bluuebunny/crossref_metadata_2025 huggingface dataset:
The Noscapine Chronicle: A Pharmaco‐Historic Biography of the Opiate Alkaloid Family and its Clinical Applications
Authors: Rida Padmashree C. G. , LiVecche Dillon , Ogden Angela , Zhou Jun , Aneja Ritu
Published: July 2015

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable “Renaissance drug” worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino‐noscapine, 9‐nitronoscapine, 9‐bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.
Radar‐based cell tracking with fuzzy logic approach
Authors: Jung Sung‐Hwa , Lee GyuWon
Published: July 2015

This study presents a new algorithm Fuzzy logic Algorithm for Storm Tracking (FAST) for tracking convective cells in 3D Cartesian co‐ordinates. A fuzzy logic approach was applied to track cells with objectively determined membership functions (MFs) and weights that were derived from a large set of convective cell tracks (2326 pairs of convective cells). Three feature parameters (cell motion speed, area change ratio and axis transformation ratio) were selected by Bayesian information criterion and combined through fuzzy logic. FAST was evaluated with three skill scores using 2561 (2456) pairs of convective cells with (without) mergers and splits. The performance was tested in comparison with Thunderstorm Identification, Tracking, Analysis, and Nowcasting (TITAN) as a baseline method. For reference tracks without merger and split, the critical success index (CSI) of FAST reaches about 0.89. FAST shows better skill scores (CSI = 0.92 and 0.89 at speed limitations of 16.1 m s−1 and 25.0 m s−1, respectively) than those of TITAN (CSI = 0.89 and 0.82 at the same speed limitations) and is independent of the number of convective cells and the speed limitation. When mergers and splits are considered in the reference, the tracking performance of FAST (FASTMS) with a merger and split process is always better than that of TITAN (TITANMS) with a merger and split process and is independent of speed limitations. When FAST (=FASTnoMS) does not include a merger and split process, its tracking performance is better than that of TITANMS at speed limitation of > 20 m s−1.
The rs3737964 single‐nucleotide polymorphism of the chloride channel‐6 gene as a risk factor for coronary heart disease
Authors: Zhang Li , Zhang Tao , Xiang Zhengkai , Lu Shengqiang
Published: July 2015

The present study investigates the association of single‐nucleotide polymorphisms (SNPs) on the chloride channel‐6 (CLC‐6) gene with coronary heart disease (CHD) in China. We carried out a large case–control study among 1193 CHD patients and 1200 unrelated healthy control subjects. Information on the participants' health status was collected through the modified Inter‐heart questionnaire. Genomic DNA from peripheral blood samples was analyzed for the genotypes of rs3737964 and rs3737965 SNPs on the CLC‐6 gene using Taqman probe‐based quantitative real‐time PCR (qPCR). We compared the collected data between the case group and the control group by chi‐square test and t/nonparametric test. Furthermore, we performed logistic regression to evaluate factors associated with CHD. The frequency of TT genotypes in rs3737964 was significantly higher in CHD patients compared to the control group, with an odds ratio (OR) of 2.32 (95% confidence interval, CI: 1.17–4.06, P = 0.016). The association of CHD with TT genotype was even stronger in smoking population after adjusting for confounders (OR = 3.19, 95% CI: 1.04–9.79, P = 0.043). Multivariate logistic regression showed the CHD risk associated with TT genotype in rs3737964 was particularly among population who were more than 60 years old, smoking, and male (P = 0.023, 0.008 and 0.043, respectively). The present study has revealed that rs3737964 SNP of CLC‐6 was associated with CHD. In particular, subjects with TT genotype who were 60‐plus years old, with smoking habit or were male were more susceptible to CHD.
Effects of phenolic acid metabolites formed after chlorogenic acid consumption on retinal degeneration in vivo
Authors: Jang Holim , Choi Yongsoo , Ahn Hong Ryul , Jung Sang Hoon , Lee Chang Yong
Published: July 2015

Scope

Although ingestion of coffee and its constituent chlorogenic acid (CGA) protects the retina from oxidative stress, the bioaccessibility and bioavailability of coffee metabolites are not well understood. The aim of this study was to determine which coffee metabolites reach the retina and protect against retinal degeneration.

Methods and results

UPLC‐MS/MS was used to detect CGA and coffee metabolites in the rat eye. The methyl thiazolyl tetrazolium assay and double staining with Hoechst and propidium iodide showed that CGA, caffeic acid (CA), and dihydrocaffeic acid (DHCA) protect retinal ganglion cells from hypoxia‐induced damage. Western blots showed that treatment with coffee metabolites up‐regulated anti‐apoptotic proteins such as Bcl‐2 and Bcl‐XL and down‐regulated pro‐apoptotic proteins such as Bad, PARP, and cleaved caspase 3. Adult ICR mice were subjected to optic nerve crush‐induced retinal ganglion cell death with intravitreal pre‐treatment with coffee metabolites 1 day before and 1 h after the procedure. Retrograde FluorogoldTM labeling showed severe retinal ganglion cell loss after optic nerve crushing, and coffee metabolites significantly reduced damage to retinal ganglion cells.

Conclusion

CGA and coffee metabolites, especially, CA, and DHCA, reach the eye, where they can significantly reduce apoptosis induced by hypoxia and optic nerve crush stress, and thus prevent retinal degeneration.
Cor a 14, the allergenic 2S albumin from hazelnut, is highly thermostable and resistant to gastrointestinal digestion
Authors: Pfeifer Sabine , Bublin Merima , Dubiela Pawel , Hummel Karin , Wortmann Judith , Hofer Gerhard , Keller Walter , Radauer Christian , Hoffmann‐Sommergruber Karin
Published: July 2015

Scope

Allergens from nuts frequently induce severe allergic reactions in sensitive individuals. The aim of this study was to elucidate the physicochemical characteristics of natural Cor a 14, the 2S albumin from hazelnut.

Methods and results

Cor a 14 was purified from raw hazelnuts using a combination of precipitation and chromatographic techniques. The protein was analyzed using gel electrophoresis, MS, and far‐UV circular dichroism (CD) analyses. The immunoglobulin E (IgE) binding of native, heat‐treated, and in vitro digested Cor a 14 was studied. We identified two different Cor a 14 isoforms and showed microclipping at the C‐terminus. CD spectra at room temperature showed the typical characteristics of 2S albumins, and temperatures of more than 80°C were required to start unfolding of Cor a 14 demonstrating its high stability to heat treatment. In vitro digestion experiments revealed that Cor a 14 is resistant to proteolytic degradation. Native and heat‐treated protein was recognized by sera from hazelnut allergic patients. However, denaturation of the allergen led to significantly reduced IgE binding.

Conclusion

We identified two different isoforms of Cor a 14 displaying high stability under heating and gastric and duodenal conditions. Data from IgE‐binding experiments revealed the existence of both, linear and conformational epitopes.
O2‐sensitive MRI distinguishes brain tumor versus radiation necrosis in murine models
Authors: Beeman Scott C. , Shui Ying‐Bo , Perez‐Torres Carlos J. , Engelbach John A. , Ackerman Joseph J. H. , Garbow Joel R.
Published: July 2015

Purpose

The goal of this study was to quantify the relationship between the 1H longitudinal relaxation rate constant, R1, and oxygen (O2) concentration (relaxivity, r1) in tissue and to quantify O2‐driven changes in R1 (ΔR1) during a breathing gas challenge in normal brain, radiation‐induced lesions, and tumor lesions.

Methods

R1 data were collected in control‐state mice (n = 4) during three different breathing gas (and thus tissue O2) conditions. In parallel experiments, pO2 was measured in the thalamus of control‐state mice (n = 4) under the same breathing gas conditions using an O2‐sensitive microprobe. The relaxivity of tissue O2 was calculated using the R1 and pO2 data. R1 data were collected in control‐state (n = 4) mice, a glioma model (n = 7), and a radiation necrosis model (n = 6) during two breathing gas (thus tissue O2) conditions. R1 and ΔR1 were calculated for each cohort.

Results

O2 r1 in the brain was 9 × 10−4 ± 3 × 10−4 mm Hg−1· s−1 at 4.7T. R1 and ΔR1 measurements distinguished radiation necrosis from tumor (P< 0.03 and P< 0.01, respectively).

Conclusion

The relaxivity of O2 in the brain is determined. R1 and ΔR1 measurements differentiate tumor lesions from radiation necrosis lesions in the mouse models. These pathologies are difficult to distinguish by traditional imaging techniques; O2‐driven changes in R1 holds promise in this regard. Magn Reson Med 75:2442–2447, 2016. © 2015 Wiley Periodicals, Inc.
Three‐dimensional echo planar imaging with controlled aliasing: A sequence for high temporal resolution functional MRI
Authors: Narsude Mayur , Gallichan Daniel , van der Zwaag Wietske , Gruetter Rolf , Marques José P.
Published: July 2015

Purpose

In this work, we combine three‐dimensional echo planar imaging (3D‐EPI) with controlled aliasing to substantially increase temporal resolution in whole‐brain functional MRI (fMRI) while minimizing geometry‐factor (g‐factor) losses.

Theory and Methods

The study was performed on a 7 Tesla scanner equipped with a 32‐channel receive coil. The proposed 3D‐EPI‐CAIPI sequence was evaluated for: (i) image quality, compared with a conventionally undersampled parallel imaging acquisition; (ii) temporal resolution, the ability to sample and remove physiological signal fluctuations from the fMRI signal of interest and (iii) the ability to distinguish small changes in hemodynamic responses in an event‐related fMRI experiment.

Results

Whole‐brain fMRI data with a voxel size of 2 × 2 × 2 mm3 and temporal resolution of 371 ms could be acquired with acceptable image quality. Ten‐fold parallel imaging accelerated 3D‐EPI‐CAIPI data were shown to lower the maximum g‐factor losses up to 62% with respect to a 10‐fold accelerated 3D‐EPI dataset. FMRI with 400 ms temporal resolution allowed the detection of time‐to‐peak variations in functional responses due to multisensory facilitation in temporal, occipital and frontal cortices.

Conclusion

3D‐EPI‐CAIPI allows increased temporal resolution that enables better characterization of physiological noise, thus improving sensitivity to signal changes of interest. Furthermore, subtle changes in hemodynamic response dynamics can be studied in shorter scan times by avoiding the need for jittering. Magn Reson Med 75:2350–2361, 2016. © 2015 Wiley Periodicals, Inc.
Morphometric model for discrimination between glioblastoma multiforme and solitary metastasis using three‐dimensional shape analysis
Authors: Yang Guang , Jones Timothy L. , Howe Franklyn A. , Barrick Thomas R.
Published: July 2015

Purpose

Glioblastoma multiforme (GBM) and brain metastasis (MET) are the most common intra‐axial brain neoplasms in adults and often pose a diagnostic dilemma using standard clinical MRI. These tumor types require different oncological and surgical management, which subsequently influence prognosis and clinical outcome.

Methods

Here, we hypothesize that GBM and MET possess different three‐dimensional (3D) morphological attributes based on their physical characteristics. A 3D morphological analysis was applied on the tumor surface defined by our diffusion tensor imaging (DTI) segmentation technique. It segments the DTI data into clusters representing different isotropic and anisotropic water diffusion characteristics, from which a distinct surface boundary between healthy and pathological tissue was identified. Morphometric features of shape index and curvedness were then computed for each tumor surface and used to build a morphometric model of GBM and MET pathology with the goal of developing a tumor classification method based on shape characteristics.

Results

Our 3D morphometric method was applied on 48 untreated brain tumor patients. Cross‐validation resulted in a 95.8% accuracy classification with only two shape features needed and that can be objectively derived from quantitative imaging methods.

Conclusion

The proposed 3D morphometric analysis framework can be applied to distinguish GBMs from solitary METs. Magn Reson Med 75:2505–2516, 2016. © 2015 Wiley Periodicals, Inc.
Quadriceps mechano‐ and electromyographic time‐frequency responses during muscular contractions to volitional exhaustion
Authors: Croce Ronald , Craft Amber , Miller John , Chamberlin Kent , Filipovic David
Published: July 2015

Introduction: Surface electromyography (SEMG) and mechanomyography (SMMG) responses of the quadriceps during muscular contractions to exhaustion were computed and analyzed by analysis of variance and polynomial regression analyses. Methods: Participants performed maximum flexion–extension movements at 180°/s until volitional exhaustion, rested for 2 minutes, and then completed a second bout of movements until exhaustion. Torque and SEMG/SMMG median frequencies and amplitudes were examined at 9 points across repetitions completed. Results: (1) Torque decreased precipitously; (2) SEMG amplitude displayed an initial increase, then a steady decrease, and SMMG amplitude showed a continuous decrease; and (3) SEMG and SMMG median frequencies displayed a continual decrease over repetitions completed. Fractional polynomial and quadratic models explained the fatigue process with the highest precision. Conclusions: Changes in electrical and mechanical properties of the quadriceps during fatigue reflect alterations in neuromuscular activation strategies and/or muscle wisdom. SEMG frequency modeled muscle fatigue more effectively than amplitude, whereas SMMG frequency and amplitude were equally effective. Muscle Nerve 53: 452–463, 2016
Electrical impedance myography discriminates congenital muscular dystrophy from controls
Authors: Schwartz Daniel P. , Dastgir Jahannaz , Salman Anam , Lear Barbara , Bönnemann Carsten G. , Lehky Tanya J.
Published: July 2015

Introduction

Electrical impedance myography (EIM) is an emerging non‐invasive, highly reproducible electrophysiological technique that objectively characterizes muscle structure and composition by measuring bioimpedance. We assessed the ability of EIM ability to discriminate 2 forms of congenital muscular dystrophy (CMD), laminin α2 (LAMA2)–deficient CMD and collagen VI–deficient (COL6) CMD, from a group of healthy children. We also investigated correlations between subcutaneous fat thickness and EIM parameters.

Methods

Twenty‐eight children with LAMA2 CMD (n = 12) or COL6 (n = 16) CMD and 18 normal children underwent EIM testing.

Results

The EIM 50‐kHz phase was decreased in LAMA2 and COL6 CMD when compared with controls (P < 0.001). Reactance, however, was decreased in COL6 but not LAMA2 CMD compared with controls (P < 0.001).

Conclusions

Our findings suggest that EIM may be useful in discriminating CMD from controls and may serve as a useful biomarker to follow disease progression in clinical trials. Muscle Nerve 53: 402–406, 2016
Finite volume approach for finite strain consolidation
Authors: Singh Rakesh Pratap , Ojha Chandra Shekhar Prasad , Singh Mahendra
Published: July 2015

The paper presents the finite volume formulation and numerical solution of finite strain one‐dimensional consolidation equation. The equation used in this study utilises a nonlinear continuum representation of consolidation with varying compressibility and hydraulic conductivity and thus inherits the material and geometric nonlinearity. Time‐marching explicit scheme has been used to achieve transient solutions. The nonlinear terms have been evaluated with the known previous time step value of the independent variable, that is, void ratio. Three‐point quadratic interpolation function of Lagrangian family has been used to evaluate the face values at discrete control volumes. It has been shown that the numerical solution is stable and convergent for the general practical cases of consolidation. Performance of the numerical scheme has been evaluated by comparing the results with an analytical solution and with the piecewise piecewise‐linear finite difference numerical model. The approach seems to work well and offers excellent potential for simulating finite strain consolidation. Further, the parametric study has been performed on soft organic clays, and the influence of various parameters on the time ate consolidation characteristics of the soil is shown. Copyright © 2015 John Wiley & Sons, Ltd.
Multiscale insights into classical geomechanics problems
Authors: Guo Ning , Zhao Jidong
Published: July 2015

We pay a revisit to some classical geomechanics problems using a novel computational multiscale modelling approach. The multiscale approach employs a hierarchical coupling of the finite element method (FEM) and the discrete element method. It solves a boundary value problem at the continuum scale by FEM and derives the material point response from the discrete element method simulation attached to each Gauss point of the FEM mesh. The multiscale modelling framework not only helps successfully bypass phenomenological constitutive assumptions as required in conventional modelling approaches but also facilitates effective cross‐scale interpretation and understanding of soil behaviour. We examine the classical retaining wall and footing problems by this method and demonstrate that the simulating results can be well validated and verified by their analytical solutions. Furthermore, the study sheds novel multiscale insights into these classical problems and offers a new tool for geotechnical engineers to design and analyse geotechnical applications based directly upon particle‐level information of soils. Copyright © 2015 John Wiley & Sons, Ltd.
Investigation of highly efficient algorithms for solving linear equations in the discontinuous deformation analysis method
Authors: Fu Xiaodong , Sheng Qian , Zhang Yonghui , Chen Jian
Published: July 2015

Large‐scale engineering computing using the discontinuous deformation analysis (DDA) method is time‐consuming, which hinders the application of the DDA method. The simulation result of a typical numerical example indicates that the linear equation solver is a key factor that affects the efficiency of the DDA method. In this paper, highly efficient algorithms for solving linear equations are investigated, and two modifications of the DDA programme are presented. The first modification is a linear equation solver with high efficiency. The block Jacobi (BJ) iterative method and the block conjugate gradient with Jacobi pre‐processing (Jacobi‐PCG) iterative method are introduced, and the key operations are detailed, including the matrix‐vector product and the diagonal matrix inversion. Another modification consists of a parallel linear equation solver, which is separately constructed based on the multi‐thread and CPU‐GPU heterogeneous platforms with OpenMP and CUDA, respectively. The simulation results from several numerical examples using the modified DDA programme demonstrate that the Jacobi‐PCG is a better iterative method for large‐scale engineering computing and that adoptive parallel strategies can greatly enhance computational efficiency. Copyright © 2015 John Wiley & Sons, Ltd.
MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment
Authors: Gianolio Eliana , Arena Francesca , Di Gregorio Enza , Pagliarin Roberto , Delbianco Martina , Baio Gabriella , Aime Silvio
Published: July 2015

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn2+ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn2+ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn2+ ions, as the addition of Ca‐DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment.

On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1‐weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.
The Family Tribute in Charitable Bequest Giving
Authors: James Russell N.
Published: July 2015

The propensity for charitable bequest giving is much lower than for current charitable giving. Some nonexperimental evidence suggests that this difference may be due to the relatively greater importance of family benefit considerations in charitable bequest giving than in current charitable giving. To test this concept experimentally, the effects of a family–charity conflict reduction message (that is, a reminder of family connections to a cause and an opportunity to make a tribute gift) are measured for both current and bequest giving. For those with family connections to a cause, the message generated increased interest in charitable bequest giving but not in current charitable giving. This result provides experimental support for previous suggestions regarding the special role of family considerations in charitable bequest giving. Managers may profitably consider the use of tribute messages to encourage bequest, but not necessarily current, charitable giving. Such messages were effective at increasing bequest intentions for all organization types and demographic groups tested, especially where the tribute was in honor of an ascendant such as a mother, grandmother, grandfather, or uncle.
The repositioning of hospitalized patients with reduced mobility: a prospective study
Authors: Latimer Sharon , Chaboyer Wendy , Gillespie Brigid M.
Published: July 2015

Aim

To determine the frequency of patient repositioning across three consecutive nursing shifts (day, evening and night) and to identify predictors of repositioning frequency.

Background

Patient repositioning is a frequently implemented pressure injury prevention strategy. Yet, little is known about how often it should be implemented, or the frequency of movement among hospitalized patients with reduced mobility.

Design

An observational prospective study.

Methods

Chart audits were used to gather clinical and demographic data. Semi‐structured observations were conducted every 30 minutes for a continuous 24‐hour period. Observational data included the patient's body position, the frequency of repositioning, assistance require to reposition and the use of support surfaces.

Results

Patients were repositioned frequently during the day and evening and least at night time. Elevation of the head of the bed (1–45°) was the most frequently adopted position. The independent predictors of repositioning frequency were age and gender, with older patients and males repositioned less frequently.
Local and parallel finite element algorithms for the Steklov eigenvalue problem
Authors: Bi Hai , Li Zhengxia , Yang Yidu
Published: July 2015

Based on the work of Xu and Zhou [Math Comput 69 (2000) 881–909], we propose and analyze in this article local and parallel finite element algorithms for the Steklov eigenvalue problem. We also prove a local error estimate which is suitable for the case that the locally refined region contains singular points lying on the boundary of domain, which is an improvement of the existing results. Numerical experiments are reported finally to validate our theoretical analysis. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 32: 399–417, 2016
Effects of an antenatal dietary intervention on maternal anthropometric measures in pregnant women with obesity
Authors: Dodd Jodie M. , Kannieappan Lavern M. , Grivell Rosalie M. , Deussen Andrea R. , Moran Lisa J. , Yelland Lisa N. , Owens Julie A.
Published: July 2015

Objective

The effect of providing antenatal dietary and lifestyle advice on secondary measures of maternal anthropometry was evaluated and their correlation with both gestational weight gain and infant birth weight was assessed.

Methods

In a multicenter, randomized controlled trial, pregnant women with BMI of ≥25 kg/m2 received either Lifestyle Advice or Standard Care. Maternal anthropometric outcomes included arm circumference, biceps, triceps, and subscapular skinfold thickness measurements (SFTM), percentage body fat (BF), gestational weight gain, and infant birth weight. The intention to treat principles were utilized by the analyses.

Results

The measurements were obtained from 807 (74.7%) women in the Lifestyle Advice Group and 775 (72.3%) women in the Standard Care Group. There were no statistically significant differences identified between the treatment groups with regards to arm circumference, biceps, triceps, and subscapular SFTM, or percentage BF at 36‐week gestation. Maternal anthropometric measurements were not significantly correlated with either gestational weight gain or infant birth weight.

Conclusions

Among pregnant women with a BMI of ≥25 kg/m2, maternal SFTM were not modified by an antenatal dietary and lifestyle intervention. Furthermore, maternal SFTM correlate poorly with both gestational weight gain and infant birth weight.
Relationship between lifestyle behaviors and obesity in children ages 9–11: Results from a 12‐country study
Authors: Katzmarzyk Peter T. , Barreira Tiago V. , Broyles Stephanie T. , Champagne Catherine M. , Chaput Jean‐Philippe , Fogelholm Mikael , Hu Gang , Johnson William D. , Kuriyan Rebecca , Kurpad Anura , Lambert Estelle V. , Maher Carol , Maia Jose , Matsudo Victor , Olds Timothy , Onywera Vincent , Sarmiento Olga L. , Standage Martyn , Tremblay Mark S. , Tudor‐Locke Catrine , Zhao Pei , Church Timothy S. ,   for the ISCOLE Research Group
Published: July 2015

Objective

The aim was to assess associations between lifestyle behaviors and obesity in a multinational study of children from 12 countries representing a wide range of human development.

Methods

The sample included 6,025 children 9–11 years of age. Behavioral risk factors included nocturnal sleep duration, moderate to vigorous physical activity (MVPA), television viewing (TV time), and healthy and unhealthy diet pattern scores. Multilevel analyses were used to obtain odds ratios for obesity expressed per standard deviation of each behavioral risk factor.

Results

The odds ratios (95% confidence intervals) for obesity from multilevel, multivariable models were 0.79 (0.71–0.90) for nocturnal sleep duration, 0.52 (0.45–0.60) for MVPA, 1.15 (1.05–1.27) for TV time, 1.08 (0.96–1.20) for healthy diet score, and 0.93 (0.83–1.04) for unhealthy diet score in boys and 0.71 (0.63–0.80) for nocturnal sleep duration, 0.43 (0.35–0.53) for MVPA, 1.07 (0.96–1.19) for TV time, 1.05 (0.93–1.19) for healthy diet score, and 0.96 (0.82–1.11) for unhealthy diet score in girls.

Conclusions

Behavioral risk factors are important correlates of obesity in children, particularly low MVPA, short sleep duration, and high TV viewing.
Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen signaling
Authors: Shearer Kirsty D. , Morrice Nicola , Henderson Claire , Reekie Jenny , Mcilroy George D. , McCaffery Peter J. , Delibegovic Mirela , Mody Nimesh
Published: July 2015

Objective

The synthetic retinoid fenretinide (FEN) inhibits adiposity in male mice fed a high‐fat diet (HFD) in association with alterations in retinoic acid (RA) signaling. Young female mice are protected from obesity via estrogen signaling. We, therefore, investigated whether FEN also influences adiposity in aged female mice differing in parity and whether such effects are mediated by retinoid and estrogen signaling.

Methods

Aged nulliparous and parous female mice were maintained on HFD ± FEN, and adiposity was assessed. Quantitative polymerase chain reaction was performed on white adipose tissue (WAT), liver, and 3T3‐L1 adipocytes treated with RA or FEN ± estrogen.

Results

Parous females were more obese than nulliparous mice independent of age. FEN‐HFD prevented the HFD‐induced increase in adiposity and leptin levels independently of parity. FEN‐HFD induced retinoid‐responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen‐responsive genes, but FEN‐HFD up‐regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA receptor‐mediated gene expression in 3T3‐L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo.

Conclusions

The prevention of adiposity by FEN in response to HFD in female mice seems to involve increased retinoid signaling in association with induction of local estrogen production and estrogen signaling in WAT.
The oncogenic potential of BK‐polyomavirus is linked to viral integration into the human genome
Authors: Kenan Daniel J , Mieczkowski Piotr A , Burger‐Calderon Raquel , Singh Harsharan K , Nickeleit Volker
Published: July 2015

It has been suggested that BK‐polyomavirus is linked to oncogenesis via high expression levels of large T‐antigen in some urothelial neoplasms arising following kidney transplantation. However, a causal association between BK‐polyomavirus, large T‐antigen expression and oncogenesis has never been demonstrated in humans. Here we describe an investigation using high‐throughput sequencing of tumour DNA obtained from an urothelial carcinoma arising in a renal allograft. We show that a novel BK‐polyomavirus strain, named CH‐1, is integrated into exon 26 of the myosin‐binding protein C1 gene (MYBPC1) on chromosome 12 in tumour cells but not in normal renal cells. Integration of the BK‐polyomavirus results in a number of discrete alterations in viral gene expression, including: (a) disruption of VP1 protein expression and robust expression of large T‐antigen; (b) preclusion of viral replication; and (c) deletions in the non‐coding control region (NCCR), with presumed alterations in promoter feedback loops. Viral integration disrupts one MYBPC1 gene copy and likely alters its expression. Circular episomal BK‐polyomavirus gene sequences are not found, and the renal allograft shows no productive polyomavirus infection or polyomavirus nephropathy. These findings support the hypothesis that integration of polyomaviruses is essential to tumourigenesis. It is likely that dysregulation of large T‐antigen, with persistent over‐expression in non‐lytic cells, promotes cell growth, genetic instability and neoplastic transformation. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
In Brief: Picturing the complex world of chromatin remodelling families
Authors: Witkowski Leora , Foulkes William D
Published: July 2015

Over the past decade, chromatin remodelling emerged as one of the most important causes of both abnormal development and cancer. Although much has been written about one or another of the complexes, no recent concise summary of the chromatin remodelling families as a whole is available. In this short review, we introduce the family members, briefly summarize their role in developmental abnormalities and neoplasia, and outline the different ways in which these families remodel chromatin. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis
Authors: Brown Gordon T , Murray Graeme I
Published: July 2015

The purpose of this review is to highlight the recent mechanistic developments elucidating the role of matrix metalloproteinases (MMPs) in tumour invasion and metastasis. The ability of tumour cells to invade, migrate, and subsequently metastasize is a fundamental characteristic of cancer. Tumour invasion and metastasis are increasingly being characterized by the dynamic relationship between cancer cells and their microenvironment and developing a greater understanding of these basic pathological mechanisms is crucial. While MMPs have been strongly implicated in these processes as a result of extensive circumstantial evidence – for example, increased expression of individual MMPs in tumours and association of specific MMPs with prognosis – the underpinning mechanisms are only now being elucidated. Recent studies are now providing a mechanistic basis, highlighting and reinforcing the catalytic and non‐catalytic roles of specific MMPs as key players in tumour invasion and metastasis. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients
Authors: Burkin Dean J , Fontelonga Tatiana M
Published: July 2015

Mesothelioma is a disease of pleural cells lining the lungs which is often caused by exposure to asbestos. The molecular mechanism(s) that regulate the transformation of pleural mesothelioma cells to a migratory and malignant phenotype are unclear. In recent work published in this journal, Laszlo et al performed a set of elegant experiments to identify a key molecular mechanism that may explain the aggressive nature of this disease. Using patient‐derived mesothelioma cells with high versus low migratory activity, the authors conducted a genome‐wide expression analysis. They identified a significant reduction in ITGA7 expression only in highly migratory malignant pleural mesothelioma cells and showed that loss of ITGA7 expression was associated with methylation of the promoter. Forced expression of integrin α7 reversed the migratory phenotype of these cells. Finally, the authors identified a strong correlation between ITGA7 expression and patient survival. Together, these results identify expression of integrin α7 as a molecular mechanism for the aggressive migratory transformation of mesothelioma and identify a potentially novel diagnostic and therapeutic target. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Concomitant expression of far upstream element (FUSE) binding protein (FBP) interacting repressor (FIR) and its splice variants induce migration and invasion of non‐small cell lung cancer (NSCLC) cells
Authors: Müller Benedikt , Bovet Michael , Yin Yi , Stichel Damian , Malz Mona , González‐Vallinas Margarita , Middleton Alistair , Ehemann Volker , Schmitt Jennifer , Muley Thomas , Meister Michael , Herpel Esther , Singer Stephan , Warth Arne , Schirmacher Peter , Drasdo Dirk , Matthäus Franziska , Breuhahn Kai
Published: July 2015

Transcription factors integrate a variety of oncogenic input information, facilitate tumour growth and cell dissemination, and therefore represent promising therapeutic target structures. Because over‐expression of DNA‐interacting far upstream element binding protein (FBP) supports non‐small cell lung cancer (NSCLC) migration, we asked whether its repressor, FBP‐interacting repressor (FIR) is functionally inactivated and how FIR might affect NSCLC cell biology. Different FIR splice variants were highly expressed in the majority of NSCLCs, with the highest levels in tumours carrying genomic gains of chromosome 8q24.3, which contained the FIR gene locus. Nuclear FIR expression was significantly enriched at the invasion front of primary NSCLCs, but this did not correlate with tumour cell proliferation. FIR accumulation was associated with worse patient survival and tumour recurrence; in addition, FIR over‐expression significantly correlated with lymph node metastasis in squamous cell carcinomas (SCCs). In vitro, we applied newly developed methods and modelling approaches for the quantitative and time‐resolved description of the pro‐migratory and pro‐invasive capacities of SCC cells. siRNA‐mediated silencing of all FIR variants significantly reduced the speed and directional movement of tumour cells in all phases of migration. Furthermore, sprouting efficiency and single cell invasiveness were diminished following FIR inhibition. Interestingly, the silencing of FIR isoforms lacking exon 2 (FIRΔexon2) alone was sufficient to reduce lateral migration and invasion. In summary, by using scale‐spanning data derived from primary human tissues, quantitative cellular analyses and mathematical modelling, we have demonstrated that concomitant over‐expression of FIR and its splice variants drives NSCLC migration and dissemination. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Diagnostic and therapeutic challenges in a child with complete Interferon‐γ Receptor 1 deficiency
Authors: Olbrich Peter , Martínez‐Saavedra Maria Teresa , Perez‐Hurtado José Maria , Sanchez Cristina , Sanchez Berta , Deswarte Caroline , Obando Ignacio , Casanova Jean‐Laurent , Speckmann Carsten , Bustamante Jacinta , Rodriguez‐Gallego Carlos , Neth Olaf
Published: July 2015

Autosomal recessive (AR) complete Interferon‐γ Receptor1 (IFN‐γR1) deficiency is a rare variant of Mendelian susceptibility to mycobacterial disease (MSMD). Although hematopoietic stem cell transplantation (HSCT) remains the only curative treatment, outcomes are heterogeneous; delayed engraftment and/or graft rejection being commonly observed. This case report and literature review expands the knowledge about this rare but potentially fatal pathology, providing details regarding diagnosis, antimicrobial treatment, transplant performance, and outcome that may help to guide physicians caring for patients with AR complete IFN‐γR1 or IFN‐γR2 deficiency. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
Biodegradable composite scaffolds of poly(lactic‐co‐glycolic acid) 85:15 and nano‐hydroxyapatite with acidic microclimate controlling additive
Authors: Ginjupalli Kishore , Averineni Ranjith Kumar , Shavi Gopal Venkat , Armugam Karthik , Bhat Mahalinga , N Udupa , Meka Srinivasa Reddy
Published: July 2015

The aim of this study was to prepare and characterize biodegradable scaffolds of poly(lactic‐co‐glycolic acid) (PLGA 85:15) and nano‐hydroxyapatite (HA) containing magnesium carbonate (MC) as acidic microclimate controlling additive. Porous and nonporous scaffolds of PLGA 85:15 and nano‐HA containing MC were prepared by solvent casting and particulate leaching method. Scaffolds were degraded at pH 7.4 phosphate buffer for 90 days. At regular intervals, pH of the degradation medium, release of degradation products, mass loss, water sorption, and tensile strength were measured. The results showed that the pH of the degradation medium significantly decreased with control specimens, whereas the scaffolds with MC did not show significant changes. In addition, acidic monomer release from the scaffolds with MC was found to be less, whereas the water sorption was found to be significantly higher. The tensile strength of the scaffold was found to be dependent on the concentration of HA and porosity. These results indicate that incorporation of MC to PLGA 85:15 scaffolds reduces the acidic microclimate with changes in mass loss, water sorption, and strength properties. POLYM. COMPOS., 38:1175–1182, 2017. © 2015 Society of Plastics Engineers
Aggregate analysis of regulatory authority assessors' comments to improve the quality of periodic safety update reports
Authors: Jullian Sandra , Jaskiewicz Lukasz , Pfannkuche Hans‐Jürgen , Parker Jeremy , Lalande‐Luesink Isabelle , Lewis David J. , Close Philippe
Published: July 2015

Purpose

Marketing authorization holders (MAHs) are expected to provide high‐quality periodic safety update reports (PSURs) on their pharmaceutical products to health authorities (HAs). We present a novel instrument aiming at improving quality of PSURs based on standardized analysis of PSUR assessment reports (ARs) received from the European Union HAs across products and therapeutic areas.

Methods

All HA comments were classified into one of three categories: “Request for regulatory actions,” “Request for medical and scientific information,” or “Data deficiencies.” The comments were graded according to their impact on patients' safety, the drug's benefit‐risk profile, and the MAH's pharmacovigilance system.

Results

A total of 476 comments were identified through the analysis of 63 PSUR HA ARs received in 2013 and 2014; 47 (10%) were classified as “Requests for regulatory actions,” 309 (65%) as “Requests for medical and scientific information,” and 118 (25%) comments were related to “Data deficiencies.” The most frequent comments were requests for labeling changes (35 HA comments in 19 ARs). The aggregate analysis revealed commonly raised issues and prompted changes of the MAH's procedures related to the preparation of PSURs.

Conclusion

The authors believe that this novel instrument based on the evaluation of PSUR HA ARs serves as a valuable mechanism to enhance the quality of PSURs and decisions about optimization of the use of the products and, therefore, contributes to improve further the MAH's pharmacovigilance system and patient safety. Copyright © 2015 John Wiley & Sons, Ltd.
Stable CdTe thin film solar cells with a MoOx back‐contact buffer layer
Authors: Yang Ruilong , Wang Dezhao , Jeng Mingjer , Ho Kaiming , Wang Deliang
Published: July 2015

MoOx thin films were employed as a buffer layer in the back contact of CdTe solar cells. A monograined CdS layer was employed as the window layer to reduce light absorption. The insertion of a MoOx buffer layer in the back contact greatly reduced the Schottky barrier leading to increased fill factor and open‐circuit voltage. A CdTe solar cell, with an efficiency as high as 14.2%, was fabricated. The use of a MoOx buffer layer made it possible to fabricate high‐efficient CdTe solar cell with much less Cu in the back contact, thus greatly enhancing the cell stability. Copyright © 2015 John Wiley & Sons, Ltd.
Distinct serum proteome profiles associated with collagen‐induced arthritis and complete Freund's adjuvant‐induced inflammation in CD38−/− mice: The discriminative power of protein species or proteoforms
Authors: Rosal‐Vela Antonio , García‐Rodríguez Sonia , Postigo Jorge , Iglesias Marcos , Longobardo Victoria , Lario Antonio , Merino Jesús , Merino Ramón , Zubiaur Mercedes , Sancho Jaime
Published: July 2015

Collagen‐type‐II‐induced arthritis (CIA) is an autoimmune disease, which involves a complex host systemic response including inflammatory and autoimmune reactions. CIA is milder in CD38−/− than in wild‐type (WT) mice. ProteoMiner‐equalized serum samples were subjected to 2D‐DiGE and MS‐MALDI‐TOF/TOF analyses to identify proteins that changed in their relative abundances in CD38−/− versus WT mice either with arthritis (CIA+), with no arthritis (CIA−), or with inflammation (complete Freund's adjuvant (CFA)‐treated mice). Multivariate analyses revealed that a multiprotein signature (n = 28) was able to discriminate CIA+ from CIA− mice, and WT from CD38−/− mice within each condition. Likewise, a distinct multiprotein signature (n = 16) was identified which differentiated CIA+ CD38−/− mice from CIA+ WT mice, and lastly, a third multiprotein signature (n = 18) indicated that CD38−/− and WT mice could be segregated in response to CFA treatment. Further analyses showed that the discriminative power to distinguish these groups was reached at protein species level and not at the protein level. Hence, the need to identify and quantify proteins at protein species level to better correlate proteome changes with disease processes. It is crucial for plasma proteomics at the low‐abundance protein species level to apply the ProteoMiner enrichment. All MS data have been deposited in the ProteomeXchange with identifiers PXD001788, PXD001799 and PXD002071 (http://proteomecentral.proteomexchange.org/dataset/PXD001788, http://proteomecentral.proteomexchange.org/dataset/PXD001799 and http://proteomecentral.proteomexchange.org/dataset/PXD002071).
Project Decision Chain
Authors: Rolstadås Asbjørn , Pinto Jeffrey K. , Falster Peter , Venkataraman Ray
Published: July 2015

To add value to project performance and help obtain project success, a new framework for decision making in projects is defined. It introduces the project decision chain inspired by the supply chain thinking in the manufacturing sector and uses three types of decisions: authorization, selection, and plan decision. A primitive decision element is defined where all the three decision types can be accommodated. Each task in the primitive element can in itself contain subtasks that in turn will comprise new primitive elements. The primitive elements are nested together in a project decision chain.
Versatile and controlled functionalization of polyferrocenylsilane‐b‐polyvinylsiloxane block copolymers using a N‐hydroxysuccinimidyl ester strategy
Authors: Boott Charlotte E. , Lunn David J. , Manners Ian
Published: July 2015

A general route for the N‐hydroxysuccinimidyl (NHS) ester functionalization of poly(ferrocenyldimethylsilane)‐b‐polyvinylsiloxane copolymers, which should be readily transferrable to other vinyl containing polymers, has been developed using a simple two step approach. Facile reaction of the NHS ester functionalized polymers with primary amines enables the incorporation of a range of functionalities previously inaccessible using standard thiol‐ene “click” reactions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 245–252