bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport
Authors: Pollard John , Rajabi-Siahboomi Ali , Badhan Raj K S , Mohammed Afzal R , Perrie Yvonne 
Published: February 2019

Abstract

Objective
In this study, we develop and apply a high-throughput screening protocol to investigate the activity of non-ionic surfactants, with a broad range of hydrophilic–lipophilic balance values, against ABCB1-mediated efflux transport and ABCC2-mediated efflux transport.

Methods
Caco-2 cells were grown for 7 days in 96-well plates, then washed and incubated with the test materials for 2 h in the presence of 2.5 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2′,7′ dichlorofluorescein diacetate as probes of ABCB1 and ABCC2, respectively.

Key findings
Of the surfactants tested, no activity against ABCC2 was detected and all surfactants showing efficacy against ABCB1 had a HLB value of 22 or below. Inhibition of ABCB1 was seen in the order of efficacy to be poloxamer 335 &gt; poloxamer 40 &gt; Crovol A-70 &gt; Myrj S-40 &gt; poloxamer 184 &gt; poloxamer 182 &gt; Etocas 40 &gt; Tween 20 &gt; Etocas 29 &gt; Tween 80 &gt; Acconon C-44 &gt; Span 20. With regard to this inhibition, the distribution of hydrophilic regions is more important than the HLB value.

Conclusion
This work demonstrates a high-throughput protocol for detecting materials that can modulate ABCB1-mediated efflux. These surfactants could be exploited to improve oral delivery of drugs prone to efflux.
Intra-articular mucilages: behavioural and histological evaluations for a new model of articular pain
Authors: Micheli Laura , Ghelardini Carla , Lucarini Elena , Parisio Carmen , Trallori Elena , Cinci Lorenzo , Di Cesare Mannelli Lorenzo 
Published: February 2019

Abstract

Objectives
The creation of a new valid preclinical model of articular pain by the intra-articular (i.a.) injection of mucilages for the screening of new treatments against arthritis.

Methods
A single intra-articular injection (20 μl) of mucilages (from Althaea officinalis roots and Linum usitatissimun seeds) or vegetal components (Amorphophallus konjac gum powder and β-glucan, used as reference standard) were assessed in the rat. The pathology progression was monitored by behavioural measurements (paw pressure test, von Frey test, incapacitance test and beam balance test) and compared to that induced by the i.a. injections of monoiodioacetate (MIA) and Complete Freund's Adjuvant (CFA), well-recognized models of osteoarthritis and rheumatoid arthritis, respectively.

Key findings
Among all, the mucilage of L. usitatissimun showed the best pro-algic profile inducing a painful long-lasting condition. Hypersensitivity was characterized as a mixed form of inflammatory and neuropathic pain by the responsiveness to ibuprofen (100 mg/kg, p.o.) and pregabalin (30 mg/kg, p.o.). The histological evaluation of joint showed a damage that represents both MIA and CFA features.

Conclusions
In conclusion, a single i.a. injection of L. usitatissimun mucilage can represent a valid model to assess articular pain in the rat for the screening of new treatments against arthritis.
The role of maternal obesity in infant outcomes in polycystic ovary syndrome—A systematic review, meta‐analysis, and meta‐regression
Authors: Bahri Khomami Mahnaz , Joham Anju E. , Boyle Jacqueline A. , Piltonen Terhi , Arora Chavy , Silagy Michael , Misso Marie L. , Teede Helena J. , Moran Lisa J. 
Published: February 2019

SummaryPolycystic ovary syndrome (PCOS) is associated with worsened pregnancy and infant outcomes, higher body mass index (BMI), and longitudinal weight gain. Despite most of the clinical features of PCOS being risk factors for worsened infant outcomes in the general population, their impact on infant outcomes in PCOS is unknown. We aimed to investigate the association of PCOS with infant outcomes considering maternal adiposity, other known risk factors, and potential confounders. The meta‐analyses included 42 studies in 7041 women with PCOS and 63 722 women without PCOS. PCOS was associated with higher gestational weight gain (GWG) and with higher preterm birth and large for gestational age and with lower birth weight with this association varying by geographic continent, PCOS phenotypes, and study quality. However, PCOS was associated with none of these outcomes on BMI‐matched studies. Gestational diabetes was significantly associated with an increased preterm birth on meta‐regression. We report for the first time that GWG is higher in PCOS. Infant outcomes vary by geographic continent and study quality but are similar in BMI‐matched women with and without PCOS. This suggests that infant outcomes in PCOS may be related to maternal obesity. These novel findings warrant future studies in PCOS investigating screening and management of infant outcomes with consideration of maternal obesity.
Modelling and forecasting world oil demand: a regional analysis accounting for asymmetric price responses and technical progress
Authors: Suleiman Mahmud 
Published: February 2019

AbstractThis study applies the structural time‐series modelling technique to investigate the relationship between aggregate oil consumption, income and prices across six regions of the world over the period 1970–2017. Following arguments in the energy economics literature on how to appropriately capture the impact of technical progress (TP) in modelling energy demand, this paper assumes a general model that incorporates asymmetric price responses (to capture endogenousTP) and an Underlying Energy Demand Trend (UEDT) (to capture exogenousTPand other factors) to estimate price and income elasticities for each region. These estimates are then used to produce future forecast scenarios of oil demand for each of the six world regions up to 2040 based on different assumptions about the future path of key variables that drive oil consumption. The results suggest that for the reference‐case scenario, global oil demand is projected to rise from 98 mb/d in 2017 to 118 mb/day in 2040 consisting of strong growth in the Middle East, Africa and Asia Pacific regions while oil consumption in North America, South/Central America and Europe/Eurasia regions is projected decline.
Mimicking natural polymorphism in eIF4E by CRISPR‐Cas9 base editing is associated with resistance to potyviruses
Authors: Bastet Anna , Zafirov Delyan , Giovinazzo Nathalie , Guyon‐Debast Anouchka , Nogué Fabien , Robaglia Christophe , Gallois Jean‐Luc 
Published: February 2019

SummaryIn many crop species, natural variation in eIF4E proteins confers resistance to potyviruses. Gene editing offers new opportunities to transfer genetic resistance to crops that seem to lack natural eIF4E alleles. However, because eIF4E are physiologically important proteins, any introduced modification for virus resistance must not bring adverse phenotype effects. In this study, we assessed the role of amino acid substitutions encoded by a Pisum sativum eIF4E virus‐resistance allele (W69L, T80D S81D, S84A, G114R and N176K) by introducing them independently into the Arabidopsis thaliana eIF4E1 gene, a susceptibility factor to the Clover yellow vein virus (ClYVV). Results show that most mutations were sufficient to prevent ClYVV accumulation in plants without affecting plant growth. In addition, two of these engineered resistance alleles can be combined with a loss‐of‐function eIFiso4E to expand the resistance spectrum to other potyviruses. Finally, we use CRISPR‐nCas9‐cytidine deaminase technology to convert the Arabidopsis eIF4E1 susceptibility allele into a resistance allele by introducing the N176K mutation with a single‐point mutation through C‐to‐G base editing to generate resistant plants. This study shows how combining knowledge on pathogen susceptibility factors with precise genome‐editing technologies offers a feasible solution for engineering transgene‐free genetic resistance in plants, even across species barriers.
The plastidial metabolite 2‐C‐methyl‐D‐erythritol‐2,4‐cyclodiphosphate modulates defence responses against aphids
Authors: Onkokesung Nawaporn , Reichelt Michael , Wright Louwrance P. , Phillips Michael A. , Gershenzon Jonathan , Dicke Marcel 
Published: February 2019

AbstractFeeding by insect herbivores such as caterpillars and aphids induces plant resistance mechanisms that are mediated by the phytohormones jasmonic acid (JA) and salicylic acid (SA). These phytohormonal pathways often crosstalk. Besides phytohormones, methyl‐D‐erythriol‐2,4‐cyclodiphosphate (MEcPP), the penultimate metabolite in the methyl‐D‐erythritol‐4‐phosphate pathway, has been speculated to regulate transcription of nuclear genes in response to biotic stressors such as aphids. Here, we show that MEcPP uniquely enhances the SA pathway without attenuating the JA pathway. Arabidopsis mutant plants that accumulate high levels of MEcPP (hds3) are highly resistant to the cabbage aphid (Brevicoryne brassicae), whereas resistance to the large cabbage white caterpillar (Pieris brassicae) remains unaltered. Thus, MEcPP is a distinct signalling molecule that acts beyond phytohormonal crosstalk to induce resistance against the cabbage aphid in Arabidopsis. We dissect the molecular mechanisms of MEcPP mediating plant resistance against the aphid B. brassicae. This shows that MEcPP induces the expression of genes encoding enzymes involved in the biosynthesis of several primary and secondary metabolic pathways contributing to enhanced resistance against this aphid species. A unique ability to regulate multifaceted molecular mechanisms makes MEcPP an attractive target for metabolic engineering in Brassica crop plants to increase resistance to cabbage aphids.
Blastemal predominant type Wilms tumor in Japan: Japan Children's Cancer Group
Authors: Koshinaga Tsugumichi , Takimoto Tetsuya , Okita Hajime , Tanaka Yukichi , Inoue Eisuke , Oue Takaharu , Nozaki Miwako , Tsuchiya Kunihiko , Haruta Masayuki , Kaneko Yasuhiko , Fukuzawa Masahiro 
Published: February 2019

AbstractBackgroundPersistence of blastemal components after chemotherapy is a marker of poor outcome in Wilms tumor (WT). Recent reports from local Japanese areas have described pre‐chemotherapy blastemal predominant type WT to also be a risk factor for relapse. The significance, however, of blastemal predominant WT remains to be evaluated in a larger study. This study retrospectively evaluated the prognostic significance of pre‐chemotherapy blastemal predominant type WT in the Japan Wilms tumor Study (JWiTS) trials.MethodsThe JWiTS trial (1996–2013) was a prospective, single‐arm study. The outcomes of blastemal predominant type WT were retrospectively evaluated compared with non‐blastemal type WT excluding anaplasia between 1996 and 2013. Relapse‐free survival (RFS) and overall survival (OS) were estimated.ResultsOf 319 primary renal tumors diagnosed by the central pathology review system, advanced stage of pre‐chemotherapy blastemal predominant type WT (n = 53; 16.1%) occurred more frequently in older children than non‐blastemal type WT (n = 225), and was especially frequent in female patients registered in the JWiTS trials. No significant difference in 10 years RFS and OS (78.8% vs 84.5; P = 0.201) or in 10 years RFS and OS (89.3% vs 93.5; P = 0.45) was seen between pre‐chemotherapy blastemal predominant type and non‐blastemal type WT.ConclusionsRelapse‐free survival and OS are not significantly different between pre‐chemotherapy blastemal predominant type and non‐blastemal type WT.
Retracted: Efficacy of vortioxetine combined cognitive behaviour intervention therapy on brain‐derived neurotrophic factor level on depressive patients
Authors: Yan Guanyun , Zhang Meng , Liu Yafang , Yin Mei 
Published: February 2019

BackgroundTo evaluate the effect of vortioxetine combined with cognitive behaviour intervention on the level of brain‐derived neurotrophic factor (BDNF) in the serum of patients with depression and its therapeutic effect.MethodsA total of 82 depressive patients treated at the School of Basic Medicine, Heilongjiang University of Chinese Medicine from January 2017 to June 2017 were randomised into a control group (n = 41) and intervention group (n = 41) according to a random number table. Both groups were given vortioxetine treatment, while the intervention group adopted an additional cognitive‐behavioural therapy at the same time. The therapeutic effect was evaluated using the Hamilton Depression Scale (HAMD). The cognitive function was evaluated using continuous performance test (CPT) and Wisconsin card sorting test (WCST). The changes of BDNF level were detected with the use of enzyme‐linked immunosorbent assay.ResultsThe HAMD score of the intervention group was obviously lower than that of the control group after treatment (P < 0.001). WCST test showed that the number of trials, perseverative errors and non‐perseverative errors in the intervention group were significantly lower than those in the control group, while the correct matching number and the number of categories achieved were significantly higher than those in the control group (all P < 0.001). Results of CPT showed that the correct number of responses to stimulus, the verbal fluency and the fluency of classification in the intervention group were significantly higher than those in the control group (all P < 0.05). Moreover, after treatment, the serum BDNF level of the intervention group was significantly higher than that in the control group (P < 0.001).ConclusionsVortioxetine combined with cognitive behavioural therapy has a good clinical effect and can largely improve the cognitive function of depressive patients.
Raf‐ERK1/2 signalling pathways mediate steroid hormone synthesis in bovine ovarian granulosa cells
Authors: Xu Dejun , He Huanshan , Jiang Xiaohan , Yang Lulu , Liu Dinbang , Yang Li , Geng Guoxia , Cheng Jianyong , Chen Huali , Hua Rongmao , Duan Jiaxin , Li Xiaoya , Wu Lin , Li Yuan , Li Qingwang 
Published: February 2019

ContentsSteroid hormones are required for normal reproductive function of female. The aim of this study was to investigate the role of Raf‐ERK1/2 on steroid hormone synthesis in bovine ovarian granulosa cells. Immunohistochemistry assay showed that both B‐Raf and C‐Raf were expressed in granulosa cells, theca cells and Sertoli cells. The protein expression of Raf or ERK1/2 was clearly decreased by Raf inhibitor GSK2118436 or ERK1/2 inhibitor SCH772984, respectively (p < 0.05). In addition, western blotting was performed for investigating the crosstalk between Raf and ERK1/2, the data showed that Raf positively regulated ERK1/2, whereas ERK1/2 had a negative feedback effect on Raf. The biosynthesis of oestradiol or testosterone was significantly decreased by treatment with GSK2118436 or SCH772984 (p < 0.05). Conversely, the progesterone biosynthesis was clearly increased by treatment with those inhibitors (p < 0.05). Furthermore, the mRNA expression of STAR, aromatase and CYP17 was blocked by Raf‐ERK1/2 signalling inhibition, which oppositely induced the mRNA expression of CYP11. Together, these findings suggested that Raf‐ERK1/2 signalling pathways mediate steroid hormone synthesis via affecting the expression of steroidogenic enzymes.
Older, Younger, or More Similar? The Use of Age as a Voting Heuristic*
Authors: Webster Steven W. , Pierce Andrew W. 
Published: February 2019

ObjectiveThe descriptive representation literature has found that individuals prefer to vote for candidates who share similar characteristics as themselves. However, the relationship between the age of a voter and the age of a candidate is a gap in the literature that remains to be filled. The objective of this study is to examine such relationships.MethodsUtilizing the 2010 and 2012 Cooperative Congressional Election Study, along with independently collected information on candidates’ ages, we use a series of logistic regressions to model the relationship between the age of a voter and the age of a co‐partisan candidate.ResultsOur analyses suggest that a candidate's age can and does act as a voting heuristic for members of the electorate. However, the strength of these findings is dependent upon the electoral context, individuals’ education levels, and the political party with which an individual affiliates.ConclusionThe effect of age has been an overlooked heuristic within the voting behavior literature. Members of the electorate prefer to vote for co‐partisan candidates who are closest to themselves in age.
Cross-sectional comparison of health-related quality of life and other features in people with and without objective and subjective binge eating using a general population sample
Authors: Li Natalie , Mitchison Deborah , Touyz Stephen , Hay Phillipa 
Published: February 2019

ObjectivesEvidence suggests that while objective binge eating (OBE) and subjective binge eating (SBE) differ in the amount of food consumed, both are associated with impairment in people with eating disorders. However, only OBE is accounted for in the diagnostic criteria of eating disorders. This study compared the sociodemographic profile and burden of OBE versus SBE at a population level.DesignPopulation-based survey.ParticipantsA representative sample of 3028 men and women. Participants were categorised into four groups based on their reporting of binge eating in the past 3 months: non-binge eating group (no OBE or SBE), OBE group, SBE group and OSBE group (both OBE and SBE).Outcome measuresDemographics (age, genderand body mass index, BMI), binge eating, distress, weight/shape overvaluation and health-related quality of life. Groups were compared on sociodemographic information, overvaluation and health-related quality of life. The OBE and SBE groups were also compared on the distress related to binge eating.ResultsNo differences were found between the SBE group and OBE group in age, gender, BMI, mental health-related quality of life and overvaluation (all p>0.05). However, differences were found in the OSBE participants, namely that they were younger, had a higher mean BMI, lower mental health-related quality of life and higher overvaluation of weight/shape than the non-binge-eating participants (all p<0.001). Proportions of participants who reported distress related to binge eating in the OBE and SBE groups also did not differ (p=0.678).ConclusionThere is little difference in the demographic profile or burden of people who engage in OBE versus SBE, supporting the proposed inclusion of SBE in the diagnostic criteria for eating disorders in International Classification of Diseases-11. People who experience both OBE and SBE may experience a relatively higher eating disorder severity and impairment.
Is liver transplantation ‘out-of-hours’ non-inferior to ‘in-hours’ transplantation? A retrospective analysis of the UK Transplant Registry
Authors: Halliday Neil , Martin Kate , Collett David , Allen Elisa , Thorburn Douglas 
Published: February 2019

ObjectivesIncreased morbidity and mortality have been associated with weekend and night-time clinical activity. We sought to compare the outcomes of liver transplantation (LT) between weekdays and weekends or night-time and day-time to determine if ‘out-of-hours’ LT has acceptable results compared with ‘in-hours’.Design, setting and participantsWe conducted a retrospective analysis of patient outcomes for all 8816 adult, liver-only transplants (2000–2014) from the UK Transplant Registry.Outcome measuresOutcome measures were graft failure (loss of the graft with or without death) and transplant failure (either graft failure or death with a functioning graft) at 30 days, 1 year and 3 years post-transplantation. The association of these outcomes with weekend versus weekday and day versus night transplantation were explored, following the construction of a risk-adjusted Cox regression model.ResultsSimilar patient and donor characteristics were observed between weekend and weekday transplantation. Unadjusted graft failure estimates were 5.7% at 30 days, 10.4% at 1 year and 14.6% at 3 years; transplant failure estimates were 7.9%, 15.3% and 21.3% respectively.A risk-adjusted Cox regression model demonstrated a significantly lower adjusted HR (95% CI) of transplant failure for weekend transplant of 0.77 (0.66 to 0.91) within 30 days, 0.86 (0.77 to 0.97) within 1 year, 0.89 (0.81 to 0.99) within 3 years and for graft failure of 0.81 (0.67 to 0.97) within 30 days. For patients without transplant failure within 30 days, there was no weekend effect on transplant failure. Neither night-time procurement nor transplantation were associated with an increased hazard of transplant or graft failure.ConclusionsWeekend and night-time LT outcomes were non-inferior to weekday or day-time transplantation, and we observed a possible small beneficial effect of weekend transplantation. The structure of LT services in the UK delivers acceptable outcomes ‘out-of-hours’ and may offer wider lessons for weekend working structures.
Detection ofEGFRmutations using target capture sequencing in plasma of patients with non-small-cell lung cancer
Authors: Bai Hao , Xia Jinjing , Zhao Xiaokai , Gong Ziying , Zhang Daoyun , Xiong liwen 
Published: February 2019

Purpose Circulating tumour DNA (ctDNA) is a promising biomarker for detection of non-invasive epidermal growth factor receptor(EGFR) mutations in patients with non-small-cell lung cancer (NSCLC). However, the existing methods have limitations in sensitivity or in availability. The aim was to evaluate the accuracy of capture target sequencing for detectingEGFRmutations in ctDNA.Methods A total of 79 patients with NSCLC and available plasma and matched tissue specimens were enrolled. Through capture target sequencing, mutations were searched in over 20 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. To evaluate the accuracy, detection ofEGFRmutations in matched tissue samples was performed by target capture sequencing and the amplification refractory mutation system (ARMS).Results EGFRmutations were discovered in 32.9 % (26/79) of the patients with NSCLC, the overall rate of consistency for the 79 paired plasma and tissue samples was 86.1 % (68/79). The sensitivity and specificity of detectingEGFRmutations in the plasma were 72.7 % and 95.7 %. In terms of theEGFRmutations identified by ARMS, the overall consistency was 78.5 % (62/79) in three groups. Of 21 patients withEGFRsensitive mutation defined by next generation sequencing in ctDNA, 20 (95.2%) showed long-term disease control with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment; the median progression-free survival was 10.8 months (95% CI 9.1 to 16.8).ConclusionsTarget capture sequencing of ctDNA can be used for genotyping ofEGFRin patients with NSCLC, which may enable a direct recommendation for EGFR TKI on the basis of positive results with plasma DNA.