bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel carvedilol paediatric nanomicelle formulation: in-vitro characterization and in-vivo evaluation
Authors: Wegmann Marcel , Parola Luciano , Bertera Facundo M , Taira Carlos A , Cagel Maximiliano , Buontempo Fabian , Bernabeu Ezequiel , Höcht Christian , Chiappetta Diego A , Moretton Marcela A 
Published: July 2016

Abstract

Objectives
Carvedilol (CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles (NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus®).

Methods
Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water. Micellar size and morphology were characterized by dynamic light scattering and transmission electron microscopy, respectively. In-vitro drug permeation studies were evaluated by conventional gut sac method. In-vivo CAR oral bioavailability from NMs dispersions and drug control solution was evaluated in Wistar rats.

Key findings
Carvedilol apparent aqueous solubility was increased (up to 60.4-folds) after its encapsulation within NMs. The micellar size was ranged between 10.9 and 81.9 nm with a monomodal size distribution. There was a significant enhancement of CAR relative oral bioavailability for both copolymers vs a micelle-free drug solution (P &lt; 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeation results.

Conclusions
The present investigation demonstrates the development of highly concentrated CAR liquid micellar formulation. The improvement on drug oral bioavailability contributes to the potential of this NMs formulation to enhance CAR paediatric treatment.
Martian meteorite Tissint records unique petrogenesis among the depleted shergottites
Authors: Basu Sarbadhikari A. , Babu E. V. S. S. K. , Vijaya Kumar T. , Chennaoui Aoudjehane H. 
Published: July 2016

AbstractTissint, a new unaltered piece of Martian volcanic materials, is the most silica‐poor and Mg‐Fe‐rich igneous rock among the “depleted” olivine‐phyric shergottites. Fe‐Mg zoning of olivine suggests equilibrium growth (<0.1 °C h−1) in the range of Fo80–56 and olivine overgrowth (Fo55–18) through a process of rapid disequilibrium (~1.0–5.0 °C h−1). The spatially extended (up to 600 μm) flat‐top Fe‐Mg profiles of olivine indicates that the early‐stage cooling rate of Tissint was slower than the other shergottites. The chemically metastable outer rim of olivine (<Fo55) consists of oscillatory phosphorus zoning at the impact‐induced melt domains and grew rapidly compared to the early to intermediate‐stage crystallization of the Tissint bulk. High‐Ca pyroxene to low‐Ca pyroxene and high‐Ca pyroxene to plagioclase ratios of Tissint are more comparable to the enriched basaltic and enriched olivine‐phyric shergottites. Dominance of augite over plagioclase induced augite to control the Ca‐buffer in the residual melt suppressing the plagioclase crystallization, which also caused a profound effect on the Al‐content in the late‐crystallized pyroxenes. Mineral chemical stability, phase‐assemblage saturation, and pressure–temperature path of evolution indicates that the parent magma entered the solidus and left the liquidus field at a depth of 40–80 km in the upper mantle. Petrogenesis of Tissint appears to be similar to LAR 06319, an enriched olivine‐phyric shergottite, during the early to intermediate stage of crystallization. A severe shock‐induced deformation resulted in remelting (10–15 vol%), recrystallization (most Fe‐rich phases), and exhumation of Tissint in a time scale of 1–8 yr. Tissint possesses some distinct characteristics, e.g., impact‐induced melting and deformation, forming phosphorus‐rich recrystallization rims of olivine, and shock‐induced melt domains without relative enrichment of LREEs compared to the bulk; and shared characteristics, e.g., modal composition and magmatic evolution with the enriched basaltic shergottites, evidently reflecting unique mantle source in comparison to the clan of the depleted members.
The regulatory factor X protein MoRfx1 is required for development and pathogenicity in the rice blast fungus Magnaporthe oryzae
Authors: Sun Dandan , Cao Huijuan , Shi Yongkai , Huang Pengyun , Dong Bo , Liu Xiaohong , Lin Fucheng , Lu Jianping 
Published: July 2016

SummaryMagnaporthe oryzae is a cereal pathogen causing 20%–30% rice yield losses. Regulatory factor X transcription factors are highly conserved proteins with diverse functions among organisms. Here, we show that MoRfx1 is required for cell division, development and pathogenicity in M. oryzae. Deletion of MoRFX1 resulted in reduced growth and conidiation, decreased appressorium turgor and impaired virulence. ΔMorfx1 displayed increased sensitivity to UV light, four DNA‐damaging agents and three cell wall‐perturbing compounds. However, ΔMorfx1 showed decreased sensitivity to bleomycin, a DNA/cell wall‐damaging agent, and increased chitin content of the cell wall in vegetative mycelium. In addition, cell division speed was reduced in ΔMorfx1, and ΔMorfx1 did not produce three‐celled conidia. RNA‐sequencing and quantitative polymerase chain reaction analyses suggested that MoRfx1 has bipartite functions in the control of the expression of genes required for cell division and chitin metabolism, not only as a transcriptional repressor, but also as a transcriptional activator. In particular, the expression of chitin deacetylase genes MoCDA2 and MoCDA1 was greatly down‐regulated in ΔMorfx1, and deletion of MoCDA2 and MoCDA1, similar to ΔMorfx1, increased resistance to bleomycin. Taken together, our results indicate that MoRFX1 regulates development and pathogenicity by modulating the expression of genes involved in cell division and cell wall integrity.
Epidemiology of onychomycosis in Crete, Greece: a 12‐year study
Authors: Maraki Sofia , Mavromanolaki Viktoria Eirini 
Published: July 2016

SummaryOnychomycosis is a chronic fungal nail infection caused by dermatophytes, yeasts or non‐dermatophyte moulds (NDMs). It occurs worldwide and accounts for about 50% of all nail disorders. The incidence of the disease and the prevalence of pathogens involved vary in different geographical areas and change with time. This study was undertaken to determine the epidemiology of onychomycosis in Crete, Greece during a 12‐year period. Mycologic nail investigation (direct microscopy and cultures) was performed in samples taken from 3317 patients with clinical suspicion of onychomycosis. Demographic characteristics, comorbidities and concurrent superficial fungal infections at other body sites were also recorded. Onychomycosis was mycologically confirmed in 547 (16.5%) patients. Fingernail onychomycosis was found in 274 (50.1%) patients, toenail onychomycosis in 271 (49.5%), and both toenail and fingernail onychomycosis in two (0.4%). Yeasts were the major causative agents, followed by dermatophytes and NDMs. Candida albicans was the most commonly isolated yeast species and Trichophyton rubrum the most common dermatophyte. Concomitant fungal skin infections were noted in 53 (19.6%) patients with toenail onychomycosis. Factors predisposing to onychomycosis were trauma, diabetes, psoriasis, peripheral circulatory insufficiency and immunosuppression. Mycological investigations are necessary to confirm clinical diagnosis and identify the pathogen, in order to select the most appropriate treatment.
Trait to gene analysis reveals that allelic variation in three genes determines seed vigour
Authors: Morris Karl , Barker Guy C. , Walley Peter G. , Lynn James R. , Finch‐Savage William E. 
Published: July 2016

SummaryPredictable seedling establishment is essential for resource‐efficient and cost‐effective crop production; it is widely accepted as a critically important trait determining yield and profitability. Seed vigour is essential to this, but its genetic basis is not understood.We used natural variation and fine mapping in the cropBrassica oleraceato show that allelic variation at three loci influence the key vigour trait of rapid germination. Functional analysis in bothB. oleraceaand the modelArabidopsisidentified and demonstrated activity of genes at these loci.Two candidate genes were identified at the principal Speed of GerminationQTL(SOG1) inB. oleracea. One geneBoLCVIG2is a homologue of the alternative‐splicing regulator (AtPTB1). The other geneBoLCVIG1was unknown, but different alleles had different splice forms that were coincident with altered abscisic acid (ABA) sensitivity. We identified a furtherQTL, ReducedABscisic Acid 1 (RABA1) that influencedABAcontent and provide evidence that this results from the activity of a homologue of theABAcatabolic geneAtCYP707A2at this locus.Lines containing beneficial alleles of these three genes had greater seed vigour. We propose a mechanism in which both seedABAcontent and sensitivity to it determines speed of germination.
Central obesity and risks of pre‐ and postmenopausal breast cancer: a dose–response meta‐analysis of prospective studies
Authors: Chen G. ‐C. , Chen S. ‐J. , Zhang R. , Hidayat K. , Qin J. ‐B. , Zhang Y. ‐S. , Qin L. ‐Q. 
Published: July 2016

SummaryEpidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist‐to‐hip ratio (WHR), and risks of pre‐ and postmenopausal breast cancer (BC). A dose–response meta‐analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10‐cm increase = 1.06, 95% CI: 1.04–1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 1.01–1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10‐cm increase = 1.05, 95% CI: 0.99–1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 0.95–1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR‐postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1‐unit increase = 1.06, 95% CI: 0.99–1.13). When considering BMI‐adjusted RRs, WC was associated with both pre‐ (five studies, RR per 10‐cm increase = 1.09, 95% CI: 1.02–1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10‐cm increase = 1.05, 95% CI: 1.02–1.08, I2 = 6.3%), whereas WHR was not associated with either pre‐ (seven studies, RR per 0.1‐unit increase = 1.12, 95% CI: 0.94–1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1‐unit increase = 1.05, 95% CI: 0.98–1.13, I2 = 57.3%). Among non‐current (former or never) users of hormone replacement therapy, the summary RR per 10‐cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03–1.05, I2 = 69.2%, seven studies; BMI‐adjusted RR = 1.05, 95% CI: 1.02–1.09, I2 = 22.8%, four studies). This meta‐analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre‐ and postmenopausal BC independent of general obesity.
Feasibility testing of a home‐based sensor system to monitor mobility and daily activities in Korean American older adults
Authors: Chung Jane , Demiris George , Thompson Hilaire J. , Chen Ke‐Yu , Burr Robert , Patel Shwetak , Fogarty James 
Published: July 2016

Aims and objectives:This study aimed to test feasibility of a home‐based sensor system that is designed to assess mobility and daily activity patterns among Korean American older adults (KAOAs; n = 6) and explore sensor technology acceptance among participants.BackgroundHome‐based sensors have the potential to support older adults' desire to remain at home as long as possible. Despite a growing interest in using home‐based sensors for older adults, there have been no documented attempts to apply this type of technology to a group of ethnic minority older adults.DesignThe study employed descriptive, quantitative and qualitative approaches.MethodsThe system was deployed for 2 months in four homes of KAOAs. Study procedures included (i) sensor‐based data collection, (ii) self‐report mobility instruments, (iii) activity logs and (iv) interviews. To explore changes in activity patterns, line graphs and sequence plots were applied to data obtained from a set of sensors. General linear models (GLMs) were used for motion in each space of the home to examine how much variability of activities is explained by several time variables.ResultsSensor data had natural fluctuation over time. Different 24‐hr patterns were observed across homes. The GLM estimates showed that effect sizes of the time variables vary across individuals. A hydro sensor deployed in one participant's bathroom inferred various water usage activities. Overall, sensors were acceptable for all participants, despite some privacy concerns.ConclusionsStudy findings demonstrate that sensor technology applications could be successfully used longitudinally in a minority population of older adults that is not often targeted as an end‐user group for the use of innovative technologies.Implications for practiceThe use of home‐based sensors provides nurses with a useful tool to detect deviations from normal patterns and to achieve proactive care for some groups of older adults.
No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene
Authors: Khoo Siew‐Kim , Mäkelä Mika , Chandler David , Schultz En Nee , Jamieson Sarra E. , Goldblatt Jack , Haahtela Tari , LeSouëf Peter , Zhang Guicheng 
Published: July 2016

AbstractBackgroundFinnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14).MethodsFive hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14.ResultsMethylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children.ConclusionsThe methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas.
Exploration of early‐life candidate biomarkers for childhood asthma using antibody arrays
Authors: Xu Haili , Radabaugh Timothy , Lu Zhenqiang , Galligan Michael , Billheimer Dean , Vercelli Donata , Wright Anne L. , Monks Terrence J. , Halonen Marilyn , Lau Serrine S. 
Published: July 2016

AbstractBackgroundProteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.MethodsWith an antibody array (RayBiotech, Norcross, GA, USA), the relative intensity and rank differences of 444 proteins were compared in 24 plasma samples obtained at age 3, 11 from children with and 12 without asthma diagnoses at ages 5 and 9. Protein candidates identified by antibody array were quantitated by ELISA in an enlarged sample. Proteins found to differentiate children with and without asthma were also examined for association with known Year 1 asthma risk factors, eczema, and wheeze.ResultsIn the antibody array, four proteins had rank differences between asthma and non‐asthma groups (FDR <0.1). By ELISA, mean log (±s.e.m.) erythropoietin (EPO) level (IU/l) was lower (0.750 ± 0.048 vs. 0.898 ± 0.035; p = 0.006) and mean (±s.e.m.) soluble GP130 (sGP130) level (ng/ml) was higher in the asthma vs. the non‐asthma group (302 ± 13 vs. 270 ± 8; p = 0.041). The other 2 array proteins (galactin‐3 and eotaxin‐3) did not differ by ELISA by asthma. EPO related to the asthma risk factor, first year eczema, whereas sGP130 related to first year wheeze.ConclusionsThrough two independent assessments, age 3 plasma levels of EPO and sGP130 were found related to childhood asthma.
The prevalence, natural history and time trends of peanut allergy over the first 10 years of life in two cohorts born in the same geographical location 12 years apart
Authors: Venter Carina , Maslin Kate , Patil Veeresh , Kurukulaaratchy Ramesh , Grundy Jane , Glasbey Gillian , Twiselton Roger , Dean Taraneh , Arshad Syed Hasan 
Published: July 2016

AbstractBackgroundThe aim of this study was to explore the natural history of peanut allergy in childhood in two birth cohorts from the same geographical region in the South of England.MethodsThe FAIR birth cohort was established on the Isle of Wight (UK) between 2001 and 2002 (n = 969). Children were followed up prospectively, skin prick tested (SPT) to peanut allergens at 1, 2, 3 and 10 years and food challenges performed. The Isle of Wight (IOW) birth cohort was established in 1989 (n = 1456). SPTs were performed at 1, 2, 4 and 10 years. Peanut allergy was based on positive SPT and a good clinical history.ResultsIn the FAIR cohort, the prevalence of sensitization to peanut was 0.4%, 2.0%, 2.0% and 2.4% at 1, 2, 3 and 10 years, respectively. At 10 years of age, 12 of 828 (1.5%) children were diagnosed with peanut allergy. One child (8%) outgrew her peanut allergy between 3 and 10 years and two children (15%) presented with new onset peanut allergy. Over the first 10 years of life, 13 of 934 (1.4%) children were diagnosed with peanut allergy. In the IOW cohort, 6 of 1034 (0.58%) were diagnosed with peanut allergy at 10 years. We found no significant differences between the FAIR and the IOW birth cohort for any of the time points studied.ConclusionPeanut allergy appears to be stable over the first 10 years of life in our cohorts. There was no significant difference in peanut sensitization or clinical peanut allergy between 1989 and 2001.
Young children's experiences of living with a parent with bipolar disorder: Understanding the child's perspective
Authors: Backer Clare , Murphy Rebecca , Fox John R. E. , Ulph Fiona , Calam Rachel 
Published: July 2016

ObjectivesTo explore the experiences of young children of living with a parent with bipolar disorder (BD) and how this impacts on their emotional well‐being.DesignQualitative study using a computer‐assisted semi‐structured interview, ‘In My Shoes’ (IMS).MethodsTen children aged between 4 and 10 years with a parent with BD identified via self‐help groups were interviewed about their experience of family life. Thematic analysis was used following transcription.ResultsFour main themes emerging from thematic analysis were as follows: perception of parents; knowledge and awareness of BD; managing family life with a ‘bipolar’ parent; and living in a family with BD. Four‐year‐old children could participate in the IMS interviews and discuss their parent's mood, behaviour, and mental health. Children had candid and insightful discussions about their parent's BD including symptoms and parenting, and could reflect on how having a parent with BD affected them emotionally and practically. Older children were better able to articulate their parent's illness and its impact.ConclusionsThis exploratory study represents an important step in examining directly experiences of young children whose parents have BD. Using IMS, it was possible to gather insightful information from children to generate hypotheses and influence service development. Children of all ages had some knowledge and understanding of their parent's illness, describing both positive and negative experiences in the family. Further research to build understanding of children's perspectives and the support they feel they and their family would benefit from would enhance the development of appropriate services and interventions.Practitioner points

Using age‐appropriate tools, it is possible to elicit the views of young children about their parent's mental health and parenting.

Young children have insight into the impact of bipolar disorder in the family on themselves and family members.
An experimental investigation of wave‐induced sediment responses in a natural silty seabed: New insights into seabed stratification
Authors: Liu Xiaolei , Jia Yonggang , Zheng Jiewen , Wen Mingzheng , Shan Hongxian 
Published: July 2016

AbstractThe widely recognized global phenomenon of wave–seabed interactions and the resulting secondary stratification processes are complex and poorly understood. To better understand the mechanisms by which the differentiation between fine‐grained and coarse‐grained materials occurs and how new sedimentary sequences form, laboratory flume experiments were performed under varying wave conditions using natural silty sediment samples collected from the Yellow River Delta (China). Detailed observations led to the description of variations in the grain‐size composition and texture of sediment under waves of progressively increasing height and the recognition of the typical, secondarily formed seabed stratification that forms during processes of increasing pore pressure and subsequent liquefaction. The development of a stratified seabed, which is characterized by a superficial fluid mud layer, a subsurface that alternates between coarse and fine sediment banding, and an internal liquefied layer from top to bottom, is closely related to wave‐driven pore‐water flow through the sediment. Localized fluidization and the onset of piping leads to progressive changes in the grain composition with initial particle dislocation, the development of macro‐voids and micro‐conduits and, finally, pipe formation. Internal liquefaction occurs in the presence of a critical value of excess pore pressure, during which most fine particles can be scoured by the pore‐water flow along the sliding surface while the coarse sediment grains settle, leading to a more compact, homogeneous seabed. These elements are combined to produce the first model of wave‐induced stratification initiation and evolution in an originally uniform silty seabed. In addition, the implications of this model for future studies are explored.