bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of an anxiolytic botanical containing Souroubea sympetala and Platanus occidentalis on in-vitro diazepam human cytochrome P450-mediated metabolism
Authors: Liu Rui , Dobson Corrine C , Foster Brian C , Durst Tony , Sanchez Pablo , Arnason John T , Harris Cory S 
Published: November 2018

Abstract

Objectives
A novel anxiolytic natural health product (NHP) containing Souroubea sympetala and Platanus occidentalis is available for the companion animal market and is currently being developed for clinical evaluation. Addressing the risk of potential NHP–drug interactions, this study investigated S. sympetala and P. occidentalis plant extracts, and their identified bioactive compounds, for effects on the activity of cytochrome P450 (CYP) isozymes and the metabolism of the conventional anti-anxiety medication diazepam.

Methods
Souroubea sympetala and P. occidentalis extracts, a 1 : 1 blend of the two extracts, and five triterpenes were tested for inhibitory effects on human recombinant CYP3A4, CYP2D6, CYP2C9 and CYP2C19 activity using a fluorometric plate assay. Direct effects on the metabolism of diazepam were evaluated using human liver microsomes with drug and metabolite quantification by ultra-high-pressure liquid chromatography and mass spectroscopy.

Key findings
The active substances betulinic acid (BA) and ursolic acid (UA) strongly inhibited CYP3A4 activity while UA and lupeol moderately inhibited CYP2C19. All extracts exhibited strong activity against the tested isozymes at 50–100 μg/ml. BA and all plant extracts blocked the formation of major diazepam metabolites.

Conclusions
Betulinic acid, UA and both the extracts and blended product are expected to affect the metabolism of diazepam when given in high dose.
Raised atmospheric CO2 levels affect soil seed bank composition of temperate grasslands
Authors: Seibert Ruben , Grünhage Ludger , Müller Christoph , Otte Annette , Donath Tobias W. 
Published: November 2018

AbstractQuestionsSoil seed banks buffer plant populations against environmental variability. But environmental changes can have profound impact on them. Several studies addressed the effect of climate change on aboveground vegetation, but studies on changes in the seed bank are rare. Thus, we studied the seed bank of a temperate grassland at a long‐term FACE (Free‐Air Carbon dioxide Enrichment) site, with the following questions: (a) Are there general differences in the species composition between aboveground vegetation and seed bank; (b) what are the impacts of elevated CO2 (eCO2) on seed density and species composition of the seed bank; and (c) are there differences in the functional traits of the seed bank species under eCO2 versus ambient CO2 (aCO2)?LocationTemperate grassland, Gießen, Germany.MethodThirty soil cores were taken in six FACE rings. Emerging seedlings were identified to species level after germination and aboveground vegetation was sampled. From the seed bank data, we derived diversity measures and weighted means of species traits, e.g., seed longevity and regeneration type, and compared eCO2 (+20% CO2 above ambient conditions) with aCO2 treatment.ResultsNonmetric multidimensional scaling ordination revealed a clear separation between seed bank and aboveground vegetation but no clear CO2 effect. Analyses revealed higher seed densities under eCO2. Species diversity and Shannon diversity were not significantly affected. Evenness decreased significantly under eCO2. There are shifts in functional traits of seed bank species. Seed density of long‐term‐persistent species increased, while short‐term‐persistent species decreased. Seed densities of species with generative reproduction increased under eCO2, while numbers of species with vegetative reproduction decreased.ConclusionThe observed trait compositions of the seed bank under eCO2 indicate that species relying on generative reproduction and production of long‐term‐persistent seeds have a competitive advantage under eCO2. The changes in the plant communities described above may lead to profound changes in the supply of grassland ecosystem services.
The Effects of Military Occupation on Growth
Authors: Vishwasrao Sharmila , Schneider Matthew , Chiang Eric P. 
Published: November 2018

SummaryA substantial literature exists on the effects of military expenditures on economic growth, yet no study has analyzed the effects of military occupation other than in anecdotal cases. This paper uses a panel of 214 countries from 1950 to 2013 to study how economic growth is impacted by different forms of military occupation. Transformative occupations aim to establish institutions to promote stability once the occupation ends, while subdual occupations are more malevolent in their objectives. Our results show that transformative occupations produce positive growth in occupied countries after the occupation period concludes. Separating these effects into the short run and long run, we find that while countries subject to a subdual occupation experience a short‐run increase in growth at the end of the occupation, countries with transformative occupation experience long‐run increases in growth. These findings are robust to the inclusion of traditional drivers of growth. Policy implications suggest that regional conflicts that are solved using military intervention may have lasting effects on growth as long as the intentions of the occupying force are transformative in nature.
What Does Trade Openness Measure?
Authors: Fujii Eiji 
Published: November 2018

AbstractAn empirical measure of trade openness is defined as the ratio of total trade to GDP, and represents a convenient variable routinely used for cross‐country studies on a variety of issues. However, the effects that the crude measure captures remain ambiguous, making it difficult to interpret the empirical results. Drawing on several strands of the literature, this study examines the informational content of the trade openness measure using intranational and international data. We find that, even for fully integrated economies within a country, trade openness is approximately half as variable as it is for segmented diverse countries around the world. The information it conveys is better characterized as the extent of the economic remoteness and idiosyncratic distribution of sectoral production. The cross‐country variation of trade openness derives more from the variability in GDP than trade.
Zinc biofortification of maize (Zea mays L.): Status and challenges
Authors: Maqbool Muhammad Amir , Beshir AbduRahman 
Published: November 2018

AbstractZn deficiency is one of the leading health problems in children and women of developing countries. Different interventions could be used to overcome malnutrition, but biofortification is most impactful, convenient, sustainable and acceptable intervention. Maize is one of the major crops grown and consumed in the regions with prevalent Zn malnutrition; therefore, this is suitable target for Zn biofortification. Zn biofortification of maize could be achieved through agronomic and genetic approaches. Discussion of agronomic approaches with genetic approaches is prerequisite because soils in developing countries are deficit of Zn and availability of Zn in soils is mandatory for estimating the genetic responses of maize genotypes through genetic approaches. Seed priming, foliar and soil applications are agronomic tools for biofortification, but solo and combined applications of these treatments have different effects on Zn enrichment. Genetic approaches include the increase of Zn bioavailability or increase of kernel Zn concentration. Zn bioavailability could be increased by reducing the anti‐nutritional factors or by increasing the bioavailability enhancers. Kernel Zn concentration could be improved through hybridization and selections, whereas genetically engineered attempts for improving Zn uptake from soil, loading in xylem, remobilization in grains and sequestration in endosperm can further improve the kernel Zn concentration. Key challenges associated with dissemination of Zn biofortified maize are also under discussion in this draft. Current review emphasized all of above‐mentioned contents to provide roadmap for the development of Zn biofortified maize genotypes to curb the global Zn malnutrition.
Population level changes in schistosome‐specific antibody levels following chemotherapy
Authors: Fukushige Mizuho , Mutapi Francisca , Woolhouse Mark E.J. 
Published: November 2018

SummaryAimsPrevious studies have reported that chemotherapy of schistosomiasis by praziquantel in humans boosts protective antibody responses against S mansoni and S haematobium. A number of studies have reported schistosome‐specific antibody levels before and after chemotherapy. Using these reports, a meta‐analysis was conducted to identify predictors of population level change in schistosome‐specific antibody levels after chemotherapy.Methods and resultsFollowing a systematic review, 92 observations from 26 articles published between 1988 and 2013 were included in this study. Observations were grouped by antigen type and antibody isotypes for the classification and regression tree (CART) analysis. The study showed that the change in antibody levels was variable: (a) between different human populations and (b) according to the parasite antigen and antibody isotypes. Thus, while anti‐worm responses predominantly increased after chemotherapy, anti‐egg responses decreased or did not show a significant trend. The change in antibody levels depended on a combination of age and infection intensity for anti‐egg IgA, IgM, IgG1, IgG2 and anti‐worm IgM and IgG.ConclusionThe study results are consistent with praziquantel treatment boosting anti‐worm antibody responses. However, there is considerable heterogeneity in post‐treatment changes in specific antibody levels that is related to host age and pre‐treatment infection intensity.
Lateral manus translation for limb‐sparing surgery in 18 dogs with distal radial osteosarcoma in dogs
Authors: Séguin Bernard , Walsh Peter J. , Ehrhart E. J. , Hayden Eva , Lafferty Mary H. , Selmic Laura E. 
Published: November 2018

AbstractObjectiveTo describe and report outcomes after lateral translation of the manus for limb‐sparing management of distal radial osteosarcoma in dogs.Study designRetrospective case series.Study populationEighteen client‐owned dogs.MethodsThe distal aspect of the affected radius and associated neoplastic tissues were excised. The distal aspect of the ulna was preserved except for its medial cortex, which was removed en bloc with the radial segment. The manus was translated laterally to place the radial carpal bone in contact with the distal aspect of the ulna. A limb‐sparing or locking compression plate was placed on the remaining proximal radius and the 3rd metacarpal bone. A 3.5‐mm SOP (string of pearls) plate was placed on the lateral aspect of the proximal ulna and the 4th metacarpal bone. Dogs were administered chemotherapy. Data were collected to assess surgical and oncologic outcomes. Limb function was subjectively assessed.ResultsThe percentage of radius removed ranged from 43% to 94% (median 54%). Complications developed in 12 limbs, with infection in 10, biomechanical complications in 6, and local recurrence in 4. Limb function was subjectively assessed as acceptable. Median disease‐free interval was 219 days, and median survival time was 370 days.ConclusionOutcomes after lateral translation of the manus compared favorably to other limb‐sparing techniques for dogs with distal radial osteosarcoma, particularly in dogs requiring excision of a large segment of the radius.Clinical significanceThe lateral manus translation provides an alternative limb‐sparing technique that does not require an allograft, endoprosthesis, or autograft.
Sources of social support and sexual behaviour advice for young adults in rural South Africa
Authors: Harling Guy , Gumede Dumile , Shahmanesh Maryam , Pillay Deenan , Bärnighausen Till W , Tanser Frank 
Published: November 2018

IntroductionWhile young people in sub-Saharan Africa (SSA) are at greatest risk of HIV acquisition, uptake of HIV prevention interventions among them has been limited. Interventions delivered through social connections have changed behaviour in many settings, but not to date in SSA. There is little systematic evidence on whom young SSA adults turn to for advice. We therefore conducted an exploratory cross-sectional study from whom young rural South Africans received support and sexual behaviour-specific advice.MethodsWe asked 119 18–34  year olds in rural KwaZulu-Natal about the important people in their lives who provided emotional, informational, financial, physical, social or other support. We also asked whether they had discussed sex or HIV prevention with each contact named. We used descriptive statistics and logistic regression to analyse support and advice provision patterns.ResultsRespondents named 394 important contacts, each providing a mean of 1.7 types of support. Most contacts were relatives, same-gender friends or romantic partners. Relatives provided most informational, financial and physical support; friends and partners more social support and sexual advice. Respondents reported discussing sexual matters with 60% of contacts. Sources of support changed with age, from friends and parents, towards siblings and partners.DiscussionSexual health interventions for young adults in rural South Africa may be able to harness friend and same-generation kin social ties through which sex is already discussed, and parental ties through which other forms of support are transmitted. The gender-segregated nature of social connections may require separate interventions for men and women.
Reliability and accuracy of delirium assessments among investigators at multiple international centres
Authors: Maybrier Hannah R , Mickle Angela M , Escallier Krisztina E , Lin Nan , Schmitt Eva M , Upadhyayula Ravi T , Wildes Troy S , Mashour George A , Palihnich Kerry , Inouye Sharon K , Avidan Michael Simon 
Published: November 2018

IntroductionDelirium is a common, serious postoperative complication. For clinical studies to generate valid findings, delirium assessments must be standardised and administered accurately by independent researchers. The Confusion Assessment Method (CAM) is a widely used delirium assessment tool. The objective was to determine whether implementing a standardised CAM training protocol for researchers at multiple international sites yields reliable inter-rater assessment and accurate delirium diagnosis.MethodsPatients consented to video recordings of CAM delirium assessments for research purposes. Raters underwent structured training in CAM administration. Training entailed didactic education, role-playing with intensive feedback, apprenticeship with experienced researchers and group discussions of complex cases. Raters independently viewed and scored nine video-recorded CAM interviews. Inter-rater reliability was determined using Fleiss kappa. Accuracy was judged by comparing raters’ scores with those of an expert delirium researcher.ResultsTwenty-seven raters from eight international research centres completed the study and achieved almost perfect agreement for overall delirium diagnosis, kappa=0.88 (95% CI 0.85 to 0.92). Agreement of the four core CAM features ranged from fair to substantial. The sensitivity and specificity for identifying delirium were 72% (95% CI 60% to 81%) and 99% (95% CI 96% to 100%), considering an expert rater’s scores as the reference standard (delirious, n=3; non-delirious, n=6). Delirium severity ratings were tightly clustered, with most scores within 5% of the median.ConclusionOur results demonstrate that, with appropriate training and ongoing scoring discussions, researchers at multiple sites can reliably detect delirium in postsurgical patients. These results support the premise that methodologically rigorous multi-centre studies can yield standardised and accurate determinations of delirium.
Prognostic significance of tumour infiltration growth pattern in patients with advanced gastric cancer
Authors: Zhao Bochao , Zhang Jiale , Mei Di , Huang Xinyu , Zou Shihui , Luo Rui , Xu Huimian , Huang Baojun 
Published: November 2018

AimsThe prognostic significance of infiltration growth pattern (INF) in patients with gastric cancer (GC) remains controversial. In the present study, we evaluated the impact of INF pattern on the prognosis of patients with advanced GC.MethodsA total of 1455 patients with advanced GC who underwent curative gastrectomy in our institution were retrospectively analysed. All patients were histopathologically classified as INFa/b and INFc pattern according to the Japanese Classification of Gastric Cancer. The prognostic difference between two patterns was compared and clinicopathological features were analysed.ResultsThe prognosis of the patients with INFc pattern was poorer than that of those with INFa/b pattern (5-year disease-free survival, INFa/b: 48.4% vs INFc: 33.5%, p < 0.001), even when they were stratified according to lymph node metastasis and the tumour, node, metastases stage. In addition, the subgroup analysis indicated that INFc pattern was significantly associated with poorer prognosis of T2–T3 stage patients (T2, INFa/b: 72.7% vs INFc: 55.4%; T3, INFa/b: 47.4% vs INFc: 33.5%; p<0.001). However, a similar result was not observed among T4a stage patients (INFa/b: 26.8% vs INFc: 24.8%, p>0.05). The prognosis of T2 stage patients with INFc pattern was similar to that of T3 stage patients with INFa/b pattern (p>0.05). Also, there was no significantly prognostic difference between T3 stage patients with INFc pattern and T4a stage patients (p>0.05). The multivariate analysis indicated that INF pattern was an independent prognostic factor for patients with advanced GC (HR 1.259, 95%CI 1.089 to 1.454).ConclusionIn view of its prognostic significance, histopathological evaluation of INF pattern in surgically resected specimens should be recommended in patients with advanced GC.
Employment trajectories in midlife and cognitive performance in later life: longitudinal study of older American men and women
Authors: Kobayashi Lindsay C , Feldman Justin Michael 
Published: November 2018

BackgroundAlthough being employed during midlife is positively associated with cognitive function in later life, little is known with respect to cumulative trajectories or durations of time spent in different kinds of work.MethodsWe investigated the relationships between employment trajectory from ages 31 years to 50 years and cognitive skills at ages 50–78 years among 2521 adults in the US Panel Study of Income Dynamics from 1968 to 2016. Sequence analysis was used to identify prototypical employment trajectories, capturing employment status and high versus lower job skill level at each year of age from 31 years to 50 years. Adjusted and weighted logistic regression was used to estimate relationships between employment trajectory and performance on each of four cognitive tests representing numerical reasoning, verbal reasoning, health literacy and financial literacy. Dose–response relationships between the duration of high-skill employment and cognitive skills were examined.ResultsSeven prototypical employment trajectories were identified, the most common being consistently lower skill employment (44%; 1105/2521). Consistently high-skill and fluctuating skill trajectories were associated with high numerical reasoning scores (OR=1.54, 95% CI 0.99 to 2.40; OR=2.52, 95% CI 1.39 to 4.58, respectively), compared with consistently lower skill employment. There was a dose–response relationship between duration of high-skill employment and numerical reasoning (OR=1.17; 95% CI 1.06 to 1.28), plateauing after approximately 4 years of high-skill employment.ConclusionsSequence analysis of exposure trajectories is a novel method for life course epidemiology that accounts for exposure timing, duration and ordering. Our results using this method indicate that the duration may be more important than the timing of high-skill midlife employment for later-life numerical reasoning skills.
SEC31A mutation affects ER homeostasis, causing a neurological syndrome
Authors: Halperin Daniel , Kadir Rotem , Perez Yonatan , Drabkin Max , Yogev Yuval , Wormser Ohad , Berman Erez M , Eremenko Ekaterina , Rotblat Barak , Shorer Zamir , Gradstein Libe , Shelef Ilan , Birk Ruth , Abdu Uri , Flusser Hagit , Birk Ohad S 
Published: November 2018

BackgroundConsanguineous kindred presented with an autosomal recessive syndrome of intrauterine growth retardation, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness and optic nerve atrophy with no eye fixation. Affected individuals died by the age of 4. Brain MRI demonstrated microcephaly, semilobar holoprosencephaly and agenesis of corpus callosum. We aimed at elucidating the molecular basis of this disease.MethodsGenome-wide linkage analysis combined with whole exome sequencing were performed to identify disease-causing variants. Functional consequences were investigated in fruit flies null mutant for the Drosophila SEC31A orthologue. SEC31A knockout SH-SY5Y and HEK293T cell-lines were generated using CRISPR/Cas9 and studied through qRT-PCR, immunoblotting and viability assays.ResultsThrough genetic studies, we identified a disease-associated homozygous nonsense mutation in SEC31A. We demonstrate that SEC31A is ubiquitously expressed, and that the mutation triggers nonsense-mediated decay of its transcript, comprising a practical null mutation. Similar to the human disease phenotype, knockdown SEC31A flies had defective brains and early lethality. Moreover, in line with SEC31A encoding one of the two coating layers comprising the Coat protein complex II (COP-II) complex, trafficking newly synthesised proteins from the endoplasmic reticulum (ER) to the Golgi, CRISPR/Cas9-mediated SEC31A null mutant cells demonstrated reduced viability through upregulation of ER-stress pathways.ConclusionWe demonstrate through human and Drosophila genetic and in vitro molecular studies, that a severe neurological syndrome is caused by a null mutation in SEC31A, reducing cell viability through enhanced ER-stress response, in line with SEC31A’s role in the COP-II complex.
Practice evaluation of biobank ethics and governance: current needs and future perspectives
Authors: Langhof Holger , Schwietering Johannes , Strech Daniel 
Published: November 2018

BackgroundBiobank research faces many ethical challenges. Ethics research aims to develop standards for governance to meet these challenges by elaborating overarching normative principles of medical ethics in the context of biobanking. Most ethical standards are widely agreed on among biobank stakeholders and entail specific governance solutions, for example, adoption of consent procedures. In order to fully meet its goal, every governance solution needs to be implemented, evaluated and, if necessary, adapted and improved in practice. This study reviews the scientific literature on biobank ethics and governance in order to identify studies that specifically focus on practice evaluation of biobank governance.MethodsA PubMed search was carried out. Retrieved literature was categorised and thematically clustered. All studies that focus on practice evaluation were reviewed and their objectives, results, and recommendations for practice summarised.ResultsThe findings show that the majority of studies on biobank ethics and governance are theoretical; only 25 out of 922 studies empirically evaluate biobank governance in practice. The majority of these (14; 59%) focused on informed consent. Six studies (24%) addressed practice evaluation of sample and data access; the rest focused on public involvement, ethics reporting and incidental findings. Other relevant governance areas such as ethics review, priority setting and sample ownership were not addressed.ConclusionIn order to fulfil the ethical goals, more empirical research is needed that provides information on how governance mechanisms perform in practice and what improvements are needed.