bluuebunny/crossref_metadata_2025 huggingface dataset:
Microdeletion 1p35.2: A recognizable facial phenotype with developmental delay
Authors: Wilson Brian T. , Omer Murwan , Hellens Stephen W. , Zwolinski Simon A. , Yates Laura M. , Lynch Sally Ann
Published: April 2015

We describe two patients with microdeletion 1p35.2, intrauterine growth retardation, small stature, hypermetropia, hearing impairment and developmental delay. Both patients have long, myopathic facies, with fine eyebrows, small mouths and micrognathia. We postulate a role for the histone deacetylase HDAC1 in the facial phenotype and suggest that deletion of KPNA6 may prevent transmission of the 1p35.2 deletion from affected girls to any offspring through impaired zygotic genome activation. © 2015 Wiley Periodicals, Inc.
Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome
Authors: Garg Abhimanyu , Kircher Martin , del Campo Miguel , Amato R. Stephen , Agarwal Anil K. ,   University of Washington Center for Mendelian Genomics
Published: April 2015

Despite remarkable progress in identifying causal genes for many types of genetic lipodystrophies in the last decade, the molecular basis of many extremely rare lipodystrophy patients with distinctive phenotypes remains unclear. We conducted whole exome sequencing of the parents and probands from six pedigrees with neonatal onset of generalized loss of subcutaneous fat with additional distinctive phenotypic features and report de novo heterozygous null mutations, c.424C>T (p.Q142*) and c.479_480delTT (p.F160*), in CAV1 in a 7‐year‐old male and a 3‐year‐old female of European origin, respectively. Both the patients had generalized fat loss, thin mottled skin and progeroid features at birth. The male patient had cataracts requiring extraction at age 30 months and the female patient had pulmonary arterial hypertension. Dermal fibroblasts of the female patient revealed negligible CAV1 immunofluorescence staining compared to control but there were no differences in the number and morphology of caveolae upon electron microscopy examination. Based upon the similarities in the clinical features of these two patients, previous reports of CAV1 mutations in patients with lipodystrophies and pulmonary hypertension, and similar features seen in CAV1 null mice, we conclude that these variants are the most likely cause of one subtype of neonatal onset generalized lipodystrophy syndrome. © 2015 Wiley Periodicals, Inc.
Total Synthesis of Diterpenoid Steenkrotin A
Authors: Pan Saiyong , Xuan Jun , Gao Beiling , Zhu An , Ding Hanfeng
Published: April 2015

A concise and diastereoselective total synthesis of the diterpenoid (±)‐steenkrotin A is described for the first time. The strategy mainly features three key ring formations: 1) a rhodium‐catalyzed OH bond insertion followed by an intramolecular carbonyl‐ene reaction to build up the tetrahydrofuran subunit; 2) sequential SmI2‐mediated Ueno–Stork and ketyl–olefin cyclizations to construct the [5,7] spirobicyclic skeleton; and 3) an intramolecular aldol condensation/vinylogous retro‐aldol/aldol sequence to form the final six‐membered ring with inversion of the relative configuration at the C7 position.
Folding and Imaging of DNA Nanostructures in Anhydrous and Hydrated Deep‐Eutectic Solvents
Authors: Gállego Isaac , Grover Martha A. , Hud Nicholas V.
Published: April 2015

There is great interest in DNA nanotechnology, but its use has been limited to aqueous or substantially hydrated media. The first assembly of a DNA nanostructure in a water‐free solvent, namely a low‐volatility biocompatible deep‐eutectic solvent composed of a 4:1 mixture of glycerol and choline chloride (glycholine), is now described. Glycholine allows for the folding of a two‐dimensional DNA origami at 20 °C in six days, whereas in hydrated glycholine, folding is accelerated (≤3 h). Moreover, a three‐dimensional DNA origami and a DNA tail system can be folded in hydrated glycholine under isothermal conditions. Glycholine apparently reduces the kinetic traps encountered during folding in aqueous solvent. Furthermore, folded structures can be transferred between aqueous solvent and glycholine. It is anticipated that glycholine and similar solvents will allow for the creation of functional DNA structures of greater complexity by providing a milieu with tunable properties that can be optimized for a range of applications and nanostructures.
Dynamic Stability of Power Systems Using UPFC: Bat‐Inspired Search and Gravitational Search Algorithms
Authors: Vijay Kumar B. , Srikanth N. V.
Published: April 2015

In this paper, the bat‐inspired algorithm and the Gravitational Search Algorithm (GSA) based optimal location and capacity of UPFC are proposed to improve the dynamic stability of power systems. The novelty of the proposed method is in improved searching ability, random reduction and reduced complexity. Here, the GSA is used to optimize the location of the UPFC if a generator fault occurs. The GSA selects the maximum power loss line as the optimum location to place UPFC as per the objective function, since the generator fault violates the system equality and inequality constraints from the secure limit. From the UPFC control parameters, the minimum voltage deviation is optimized using the bat algorithm. The minimum voltage deviation has been used to find the optimum capacity of the UPFC. Then the optimum UPFC capacity is applied in the optimum location, which enhances the dynamic stability of the system. The proposed method is implemented in the MATLAB/Simulink platform and the performance is evaluated by means of comparison with the different techniques like GSA and bat‐inspired algorithm. The comparison results demonstrate the superiority of the proposed approach and confirm its potential to solve the problem.
Enhanced Shewanella biofilm promotes bioelectricity generation
Authors: Liu Ting , Yu Yang‐Yang , Deng Xiao‐Peng , Ng Chun Kiat , Cao Bin , Wang Jing‐Yuan , Rice Scott A. , Kjelleberg Staffan , Song Hao
Published: April 2015

Electroactive biofilms play essential roles in determining the power output of microbial fuel cells (MFCs). To engineer the electroacitve biofilm formation of Shewanella oneidensis MR‐1, a model exoelectrogen, we herein heterologously overexpressed a c‐di‐GMP biosynthesis gene ydeH in S. oneidensis MR‐1, constructing a mutant strain in which the expression of ydeH is under the control of IPTG‐inducible promoter, and a strain in which ydeH is under the control of a constitutive promoter. Such engineered Shewanella strains had significantly enhanced biofilm formation and bioelectricity generation. The MFCs inoculated with these engineered strains accomplished a maximum power density of 167.6 ± 3.6 mW/m2, which was ∼ 2.8 times of that achieved by the wild‐type MR‐1 (61.0 ± 1.9 mW/m2). In addition, the engineered strains in the bioelectrochemical system at poised potential of 0.2 V vs. saturated calomel electrode (SCE) generated a stable current density of 1100 mA/m2, ∼ 3.4 times of that by wild‐type MR‐1 (320 mA/m2). Biotechnol. Bioeng. 2015;112: 2051–2059. © 2015 Wiley Periodicals, Inc.
Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva
Authors: Begas Elias , Kouvaras Evangelos , Tsakalof Andreas K. , Bounitsi Maria , Asprodini Eftihia Konstadinos
Published: April 2015

CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C18 column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R2>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd.
Reverse‐phase HPLC method for the quantification of two antihyperglycemic glycolipids in Oplismenus burmannii
Authors: Verma Surjeet , Verma Ram Kishor , Sahoo Dibyaranjan , Srivastava Santosh Kumar
Published: April 2015

Glycolipids and sphingolipids are well known for their diverse biological activities like anticancer, anti‐inflammatory, antistress, anti‐HIV, hepatoprotective and antimicrobial. The present study deals with the activity‐guided isolation and characterization of two antihyperglycemic glycolipids, (2S)‐1,2‐di‐O‐octadecanoyl‐3‐O‐[α‐d‐galctopyranosyl‐(1′′ → 6′)‐O‐β‐d‐galactopyranosyl] glycerol (1) and 1‐O‐β‐d‐glucopyranosyl‐(2S,3S,4R,8E)‐2‐[(2R)‐2‐hydroxy‐tetracosanoylamino]‐2,3,4‐octadecanetriol‐8‐ene (2) from Oplismenus burmannii and the development of a simple and validated reverse‐phase HPLC analytical method for their quantification in the methanolic extracts of O. burmannii. The marker compounds 1 and 2 were isolated from the methanolic extract of O. burmannii and characterized on the basis of their spectroscopic data. Their antihyperglycemic potential was evaluated by determining their glucose uptake‐stimulating potential in L6‐GLUT4myc myotube cells. Finally, these analytes were separated on a Waters Spherisorb ODS 2 column with a binary gradient of methanol and water at a constant flow rate of 0.8 mL/min and detected using a photodiode array detector at 230 nm. The calibration curve was linear (r2 > 0.999) over 1.2 orders of magnitude with acceptable accuracy, reproducibility and recovery (98.16–100.50%). The limits of detection and quantification for 1 and 2 were 1.36, 4.11 and 1.11, 3.35 µg/mL respectively. The method is simple, accurate, precise and selective and may be routinely used for the quality control analysis of whole plant extract of O. burmannii for these two glycolipids. Copyright © 2015 John Wiley & Sons, Ltd.
MS Binding Assays for the Three Monoamine Transporters Using the Triple Reuptake Inhibitor (1R,3S)‐Indatraline as Native Marker
Authors: Grimm Stefanie H. , Höfner Georg , Wanner Klaus T.
Published: April 2015

We herein present label‐free, mass‐spectrometry‐based binding assays (MS Binding Assays) for the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT). Using this approach both enantiomers of the triple reuptake inhibitor indatraline as well as itscis‐configured diastereomer were investigated toward hDAT, hNET, and hSERT in saturation experiments. The dissociation rate constants for (1R,3S)‐indatraline binding at hDAT, hNET, and hSERT were determined in kinetic studies. These experiments revealed an allosteric effect of clomipramine on the dissociation of (1R,3S)‐indatraline from hSERT. Finally, a comprehensive set of known monoamine transport inhibitors and substrates was studied in competition experiments at hDAT, hNET, and hSERT, using (1R,3S)‐indatraline as nonlabeled marker. The results are in excellent agreement with those reported for radioligand binding assays. Therefore, the established MS Binding Assays are a promising alternative to the latter for the characterization of new monoamine reuptake inhibitors at DAT, NET, and SERT.
Compressively sampled magnetic resonance image reconstruction using separable surrogate functional method
Authors: Shah Jawad Ali , Qureshi Ijaz M. , Omer Hammad , Khaliq Amir A. , Deng Yiming
Published: April 2015

According to the theory of compressed sensing, magnetic resonance (MR) images can be well reconstructed from randomly sub‐Nyquist sampling of the k‐space data using a nonlinear recovery technique if certain conditions are satisfied. The sparse coefficients of the partial Fourier data can be estimated by minimizing the reconstruction cost function. Separable surrogate functional (SSF) method is one of the effective numerical techniques for minimizing mixed
convex optimization problems. This article presents a novel recovery technique for compressively sampled MR images that uses SSF method subject to the data consistency constraints. The experimental results show that the proposed recovery algorithm outperforms the projection onto convex sets and low resolution‐based reconstruction techniques in terms of artifact power, improved signal‐to‐noise ratio, and correlation for the same number of iterations. The results are validated using the phantom and original human head MR images taken from the magnetic resonance imaging scanner at St. Mary's Hospital, London. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 43A: 157–165, 2015.
Docetaxel, bevacizumab, and androgen deprivation therapy for biochemical disease recurrence after definitive local therapy for prostate cancer
Authors: McKay Rana R. , Gray Kathryn P. , Hayes Julia H. , Bubley Glenn J. , Rosenberg Jonathan E. , Hussain Arif , Kantoff Philip W. , Taplin Mary‐Ellen
Published: April 2015

BACKGROUND

Patients with biochemical disease recurrence (BCR) after definitive treatment for prostate cancer comprise a heterogeneous population for whom standard therapy options are lacking. The purpose of the current trial was to evaluate the feasibility, toxicity, and efficacy of early multimodality systemic therapy in men with BCR.

METHODS

Eligible patients had an increasing prostate‐specific antigen (PSA) level, a PSA doubling time ≤10 months, and no evidence of metastases after radical prostatectomy (RP) and/or radiotherapy (RT) for localized disease. Treatment consisted of docetaxel at a dose of 75 mg/m2 every 3 weeks for 4 cycles, bevacizumab at a dose of 15 mg/kg every 3 weeks for 8 cycles, and androgen deprivation therapy (ADT) for 18 months. The primary endpoint was the percentage of patients who were free from PSA progression 1 year after the completion of therapy.

RESULTS

A total of 41 patients were included in the analysis. At 1 year after the completion of ADT, 45% of patients (13 of 29 patients) and 29% of patients (5 of 17 patients) with a testosterone level ≥100 ng/dL and ≥240 ng/dL, respectively, had a PSA <0.2 ng/mL. The median follow‐up was 27.5 months (interquartile range, 21.8‐38.1 months). Eight patients (20%) were free from PSA progression, 19 patients (46%) did not reinitiate ADT, and 34 patients (83%) were free from metastasis. Sixteen patients (39%) experienced grade 3 and 5 patients (12%) experienced grade 4 toxicities (toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]).

CONCLUSIONS

Multimodality systemic therapy with docetaxel, bevacizumab, and ADT is feasible and produces PSA responses in men with BCR. Long‐term follow‐up is needed to determine the percentage of patients with a durable PSA response who are able to avoid having to reinitiate prostate cancer therapy. Cancer 2015;121:2603–2611. © 2015 American Cancer Society.
Physician's peer exposure and the adoption of a new cancer treatment modality
Authors: Pollack Craig Evan , Soulos Pamela R. , Gross Cary P.
Published: April 2015

BACKGROUND

New technologies, often with limited evidence to support their effectiveness, frequently diffuse into clinical practice and increase the costs of cancer care. The authors studied whether physician peer exposure was associated with the subsequent adoption of a new approach to adjuvant radiotherapy (brachytherapy) for the treatment of women with early‐stage breast cancer.

METHODS

A retrospective cohort study was performed using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data. Data from 2003 through 2004 were used to classify surgeons as early brachytherapy adopters and, among non‐early adopters, whether they shared patients with early adopters (peer exposure). Data from 2005 through 2006 were used to examine whether women were more likely to receive brachytherapy if their surgeons were exposed to early adopters.

RESULTS

Overall, the percentage of women receiving brachytherapy increased from 3.2% in 2003 through 2004 to 4.7% in 2005 through 2006. In this latter period, a total of 2087 patients were assigned to 328 non‐early adopting surgeons. In unadjusted analyses, patients whose surgeons were connected to early adopters during 2003 through 2004 were found to be significantly more likely to receive brachytherapy in 2005 through 2006 compared with those whose surgeons were not connected to early adopters (8.0% vs 4.1%; P = .003). In adjusted analyses, the predicted probability of receiving brachytherapy among patients whose surgeon did have an early‐adopting peer was 3.9% versus 1.0% among those whose surgeons did not have an early‐adopting peer (P = .03).

CONCLUSIONS

Exposure to peers who were early adopters of brachytherapy was found to be associated with a surgeon's subsequent uptake of brachytherapy. The results of the current study provide an example of a novel approach to examining the diffusion of innovation in cancer care. Cancer 2015;121:2799‐2807. © 2015 American Cancer Society
Non‐16/18 high‐risk HPV infection predicts disease persistence and progression in women with an initial interpretation of LSIL
Authors: Lyons Yasmin A. , Kamat Aparna A. , Zhou Haijun , Mody Dina R. , Schwartz Mary R. , Hobday Christopher , Ge Yimin
Published: April 2015

BACKGROUND

The current management strategy for women with low‐grade squamous intraepithelial lesions (LSILs) is inefficient and expensive because of the inability to identify patients at high risk for disease progression. The current study was designed to determine the genotypic patterns of human papillomavirus (HPV) associated with the persistence and progression of cervical lesions in women with an initial interpretation of LSIL.

METHODS

One hundred sixty‐seven women with LSIL on Papanicolaou tests collected between December 1, 2009 and March 30, 2011 were studied. HPV DNA was extracted from residual SurePath specimens, genotypes were determined with a DNA microarray containing 40 HPV genotype probes, and microarray data were confirmed by sequencing. Follow‐up Papanicolaou tests and/or biopsies were performed within a 20‐ to 46‐month period after the initial diagnosis.

RESULTS

Ninety‐seven of the 167 cases with follow‐up results were included in the study. Compared with the women with a regressed cervical lesion, those with a persistent cervical lesion (PCL) were significantly more commonly infected with high‐risk human papillomavirus (HR‐HPV) genotypes (P < .01) and particularly with non‐16/18 HR‐HPV genotypes (P < .05). The PCL group also had a significantly higher average number of HR‐HPV genotypes and non‐16/18 HPV genotypes per specimen (P < .01). Infection with HPV‐16/18 genotypes was not significantly associated with the persistence or progression of cervical lesions.

CONCLUSIONS

Infection with non‐16/18 HR‐HPV genotypes but not with HPV‐16/18 genotypes was a strong predictor of the persistence and progression of cervical disease upon follow‐up. Genotyping solely for HPV‐16/18 would miss the majority of patients with LSIL who progress to high‐grade squamous intraepithelial lesions. Pooled HR‐HPV tests provide a better predictive value than HPV‐16/18 genotyping alone in guiding the clinical management of patients with LSIL. Cancer (Cancer Cytopathol) 2015;123:435‐42. © 2015 American Cancer Society.
Eya‐six are necessary for survival of nephrogenic cord progenitors and inducing nephric duct development before ureteric bud formation
Authors: Xu Jinshu , Xu Pin‐Xian
Published: April 2015

Background: Specification of the metanephric mesenchyme is a central step of kidney development as this mesenchyme promotes nephric duct induction to form a ureteric bud near its caudal end. Before ureteric bud formation, the caudal nephric duct swells to form a pseudostratified epithelial domain that later emerges as the tip of the bud. However, the signals that promote the formation of the transient epithelial domain remain unclear. Here, we investigated the early roles of the mesenchymal factor Six family and its cofactor Eya on the initial induction of nephric duct development.

Results: The nephrogenic progenitor population is initially present but significantly reduced in mice lacking both Six1 and Six4 and undertakes an abnormal cell death pathway to be completely eliminated by ∼E10.5–E11.0, similar to that observed in Eya1‐/‐ embryos. Consequently, the nephric duct fails to be induced to undergo normal proliferation to pseudostratify and form the ureteric bud in Six1‐/‐;Six4‐/‐ or Eya1‐/‐ embryos.

Conclusions: Our data support a model where Eya‐Six may form a complex to regulate nephron progenitor cell development before metanephric specification and are critical mesenchymal factors for inducing nephric duct development. Developmental Dynamics 244:866–873, 2015. © 2015 Wiley Periodicals, Inc.
From experimental plots to experimental landscapes: topography, erosion and deposition in sub‐humid badlands from Structure‐from‐Motion photogrammetry
Authors: Smith Mark William , Vericat Damià
Published: April 2015

In the last decade advances in surveying technology have opened up the possibility of representing topography and monitoring surface changes over experimental plots (<10 m2) in high resolution (~103 points m‐1). Yet the representativeness of these small plots is limited. With ‘Structure‐from‐Motion’ (SfM) and ‘Multi‐View Stereo’ (MVS) techniques now becoming part of the geomorphologist's toolkit, there is potential to expand further the scale at which we characterise topography and monitor geomorphic change morphometrically. Moving beyond previous plot‐scale work using Terrestrial Laser Scanning (TLS) surveys, this paper validates robustly a number of SfM‐MVS surveys against total station and extensive TLS data at three nested scales: plots (<30 m2) within a small catchment (4710 m2) within an eroding marl badland landscape (~1 km2). SfM surveys from a number of platforms are evaluated based on: (i) topography; (ii) sub‐grid roughness; and (iii) change‐detection capabilities at an annual scale. Oblique ground‐based images can provide a high‐quality surface equivalent to TLS at the plot scale, but become unreliable over larger areas of complex terrain. Degradation of surface quality with range is observed clearly for SfM models derived from aerial imagery. Recently modelled ‘doming’ effects from the use of vertical imagery are proven empirically as a piloted gyrocopter survey at 50m altitude with convergent off‐nadir imagery provided higher quality data than an Unmanned Aerial Vehicle (UAV) flying at the same height and collecting vertical imagery. For soil erosion monitoring, SfM can provide data comparable with TLS only from small survey ranges (~5 m) and is best limited to survey ranges ~10–20 m. Synthesis of these results with existing validation studies shows a clear degradation of root‐mean squared error (RMSE) with survey range, with a median ratio between RMSE and survey range of 1:639, and highlights the effect of the validation method (e.g. point‐cloud or raster‐based) on the estimated quality. Copyright © 2015 John Wiley & Sons, Ltd.
Long-term effects of the antibacterial agent triclosan on marine periphyton communities
Authors: Eriksson K. Martin , Johansson C. Henrik , Fihlman Viktor , Grehn Alexander , Sanli Kemal , Andersson Mats X. , Blanck Hans , Arrhenius Åsa , Sircar Triranta , Backhaus Thomas
Published: April 2015

Triclosan is a widely used antibacterial agent that has become a ubiquitous contaminant in freshwater, estuary, and marine environments. Concerns about potential adverse effects of triclosan have been described in several recent risk assessments. Its effects on freshwater microbial communities have been well studied, but studies addressing effects on marine microbial communities are scarce. In the present study, the authors describe short- and long-term effects of triclosan on marine periphyton (microbial biofilm) communities. Short-term effects on photosynthesis were estimated after 60 min to 210 min of exposure. Long-term effects on photosynthesis, chlorophyll a fluorescence, pigment content, community tolerance, and bacterial carbon utilization were studied after exposing periphyton for 17 d in flow-through microcosms to 0.316 nM to 10 000 nM triclosan. Results from the short-term studies show that triclosan is toxic to periphyton photosynthesis. Half maximal effective concentration (EC50) values of 1080 nM and 3000 nM were estimated using 14CO2-incorporation and pulse amplitude modulation (PAM) fluorescence measurements, respectively. After long-term triclosan exposure in flow-through microcosms, photosynthesis estimated using PAM fluorometry was not inhibited by triclosan concentrations up to 1000 nM but instead increased with increasing triclosan concentration. Similarly, at exposure concentrations of 31.6 nM and higher, triclosan caused an increase in photosynthetic pigments. At 316 nM triclosan, the pigment amounts were increased by a factor of 1.4 to 1.9 compared with the control level. Pollution-induced community tolerance was observed for algae and cyanobacteria at 100 nM triclosan and higher. Despite the widespread use of triclosan as an antibacterial agent, the compound did not have any effects on bacterial carbon utilization after long-term exposure. Environ Toxicol Chem 2015;34:2067–2077. © 2015 SETAC
Transfer model of lead in soil–carrot (Daucus carota L.) system and food safety thresholds in soil
Authors: Ding Changfeng , Li Xiaogang , Zhang Taolin , Wang Xingxiang
Published: April 2015

Reliable empirical models describing lead (Pb) transfer in soil–plant systems are needed to improve soil environmental quality standards. A greenhouse experiment was conducted to develop soil–plant transfer models to predict Pb concentrations in carrot (Daucus carota L.). Soil thresholds for food safety were then derived inversely using the prediction model in view of the maximum allowable limit for Pb in food. The 2 most important soil properties that influenced carrot Pb uptake factor (ratio of Pb concentration in carrot to that in soil) were soil pH and cation exchange capacity (CEC), as revealed by path analysis. Stepwise multiple linear regression models were based on soil properties and the pseudo total (aqua regia) or extractable (0.01 M CaCl2 and 0.005 M diethylenetriamine pentaacetic acid) soil Pb concentrations. Carrot Pb contents were best explained by the pseudo total soil Pb concentrations in combination with soil pH and CEC, with the percentage of variation explained being up to 93%. The derived soil thresholds based on added Pb (total soil Pb with the geogenic background part subtracted) have the advantage of better applicability to soils with high natural background Pb levels. Validation of the thresholds against data from field trials and literature studies indicated that the proposed thresholds are reasonable and reliable. Environ Toxicol Chem 2015;34:2078–2086. © 2015 SETAC
Large eddy simulation of incompressible free round jet with discontinuous Galerkin method
Authors: Marek M. , Tyliszczak A. , Bogusławski A.
Published: April 2015

In the paper, discontinuous Galerkin method is applied to simulation of incompressible free round turbulent jet using large eddy simulation with eddy viscosity approach. The solution algorithm is based on the classical projection method, but instead of the solution of the Poisson equation, a parabolic equation is advanced in pseudo‐time, which provides the pressure field ensuring the proper pressure–velocity coupling. For time and pseudo‐time integration, explicit Runge–Kutta method is employed. The computational meshes consist of hexahedral elements with flat faces. Within a given finite element, all flow variables are expressed with modal expansions of the same order (including velocity and pressure). Discretisation of the viscous terms in the Navier–Stokes equations and Laplacian in the Poisson equation is stabilised with mixed finite element approach. The correctness of the solution algorithm is verified in a commonly used test case of laminar flow in 3D lid‐driven cavity. The results of computations of the free jet are compared with experimental and numerical reference data, the latter obtained from the high‐order pseudospectral code. The statistics of centerline flow velocity – mean velocity and its fluctuations – show satisfactory agreement with the reference data. Copyright © 2015 John Wiley & Sons, Ltd.
Aberrant extracranial internal carotid arteries: New insights, implications, and demand for a clinical grading system
Authors: Pfeiffer Jens , Becker Christoph , Ridder Gerd J.
Published: April 2015

abstract

Background

Aberrant internal carotid arteries (ICAs) are not rare anatomic variations. The purpose of this study was for us to highlight their relevance and underline the need for a clinical grading system in addition to the currently used anatomic classification.

Methods

This systematic quality assessment study over 7 years includes 125 adults with 231 aberrant ICAs. Digital imaging datasets were analyzed and ICAs classified according to the anatomic classification in tortuosity, kinking, and coiling. Risk potential for ICA injury was estimated from the vessel's relation to the pharynx and neck.

Results

The analysis revealed a high frequency of medial and lateral ICA aberrations that seem surgically relevant, but the risk potential for injury was not reflected by the anatomic classification. Our previously proposed clinical grading system was reviewed and updated.

Conclusion

Aberrant ICAs are underestimated anatomic variations with high clinical impact for transoral and transcervical interventions. The introduced clinicoradiologic grading system could be of major benefit. © 2015 Wiley Periodicals, Inc. Head Neck 38: E687–E693, 2016
Endothelial growth factor receptor inhibitors in recurrent metastatic cancer of the head and neck
Authors: Misiukiewicz Krzysztof , Dang Rajan P. , Parides Michael , Camille Nadia , Uczkowski Helen , Sarlis Nicholas J. , Posner Marshall
Published: April 2015

Targeted therapy has become an important new class of therapeutic agents used in squamous cell carcinoma of the head and neck (SCCHN). Among them epidermal growth factor receptor (EGFR) inhibitors have been studied the most. Today, two classes of EGFR inhibitors are routinely used in the clinic; anti‐EGFR monoclonal antibodies and small‐molecule inhibitors of the EGFR tyrosine kinase activity. These agents have been used clinically in the recurrent metastatic (R/M) settings but only cetuximab has reached a regulatory approval. Current research is focused on innovative compound design, predictive biomarker discovery, and combination strategies in order to overcome resistance. Efforts should also be focused on endpoints other than overall survival, which is the current gold standard, such as surrogate endpoints. This article summarizes the clinical evidence of the anticancer activity of EGFR inhibitors in patients with R/M SCCHN, and analyzes the current, controversial clinical issues with respect to their interpretation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2221–E2228, 2016
Improved survival of older patients with multiple myeloma in the era of novel agents
Authors: Mey Ulrich J. M. , Leitner Christoph , Driessen Christoph , Cathomas Richard , Klingbiel Dirk , Hitz Felicitas
Published: April 2015

Multiple myeloma (MM) is the most common hematologic malignancy in Europe. Although remaining an incurable disease, substantial progress has been made within the last two decades. However, until recently, improvement in overall survival (OS) was only documented in younger, transplant‐eligible patients. In this analysis, we retrospectively investigated the outcome of older patients with newly diagnosed MM in an unselected patient population with a special focus on the use of novel agents in a routine care community‐based, non‐university setting. A total of 107 patients older than 65 years of age or patients aged 60–65 years with relevant comorbidities precluding the use of autologous stem cell transplantation diagnosed with MM between 2000 and 2011 at the two largest non‐university hospitals of Eastern Switzerland were analyzed. Patients were grouped into two six‐year periods by date of initial diagnosis, 2000–2005 and 2006–2011. The median follow‐up was 6.9 (range of 2.1 to 9.4) years. The median OS for the entire cohort was 3.0 years (95% confidence interval, 2.4–4.4). The median OS was significantly longer for patients in the 2006–2011 group (4.3 years) compared with the 2000–2005 group (2.6 years, p = 0.04). The 5‐year estimated OS improved from 26% to 38%; 1‐year survival was similar in both groups (86% in the 2000–2005 group and 84% in the 2006–2011 group respectively). The use of novel agents showed a statistically significant correlation with OS, whereas the impact of age was only of borderline significance. In conclusion, we demonstrate improved OS outcomes in an unselected population of older patients with MM during the last decade. This improvement is associated with an increased use of novel agents for the treatment of transplant‐ineligible MM patients in daily clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.
Cannabidiol stimulates Aml‐1a‐dependent glial differentiation and inhibits glioma stem‐like cells proliferation by inducing autophagy in a TRPV2‐dependent manner
Authors: Nabissi Massimo , Morelli Maria Beatrice , Amantini Consuelo , Liberati Sonia , Santoni Matteo , Ricci‐Vitiani Lucia , Pallini Roberto , Santoni Giorgio
Published: April 2015

Glioma stem‐like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug‐induced differentiation is considered as a promising approach to eradicate this tumor‐driving cell population. Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating transient receptor potential vanilloid‐2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability. Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death. Acute myeloid leukemia (Aml‐1) transcription factors play a pivotal role in GBM proliferation and differentiation and it is known that Aml‐1 control the expression of several nociceptive receptors. So, we evaluated the expression levels of Aml‐1 spliced variants (Aml‐1a, b and c) in GSCs and during their differentiation. We found that Aml‐1a is upregulated during GSCs differentiation, and its downregulation restores a stem cell phenotype in differentiated GSCs. Since it was demonstrated that CBD induces also TRPV2 expression and that TRPV2 is involved in GSCs differentiation, we evaluated if Aml‐1a interacted directly with TRPV2 promoters. Herein, we found that Aml‐1a binds TRPV2 promoters and that Aml‐1a expression is upregulated by CBD treatment, in a TRPV2 and PI3K/AKT dependent manner. Altogether, these results support a novel mechanism by which CBD inducing TRPV2‐dependent autophagic process stimulates Aml‐1a‐dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.
in vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue‐derived progenitor cells
Authors: Castells‐Sala Cristina , Martínez‐Ramos Cristina , Vallés‐Lluch Ana , Monleón Pradas Manuel , Semino Carlos
Published: April 2015

Myocardial tissue lacks the ability to regenerate itself significantly following a myocardial infarction. Thus, new strategies that could compensate this lack are of high interest. Cardiac tissue engineering (CTE) strategies are a relatively new approach that aims to compensate the tissue loss using combination of biomaterials, cells and bioactive molecules. The goal of the present study was to evaluate cell survival and growth, seeding capacity and cellular phenotype maintenance of subcutaneous adipose tissue‐derived progenitor cells in a new synthetic biomaterial scaffold platform. Specifically, here we tested the effect of the RAD16‐I peptide gel in microporous poly(ethyl acrylate) polymers using two‐dimensional PEA films as controls. Results showed optimal cell adhesion efficiency and growth in the polymers coated with the self‐assembling peptide RAD16‐I. Importantly, subATDPCs seeded into microporous PEA scaffolds coated with RAD16‐I maintained its phenotype and were able to migrate outwards the bioactive patch, hopefully toward the infarcted area once implanted. These data suggest that this bioimplant (scaffold/RAD16‐I/cells) can be suitable for further in vivo implantation with the aim to improve the function of affected tissue after myocardial infarction. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3419–3430, 2015.
Parthenolide reduces empty lacunae and osteoclastic bone surface resorption induced by polyethylene particles in a murine calvarial model of peri‐implant osteolysis
Authors: Zawawi Muhamad S. F. , Marino Victor , Perilli Egon , Cantley Melissa D. , Xu Jiake , Purdue P. Edward , Dharmapatni Anak A. S. S. K. , Haynes David R. , Crotti Tania N.
Published: April 2015

The study aimed to determine the effects of parthenolide (PAR) on bone volume (BV) and bone surface resorption as assessed by live‐animal microcomputed tomography (μCT) and possible osteocyte death as indicated by empty lacunae histologically in polyethylene (PE) particle‐induced calvarial osteolysis in mice. Baseline μCT scans were conducted 7 days preimplantation of 2 × 108 PE particles/mL over the calvariae (day 0). PAR at 1 mg/kg/day was subcutaneously injected on days 0, 4, 7, and 10. At day 14, BV and surface resorption was analyzed with μCT. Calvarial tissue was processed for histomorphometric osteocyte evaluation. Serum was analyzed for type‐1 carboxy‐terminal collagen crosslinks (CTX‐1) and osteoclast associated receptor (OSCAR) levels by ELISA. PE significantly decreased BV (p = 0.0368), increased surface bone resorption area (p = 0.0022), and increased the percentage of empty lacunae (p = 0.0043). Interestingly, PAR significantly reduced the resorption surface area (p = 0.0022) and the percentage of empty osteocyte lacunae (p = 0.0087) in the PE‐calvariae, but it did not affect BV, serum CTX‐1 or OSCAR levels. The ability of PAR to inhibit PE‐induced surface bone erosion may better reflect the in vivo situation, where bone resorption occurs on the surface at the bone‐implant interface and may also be related to the role of osteocytes in this pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3572–3579, 2015.
The Balanced Scorecard and Twenty‐First‐Century Thoughts on Motivation
Authors: Albright Thomas L. , Burgess Christopher M. , Davis Stan
Published: April 2015

How can you motivate people to accomplish an organization's goals? Is a carrot‐and‐stick approach the only—or even the best—way? This article suggests an approach that is potentially more effective by focusing less on the traditional approach of rewards versus punishment, relying instead largely on intrinsic motivations to help bring about desired outcomes. These efforts are consistent with the balanced scorecard concepts of goal setting and rewards that have been widely adopted as performance measurement and strategic communication systems since the early 1990s. © 2015 Wiley Periodicals, Inc.
Melanoma Treatments: Advances and Mechanisms
Authors: Marzuka Alexander , Huang Laura , Theodosakis Nicholas , Bosenberg Marcus
Published: April 2015

Advances in the understanding of the molecular pathogenesis of melanoma and in cancer immunology have led to the rational design and recent clinical implementation of a variety of novel therapies for metastatic melanoma. BRAF and MEK inhibitors that target the MAPK pathway have high rates of clinical response in BRAF‐mutant melanoma. Therapies that modulate the immune response to melanoma, including monoclonal antibodies that interfere with pathways that inhibit T‐cell function, have been shown to be effective in melanoma. Lessons learned from these encouraging results are driving the development of new treatments for melanoma and other cancers. This review will focus on the science and clinical findings related to targeted therapies that inhibit BRAF or MEK as well as the immunotherapies that block the CTLA‐4 or PD‐1 pathways. Other experimental and combinatorial therapeutic approaches will also be discussed. J. Cell. Physiol. 9999: 2626–2633, 2015. © 2015 Wiley Periodicals, Inc.
Revised Japanese guidelines for the management of acute pancreatitis 2015: revised concepts and updated points
Authors: Isaji Shuji , Takada Tadahiro , Mayumi Toshihiro , Yoshida Masahiro , Wada Keita , Yokoe Masamichi , Itoi Takao , Gabata Toshifumi
Published: April 2015

Background

Taking together the recent dramatic changes of the revised Atlanta classification and evidence newly obtained such as the role of step‐up approach for necrotizing pancreatitis, the revision committee of the Japanese (JPN) Guidelines 2015 was prompted to perform an extensive revision of the guidelines.

Methods

The JPN Guidelines 2015 was compared to the former edition 2010, and revision concepts and major revision points were reviewed. We compared the JPN 2015 with the other two guidelines, International Association of Pancreatology (IAP)/American Pancreas Association (APA) 2013 and American College of Gastroenterology (ACG) 2013, in order to clarify the distinct points.

Results

The meta‐analysis team conducted a new meta‐analysis of four subjects that have been associated with conflicting results. It is apparent that the revised guidelines have been created more systematically and more objectively. As of antibiotics prophylaxis, its use in early phase (within 72 h of onset) for severe acute pancreatitis is recommended in JPN 2015 according to the results of original meta‐analysis, whereas the other two guidelines do not recommend its routine use. An approach and management of local complications in necrotizing pancreatitis including infected necrosis are almost similar in the three guidelines. JPN 2015 alone emphasizes the implementation of the pancreatitis bundles that specify the management and treatment within the first 48 h after the onset of severe acute pancreatitis.

Conclusion

The JPN Guidelines 2015 prove to be the highest quality in terms of systematic literature review conducting original analyses by the meta‐analysis team, determining the grading of recommendations and providing pancreatitis bundles.
The Synthesis and Biological Evaluation of N‐Substituted 1H‐Benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines
Authors: Jedinák Lukáš , Kryštof Vladimír , Cankař Petr
Published: April 2015

The synthesis of 1H‐benzimidazol‐2‐yl‐1H‐pyrazole‐3,5‐diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three‐step synthesis includes the Mitsunobu N‐alkylation of benzimidazole and subsequent one‐pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin‐dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin‐dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7.
Monolithic capillary columns based on pentaerythritol acrylates for molecular‐size‐based separations of synthetic polymers
Authors: Kurganov Alexander , Victorova Elena , Kanateva Anastasiia
Published: April 2015

Monolithic capillary columns based on pentaerythritol triacrylate and pentaerythritol tetraacrylate were synthesized using different compositions of polymerization mixtures and different polymerization conditions. The impact of porogen type and porogen/monomer ratio on the porosity of synthesized monoliths was investigated. Porogen type appears to be the main factor influencing the separating properties of the monolithic sorbent. Using optimal polymerization conditions (porogen type, porogen/monomer ratio, reaction temperature, time etc.) monoliths with a porous structure optimized for polymer separations can be obtained. The monolithic capillary columns containing porous sorbents with optimized porosity are capable of separating 10 to 12 polystyrene standards in one chromatographic run utilizing both size exclusion chromatography and hydrodynamic chromatography separation mechanisms.
Development of Clinical Dementia Rating Scale Cut‐off Scores for Patients With Parkinson's Disease
Authors: Wyman‐Chick Kathryn A. , Scott BJ
Published: April 2015

Background

The aim of this study was to explore validity of the Clinical Dementia Rating Scale (CDR) in measuring cognitive impairment among individuals with Parkinson's disease (PD). The scale was created for use in patients with Alzheimer's disease, and, to date, there have been no published studies examining whether this tool is appropriate for patients with PD.

Methods

The data were obtained from the National Alzheimer's Coordinating Center database and included 490 subjects diagnosed with PD, further categorized as having PD dementia (n = 151), mild cognitive impairment (n = 186), or normal cognition (n = 153) by a treating physician. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the CDR Scale Global Score as well as the Sum of Boxes Score using existing cut‐off scores. Finally, new cut‐off scores were calculated using sensitivity and specificity values derived using receiver operating characteristic curves.

Results

Sensitivity and specificity of the published Global Score cut‐off scores for patients with dementia were 0.34 and 0.10, respectively. The newly calculated cut‐off scores for patients with dementia yielded a sensitivity of 0.79 and a specificity of 0.96. The area under the curve was 0.92 (95% confidence interval = 0.90–0.95).

Conclusion

The CDR is a useful tool in identifying dementia in patients with PD when the cut‐off scores are adjusted.
Why Are Extraverts More Popular? Oral Fluency Mediates the Effect of Extraversion on Popularity in Middle Childhood
Authors: Ilmarinen Ville–Juhani , Vainikainen Mari–Pauliina , Verkasalo Markku , Lönnqvist Jan–Erik
Published: April 2015

In a sample of 7– to 8–year–old children (N = 760), we examined the associations between personality traits, oral fluency and sociometric popularity. Extending upon research conducted with older populations, we found parent ratings of extraversion at age 7 to predict popularity one year later. More importantly, we expected and found teacher–rated oral fluency to partially mediate the positive association between extraversion and popularity. This mediation effect was independent of psychometrically assessed working memory, academic skills and gender. Our results can be interpreted as suggesting that a Matthew effect, similar to the one proposed for early reading skills and cognitive ability, may be operating in the domain of social competence. Copyright © 2015 European Association of Personality Psychology