , Moser Kathy L. , Gaffney Patrick M. , James Judith A. , Harley John B. , Tusié‐Luna Teresa , Pons‐Estel Bernardo A. , Jacob Chaim O. , Alarcón‐Riquelme Marta E. 
Published: August 2012

AbstractObjectiveAmerican Indian–Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian–European SLE patients.MethodsA total of 2,116 SLE patients of American Indian–European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry‐informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63– 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44–0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42–0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41–0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.
Murine tumor necrosis factor α–induced adipose‐related protein (tumor necrosis factor α–induced protein 9) deficiency leads to arthritis via interleukin‐6 overproduction with enhanced NF‐κB, STAT‐3 signaling, and dysregulated apoptosis of macrophages
Authors: Inoue Asuka , Matsumoto Isao , Tanaka Yoko , Umeda Naoto , Tanaka Yuki , Mihara Masahiko , Takahashi Satoru , Sumida Takayuki 
Published: August 2012

AbstractObjectiveTo elucidate the role of tumor necrosis factor α–induced adipose‐related protein (TIARP; or tumor necrosis factor α–induced protein 9 [TNFAIP‐9]) in the development and pathogenesis of arthritis.MethodsWe generated TIARP‐deficient (TIARP−/−) mice and investigated several organs in aged mice. Peritoneal macrophages were collected and cultured with lipopolysaccharide (LPS) and TNFα, and then the production of cytokines and subsequent NF‐κB signal transduction were analyzed. We also examined the susceptibility of young TIARP−/− mice to collagen‐induced arthritis (CIA). Draining lymph nodes and splenocytes were isolated and cultured, and serum levels of anti–type II collagen (anti‐CII) antibodies, interleukin‐6 (IL‐6), and TNFα on day 60 were measured. We further investigated the effects of anti–IL‐6 receptor monoclonal antibody (mAb) on the development of arthritis in TIARP−/− mice. IL‐6/STAT‐3 signaling was also analyzed using TIARP−/− macrophages.ResultsTIARP−/− mice developed spontaneous enthesitis and synovitis, had high serum levels of IL‐6, had increased CD11b+ cell counts in the spleen, and showed enhanced LPS‐ and TNFα‐induced IL‐6 expression in macrophages. Sustained degradation of IκBα with dysregulated apoptosis was also noted in TIARP−/− macrophages. CIA was clearly exacerbated in TIARP−/− mice, accompanied by marked neutrophil and macrophage infiltration in joints. The levels of anti‐CII antibodies in serum were unchanged, whereas autoreactive Th1 cell and Th17 cell responses were higher in TIARP−/− mice. Treatment with anti–IL‐6 receptor mAb prevented the development of CIA in TIARP−/− mice, and TIARP−/− macrophages showed increased IL‐6–induced STAT‐3 phosphorylation.ConclusionThese findings suggest that TIARP acts as a negative regulator of arthritis by suppressing IL‐6 production, its signaling and TNFα‐induced NF‐κB signaling, resulting in enhanced apoptosis in macrophages.
Dexamethasone prodrug treatment prevents nephritis in lupus‐prone (NZB × NZW)F1 mice without causing systemic side effects
Authors: Yuan Fang , Nelson Richard K. , Tabor Dana E. , Zhang Yijia , Akhter Mohammed P. , Gould Karen A. , Wang Dong 
Published: August 2012

AbstractObjectiveTo evaluate the potentially improved therapeutic efficacy and safety of nephrotropic macromolecular prodrugs of glucocorticoids (GCs) for the treatment of lupus nephritis.MethodsLupus‐prone female (NZB × NZW)F1 mice received monthly injections of N‐(2‐hydroxypropyl) methacrylamide copolymer–based dexamethasone prodrug (P‐Dex) or daily injections of dexamethasone phosphate sodium (Dex; overall dose equivalent to that of P‐Dex) for 2 months. During treatment, the mice were monitored for albuminuria, mean arterial pressure, and serum autoantibody levels. Nephritis, renal immune complex levels, and macrophage infiltration were evaluated histologically. Bone quality was analyzed using peripheral dual x‐ray absorptiometry and micro–computed tomography. The in vivo distribution of P‐Dex was investigated using optical imaging, immunohistochemistry, and fluorescence‐activated cell sorting (FACS). The antiinflammatory effect of P‐Dex was validated using lipopolysaccharide‐activated human proximal tubule epithelial (HK‐2) cells.ResultsMonthly P‐Dex injections completely abolished albuminuria in the (NZB × NZW)F1 mice; this approach was significantly more efficacious than daily Dex treatment. P‐Dex treatment did not reduce serum levels of anti–double‐stranded DNA antibodies or renal immune complexes but did decrease macrophage infiltration, which is a marker of chronic inflammation. Immunohistochemical and FACS analyses revealed that P‐Dex was primarily sequestered by proximal tubule epithelial cells, and that it could attenuate the inflammatory response in HK‐2 cell culture. In contrast to Dex treatment, P‐Dex treatment did not lead to any significant deterioration of bone quality or reduction in the level of total serum IgG.ConclusionMacromolecularization of GCs renders them nephrotropic. Protracted retention, subcellular processing, and activation of GC prodrugs by kidney cells would potentiate nephritis resolution, with a reduced risk of systemic toxicities.
Multicriteria evaluation on accessibility‐based transportation equity in road network design problem
Authors: Feng Tao , Zhang Junyi 
Published: August 2012

SUMMARYThis paper investigates the performance of accessibility‐based equity measurements in transportation and proposes a multiobjective optimization model to simulate the trade‐offs between equity maximization and cost minimization of network construction. The equity is defined as the spatial distribution of accessibilities across zone areas. Six representative indicators were formulated, including GINI coefficient, Theil index, mean log deviation, relative mean deviation, coefficient of variation, and Atkinson index, and incorporated into an equity maximization model to evaluate the performance sensitivity. A bilevel multiobjective optimization model was proposed to obtain the Pareto‐optimal solutions for link capacity enhancement in a stochastic road network design problem. A numerical analysis using the Sioux Falls data was implemented. Results verified that the equity indicators are quite sensitive to the pattern of network scenarios in the sense that the level of equity varies according to the amount of overall capacity enhancement as well as the assignment of improved link segments. The suggested multiobjective model that enables representing the Pareto‐optimal solutions can provide multiple options in the decision making of road network design. Copyright © 2012 John Wiley & Sons, Ltd.
The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: An open label pilot study
Authors: Mezawa Morito , Takemoto Minoru , Onishi Shunichiro , Ishibashi Ryoichi , Ishikawa Takahiro , Yamaga Masaya , Fujimoto Masaki , Okabe Emiko , He Peng , Kobayashi Kazuki , Yokote Koutaro 
Published: August 2012

AbstractCoenzyme Q10 (CoQ10) provides the energy for vital cellular functions and is known to act as an antioxidant. We conducted an open label study to examine the clinical effects of supplementation of the reduced form of CoQ10, ubiquinol, in addition to conventional glucose‐lowering agents in patients with type 2 diabetes. Nine subjects (3 males and 6 females) with type 2 diabetes and receiving conventional medication were recruited. The subjects were assigned to receive an oral dose of 200 mg ubiquinol daily for 12 weeks. The effect of ubiquinol on blood pressure, lipid profile, glycemic control, oxidative stress, and inflammation were examined before and after ubiquinol supplementation. In addition, five healthy volunteers were also assigned to receive an oral dose of 200 mg ubiquinol daily for 4 weeks to examine the effects of ubiquinol on insulin secretion. In patients with diabetes, there were no differences with respect to blood pressure, lipid profile, oxidative stress marker, and inflammatory markers. However, there were significant improvements in glycosylated hemoglobin (53.0 ± 4.3 to 50.5 ± 3.7 mmol/mol, P = 0.01) (7.1 ± 0.4 to 6.8 ± 0.4%, P = 0.03). In healthy volunteers, the insulinogenic index (0.65 ± 0.29 to 1.23 ± 0.56, P = 0.02) and the ratio of proinsulin to insulin were significantly improved (3.4 ± 1.8 to 2.1 ± 0.6, P = 0.03). The results of our study are consistent with the suggestion that the supplementation of ubiquinol in subjects with type 2 diabetes, in addition to conventional antihyperglycemic medications, improves glycemic control by improving insulin secretion without any adverse effects.© 2012 International Union of Biochemistry and Molecular Biology, Inc.
Strategic Assay Selection for analytics in high‐throughput process development: Case studies for downstream processing of monoclonal antibodies
Authors: Konstantinidis Spyridon , Kong Simyee , Chhatre Sunil , Velayudhan Ajoy , Heldin Eva , Titchener‐Hooker Nigel 
Published: August 2012

AbstractDuring bioprocess development a potentially large number of analytes require measurement. Selection of the best set of analytical methods to deploy can reduce the analytical requirements for process investigation but currently relies on application of heuristics. This paper introduces a generic methodology, Strategic Assay Selection, for screening a large number of analytical methods to produce a subset of analytics that best suit high‐throughput studies. The methodology uses a stochastic ranking approach where analytics are ranked based on their holistic performance in a set of criteria. Strategic Assay Selection can be used to help minimizing the impact of analytics in the generation of bottlenecks often encountered during high‐throughput process development studies. This is illustrated by using a typical downstream purification process for a monoclonal antibody product. A list of assays is populated for routinely measured analytes across the different units of operation followed by the calculation of their performances in four criteria. The methodology is then applied to select analytics testing for three analytes and the results are analyzed to demonstrate how it can lead to the selection of analytical methods with the most favorable features.
Investigation of ifosfamide nephrotoxicity induced in a liver–kidney co‐culture biochip
Authors: Choucha‐Snouber Leila , Aninat Caroline , Grsicom Laurent , Madalinski Geoffrey , Brochot Céline , Poleni Paul Emile , Razan Florence , Guillouzo Christiane Guguen , Legallais Cécile , Corlu Anne , Leclerc Eric 
Published: August 2012

AbstractIn this article, we present a liver–kidney co‐culture model in a micro fluidic biochip. The liver was modeled using HepG2/C3a and HepaRG cell lines and the kidney using MDCK cell lines. To demonstrate the synergic interaction between both organs, we investigated the effect of ifosfamide, an anticancerous drug. Ifosfamide is a prodrug which is metabolized by the liver to isophosforamide mustard, an active metabolite. This metabolism process also leads to the formation of chloroacetaldehyde, a nephrotoxic metabolite and acrolein a urotoxic one. In the biochips of MDCK cultures, we did not detect any nephrotoxic effects after 72 h of 50 µM ifosfamide exposure. However, in the liver–kidney biochips, the same 72 h exposure leads to a nephrotoxicity illustrated by a reduction of the number of MDCK cells (up to 30% in the HepaRG‐MDCK) when compared to untreated co‐cultures or treated MDCK monocultures. The reduction of the MDCK cell number was not related to a modification of the cell cycle repartition in ifosfamide treated cases when compared to controls. The ifosfamide biotransformation into 3‐dechloroethylifosfamide, an equimolar byproduct of the chloroacetaldehyde production, was detected by mass spectrometry at a rate of apparition of 0.3 ± 0.1 and 1.1 ± 0.3 pg/h/biochips in HepaRG monocultures and HepaRG‐MDCK co‐cultures respectively. Any metabolite was detected in HepG2/C3a cultures. Furthermore, the ifosfamide treatment in HepaRG‐MDCK co‐culture system triggered an increase in the intracellular calcium release in MDCK cells on contrary to the treatment on MDCK monocultures. As 3‐dechloroethylifosfamide is not toxic, we have tested the effect of equimolar choloroacetaldehyde concentration onto the MDCK cells. At this concentration, we found a quite similar calcium perturbation and MDCK nephrotoxicity via a reduction of 30% of final cell numbers such as in the ifosfamide HepaRG‐MDCK co‐culture experiments. Our results suggest that ifosfamide nephrotoxicity in a liver–kidney micro fluidic co‐culture model using HepaRG‐MDCK cells is induced by the metabolism of ifosfamide into chloroacetaldehyde whereas this pathway is not functional in HepG2/C3a‐MDCK model. This study demonstrates the interest in the development of systemic organ–organ interactions using micro fluidic biochips. It also illustrated their potential in future predictive toxicity model using in vitro models as alternative methods. Biotechnol. Bioeng. 2013; 110: 597–608. © 2012 Wiley Periodicals, Inc.
Statistical analysis of effects of experimental variables on mass transfer coefficient in a novel hybrid bubble column using Box–Behnken design
Authors: Dhanasekaran S. , Karunanithi T. 
Published: August 2012

AbstractStatistical analysis of effects of experimental variables on volumetric mass transfer coefficient in a novel hybrid rotating and reciprocating perforated plate bubble column is studied. The novel bubble column is designed indigenously using bevel gear arrangement. Agitation level, superficial gas velocity, superficial liquid velocity, perforation diameter and plate spacing are the experimental variables. Air–sodium sulphite solution system is used in this investigation. The Box–Behnken design in response surface methodology is employed for statistical analysis. The relationship between experimental variables and the desired response of volumetric mass transfer coefficient is established for this novel hybrid column. The linear, quadratic and interactive effects of experimental variables are found to be significant on the desired response of volumetric mass transfer coefficient. Results show that the data adequately fit into the second‐order polynomial model. An F‐test and P‐value show the significance of parameters on volumetric mass transfer coefficient. © 2012 Canadian Society for Chemical Engineering
Likelihood‐based and marginal inference methods for recurrent event data with covariate measurement error
Authors: Yi Grace Y. , Lawless Jerald F. 
Published: August 2012

AbstractRecurrent event data arise commonly in medical and public health studies. The analysis of such data has received extensive research attention and various methods have been developed in the literature. Depending on the focus of scientific interest, the methods may be broadly classified as intensity‐based counting process methods, mean function‐based estimating equation methods, and the analysis of times to events or times between events. These methods and models cover a wide variety of practical applications. However, there is a critical assumption underlying those methods–variables need to be correctly measured. Unfortunately, this assumption is frequently violated in practice. It is quite common that some covariates are subject to measurement error. It is well known that covariate measurement error can substantially distort inference results if it is not properly taken into account. In the literature, there has been extensive research concerning measurement error problems in various settings. However, with recurrent events, there is little discussion on this topic. It is the objective of this paper to address this important issue. In this paper, we develop inferential methods which account for measurement error in covariates for models with multiplicative intensity functions or rate functions. Both likelihood‐based inference and robust inference based on estimating equations are discussed.The Canadian Journal of Statistics40: 530–549; 2012 © 2012 Statistical Society of Canada
Physico‐Chemical and Bacterial Characteristics of Water Quality in Three Villages West of Lake Nasser, Egypt
Authors: Rashed Mohamed Nageeb , Younis Magdy 
Published: August 2012

AbstractThe present study aims to investigate physico‐chemical and bacterial characteristics of Nasser Lake water and houses drinking water, as well as fish cultures and its wastewater, in three villages west of Lake Nasser, Egypt. Fifteen representative water samples (Nasser Lake, different drinking water, fish cultures, and wastewater sources) were collected from three villages (Garf Hussein, Bashaier, and Kalabsha) in the west of Lake Nasser. Physico‐chemical, total viable counts, and bacterial qualification of water were achieved. The obtained results indicated that the produced water, supposed to be for domestic use in the three villages, contained all the tested organisms. The investigated water samples of the lake and drinking water in the selected three villages are supposed to be chemically safe according to World Health Organization and to Egyptian standards for drinking water. Water pollution index (WPI) was used in this study and the result concluded that for irrigation canals from the lake to the agriculture site, fish cultures (both concrete and earth pond systems), and drainage canal of fish ponds need to be treated before it is discharged to the lake. It is better to reuse it after treatment for agricultural purposes or recycled it to the fish cultures.
Distinct synaptic localization patterns of brefeldin A‐resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina
Authors: Sakagami Hiroyuki , Katsumata Osamu , Hara Yoshinobu , Tamaki Hideaki , Watanabe Masahiko , Harvey Robert J. , Fukaya Masahiro 
Published: August 2012

AbstractThe BRAG/IQSEC is a family of guanine nucleotide exchange factors for ADP ribosylation factors, small GTPases that regulate membrane trafficking and actin cytoskeleton, and comprises three structurally related members (BRAG1–3) generated from different genes. In the mouse retina, BRAG1 (also known as IQSEC2) was previously shown to localize at synaptic ribbons of photoreceptor terminals and to form a protein complex with RIBEYE. In this study, we examined the immunohistochemical localization of BRAG2 (IQSEC1) and BRAG3 (IQSEC3) in the adult mouse retina at the light and electron microscopic levels. In the outer plexiform layer, BRAG2 showed a punctate distribution in intimate association with dystrophin and β‐dystroglycan. Immunoelectron microscopic analysis revealed that BRAG2 localized at specific subcompartments of photoreceptor terminals in both rod spherules and cone pedicles. In the inner plexiform layer, immunolabeling for both BRAG2 and BRAG3 had a punctate appearance, suggestive of synaptic labeling. Double immunostaining demonstrated that BRAG2 colocalized preferentially with PSD‐95 and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate‐type glutamate receptors (AMPARs). By contrast, BRAG3 colocalized with gephyrin and a subpopulation of inhibitory synapses expressing glycine receptors or γ‐aminobutyric acid type A receptors (GABAARs). Immunoelectron microscopic analysis revealed that BRAG2 localized to postsynaptic processes at bipolar dyads, while BRAG3 localized to postsynaptic components at conventional synapses. These findings suggest that BRAG/IQSEC family members have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. J. Comp. Neurol. 521:860–876, 2013. © 2012 Wiley Periodicals, Inc.
Sensory and sympathetic innervation of the mouse and guinea pig corneal epithelium
Authors: Ivanusic Jason J. , Wood Rhiannon J. , Brock James A. 
Published: August 2012

AbstractThis study used immunohistochemistry, retrograde tracing, and high‐resolution confocal microscopy to explore the structure and neurochemistry of nerve terminals in the corneal epithelium of mice and guinea pigs. In both species, sub‐basal nerves formed a plexus in the basal epithelium. Some axons had bulbar endings within the basal epithelium, but most projected perpendicularly from sub‐basal nerves to within a few micrometers of the epithelial surface. Three morphologies for these nerve terminals were identified. Simple terminals did not branch after leaving the sub‐basal nerves and ended with a single, bulbar swelling. Ramifying terminals branched in the squamous cell layer, forming horizontal fibers that ran parallel to the surface and terminated with single bulbar swellings. Complex terminals branched as they approached the epithelial surface, forming a cluster of highly branched fibers with multiple bulbar endings. Calcitonin gene‐related peptide immunolabeled (peptidergic) axons ended mostly in simple terminals, whereas transient receptor potential cation channel subfamily M member 8 immunolabeled (cold receptor) axons ended almost exclusively in complex terminals. Retrograde labeling identified discrete subpopulations of corneal afferent neurons in the trigeminal ganglion. Tyrosine hydroxylase‐immunolabeled (sympathetic) nerve terminals originating from the superior cervical ganglion occurred throughout the corneal epithelium of mice, but only in the basal epithelium of guinea pigs. These findings demonstrate that nerve terminals in the corneal epithelium of mice and guinea pigs can be distinguished on the basis of their morphology and neurochemistry, and suggest that nerve terminals with different sensory modalities can be defined on the basis of their morphology. J. Comp. Neurol. 521:877–893, 2013. © 2012 Wiley Periodicals, Inc.