bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of combinations of in vitro sensitization test descriptors for the artificial neural network‐based risk assessment model of skin sensitization
Authors: Hirota Morihiko , Fukui Shiho , Okamoto Kenji , Kurotani Satoru , Imai Noriyasu , Fujishiro Miyuki , Kyotani Daiki , Kato Yoshinao , Kasahara Toshihiko , Fujita Masaharu , Toyoda Akemi , Sekiya Daisuke , Watanabe Shinichi , Seto Hirokazu , Takenouchi Osamu , Ashikaga Takao , Miyazawa Masaaki 
Published: April 2015

AbstractThe skin sensitization potential of chemicals has been determined with the use of the murine local lymph node assay (LLNA). However, in recent years public concern about animal welfare has led to a requirement for non‐animal risk assessment systems for the prediction of skin sensitization potential, to replace LLNA. Selection of an appropriate in vitro test or in silico model descriptors is critical to obtain good predictive performance. Here, we investigated the utility of artificial neural network (ANN) prediction models using various combinations of descriptors from several in vitro sensitization tests. The dataset, collected from published data and from experiments carried out in collaboration with the Japan Cosmetic Industry Association (JCIA), consisted of values from the human cell line activation test (h‐CLAT), direct peptide reactivity assay (DPRA), SH test and antioxidant response element (ARE) assay for chemicals whose LLNA thresholds have been reported. After confirming the relationship between individual in vitro test descriptors and the LLNA threshold (e.g. EC3 value), we used the subsets of chemicals for which the requisite test values were available to evaluate the predictive performance of ANN models using combinations of h‐CLAT/DPRA (N = 139 chemicals), the DPRA/ARE assay (N = 69), the SH test/ARE assay (N = 73), the h‐CLAT/DPRA/ARE assay (N = 69) and the h‐CLAT/SH test/ARE assay (N = 73). The h‐CLAT/DPRA, h‐CLAT/DPRA/ARE assay and h‐CLAT/SH test/ARE assay combinations showed a better predictive performance than the DPRA/ARE assay and the SH test/ARE assay. Our data indicates that the descriptors evaluated in this study were all useful for predicting human skin sensitization potential, although combinations containing h‐CLAT (reflecting dendritic cell‐activating ability) were most effective for ANN‐based prediction. Copyright © 2015 John Wiley & Sons, Ltd.
Gene expression profiling of the hippocampal dentate gyrus in an adult toxicity study captures a variety of neurodevelopmental dysfunctions in rat models of hypothyroidism
Authors: Shiraki Ayako , Saito Fumiyo , Akane Hirotoshi , Akahori Yumi , Imatanaka Nobuya , Itahashi Megu , Yoshida Toshinori , Shibutani Makoto 
Published: April 2015

AbstractWe previously found that developmental hypothyroidism changed the expression of genes in the rat hippocampal dentate gyrus, a brain region where adult neurogenesis is known to occur. In the present study, we performed brain region‐specific global gene expression profiling in an adult rat hypothyroidism model to see if it reflected the developmental neurotoxicity we saw in the developmental hypothyroidism model. Starting when male rats were 5 weeks old, we administered 6‐propyl‐2‐thiouracil at a doses of 0, 0.1 and 10 mg kg−1 body weight by gavage for 28 days. We selected four brain regions to represent both cerebral and cerebellar tissues: hippocampal dentate gyrus, cerebral cortex, corpus callosum and cerebellar vermis. We observed significant alterations in the expression of genes related to neural development (Eph family genes and Robo3) in the cerebral cortex and hippocampal dentate gyrus and in the expression of genes related to myelination (Plp1 and Mbp) in the hippocampal dentate gyrus. We observed only minor changes in the expression of these genes in the corpus callosum and cerebellar vermis. We used real‐time reverse‐transcription polymerase chain reaction to confirm Chrdl1, Hes5, Mbp, Plp1, Slit1, Robo3 and the Eph family transcript expression changes. The most significant changes in gene expression were found in the dentate gyrus. Considering that the gene expression profile of the adult dentate gyrus closely related to neurogenesis, 28‐day toxicity studies looking at gene expression changes in adult hippocampal dentate gyrus may also detect possible developmental neurotoxic effects. Copyright © 2015 John Wiley & Sons, Ltd.
Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610CMice With and Without Weight-Bearing Exercise
Authors: Jeong Youngjae , Carleton Stephanie M , Gentry Bettina A , Yao Xiaomei , Ferreira J Andries , Salamango Daniel J , Weis MaryAnn , Oestreich Arin K , Williams Ashlee M , McCray Marcus G , Eyre David R , Brown Marybeth , Wang Yong , Phillips Charlotte L 
Published: April 2015

Abstract Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild-type mice. The +/G610C mice were also able to complete an 8-week treadmill regimen. Biomechanical integrity of control and exercised wild-type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight-bearing exercise regimen as wild-type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice. © 2015 American Society for Bone and Mineral Research.
In vitro metabolism of canagliflozin in human liver, kidney, intestine microsomes, and recombinant uridine diphosphate glucuronosyltransferases (UGT) and the effect of genetic variability of UGT enzymes on the pharmacokinetics of canagliflozin in humans
Authors: Francke Stephan , Mamidi Rao N. V. S. , Solanki Bhavna , Scheers Ellen , Jadwin Andrew , Favis Reyna , Devineni Damayanthi 
Published: April 2015

AbstractO‐glucuronidation is the major metabolic elimination pathway for canagliflozin. The objective was to identify enzymes and tissues involved in the formation of 2 major glucuronidated metabolites (M7 and M5) of canagliflozin and subsequently to assess the impact of genetic variations in these uridine diphosphate glucuronosyltransferases (UGTs) on in vivo pharmacokinetics in humans. In vitro incubations with recombinant UGTs revealed involvement of UGT1A9 and UGT2B4 in the formation of M7 and M5, respectively. Although M7 and M5 were formed in liver microsomes, only M7 was formed in kidney microsomes. Participants from 7 phase 1 studies were pooled for pharmacogenomic analyses. A total of 134 participants (mean age, 41 years; men, 63%; white, 84%) were included in the analysis. In UGT1A9*3 carriers, exposure of plasma canagliflozin (Cmax,ss, 11%; AUCτ,ss, 45%) increased relative to the wild type. An increase in exposure of plasma canagliflozin (Cmax,ss, 21%; AUCt,ss, 18%) was observed in participants with UGT2B4*2 genotype compared with UGT2B4*2 noncarriers. Metabolites further delineate the role of both enzymes. The pharmacokinetic findings in participants carrying the UGT1A9*3 and UGT2B4*2 allele implicate that UGT1A9 and UGT2B4 are involved in the metabolism of canagliflozin to M7 and M5, respectively.
Improved body weight and performance status and reduced serum PGE2 levels after nutritional intervention with a specific medical food in newly diagnosed patients with esophageal cancer or adenocarcinoma of the gastro‐esophageal junction
Authors: Faber Joyce , Uitdehaag Madeleen J. , Spaander Manon , van Steenbergen‐Langeveld Sabine , Vos Paul , Berkhout Marloes , Lamers Cor , Rümke Hans , Tilanus Hugo , Siersema Peter , van Helvoort Ardy , van der Gaast Ate 
Published: April 2015

AbstractBackgroundThe majority of cancer patients loses weight and becomes malnourished during the course of their disease. Metabolic alterations and reduced immune competence lead to wasting and an increased risk of infectious complications. In the present study, the effect of a nutritionally complete medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides, was investigated on immune function, nutritional status, and inflammation in patients with esophageal cancer and compared with routine care.MethodsIn this exploratory double‐blind study, 64 newly diagnosed esophageal cancer patients were randomized. All patients received dietary counselling and dietary advice. In the Active group, all patients received the specific medical food for 4 weeks before the start of anticancer therapy. In the routine care control arm, patients with <5% weight loss received a non‐caloric placebo product, and patients with weight loss ≥5% received an iso‐caloric control product to secure blinding of the study. The required study parameters of body weight and performance status were recorded at baseline and after 4 weeks of nutritional intervention, and patients were asked to complete quality of life questionnaires. In addition, blood samples were taken for the measurement of several immune, nutritional, and safety‐parameters.ResultsNo effect of the specific nutritional intervention could be detected on ex vivo stimulations of blood mononuclear cells. By contrast, body weight was significantly increased (P < 0.05) and ECOG performance status was improved after intervention with the specific medical food (P < 0.05). In addition, serum Prostaglandin E2 (PGE2) levels were significantly decreased in the specific medical food group and increased in the control group (P = 0.002).ConclusionsNutritional intervention with the specific medical food significantly increased body weight and improved performance status compared with routine care in newly diagnosed esophageal cancer patients. This effect was accompanied by significantly reduced serum PGE2 levels.
Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic
Authors: Dev Rony , Hui David , Chisholm Gary , Delgado‐Guay Marvin , Dalal Shalini , Del Fabbro Egidio , Bruera Eduardo 
Published: April 2015

AbstractBackgroundElevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients.AimsThe aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high‐sensitivity C‐reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE.MethodsA retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two‐sample Student's t‐tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups.ResultsThirty‐seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty‐five patients (58%) were hypermetabolic. Non‐Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C‐reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively.ConclusionHypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non‐Caucasian patients. No association among velocity of weight loss, symptom burden, C‐reactive protein, and survival was noted in advanced cancer patients with elevated REE.
Hydrogen peroxide obtained via direct synthesis as alternative raw material for ultrapurification process to produce electronic grade chemical
Authors: Abejón Ricardo , Abejón Azucena , Biasi Pierdomenico , Gemo Nicola , Garea Aurora , Salmi Tapio , Irabien Jose Angel 
Published: April 2015

AbstractBACKGROUNDThe catalytic direct synthesis of hydrogen peroxide is a highly interesting alternative process to avoid the current anthraquinone route because it implies significant sustainability improvements. Among all the peroxide applications, its use as an electronic chemical requires very low metallic content. The employment of direct synthesis peroxide as raw material for the ultrapurification process has not been investigated before, so its viability is still pending evaluation.RESULTSAlthough the improvements of catalyst or reactor performance of the direct synthesis process were not defined as objectives of the work, a maximum peroxide concentration of 2.3% was obtained, which is a very good result considering the low pressure used. Some relationships between the measured metallic concentrations in the obtained chemical and the operating conditions have been very useful to identify the most important conditions (selection of appropriate quality chemicals and proper materials for the installation) to promote the production of hydrogen peroxide with low metallic content. The technical competitiveness of this alternative ultrapurification process was clearly demonstrated as the number of required membrane stages (from 1 to 6 depending on the product quality) is lower than that required by the traditional case. Besides, the process can be considered economically viable if the direct synthesis peroxide can be produced with a total cost below 36.5 $ m−3.CONCLUSIONFurther investigation, specifically focused on holistic approaches, is still necessary in order to assess the total costs of hydrogen peroxide production by direct synthesis. This way, the current available information could be complemented and the competitiveness of this direct route to obtain hydrogen peroxide for electronic grade chemical production could be more clearly defined. © 2015 Society of Chemical Industry
Numerical study of particle chains of a large number of randomly distributed DEP particles using iterative dipole moment method
Authors: Liu Le , Xie Chuanchuan , Chen Bo , Wu Jiankang 
Published: April 2015

AbstractBACKGROUNDDielectrophoresis (DEP) has widely been used to manipulate bio‐particles in microfluidic system. The calculation of DEP interaction of a large number of dense particles has been a challenging issue. The Maxwell stress tensor (MST) method is strictly accurate in theory for DEP forces, but the complicated numerical computation is very difficult to implement. An iterative dipole moment method (IDM) is proposed in this paper to study the interaction forces and particle chains of a large number of dense particles in a uniform electrical field.RESULTSThe numerical example of ten particles interaction confirms that the IDM is able to calculate particle interaction forces in good agreement with the MST method. Particle chains of fifty randomly distributed dense particles in a uniform electrical field were simulated using the IDM method and were well consistent with experimental observations. Particle chains of different particle sizes are also investigated.CONCLUSIONThe interaction forces of DEP particles calculated by the IDM method are found to be in good agreement with those obtained using the Maxwell stress tensor (MST) method and easy to implement. The simulated particle chains show essential characteristics well consistent with experimental observations. © 2015 Society of Chemical Industry
Purification and characterization of a ∼43 kDa antioxidant protein with antitumor activity from Pholiota nameko
Authors: Qian Lei , Zhang Yeni , Liu Fang 
Published: April 2015

AbstractBACKGROUNDPholiota nameko water‐soluble protein (PNWSP), isolated from the dried fruiting bodies of Pholiota nameko, was purified by a successive chromatographic process using Q anion exchange column, SP cation exchange column and Superdex 200 gel filtration column. PNWSP was assessed for antioxidant activities in different assay systems, and the effect on cell proliferation of human breast cancer MCF7 cells was investigated.RESULTSSodium dodecyl sulfate–polyacrylamide gel electrophoresis and analytical ultracentrifugation analysis revealed the homogeneity of PNWSP with apparent molecular weight of ∼43 kDa, and the identification was confirmed by peptide mass fingerprint analysis. It showed potential antioxidant activities in scavenging free radicals, reducing power and chelating effect on Fe2+, and had a protective effect against DNA amage. Moreover, it inhibited the proliferation of MCF7 cells by inducing apoptosis, in which the change in cell cycle distribution and the loss of mitochondrial transmembrane potential were observed by flow cytometry.ConcluSIONSThe results showed that PNWSP could be a natural antioxidant and developed as a potential chemotherapeutic agent candidate against human breast cancer. © 2015 Society of Chemical Industry
Adaptive neural control for a class of stochastic nonlinear time‐delay systems with unknown dead zone using dynamic surface technique
Authors: Li Zifu , Li Tieshan , Feng Gang 
Published: April 2015

SummaryThis paper investigates the problem of adaptive control for a class of stochastic nonlinear time‐delay systems with unknown dead zone. A neural network‐based adaptive control scheme is developed by using the dynamic surface control (DSC) technique and the minimal learning parameters algorithm. The dynamic surface control technique, which can avoid the problem of ‘explosion of complexity’ inherent in the conventional backstepping design procedure, is first extended to the stochastic nonlinear time‐delay system with unknown dead zone. The unknown nonlinearities are approximated by the function approximation technique using the radial basis function neural network. For the purpose of reducing the numbers of parameters, which are updated online for each subsystem in the process of approximating the unknown functions, the minimal learning parameters algorithm is then introduced. Also, the adverse effects of unknown time‐delay are removed by using the appropriate Lyapunov–Krasovskii functionals. In addition, the proposed control scheme is systematically derived without requiring any information on the boundedness of the dead zone parameters and avoids the possible controller singularity problem in the approximation‐based adaptive control schemes with feedback linearization technique. It is shown that the proposed control approach can guarantee that all the signals of the closed‐loop system are bounded in probability, and the tracking errors can be made arbitrary small by choosing the suitable design parameters. Finally, a simulation example is provided to illustrate the performance of the proposed control scheme. Copyright © 2015 John Wiley & Sons, Ltd.
IER3 Promotes Expansion of Adipose Progenitor Cells in Response to Changes in Distinct Microenvironmental Effectors
Authors: Ravaud Christophe , Esteve David , Villageois Phi , Bouloumie Anne , Dani Christian , Ladoux Annie 
Published: April 2015

Abstract
Adipose tissue expansion is well-orchestrated to fulfill the energy demand. It results from adipocyte hypertrophy and hyperplasia due to adipose progenitor cell (APC) expansion and differentiation. Chronic low grade inflammation and hypoxia take place in obese adipose tissue microenvironment. Both of these events were shown to impact the APC pool by promoting increased self-renewal along with a decrease in the APC differentiation potential. However, no common target has been identified so far. Here we show that the immediate early response 3 gene (IER3) is preferentially expressed in APCs and is essential for APC proliferation and self-renewal. Experiments based on RNA interference revealed that impairing IER3 expression altered cell proliferation through ERK1/2 phosphorylation and clonogenicity. IER3 expression was induced by Activin A, which plays a crucial role in adipocyte differentiation as well as by a decrease in oxygen tension through HIF1-induced transcriptional activation. Interestingly, high levels of IER3 were detected in native APCs (CD34+/CD31− cells) isolated from obese patients and conditioned media from obese adipose tissue-macrophages stimulated its expression. Overall, these results indicate that IER3 is a key player in expanding the pool of APC while highlighting the role of distinct effectors found in an obese microenvironment in this process. Stem Cells 2015;33:2564–2573
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone
Authors: Azim Kasum , Hurtado-Chong Anahí , Fischer Bruno , Kumar Nitin , Zweifel Stefan , Taylor Verdon , Raineteau Olivier 
Published: April 2015

AbstractThroughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to probe heterogeneity of the postnatal SVZ, we microdissected its dorsal and lateral walls at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors (loss-of-function or ectopic gain-of-function in vivo) influenced NSC specification indicating that the fate of regionalized postnatal SVZ-NSCs can be readily modified. These findings reveal the pronounced transcriptional heterogeneity of the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Stem Cells 2015;33:2232–2242