bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats
Authors: Darweesh Ruba S. , El-Elimat Tamam , Zayed Aref , Khamis Tareq N. , Babaresh Wahby M. , Arafat Tawfiq , Al Sharie Ahmed H. 
Published: November 2020

AbstractBackgroundImatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, withN-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite,N-desmethyl imatinib, in SD-rats.MethodsStandardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib andN-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined.Resultsh-GS dose significantly decreased imatinib’s Cmaxand the$$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞by 61.1 and 72.2%, respectively. Similar effects onN-desmethyl imatinib’s exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold.l-GT caused a significant decrease in imatinib’s Cmaxand$$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞by 53.6 and 63.5%, respectively, with more significant effects onN-desmethyl imatinib’s exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively.h-GT showed similar effects as those ofl-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in CmaxofN-desmethyl imatinib by 71.5%.ConclusionsThese results demonstrated that the pharmacokinetics of imatinib andN-desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized.Graphical abstract
Open access in vocational education and training research: results from four structured group discussions
Authors: Getz Laura , Langenkamp Karin , Rödel Bodo , Taufenbach Kerstin , Weiland Meike 
Published: November 2020

AbstractAimOpen Access fosters the exchange of academic research information by making publications free of charge and, wherever possible, available through open licences and without any technical barriers. Although the Open Access publication model is already well established in the natural sciences, there seems to be more resistance towards Open Access in the social sciences, including the field of vocational education and training research. The research project “Open Access in Vocational Education and Training Research” aims to uncover the conditions influencing the acceptance, dissemination and use of Open Access in vocational education and training research. The project is grounded in a sociology of knowledge approach and in media theory. It comprises of two parts. First, four structured group discussions are conducted as focus groups and analysed using a qualitative content analysis. This paper focusses on this first part of the research project, the implementation and analysis of the group discussions as well as the results thereof. The second part of the research project will be based on an online questionnaire built upon these results. The questionnaire will be sent out to authors involved in vocational education and training research in the second part of the research project.FindingsThe analysis of the group discussions reveals several thematic clusters. According to group discussion participants, the scope of their publications as well as transparent quality assurance procedures in publishing are particularly relevant. The reputation of their chosen publication medium is another central aspect. It also becomes clear that in some cases an information deficit regarding the financing of Open Access publications or accompanying licensing models exists. Finally, participants discuss changing literature research strategies and changes of work and reading practices. The latter being clearly discernible in an increasingly digitalised daily work routine of vocational education and training researchers, while academic research communication is also an important topic discussed.
Does tertiary vocational education beat academic education? A matching analysis of young men’s earnings developments
Authors: Lukesch Veronika , Zwick Thomas 
Published: November 2020

AbstractThis paper shows that young men who completed an apprenticeship education plus a tertiary vocational education have considerably higher earnings during the first half of their career than those who obtained an academic education in addition to their apprenticeship education. We match employees with a tertiary vocational and an academic education based on their labour market experience and their individual and employer characteristics during their formative apprenticeship training years in which they presumably decided on their further education track. Then we compare the earnings developments in both groups of the matched sample during their tertiary education phase and after its completion for maximally 16 years after apprenticeship completion. We use linked employer-employee data of the IAB (LIAB9310).
Phylogenetic positions of “pico-sized” radiolarians from middle layer waters of the tropical Pacific
Authors: Li Luyan , Endo Kazuyoshi 
Published: November 2020

AbstractIn order to determine whether truly pico-sized adult radiolarians exist, we compared spumellarian sequences from individual adult samples collected in the central Pacific, with filtered sea water samples of juvenile (5–42 μm) and gamete (0.2–5 μm) sized fractions to see whether the gene sequences are similar or different. Environmental spumellarian-affiliated sequences we sampled were mostly concentrated in samples from 250 to 400 m depth and only appeared in the RAD-III clade, which corresponds to the family Astrosphaeridae (including Arachnosphaera, Astrosphaera, and Cladococcus). None of the same ITS (internal transcribed spacer) sequences were found in both filter membranes of the same sea water samples. Pairwise distances among these environmental spumellarian-affiliated sequences are within or slightly above the range of intra-morphospecific variations. We propose a model to explain our observations based on the hypothesis that the “pico-sized radiolarians” represent gametes of radiolarians of normal size, assuming different sinking speeds of parents and offspring.
Fully automated radiosynthesis of [18F]LBT999 on TRACERlab FXFN and AllinOne modules, a PET radiopharmaceutical for imaging the dopamine transporter in human brain
Authors: Vala Christine , Mothes Céline , Chicheri Gabrielle , Magadur Pauline , Viot Gilles , Deloye Jean-Bernard , Maia Serge , Bouvet Yann , Dupont Anne-Claire , Arlicot Nicolas , Guilloteau Denis , Emond Patrick , Vercouillie Johnny 
Published: November 2020

Abstract
Background
Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 was produced on a TRACERlab FXFN for the Phase I study but for Phase III and a potent industrial production transfer, production was also implemented on an AllinOne (AIO) system requiring a single use cassette. Both production methods are reported herein.

Results
Automation of [18F]LBT999 radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n = 16), with a radiochemical purity higher than 99% and a molar activity of 158 GBq/μmol at the end of synthesis. The transfer to the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n = 5), with a radiochemical purity better than 98% and a molar activity above 154 GBq/μmol on average at the end of synthesis. Quality controls of both methods met the specification for clinical application.

Conclusion
Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time. The developments made on AIO, such as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements, make it an optimal approach for the potent industrial production of [18F]LBT999 and future wider use.
Prevalence of incidental thyroid malignancy on routine 18F-fluorodeoxyglucose PET-CT in a large teaching hospital
Authors: Roddy Shea , Biggans Thomas , Raofi Ahmad K. , Kanodia Avinash , Sudarshan Thiru , Guntur Ramkumar Prasad 
Published: November 2020

Abstract
Purpose
To quantify incidental thyroid pathology including malignancy on routine 18F-FDG PET-CT scans
To compare standardised uptake values (SUVmax) in thyroid malignancy subtypes

Methods and materials
This is a retrospective study of all 18F-FDG PET-CT scans (n = 6179) performed in a teaching hospital between June 2010 and May 2019. RIS database search of reports for the word “thyroid” was performed. Studies with evidence of thyroid uptake were included. Patient age and gender, primary indication for PET scan (malignant or non-malignant), thyroid result on PET (diffuse or focal tracer uptake, SUVmax), ultrasound and FNAC results were recorded.

Results
Incidental abnormal thyroid tracer uptake as a proportion of all 18F-FDG PET-CT scans was 4.37% (n = 270). Out of region patients (n = 87) whose records could not be obtained were excluded leaving a study group of n = 183. Ninety-four in this group had focal uptake, and 89 had diffuse uptake. Fifty-five patients in the focal group had undergone further investigations. Of these, 30 were thought to be benign on USS alone, and 25 patients underwent USS/FNAC. Thirteen (24%) malignancies were identified (5 papillary, 6 follicular, 1 poorly differentiated thyroid cancer, 1 metastatic malignancy). Mean SUVmax for papillary carcinoma was noted to be 8.2 g/ml, and follicular carcinoma was 12.6 g/ml.

Conclusion
Incidental abnormal thyroid 18F-FDG PET-CT uptake in PET-CT scans of 4.37% is in keeping with the known limited literature. Rather similar number of patients was noted in the focal and diffuse tracer uptake categories in the final study group. Around quarter of the focal lesions were identified to be malignant, implying focal lesions should always be further investigated.
A deep learning model to predict recurrence of atrial fibrillation after pulmonary vein isolation
Authors: Kim Ju Youn , Kim Younghoon , Oh Gil-Hwan , Kim Sun Hwa , Choi Young , Hwang Youmi , Kim Tae-Seok , Kim Sung-Hwan , Kim Ji-Hoon , Jang Sung-Won , Oh Yong-Seog , Lee Man Young 
Published: November 2020

Abstract
Background and Objectives
The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI.

Materials and methods
This study was a retrospective cohort study that enrolled consecutive patients who underwent catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recurrence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images.

Results
We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolutional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7).

Conclusion
In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly; therefore, further large-scale study is needed.
Helping to heal nature and ourselves through human-rights-based and gender-responsive One Health
Authors: Garnier Julie , Savic Sara , Boriani Elena , Bagnol Brigitte , Häsler Barbara , Kock Richard 
Published: November 2020

AbstractThe health of our planet and humanity is threatened by biodiversity loss, disease and climate crises that are unprecedented in human history, driven by our insatiable consumption and unsustainable production patterns, particularly food systems. The One Health approach is a pathway to synergistically addressing outcomes in term of health and sustainability, but gender issues at the One Health and biodiversity nexus are largely ignored.By examining the roles and responsibilities of Indigenous and Local People, and especially women, in conserving natural resources, and the social costs of living at the Human-Animal-Environment interface under current conservation strategies, we show that women bear a disproportionate health, poverty and climate burden, despite having pivotal roles in conserving biodiversity. To mitigate risks of emerging infectious diseases, food insecurity and climate change impacts, a gender perspective has previously been proposed, but implementation lags behind. Endemic zoonotic diseases, human-wildlife conflict and environmental pollution lack gender-sensitive frameworks. We demonstrate that women can be powerful agents for change at all levels of society, from communities to businesses, and policy-making institutions, but gender inequalities still persist.We develop a framework for mainstreaming a gender-responsive and rights-based One Health approach, in order to heal ourselves and nature. Using a leverage-points perspective, we suggest a change of paradigm, from the pursuit of GDP and over-consumption, to a focus on human well-being and their reconnection with healthy environments, using a One Health understanding of nature and health. We recommend learning from Indigenous People to re-position ourselves within nature and to better conserve biodiversity. We also propose integration of gender equity in leadership, the respect of human rights, women’s rights (access to health care, healthy food, land tenure, natural resources, education, and economic opportunities), and the rights of nature, through the implementation of gender-responsive and rights-based One Health Action Plans, at policy-making level, in the private sector and the civil society. As the COVID-19 pandemic continues to unveil deep socio-economic inequities in the wealthiest economies and the vital role of nature in supporting our health, we argue to seize this opportunity to build back better and improve resilience and sustainability by using a gender-responsive and rights-based One Health approach.
Educational attainment inequalities in depressive symptoms in more than 100,000 individuals in Europe
Authors: Chlapecka Adam , Kagstrom Anna , Cermakova Pavla 
Published: November 2020

AbstractBackgroundIncreasing educational attainment (EA) could decrease the occurrence of depression. We investigated the relationship between EA and depressive symptoms in older individuals across four European regions.MethodsWe studied 108,315 Europeans (54% women, median age 63 years old) from the Survey on Health, Ageing and Retirement in Europe assessing EA (seven educational levels based on International Standard Classification of Education [ISCED] classification) and depressive symptoms (≥4 points on EURO-D scale). Logistic regression estimated the association between EA and depressive symptoms, adjusting for sociodemographic and health-related factors, testing for sex/age/region and education interactions.ResultsHigher EA was associated with lower odds of depressive symptoms, independent of sociodemographic and health-related factors. A threshold of the lowest odds of depressive symptoms was detected at the first stage of tertiary education (OR 0.60; 95% confidence interval [CI] 0.55–0.65;p < 0.001; relative to no education). Central and Eastern Europe showed the strongest association (OR for high vs. low education 0.37; 95% CI 0.33–0.40;p < 0.001) and Scandinavia the weakest (OR for high vs. low education 0.69; 95% CI 0.60–0.80;p < 0.001). The association was strongest among younger individuals. There was a sex and education interaction only within Central and Eastern Europe.ConclusionsLevel of EA is reflected in later-life depressive symptoms, suggesting that supporting individuals in achieving EA, and considering those with lower EA at increased risk for depression, could lead to decreased burden of depression across the life course. Further educational support in Central and Eastern Europe may decrease the higher burden of depressive symptoms in women.
Comparison of the ELISA and ECL Assay for Vedolizumab Anti-drug Antibodies: Assessing the Impact on Pharmacokinetics and Safety Outcomes of the Phase 3 GEMINI Trials
Authors: Wyant Timothy , Yang Lili , Rosario Maria 
Published: November 2020

AbstractVedolizumab immunogenicity has been assessed using an enzyme-linked immunosorbent assay (ELISA) with a ~ 0.5 μg/mL drug interference, which may underestimate on-drug immunogenicity. We aimed to compare immunogenicity results between ELISA and the new drug-tolerant electrochemiluminescence (ECL) assay (and the two versions of neutralizing assays, drug-sensitive versus drug-tolerant). The ECL assay drug tolerance is ~ 100 times higher than that of the ELISA (≥ 50 μg/mL vs. 0.5 μg/mL with a 500 ng/mL positive control), and assay sensitivity is < 5 ng/mL for both assays. Vedolizumab immunogenicity was assessed in 2000 GEMINI 1 and 2 patients originally tested by ELISA and retested by ECL assay. Anti-drug antibody (ADA) impact on infusion-related reactions and pharmacokinetics (PK) was examined using descriptive statistics and population PK analyses. By ECL assay, 6% (86/1427) of patients treated with vedolizumab as induction and maintenance therapy tested ADA-positive. Of these, 20 patients were persistently positive and 56 had neutralizing antibodies. By ELISA, 4% (56/1434) of these patients were ADA-positive, 9 were persistently positive, and 33 had neutralizing antibodies. Among 61 patients with infusion-related reactions, 6 (10%) were ADA-positive (2 persistently positive) by ECL assay. By ELISA, 3 (5%) patients were both ADA-positive and persistently positive. Most results (96%) were similar with both assays. In the updated population PK model, ADA-positive status was estimated to increase vedolizumab linear clearance by a factor of 1.10 (95% credible interval 1.03–1.17), which is consistent with previous reports. The impact of ADA on safety and PK modeling remained generally consistent using either ELISA or ECL assay. ClinicalTrials.gov: NCT00783718 and NCT00783692
Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers
Authors: Acosta Maria F. , Abrahamson Michael D. , Encinas-Basurto David , Fineman Jeffrey R. , Black Stephen M. , Mansour Heidi M. 
Published: November 2020

AbstractMetformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs. Organic solution advanced spray drying in the absence of water in closed-mode was used to design and develop respirable dry powders. Following comprehensive characterization, the influence of physicochemical properties was correlated with performance as aerosols using inertial impaction and three different human dry powder inhaler (DPI) devices varying in device properties.In vitrocell assays were conducted to test safety in 2D human pulmonary cell lines and in 3D small airway epithelia comprising primary cells at the air-liquid interface (ALI). In addition,in vitrotransepithelial electrical resistance (TEER) was carried out. Metformin remained crystalline following advanced spray drying under these conditions. All SD powders consisted of nanoparticles/microparticles in the solid state.In vitroaerosol dispersion performance showed high aerosolization for all SD metformin powders with all DPI devices tested. High emitted dose for all powders with all three DPI devices was measured. Differences in other aerosol performance parameters and the interplay between the properties of different formulations produced at specific pump rates and the three different DPI devices were correlated with spray drying pump rate and device properties. Safety over a wide metformin dose range was also demonstratedin vitro. Aerosol delivery of metformin nanoparticles/microparticles has the potential to be a new “first-in-class” therapeutic for the treatment of a number of pulmonary diseases including pulmonary vascular diseases such as pulmonary hypertension.
Dinuclear Triple-Stranded Helicates Comprising Al(III), Ga(III), or In(III) and a Hydrazine-Linked Bisiminopyrrolyl Ligand: Synthesis, Structure, Optical Resolution, and Chiroptical Properties
Authors: Ishihama Kohei , Ono Toshikazu , Okawara Toru , Harada Takunori , Furusho Kiyonao , Hasegawa Masashi , Nojima Yuki , Koide Taro , Abe Masaaki , Hisaeda Yoshio 
Published: November 2020

Abstract
The synthesis of helical complexes is attracting increased attention because their chiral properties lead to a variety of functional applications. In this work, a series of neutral, dinuclear M(III) (M = Al, Ga, or In) triple-stranded helicates were prepared using a tetradentate bisiminopyrrole ligand (H2L). An X-ray crystallographic analysis revealed that both right- (P) and left-handed (M) helical structures exist in the solid state for Al2L3, Ga2L3, and In2L3. The enantiomers were successfully resolved by chiral column chromatography, and the chiroptical properties of the complexes were characterized by circular dichroism, circularly polarized emission spectroscopy, and time-dependent density functional theory calculations.