bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma extracellular nanovesicle (exosome)‐derived biomarkers for drug metabolism pathways: a novel approach to characterize variability in drug exposure
Authors: Rowland Andrew , Ruanglertboon Warit , van Dyk Madelé , Wijayakumara Dhilushi , Wood Linda S. , Meech Robyn , Mackenzie Peter I. , Rodrigues A. David , Marshall Jean‐Claude , Sorich Michael J. 
Published: October 2018

AimsDemonstrate the presence of cytochrome P450 (CYP) and UDP‐glucuronosyltransferase (UGT) proteins and mRNAs in isolated human plasma exosomes and evaluate the capacity for exosome‐derived biomarkers to characterize variability in CYP3A4 activity.MethodsThe presence of CYP and UGT protein and mRNA in exosomes isolated from human plasma and HepaRG cell culture medium was determined by mass spectrometry and reverse transcription–polymerase chain reaction, respectively. The concordance between exosome‐derived CYP3A4 biomarkers and midazolam apparent oral clearance (CL/F) was evaluated in a small proof‐of‐concept study involving six genotyped (CYP3A4 *1/*1 and CYP3A5 *3/*3) Caucasian males.ResultsExosomes isolated from human plasma contained peptides and mRNA originating from CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2 J2, 3A4 and 3A5, UGT 1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10 and 2B15, and NADPH‐cytochrome P450 reductase. Mean (95% confidence interval) exosome‐derived CYP3A4 protein expression pre‐ and post‐rifampicin dosing was 0.24 (0.2–0.28) and 0.42 (0.21–0.65) ng ml–1 exosome concentrate. Mean (95% confidence interval) exosome CYP3A4 mRNA expression pre‐ and post‐rifampicin dosing was 6.0 (1.1–32.7) and 48.3 (11.3–104) × 10–11 2‐ΔΔCt, respectively. R2 values for correlations of exosome‐derived CYP3A4 protein expression, CYP3A4 mRNA expression, and ex vivo CYP3A4 activity with midazolam CL/F were 0.905, 0.787 and 0.832, respectively.ConclusionsConsistent strong concordance was observed between exosome‐derived CYP3A4 biomarkers and midazolam CL/F. The significance of these results is that CYP3A4 is the drug‐metabolizing enzyme of greatest clinical importance and variability in CYP3A4 activity is poorly described by existing precision dosing strategies.
Venous thromboembolism and women's health
Authors: Speed Victoria , Roberts Lara N. , Patel Jignesh P. , Arya Roopen 
Published: October 2018

SummaryThe prevention and treatment of venous thromboembolism (VTE) poses distinct gender‐specific challenges. Women of childbearing age are at an increased risk of VTE secondary to the transient risk factors of combined hormonal contraception (CHC) and pregnancy. Cancers specific to women are associated with a significant burden of VTE; whilst the incidence of VTE in localised breast cancer is 5 per 1000 person‐years, more cases are seen due to the prevalence of breast cancer. Treatment of VTE in women can be complicated by abnormal uterine bleeding, now increasingly reported with direct oral anticoagulants (DOACs) as well as vitamin K antagonists. Divergence between international guidelines regarding the use of CHC following an oestrogen‐associated VTE and appropriate withdrawal of such contraception requires clarification for clinicians. Additionally, there is uncertainty as to whether to consider such events provoked or unprovoked and, consequently, the optimal duration of treatment in these women remains unclear. During pregnancy and the puerperium, the traditional anticoagulants remain the agents of choice with no further advances in DOAC safety data, and similarly in lactation. Further studies evaluating the safety and optimal treatment strategies in these women are awaited.
The effects of long‐distance migration on the evolution of moult strategies in Western‐Palearctic passerines
Authors: Kiat Yosef , Izhaki Ido , Sapir Nir 
Published: October 2018

ABSTRACTAlthough feathers are the unifying characteristic of all birds, our understanding of the causes, mechanisms, patterns and consequences of the feather moult process lags behind that of other major avian life‐history phenomena such as reproduction and long‐distance migration. Migration, which evolved in many species of the temperate and arctic zones, requires high energy expenditure to endure long‐distance journeys. About a third of Western‐Palearctic passerines perform long‐distance migrations of thousands of kilometres each year using various morphological, physiological, biomechanical, behavioural and life‐history adaptations. The need to include the largely non‐overlapping breeding, long‐distance migration and feather moult processes within the annual cycle imposes a substantial constraint on the time over which the moult process can take place. Here, we review four feather‐moult‐related adaptations which, likely due to time constraints, evolved among long‐distance Western‐Palearctic migrants: (i) increased moult speed; (ii) increased overlap between moult and breeding or migration; (iii) decreased extent of plumage moult; and (iv) moult of part or all of the plumage during the over‐wintering period in the tropics rather than in the breeding areas. We suggest that long‐distance migration shaped the evolution of moult strategies and increased the diversity of these strategies among migratory passerines. In contrast to this variation, all resident passerines in the Western Palearctic moult immediately after breeding by renewing the entire plumage of adults and in some species also juveniles, while in other species juvenile moult is partial. We identify important gaps in our current understanding of the moult process that should be addressed in the future. Notably, previous studies suggested that the ancestral moult strategy is a post‐breeding summer moult in the Western Palearctic breeding areas and that moult during the winter evolved due to the scheduling of long‐distance migration immediately after breeding. We offer an alternative hypothesis based on the notion of southern ancestry, proposing that the ancestral moult strategy was a complete moult during the ‘northern winter’ in the Afro‐tropical region in these species, for both adults and juveniles. An important aspect of the observed variation in moult strategies relates to their control mechanisms and we suggest that there is insufficient knowledge regarding the physiological mechanisms that are involved, and whether they are genetically fixed or shaped by environmental factors. Finally, research effort is needed on how global climate changes may influence avian annual routines by altering the scheduling of major processes such as long‐distance migration and feather moult.
Caries reporting in studies that used the International Caries Detection and Assessment System: A scoping review
Authors: ElSalhy Mohamed , Ali Ussama , Lai Hollis , Flores‐Mir Carlos , Amin Maryam 
Published: October 2018

AbstractObjectiveTo explore how caries was reported in studies that employed the International Caries Detection and Assessment System (ICDAS).MethodsA systematic database search up to August 2017 was carried out using PubMed, Ovid MEDLINE, Cochrane library and ISI Web of Science electronic databases. Only studies that used the ICDAS for dental caries examinations were included. Studies were excluded if the examination was done only for the validation or the calibration of the ICDAS and/or if the examination was not done for the whole dentition. Measures used to report caries were considered.ResultsA total of 126 papers met the inclusion criteria. Forty‐four different synthesis measures were used to report caries. Most of the studies used a combination of multiple measures to report patient's caries level. These reporting measures cluster into four main groups: the number of individual ICDAS scores (ie, total counts of every score); the number of decayed surfaces/teeth (ie, total counts of combined caries scores for surfaces or teeth); measures of caries experience (ie, total counts of combined caries scores, filled and/or missing surfaces or teeth); and measures of central tendency and dispersion. The number of decayed surfaces and individual ICDAS scores were the most commonly used measures. Three studies used mean ICDAS score (ie, total ICDAS scores divided by the number of teeth), two used mean ICDAS score of carious teeth (ie, total ICDAS scores divided by the number of carious teeth) and two used the maximum ICDAS score (ie, highest ICDAS score recorded). The total ICDAS score was used only once. Many studies synthesized from the ICDAS the number of decayed, missing and filled teeth/surfaces (dmft/DMFT, dmfs/DMFS) as a measure of caries experience.ConclusionsThere are variations among studies in the utilization of the system to summarize caries. Most studies presented caries data using the categorical characteristics of the ICDAS.
Development of a novel risk prediction and risk stratification score for polycystic ovary syndrome
Authors: Deshmukh Harshal , Papageorgiou Maria , Kilpatrick Eric S. , Atkin Stephen L. , Sathyapalan Thozhukat 
Published: October 2018

SummaryObjectiveThe aim of this study was to develop a simple phenotypic algorithm that can capture the underlying clinical and hormonal abnormalities to help in the diagnosis and risk stratification of polycystic ovary syndrome (PCOS).MethodsThe study consisted of 111 women with PCOS fulfilling the Rotterdam diagnostic criteria and 67 women without PCOS. A Firth's penalized logistic regression model was used for independent variable section. Model optimism, discrimination and calibration were assessed using bootstrapping, area under the curve (AUC) and Hosmer‐Lemeshow statistics, respectively. The prognostic index (PI) and risk score for developing PCOS were calculated using independent variables from the regression model.ResultsFirth penalized logistic regression model with backward selection identified four independent predictors of PCOS namely free androgen index [β 0.30 (0.12), P = 0.008], 17‐OHP [β = 0.20 (0.01), P = 0.026], anti‐mullerian hormone [AMH; β = 0.04 (0.01) P < 0.0001] and waist circumference [β = 0.08 (0.02), P < 0.0001]. The model estimates indicated high internal validity (minimal optimism on 1000‐fold bootstrapping), good discrimination ability (bias corrected c‐statistic = 0.90) and good calibration (Hosmer‐Lemeshow χ2 = 3.7865). PCOS women with a high‐risk score (q1 + q2 + q3 vs q4) presented with a worse metabolic profile characterized by a higher 2‐hour glucose (P = 0.01), insulin (P = 0.0003), triglycerides (P = 0.0005), C‐reactive protein (P < 0.0001) and low HDL‐cholesterol (P = 0.02) as compared to those with lower risk score for PCOS.ConclusionsWe propose a simple four‐variable model, which captures the underlying clinical and hormonal abnormalities in PCOS and can be used for diagnosis and metabolic risk stratification in women with PCOS.
The grand challenges of migration ecology that radar aeroecology can help answer
Authors: Bauer Silke , Shamoun‐Baranes Judy , Nilsson Cecilia , Farnsworth Andrew , Kelly Jeffrey F. , Reynolds Don R. , Dokter Adriaan M. , Krauel Jennifer F. , Petterson Lars B. , Horton Kyle G. , Chapman Jason W. 
Published: October 2018

Many migratory species have experienced substantial declines that resulted from rapid and massive expansions of human structures and activities, habitat alterations and climate change. Migrants are also recognized as an integral component of biodiversity and provide a multitude of services and disservices that are relevant to human agriculture, economy and health. The plethora of recently published studies reflects the need for better fundamental knowledge on migrations and for better management of their ecological and human‐relevant effects. Yet, where are we in providing answers to fundamental questions and societal challenges?Engaging a broad network of researchers worldwide, we used a horizon‐scan approach to identify the most important challenges which need to be overcome in order to gain a fuller understanding of migration ecology, and which could be addressed using radar aeroecological and macroecological approaches. The top challenges include both long‐standing and novel topics, ranging from fundamental information on migration routes and phenology, orientation and navigation strategies, and the multitude of effects migrants may have on resident communities, to societal challenges, such as protecting or preventing migrant services and disservices, and the conservation of migrants in the face of environmental changes. We outline these challenges, identify the urgency of addressing them and the primary stakeholders – researchers, policy makers and practitioners, or funders of research.
On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis
Authors: Hubaux Roland , Bastin Coralie , Salmon Michel 
Published: October 2018

AbstractRecent advances in the development of human‐based in vitro models offer new tools for drug screening and mechanistic investigations of new therapeutic agents. However, there is a lack of evidence that disease models respond favourably to potential drug candidates. Atopic dermatitis (AD) is a very common disease associated with an altered skin barrier and chronic inflammation. Here, we demonstrate that the AD‐like features of a reconstructed human epidermis (RHE) model treated with Th2 cytokines are reversed in the presence of molecules known to have a beneficial effect on damaged skin as a result of modulating various signalling cascades including the Liver X Receptors and JAK/STAT pathways. This work shows that standardized and reproducible RHE are relevant models for therapeutic research assessing new drug candidates aiming to restore epidermal integrity in an inflammatory environment.
Dynamic analysis and simulation study of knowledge flow under the perspective of industrial transfer
Authors: Zhou Yong , Wu Haizhen 
Published: October 2018

AbstractBased on the actual situation of the knowledge flow during industrial transfer, a dynamic model of knowledge flow in a complex network is built. The mechanism of the knowledge flow in the network is analysed, and an analogue simulation is conducted using the Netlogo platform to identify the effects of the network's average degree, the number of enterprises involved in the transfer, the network size, and the effective transmission rate of the knowledge on the efficiency of the knowledge flow in the network. According to the final steady state of the knowledge, the technology spillover effect of the industrial transfer is then discussed. The research results show that the average degree of the network, the number of enterprises involved in the transfer, and the effective transmission rate of the knowledge have significant influences on the efficiency of the knowledge flow in the network, and increasing the network size is beneficial to increasing the number of final knowledge owners. Thus, the final steady state of the knowledge flow plays a decisive role in the technology spillover effect of industrial transfer.
LncRNA‐PCAT1 targeting miR‐145‐5p promotes TLR4‐associated osteogenic differentiation of adipose‐derived stem cells
Authors: Yu Lingjia , Qu Hao , Yu Yifeng , Li Wenjing , Zhao Yu , Qiu Guixing 
Published: October 2018

AbstractThis study was aimed to explore the differential expression of long noncoding RNAs (lncRNA)‐PCAT1, miR‐145‐5p and TLR4 in osteogenic differentiation via the Toll‐like receptor (TLR) signalling pathway and consequently determine the potential molecular mechanism. The mRNAs and pathways related to the osteogenic differentiation in human adipose‐derived stem cells (hADSCs) were analysed by bioinformatics. The MiRanda and TargetScan database were employed to detect the potential binding sites of miRNAs on lncRNAs and mRNAs. The differential expression of lncRNA‐PCAT1, miR‐145‐5p and TLR4 were detected by qRT‐PCR. Rrelated protein expression was analysed by Western blot. The targeted relationships between lncRNA‐PCAT1, miR‐145‐5p and TLR4 were verified by dual‐luciferase reporter assay. Alkaline phosphatase (ALP) activity and ARS staining assays were used to measure the impacts exerted by lncRNA PCAT1, miR‐145‐5p and TLR4 mRNA on osteogenic differentiation. After the induction of osteoblast differentiation, the expression of lncRNA‐PCAT1 and TLR4 increased, while the expression of miR‐145‐5p decreased. Dual‐luciferase reporter assay confirmed the targeted relationship between lncRNA‐PCAT1, miR‐145‐5p, and TLR4. LncRNA‐PCAT1 negatively regulated miR‐145‐5p and positively regulated TLR4. Knockdown of lncRNA‐PCAT1 or TLR4 decreased the expression of osteogenic differentiation‐related proteins, reduced the ALP and ARS levels and the activity of the TLR signalling pathway. MiR‐145‐5p could reverse the effects of PCAT1 and TLR4 in hADSCs osteogenic differentiation. LncRNA‐PCAT1 negatively regulated miR‐145‐5p, which promoted TLR4 expression to promote osteogenic differentiation by activating the TLR signalling pathway.
Transgelin as a potential target in the reversibility of pulmonary arterial hypertension secondary to congenital heart disease
Authors: Huang Li , Li Li , Yang Tao , Li Wen , Song Li , Meng Xianmin , Gu Qing , Xiong Changming , He Jianguo 
Published: October 2018

AbstractBackgroundThe reversibility of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is of great importance for the operability of CHD. Proteomics analysis found that transgelin was significantly up‐regulated in the lung tissue of CHD‐PAH patients, especially in the irreversible group. However, how exactly it participated in CHD‐PAH development is unknown.MethodsImmunohistochemical staining and Western blot were performed for further qualitative and quantitative analysis of transgelin in the lung tissues of CHD‐PAH patients. The mechanism of transgelin in CHD‐PAH development was explored in vitro. Primary human pulmonary arterial smooth muscle cells (hPASMCs) were cultured and infected with TAGLN siRNA or TAGLN lentiviral vector. Cell morphologic change (Coomassie Brilliant Blue staining), proliferation (cell count and EdU assay), apoptosis (terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling assay and Annexin‐V flow cytometry) and migration (transwell) were evaluated following the cell treatment. The mRNA and protein expression levels were detected in real‐time PCR and Western blot.ResultsIn line with the proteomic findings, transgelin was obviously expressed in PASMC of the middle pulmonary arterioles, especially in the irreversible PAH group. Also, transgelin expression showed positive relation with pathological grading. Experiment in vitro demonstrated that transgelin overexpression promoted PASMC proliferation and migration, strengthened cytoskeleton and was accompanied by increased expression of synthetic phenotype markers (osteopontin, proliferating cell nuclear antigen) and anti‐apoptotic protein (bcl‐2). On the other hand, suppression of transgelin expression activated PASMC apoptosis, reducing cell proliferation and migration.ConclusionsTransgelin may be a potential target in the development of irreversible CHD‐PAH through inducing PASMC phenotype change, proliferation, migration and reducing cell apoptosis.
Investigating the childhood symptom profile of community‐based individuals diagnosed with attention‐deficit/hyperactivity disorder as adults
Authors: Taylor Mark J. , Larsson Henrik , Gillberg Christopher , Lichtenstein Paul , Lundström Sebastian 
Published: October 2018

BackgroundAttention‐deficit/hyperactivity disorder (ADHD) is currently defined as a disorder with onset during childhood. Although ADHD occurs in adults as well as children, recent debate has focused on whether adult ADHD represents a continuation of a child‐onset disorder or if ADHD may, in at least some cases, have an adult onset. We therefore aimed to test the hypothesis of adult‐onset ADHD using a sample born relatively recently (1992–1999) in order to minimize confounding by secular changes in diagnostic practices.MethodsWe identified 74 individuals with a community diagnosis of ADHD first assigned during adulthood. We also identified individuals with childhood (N = 194) and adolescent (N = 394) community diagnoses of ADHD. These groups were compared with a comparison group (N = 14,474) on their childhood ADHD and neuropsychiatric symptoms, and rate of other psychiatric diagnoses during childhood.ResultsHaving an adulthood community diagnosis of ADHD was associated with a mean increase in childhood ADHD symptoms of approximately three times that of the comparison group. Individuals with an adult community diagnosis of ADHD also displayed more autistic traits, motor problems, learning difficulties, tics, and oppositional behavior. Forty two percent of these individuals, compared with 1% of comparison cases, had a psychiatric diagnosis other than ADHD as children. In post‐hoc analyses of 21 ADHD cases showing few or no ADHD symptoms in childhood, we were unable to detect any other childhood symptomatology in only nine cases, of whom six were female.ConclusionsOur results indicate that alternative explanations for data that appear to show adult onset ADHD, such as sex biases in diagnostic practices, need rigorous testing before adult onset ADHD can be accepted as a valid clinical construct.
Impact of microwave drying on sesame coats quality
Authors: Khaldi Yakouta , Tounsi Leila , Balti Mohamed Amine , Kechaou Nabil 
Published: October 2018

AbstractThis work focused on studying the drying kinetics of sesame coat at different microwave drying levels (100, 180, 450, 700, and 850 W) and investigating its effect on physico‐chemical and functional properties. Results showed that the drying time was significantly affected by microwave power level. In fact, it decreased from 14 min at 100 W to 2 min at 850 W. Raw sesame coat, as an industrial by‐product, is characterized by a high water activity value (0.98) and fiber content (47.91 ± 3.60 g/100 g dry basis). The microwave drying had reduced significantly (p < .05) water activity to about 0.5. ANOVA test indicated that increasing microwave power level had no significant (p > .05) effect on both total phenol content and browning index. However, it had improved the functional properties (water and oil holding capacities).Practical applicationThe by‐products of sesame seed (Sesamum indicum L.) processing industries are considered as an excellent source of dietary fiber and may be used as a functional ingredient in food industry. This work evaluated the impact of microwave drying, as a new trend, on sesame coats’ quality. Experimental results showed that microwave application had a shorter processing time and it enhanced the quality of final products.