bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effect and drug‐resistance relief of paclitaxel and cisplatin caused by Co‐delivery using polymeric micelles
Authors: Li Jing , Li Zhihong , Li Minghe , Zhang Hong , Xie Zhigang 
Published: September 2014

ABSTRACTCombination therapy of paclitaxel (PTX) and cisplatin has been used to treat several cancers in clinic practice, but often causes serious systemic toxicity. Co‐delivery of PTX and cisplatin by means of polymeric micelles can reduce the systemic toxicity, but often needs two carrier polymers because of the solubility difference between them. Therefore, a strategy is developed to co‐deliver both PTX and cisplatin with only one carrier polymer by encapsulating PTX in the core of a polymeric micelle and cross‐linking the micelle with cisplatin. The PTX and Pt contents in the micellar formulation M(PTX/Pt) were 10 and 14 wt %, respectively. In vitro cytotoxicity of M(PTX/Pt) was evaluated via 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide assay in comparison with PTX and its micelle M(PTX), cisplatin and its micelle M(Pt), and PTX/cisplatin combination towards human hepatocarcinoma (SMMC‐7721) cells and chemoresistant SMMC‐7721(SMMC‐7721R) cells. The M(PTX/Pt) exhibited a high synergistic effect in the inhibition of cell growth and proliferation of both SMMC‐7721 and SMMC‐7721R cells and showed reasonable drug‐resistance relief. The synergistic effect and resistance relief were further supported or explained by intracellular uptake measurement of dye‐labeled micelles and by the confocal laser scanning microscopy observation of SMMC‐7721 and SMMC‐7721R cells treated with various formulations. Therefore, M(PTX/Pt) micelles were expected to find potential application in cancer chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41440.
Validation of RetroPath, a computer‐aided design tool for metabolic pathway engineering
Authors: Fehér Tamás , Planson Anne‐Gaëlle , Carbonell Pablo , Fernández‐Castané Alfred , Grigoras Ioana , Dariy Ekaterina , Perret Alain , Faulon Jean‐Loup 
Published: September 2014

AbstractMetabolic engineering has succeeded in biosynthesis of numerous commodity or high value compounds. However, the choice of pathways and enzymes used for production was many times made ad hoc, or required expert knowledge of the specific biochemical reactions. In order to rationalize the process of engineering producer strains, we developed the computer‐aided design (CAD) tool RetroPath that explores and enumerates metabolic pathways connecting the endogenous metabolites of a chassis cell to the target compound. To experimentally validate our tool, we constructed 12 top‐ranked enzyme combinations producing the flavonoid pinocembrin, four of which displayed significant yields. Namely, our tool queried the enzymes found in metabolic databases based on their annotated and predicted activities. Next, it ranked pathways based on the predicted efficiency of the available enzymes, the toxicity of the intermediate metabolites and the calculated maximum product flux. To implement the top‐ranking pathway, our procedure narrowed down a list of nine million possible enzyme combinations to 12, a number easily assembled and tested. One round of metabolic network optimization based on RetroPath output further increased pinocembrin titers 17‐fold. In total, 12 out of the 13 enzymes tested in this work displayed a relative performance that was in accordance with its predicted score. These results validate the ranking function of our CAD tool, and open the way to its utilization in the biosynthesis of novel compounds.
Late-onset palsy of the recurrent laryngeal nerve after thyroid surgery
Authors: Bures C , Bobak-Wieser R , Koppitsch C , Klatte T , Zielinski V , Freissmuth M , Friedrich G , Repasi R , Hermann M 
Published: September 2014

Abstract

Background
A small subset of patients may develop late-onset palsy of the recurrent laryngeal nerve (RLN) after thyroid surgery. However, no conclusive data have been published regarding the incidence of, and possible risk factors for, this complication.

Methods
Preoperative, intraoperative and postoperative data from consecutive patients who underwent thyroid surgery at a single centre between 1999 and 2012 were analysed. Late-onset palsy of the RLN was defined as deterioration of RLN function after normal vocal cord function as investigated by routine preoperative and postoperative laryngoscopy.

Results
The cohort included 16 692 patients with 28 757 nerves at risk. Early postoperative palsy of the RLN was diagnosed in 1183 nerves at risk (4·1 per cent), whereas late-onset RLN palsy was found in 41 (0·1 per cent). Late-onset palsy of the RLN was diagnosed after a median interval of 2·5 (range 0·5–12) weeks and nerve function recovered completely in 28 patients after a median interval of 3 months. This recovery rate was significantly lower than that for early-onset RLN palsy: 1068 (90·3 per cent) of 1183 nerves (P &lt; 0·001). No particular risk factor for late-onset RLN palsy was identified.

Conclusion
Late-onset palsy of the RLN was diagnosed in a small subset of patients after thyroid surgery, and recovery of nerve function occurred less frequently than in patients with early-onset RLN palsy.
A Nationwide Survey of Peer Review Practices in Child Maltreatment Teams
Authors: Greeley Christopher , Yoon Jaennie , Tran Xuan , Giardino Angelo 
Published: September 2014

Medical evaluations for suspected child sexual abuse carry a significant medico‐legal burden and are often performed in a variety of clinical settings, by clinicians with different levels of expertise and experience. Peer review or professional practice evaluation is an important component for quality assurance. We surveyed 255 programmes which provided sexual abuse evaluations which were identified through queries with national child abuse professional organisations. We sought information on team composition and setting, patient population characteristics and each site's peer review process. Of the 129 responding programmes, 42 per cent (n = 44) reported having a written peer review process. There were no differences between practice types with regards to having a written peer review process, the percentage of cases reviewed, the documentation type reviewed or the percentage reporting an external review process. The majority of programmes (n = 89, 85%) reported that they review both chart and photo documentation during the peer review process. Our data support that most programmes involved in child maltreatment evaluations undergo some form of peer review, but there exists a large amount of heterogeneity in the process by which it occurs. Copyright © 2014 John Wiley & Sons, Ltd.‘We surveyed 255 programmes which provided sexual abuse evaluations’Key Practitioner Messages:

Peer review is an important process to ensure high quality of clinical practice.
The majority (80%) of programmes which perform child sexual abuse evaluations reported performing some form of peer review.
Most peer review involves both chart and photo documentation reviews.
‘Most peer review involves both chart and photo documentation reviews’
Childhood Trauma among Mexican American Gang Members and Delinquent Youth: A Comparative Exploratory Study
Authors: Cepeda Alice , Valdez Avelardo , Nowotny Kathryn M. 
Published: September 2014

AbstractThis paper examines the association between childhood trauma and gang membership. Specifically, this study compares histories of potentially traumatic events as assessed by the Childhood Trauma Questionnaire among a street‐recruited random sample of Mexican American male gang members and a matched comparison group of delinquent youth. The gang and delinquent youth samples are then compared to normative samples of adolescent male psychiatric inpatients and male undergraduates. The findings show that gang members generally report experiencing lower levels of childhood trauma compared to those in the sample of delinquent youth. In fact, gang members' levels of childhood trauma more closely resemble those of the undergraduate sample. However, this analysis suggests that gang membership, and delinquency in general, may be associated with physical neglect. Copyright © 2014 John Wiley & Sons, Ltd.‘Gang membership, and delinquency in general, may be associated with physical neglect’Key Practitioner Messages:Childhood trauma prevalence and delinquent youth comparison groups are rare in gang research.Childhood trauma rates (emotional, physical and sexual abuse) were found to be lower among a sample of gang‐involved Mexican American males compared to non‐gang delinquent youth.Levels of physical neglect should be assessed for in youth regardless of gang membership.Future research should focus on family‐level sociocultural interventions that may be beneficial for gang‐involved youth and trauma‐informed interventions that may be particularly beneficial for delinquent youth in low‐income communities.
Evaluating Programmes for Violent Fathers: Challenges and Ethical Review
Authors: McConnell Nicola , Taylor Julie 
Published: September 2014

A range of challenges exist when evaluating programmes for violent men about domestic abuse. Delivered in five UK sites, the Caring Dads Safer Children programme is designed to enhance the parenting behaviour of violent men. At the end of the first delivery programme in each site, a review was undertaken at the request of the ethics committee: to ensure that the evaluation was not raising further ethical issues; to check on the wellbeing of service users and their families; to scrutinise the evaluation process in terms of data quality and quantity; and to inform service and evaluation changes as necessary. In‐depth interviews were undertaken with practitioners delivering the service and analysed inductively. While some practitioners expressed concerns about the burden on service delivery and challenges to their relationship with families due to the use of standardised measures in the evaluation, others demonstrated how robust evaluation procedures enhanced assessment and service delivery. Organisations need to be confident that the cumulative effects of any disadvantages posed by the use of standardised measures do not outweigh the benefits and plan for potential barriers and resistance to their implementation. Copyright © 2014 John Wiley & Sons, Ltd.‘Delivered in five UK sites, the Caring Dads Safer Children programme is designed to enhance the parenting behaviour of violent men’Key Practitioner Messages

Programmes for violent men present a number of challenges for practitioners including difficulty in engagement and high attrition rates.
Robust evaluation is important in illuminating the efficacy of programmes for violent men.
Using routine or standardised measures can positively inform work with perpetrators and their families when used alongside practice wisdom.
Practitioners may become sceptical of evaluation if the use of measures is perceived to impact negatively on service delivery.
‘Practitioners may become sceptical of evaluation if the use of measures is perceived to impact negatively on service delivery’
The visual system of a Palaeognathous bird: Visual field, retinal topography and retino‐central connections in the Chilean Tinamou (Nothoprocta perdicaria)
Authors: Krabichler Quirin , Vega‐Zuniga Tomas , Morales Cristian , Luksch Harald , Marín Gonzalo J. 
Published: September 2014

ABSTRACTMost systematic studies of the avian visual system have focused on Neognathous species, leaving virtually unexplored the Palaeognathae, comprised of the flightless ratites and the South American tinamous. We investigated the visual field, the retinal topography, and the pattern of retinal and centrifugal projections in the Chilean tinamou, a small Palaeognath of the family Tinamidae. The tinamou has a panoramic visual field with a small frontal binocular overlap of 20°. The retina possesses three distinct topographic specializations: a horizontal visual streak, a dorsotemporal area, and an area centralis with a shallow fovea. The maximum ganglion cell density is 61,900/ mm2, comparable to Falconiformes. This would provide a maximal visual acuity of 14.0 cycles/degree, in spite of relatively small eyes. The central retinal projections generally conform to the characteristic arrangement observed in Neognathae, with well‐differentiated contralateral targets and very few ipsilateral fibers. The centrifugal visual system is composed of a considerable number of multipolar centrifugal neurons, resembling the “ectopic” neurons described in Neognathae. They form a diffuse nuclear structure, which may correspond to the ancestral condition shared with other sauropsids. A notable feature is the presence of terminals in deep tectal layers 11–13. These fibers may represent either a novel retinotectal pathway or collateral branches from centrifugal neurons projecting to the retina. Both types of connections have been described in chicken embryos. Our results widen the basis for comparative studies of the vertebrate visual system, stressing the conserved character of the visual projections' pattern within the avian clade. J. Comp. Neurol. 523:226–250, 2015. © 2014 Wiley Periodicals, Inc.
He hears, she hears: Are there sex differences in auditory processing?
Authors: Yoder Kathleen M. , Phan Mimi L. , Lu Kai , Vicario David S. 
Published: September 2014

ABSTRACTSongbirds learn individually unique songs through vocal imitation and use them in courtship and territorial displays. Previous work has identified a forebrain auditory area, the caudomedial nidopallium (NCM), that appears specialized for discriminating and remembering conspecific vocalizations. In zebra finches (ZFs), only males produce learned vocalizations, but both sexes process these and other signals. This study assessed sex differences in auditory processing by recording extracellular multiunit activity at multiple sites within NCM. Juvenile female ZFs (n =46) were reared in individual isolation and artificially tutored with song. In adulthood, songs were played back to assess auditory responses, stimulus‐specific adaptation, neural bias for conspecific song, and memory for the tutor's song, as well as recently heard songs. In a subset of females (n =36), estradiol (E2) levels were manipulated to test the contribution of E2, known to be synthesized in the brain, to auditory responses. Untreated females (n =10) showed significant differences in response magnitude and stimulus‐specific adaptation compared to males reared in the same paradigm (n =9). In hormone‐manipulated females, E2 augmentation facilitated the memory for recently heard songs in adulthood, but neither E2 augmentation (n =15) nor E2 synthesis blockade (n =9) affected tutor song memory or the neural bias for conspecific song. The results demonstrate subtle sex differences in processing communication signals, and show that E2 levels in female songbirds can affect the memory for songs of potential suitors, thus contributing to the process of mate selection. The results also have potential relevance to clinical interventions that manipulate E2 in human patients. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 302–314, 2015
Age‐dependent alterations of the NMDA receptor developmental profile and adult behavior in postnatally ketamine‐treated mice
Authors: Lecointre Maryline , Vézier Claire , Bénard Magalie , Ramdani Yasmina , Dupré Nicolas , Brasse‐Lagnel Carole , Henry Vincent J. , Roy Vincent , Marret Stéphane , Gonzalez Bruno J. , Jégou Sylvie , Leroux‐Nicollet Isabelle 
Published: September 2014

ABSTRACTKetamine is a NMDA receptor (NMDAR) antagonist used in pediatric anesthesia. Given the role of glutamatergic signaling during brain maturation, we studied the effects of a single ketamine injection (40 mg/kg s.c) in mouse neonates depending on postnatal age at injection (P2, P5, or P10) on cortical NMDAR subunits expression and association with Membrane‐Associated Guanylate Kinases PSD95 and SAP102. The effects of ketamine injection at P2, P5, or P10 on motor activity were compared in adulthood. Ketamine increased GluN2A and GluN2B mRNA levels in P2‐treated mice without change in proteins, while it decreased GluN2B protein in P10‐treated mice without change in mRNA. Ketamine reduced GluN2A mRNA and protein levels in P5‐treated mice without change in GluN2B and GluN1. Ketamine affected the GluN2A/PSD95 association regardless of the age at injection, while GluN2B/PSD95 association was enhanced only in P5‐treated mice. Microdissection of ketamine‐treated mouse cortex showed a decrease in GluN2A mRNA level in superficial layers (I–IV) and an increase in all subunit expressions in deep layers (V–VI) in P5‐ and P10‐treated mice, respectively. Our data suggest that ketamine impairs cortical NMDAR subunit developmental profile and delays the synaptic targeting of GluN2A‐enriched NMDAR. Ketamine injection at P2 or P10 resulted in hyperlocomotion in adult male mice in an open field, without change in females. Voluntary running‐wheel exercise showed age‐ and sex‐dependent alterations of the mouse activity, especially during the dark phase. Overall, a single neonatal ketamine exposure led to short‐term NMDAR cortical developmental profile impairments and long‐term motor activity alterations persisting in adulthood. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 315–333, 2015
Suzuki–Miyaura Coupling of Aryl Chlorides with Arylboronic Acids Using the Morpholine–NiCl2 Catalyst System
Authors: Abe Taichi , Mino Takashi , Watanabe Kohei , Sakamoto Masami 
Published: September 2014

AbstractWe report a new catalyst system, morpholine–NiCl2, for the Suzuki–Miyaura coupling of aryl chlorides with aryl‐ or alkenylboronic acids to give biaryl compounds. This catalyst system is easy to apply on a large scale because of its easy preparation and the use of inexpensive reagents. In addition, analysis of the residual nickel shows only 9.7 ppm remaining after normal work‐up. This catalyst system has been applied to 26 compounds to give a variety of biaryl products, including hetero‐biaryl compounds.
Evaluation of cytotoxic, genotoxic and inflammatory response in human alveolar and bronchial epithelial cells exposed to titanium dioxide nanoparticles
Authors: Ursini Cinzia Lucia , Cavallo Delia , Fresegna Anna Maria , Ciervo Aureliano , Maiello Raffaele , Tassone Paola , Buresti Giuliana , Casciardi Stefano , Iavicoli Sergio 
Published: September 2014

ABSTRACTThe toxicity of titanium dioxide nanoparticles (TiO2‐NPs), used in several applications, seems to be influenced by their specific physicochemical characteristics. Cyto‐genotoxic and inflammatory effects induced by a mixture of 79% anatase/21% rutile TiO2‐NPs were investigated in human alveolar (A549) and bronchial (BEAS‐2B) cells exposed to 1–40 µg ml–1 30 min, 2 and 24 h to assess potential pulmonary toxicity. The specific physicochemical properties such as crystallinity, NP size and shape, agglomerate size, surface charge and specific surface area (SSA) were analysed. Cytotoxic effects were studied by evaluating cell viability using the WST1 assay and membrane damage using LDH analysis. Direct/oxidative DNA damage was assessed by the Fpg‐comet assay and the inflammatory potential was evaluated as interleukin (IL)‐6, IL‐8 and tumour necrosis factor (TNF)‐α release by enzyme‐linked immunosorbant assay (ELISA). In A549 cells no significant viability reduction and moderate membrane damage, only at the highest concentration, were detected, whereas BEAS‐2B cells showed a significant viability reduction and early membrane damage starting from 10 µg ml–1. Direct/oxidative DNA damage at 40 µg ml–1 and increased IL‐6 release at 5 µg ml–1 were found only in A549 cells after 2 h. The secretion of pro‐inflammatory cytokine IL‐6, involved in the early acute inflammatory response, and oxidative DNA damage indicate the promotion of early and transient oxidative‐inflammatory effects of tested TiO2‐NPs on human alveolar cells. The findings show a higher susceptibility of normal bronchial cells to cytotoxic effects and higher responsiveness of transformed alveolar cells to genotoxic, oxidative and early inflammatory effects induced by tested TiO2‐NPs. This different cell behaviour after TiO2‐NPs exposure suggests the use of both cell lines and multiple end‐points to elucidate NP toxicity on the respiratory system. Copyright © 2014 John Wiley &#38; Sons, Ltd.
Comparative genotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by a flow cytometricin vitromicronucleus assay
Authors: Sahu Saura C. , Njoroge Joyce , Bryce Steven M. , Yourick Jeffrey J. , Sprando Robert L. 
Published: September 2014

ABSTRACTTwo widely usedin vitrocell culture models, human liver HepG2 cells and human colon Caco2 cells, and flow cytometry techniques were evaluated as tools for rapid screening of potential genotoxicity of food‐related nanosilver. Comparative genotoxic potential of 20 nm silver was evaluated in HepG2 and Caco2 cell cultures by a flow cytometric‐basedin vitromicronucleus assay. The nanosilver, characterized by the dynamic light scattering, transmission electron microscopy and inductively coupled plasma–mass spectrometry analysis, showed no agglomeration of the silver nanoparticles. The inductively coupled plasma–mass spectrometry and transmission electron microscopy analysis demonstrated the uptake of 20 nm silver by both cell types. The 20 nm silver exposure of HepG2 cells increased the concentration‐dependent micronucleus formation sevenfold at 10 µg ml–1concentration in attached cell conditions and 1.3‐fold in cell suspension conditions compared to the vehicle controls. However, compared to the vehicle controls, the 20 nm silver exposure of Caco2 cells increased the micronucleus formation 1.2‐fold at a concentration of 10 µg ml–1both in the attached cell conditions as well as in the cell suspension conditions. Our results of flow cytometricin vitromicronucleus assay appear to suggest that the HepG2 cells are more susceptible to the nanosilver‐induced micronucleus formation than the Caco2 cells compared to the vehicle controls. However, our results also suggest that the widely usedin vitromodels, HepG2 and Caco2 cells and the flow cytometricin vitromicronucleus assay are valuable tools for the rapid screening of genotoxic potential of nanosilver and deserve more careful evaluation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Using chiral molecules as an approach to address low‐druggability recognition sites
Authors: Lucas Xavier , Günther Stefan 
Published: September 2014

The content of chiral carbon atoms or structural complexity, which is known to correlate well with relevant physicochemical properties of small molecules, represents a promising descriptor that could fill the gap in existing drug discovery between ligand library filtering rules and the corresponding properties of the target's recognition site.Herein, we present an in silico study on the yet unclear underlying correlations between molecular complexity and other more sophisticated physicochemical and biological properties. By analyzing thousands of protein–ligand complexes from DrugBank, we show that increasing molecular complexity of drugs is an approach to addressing particularly low‐druggability and polar recognition sites. We also show that biologically relevant protein classes characteristically bind molecules with a certain degree of structural complexity. Three distinct behaviors toward drug recognition are described.The reported results set the basis for a better understanding of protein–drug recognition, and open the possibility of including target information in the filtering of large ligand libraries for screening. © 2014 Wiley Periodicals, Inc.