bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diacylglycerol kinase α‐selective inhibitors induce apoptosis and reduce viability of melanoma and several other cancer cell lines
Authors: Yamaki Atsumi , Akiyama Rino , Murakami Chiaki , Takao Saki , Murakami Yuki , Mizuno Satoru , Takahashi Daisuke , Kado Sayaka , Taketomi Akinobu , Shirai Yasuhito , Goto Kaoru , Sakane Fumio 
Published: December 2018

AbstractDiacylglycerol (DG) kinase (DGK), which phosphorylates DG to generate phosphatidic acid (PA), consists of ten isozymes (α–к). Recently, we identified a novel small molecule inhibitor, CU‐3, that selectively inhibits the activity of the α isozyme. In addition, we newly obtained Compound A, which selectively and strongly inhibits type I DGKs (α, β, and γ). In the present study, we demonstrated that both CU‐3 and Compound A induced apoptosis (caspase 3/7 activity and DNA fragmentation) and viability reduction of AKI melanoma cells. Liquid chromatography‐mass spectrometry revealed that the production of 32:0‐ and 34:0‐PA species was commonly attenuated by CU‐3 and Compound A, suggesting that lower levels of these PA molecular species are involved in the apoptosis induction and viability reduction of AKI cells. We determined the effects of the DGKα inhibitors on several other cancer cell lines derived from refractory cancers. In addition to melanoma, the DGKα inhibitors enhanced caspase 3/7 activity and reduced the viability of hepatocellular carcinoma, glioblastoma, and pancreatic cancer cells, but not breast adenocarcinoma cells. Interestingly, Western blot analysis indicated that the DGKα expression levels were positively correlated with the sensitivity to the DGK inhibitors. Because both CU‐3 and Compound A induced interleukin‐2 production by T cells, it is believed that these two compounds can enhance cancer immunity. Taken together, our results suggest that DGKα inhibitors are promising anticancer drugs.
Functional analysis of DNA methylation of the PACSIN1 promoter in pig peripheral blood mononuclear cells
Authors: Feng Wen , Zhou Lei , Wang Haifei , Hu Zhengzheng , Wang Xiaomei , Fu Jianlian , Wang Aiguo , Liu Jian‐Feng 
Published: December 2018

AbstractDNA methylation plays essential roles in regulating the activity of genes and may contribute to understanding the potential epigenetic biomarkers response to viruses. To explore the function of DNA methylation of protein kinase C and casein kinase substrate in neurons 1 (PACSNI1) promoter, herein we performed the bisulfite sequencing polymerase chain reaction and Western blot analysis to verify hypermethylation and downregulation of PACSIN1 expression in peripheral blood mononuclear cells of pig as the vitro model. Promoter methylation could reduce the transcriptional activity of the PACSIN1 gene potentially by affecting the binding of transcription factor Sp1. In addition, downregulation of the PACSIN1 gene expression could facilitate the production of interleukin‐6 (IL‐6), IL‐8, tumor necrosis factor α, and NECAP2. The comprehensive analysis of PACSIN1 methylation and its function will help us to understand the gene to be served as an important candidate gene in pig for disease resistance breeding and aid in the identification of potential epigenetic biomarkers associated with responsiveness to viruses.
Food Effect Study Design With Oral Drugs: Lessons Learned From Recently Approved Drugs in Oncology
Authors: Farha Mark , Masson Eric , Tomkinson Helen , Mugundu Ganesh 
Published: December 2018

AbstractEvaluation of the effect of food on the pharmacokinetics of oral oncology drugs is critical to drug development, as food can mitigate or exacerbate toxicities and alter systemic exposure. Our aim is to expand on current US Food and Drug Administration (FDA) guidance and provide data‐driven food‐effect study design recommendations specific to the oncology therapeutic area. Data for recently approved small‐molecule oncology drugs was extracted from the clinical pharmacology review in the sponsor's FDA submission package. Information on subject selection, meal types, timing of the study relative to the pivotal trial, and study outcomes was analyzed. The number of subjects enrolled ranged from 12 to 60, and the majority of studies (19 of 29) were conducted in healthy volunteers. Using AstraZeneca cost data, healthy volunteer studies were estimated to cost 10‐fold less than cancer patient studies. Nine of 29 (31%) studies included meals with multiple levels of fat content. Analysis of a subset of 16 drugs revealed that final results for the food‐effect study were available before the start of the pivotal trial for only 2 drugs. Conducting small food‐effect studies powered to estimate effect, rather than confirm no effect, with only a standardized high‐fat meal according to FDA guidance may eliminate unnecessary studies, reduce cost, and improve efficiency in oncology drug development. Starting food‐effect studies as early as possible is key to inform dosing in pivotal trials.
Population Pharmacokinetics and Bayesian Estimation of Mycophenolic Acid Exposure in Chinese Renal Allograft Recipients After Administration of EC‐MPS
Authors: Chen Bing , Shao Kun , An Hui‐Min , Shi Hao‐Qiang , Lu Jia‐Qian , Zhai Xiao‐Hui , Liu Xiao‐Xue , Wang Xiang‐Hui , Xu Da , Zhou Pei‐Jun 
Published: December 2018

AbstractThe aim of the present study is to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA) and limited sampling strategy models for the estimation of MPA exposure in Chinese adult renal allograft recipients following oral administration of enteric coated mycophenolate sodium (EC‐MPS). A total of 74 sets of full pharmacokinetic profiles and 47 sets of MPA‐sparing samples were collected from 102 renal transplant recipients who received oral EC‐MPS. The MPA concentration was determined by an enzyme‐multiplied immunoassay technique, and the pathophysiologic data were recorded. The PPK model was constructed using nonlinear mixed‐effects modeling, and the limited sampling strategy models for MPA were established by using multiple regression analysis and the maximum a posteriori Bayesian assay based on 2 to 4 sampling time points following EC‐MPS administration. The pharmacokinetics of MPA were best described by a 2‐compartment model with a first‐order absorption process and a lag time of absorption. The clearance of MPA was 12.3 ± 1.14 L/h. Comedicating with cyclosporine A was found to have a significant impact on the clearance/bioavailability of MPA (P < .01). Sampling strategies consisted of plasma concentration at 1.5, 2, 4 (C1.5‐C2‐C4) hours and 1.5, 2, 4, 6 (C1.5‐C2‐C4‐C6) hours after EC‐MPS administration were shown to be suitable for the estimation of the MPA area under the concentration‐time curve in these patients. The PPK model was acceptable and can describe the pharmacokinetics of MPA in Chinese renal transplant recipients administered EC‐MPS. The area under the concentration‐time curve of MPA in Chinese renal transplant recipients could be estimated through a limited sampling strategy method, based on which individualized immunosuppressive regimens could be designed.
Synthesis and Biological Evaluation of New Ibuprofen‐1,3,4‐oxadiazole‐1,2,3‐triazole Hybrids
Authors: Rayam Parsharamulu , Polkam Naveen , Kummari Bhaskar , Banothu Venkanna , Gandamalla Durgaiah , Yellu Narsimha Reddy , Anireddy Jaya Shree 
Published: December 2018

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4‐oxadiazole, and 1,2,3‐triazole linked through a thioether bridge was achieved by one‐pot synthesis by exploring multicomponent Cu‐catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC‐Mass. The X‐ray analysis of 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐(3‐nitrophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole (8a) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole (8b) demonstrated more potent antibacterial activity against Gram‐negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2‐(((1‐(2,4‐dimethylphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐5‐(1‐(4 isobutylphenyl)ethyl)‐1,3,4‐oxadiazole (8e) exhibited anticancer activity with IC50 of 27.50 and 31.03 μg/mL against HeLa and MCF‐7 cell lines, respectively.
The impact of freeze–thaw cycles and soil moisture content at freezing on runoff and soil loss
Authors: Wei Xia , Huang Chihua , Wei Ning , Zhao Hengce , He Yan , Wu Xiaodong 
Published: December 2018

AbstractThe freeze–thaw (F‐T) cycles play an important role in soil erosion, although quantitative description of this effect is challenging due to the complicated interactions of soil moisture content (SMC), surface hydrology, and flow hydraulics involved in processes of erosion. In this study, we investigated the influences of F‐T cycles and SMC at freezing on runoff and soil loss under simulated rainfall in the U.S. Department of Agriculture Agricultural Research Service National Soil Erosion Research Lab. The SMCs at the start of freezing were adjusted to 10% and 20%, undergone 1, 3, and 6 F‐T cycles with freezing at −12°C for 24 hr and followed by thawing at 4°C for 24 hr. After designed F‐T cycle, the air‐dried soils were packed into the 0.5‐m‐long, 0.2‐m‐wide, 0.1‐m‐deep soil boxes and subjected to simulated rainfall. The results showed that the impact of 20% SMC was greater than that of 10% SMC under the same F‐T cycles and rainfall intensities. The impact of F‐T cycles on runoff and soil loss increased with the number of F‐T cycles at 10% SMC. However, at 20% SMC, the impact on runoff and soil loss increased after 1 and 3 F‐T cycles and declined after 6 F‐T cycles. Furthermore, the impact of SMC on runoff and soil loss was greater than the impact from different F‐T cycles. This research fills a gap in the current literature on Alfisols affected by the F‐T processes, and results are useful in the assessment of runoff and soil loss in regions where winter processes are significant.
Sawyer's duality principle for grand Lebesgue spaces
Authors: Jain Pankaj , Singh Arun Pal , Singh Monika , Stepanov Vladimir D. 
Published: December 2018

AbstractThe aim of this paper is to extend Sawyer's duality principle from the cone of decreasing functions of the Lebesgue space to the cone of decreasing functions of the grand Lebesgue space and to prove the boundedness of classical Hardy operators in the grand Lebesgue spaces.
Utility and implications of exome sequencing in early‐onset Parkinson's disease
Authors: Trinh Joanne , Lohmann Katja , Baumann Hauke , Balck Alexander , Borsche Max , Brüggemann Norbert , Dure Leon , Dean Marissa , Volkmann Jens , Tunc Sinem , Prasuhn Jannik , Pawlack Heike , Imhoff Sophie , Lill Christina M. , Kasten Meike , Bauer Peter , Rolfs Arndt ,   International Parkinson's Disease Genomics Consortium (IPDGC), Klein Christine 
Published: December 2018

ABSTRACTBackgroundAlthough the genetic load is high in early‐onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early‐onset PD.MethodsWe searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes. Further, exome data from 1148 European PD patients (International Parkinson Disease Genomics Consortium) were used for association testing.ResultsSeven patients (14%) carried pathogenic or likely pathogenic variants in Parkin, PLA2G6, or GBA. In addition, rare missense variants in DNAJC13:p.R1830C and in PPM1K:p.Y352C were detected. SPG7:p.A510V and PPM1K:p.Y352C revealed significant association with PD risk (P < 0.05).ConclusionsAlthough we identified pathogenic variants in 14% of our early‐onset PD patients, the majority remain unexplained, and novel candidates need to be validated independently to better further evaluate their role in PD. © 2018 International Parkinson and Movement Disorder Society
Evaluating the impact of an assertiveness communication training programme for Japanese nursing students: A quasi‐experimental study
Authors: Omura Mieko , Levett‐Jones Tracy , Stone Teresa E. 
Published: December 2018

AbstractAimTo examine the impact of an assertiveness communication training programme on Japanese nursing students’ level of assertiveness and intention to speak up when concerned about patient safety.DesignA quasi‐experimental design with two parallel groups was used.MethodsThird‐year nursing students from two Japanese educational institutions were allocated to an intervention and control group. The intervention group completed the Theory of Planned Behaviour–Assertive Communication Questionnaire and the Japanese version of the Rathus Assertiveness Schedule after attending assertive communication workshops. The second group completed the surveys before attending the workshop and were referred as the control group. Data were collected in December 2017–January 2018.ResultsA total of 123 out of 150 nursing students completed the surveys. Following the assertiveness communication training programme, a higher percentage of students from the intervention group demonstrated the intention to speak up. The intervention group also displayed higher levels of assertiveness, although the results were not statistically significant.
An examination of children's eating behaviours as mediators of the relationship between parents' feeding practices and early childhood body mass index z‐scores
Authors: Boswell N. , Byrne R. , Davies P. S. W. 
Published: December 2018

SummaryObjectiveParent's use of restrictive feeding practices is associated with child weight. Similarly, the literature shows that children's eating behaviours are also associated with child weight. Given this interrelationship between children's eating behaviours, restrictive feeding practices and child weight, examination of possible mediator relationships is warranted. This study aimed to examine the relationships between overt restriction and covert restriction with child body mass index z‐scores (BMIz) and determine if children's eating behaviours (satiety responsiveness and food responsiveness) act as mediators.MethodParents of Australian children (n = 977) 2.0–5.0 years of age (49.4% male) provided data in an online survey on child eating behaviours, parent's restrictive feeding practices and child anthropometrics (modified z‐scores were created to screen for biologically implausible values). Correlation analysis was used to determine variables to include in mediation models. Hayes' PROCESS macros in spss was used to examine mediation, controlling for covariates of child BMIz.ResultsOvert restriction was the only parent feeding practice related to child BMIz (B = 0.132, P = 0.04). Mediation analysis showed that the indirect effect of overt restriction on child BMIz (controlling for child age, gender, parent BMI and income) became non‐significant when controlling for food responsiveness, thus suggesting full mediation, explaining 5.75% of the relation.ConclusionOvert restriction and covert restriction have distinctly different relationships with children's eating behaviours. Food responsiveness appears an important intermediary in the relationship between overt restriction and child BMIz.
Integrating a photovoltaic storage system in one device: A critical review
Authors: Vega‐Garita Victor , Ramirez‐Elizondo Laura , Narayan Nishant , Bauer Pavol 
Published: December 2018

AbstractDue to the variable nature of the photovoltaic generation, energy storage is imperative, and the combination of both in one device is appealing for more efficient and easy‐to‐use devices. Among the myriads of proposed approaches, there are multiple challenges to overcome to make these solutions realistic alternatives to current systems. This paper classifies and identifies previous efforts to achieve integrated photovoltaic storage devices. Moreover, the gaps and future perspectives are analysed to give an overview of the field, paying attention to low‐power devices (<10 W) as well as high‐power devices (>10 W). We focus on devices that combine solar cells with supercapacitors or batteries, providing information about the structure, materials used, and performance. On the one hand, small power devices must concentrate on including power electronics to increase the efficiency of the system as well as ensuring a safe operation; likewise, more attention should be drawn to validate the feasibility of novel concepts by carrying out more realistic and standardised tests, including long‐term testing. On the other hand, high‐power devices must be researched thoroughly to evaluate the impact of high temperatures on energy storage and solar module ageing; furthermore, optimum system sizing is a relevant topic that deserves attention and its relation to modular solutions. This critical literature review serves as a guide to understand the characteristics of the approaches followed to integrate photovoltaic devices and storage in one device, shedding light on the improvements required to develop more robust products for a sustainable future.
The Calotropis procera Transformed Green NiO and Fe‐NiO Nanoparticles for Diaryl Pyrimidinones Synthesis in Hydrotropic Medium at Room Temperature
Authors: Shinde Bipin , Kamble Santosh B. , Jadhav Harsharaj S. , Karale Bhausaheb K. , Kanade Kaluram G. , Burungale Arvind S. 
Published: December 2018

AbstractWe report the synthesis of NiO and Fe doped NiO nanoparticles by simple and cost effective Calotropis procera leaf extract assisted green co‐precipitation method. The leaf extract of Calotropis procera acts as reducing as well as capping agent for the synthesis of NiO and Fe doped NiO. The presence of –OH and aldehydic group (‐CHO) on synthesized nanoparticle imparts their strong interaction with synthesized nanoparticles, conveying efficient catalyst for heterocycle synthesis. The proficient catalytic application of biogenic NiO and Fe doped NiO NPs were explored in aqueous hydrotropic solution for syntheses of diaryl pyrimidinones at room temperature. The synthesized catalysts are efficient in terms of yield, reaction time and reusability. The NiO or Fe doped NiO/NaPTS/27°C is efficient, highly sustainable catalytic system for heterocycle synthesis at room temperature. Accordingly, Fe doped NiO/NaPTS proved to be a better catalytic system than NiO/NaPTS in water.
Bismuth Ferrite Second Harmonic Nanoparticles for Pulmonary Macrophage Tracking
Authors: Ramos‐Gomes Fernanda , Möbius Wiebke , Bonacina Luigi , Alves Frauke , Markus Marietta Andrea 
Published: December 2018

AbstractRecently, second harmonic generation (SHG) nanomaterials have been generated that are efficiently employed in the classical (NIR) and extended (NIR‐II) near infrared windows using a multiphoton microscope. The aim was to test bismuth ferrite harmonic nanoparticles (BFO‐HNPs) for their ability to monitor pulmonary macrophages in mice. BFO‐loaded MH‐S macrophages are given intratracheally to healthy mice or BFO‐HNPs are intranasally instilled in mice with allergic airway inflammation and lung sections of up to 100 μM are prepared. Using a two‐photon‐laser scanning microscope, it is shown that bright BFO‐HNPs signals are detected from superficially localized cells as well as from deep within the lung tissue. BFO‐HNPs are identified with an excellent signal‐to‐noise ratio and virtually no background signal. The SHG from the nanocrystals can be distinguished from the endogenous collagen–derived SHG around the blood vessels and bronchial structures. BFO‐HNPs are primarily taken up by M2 alveolar macrophages in vivo. This SHG imaging approach provides novel information about the interaction of macrophages with cells and the extracellular matrix in lung disease as it is capable of visualizing and tracking NP‐loaded cells at high resolution in thick tissues with minimal background fluorescence.
Advantaging Synergy Photocatalysis with Graphene‐Related Carbon as a Counterpart Player of Titania
Authors: Wang Zheng‐Ming , Hirotsu Takahiro , Wu Haoyi , Kanoh Hirofumi 
Published: December 2018

AbstractThe enhancement of photocatalytic activity of TiO2 can be made either by promoting absorption efficiency of photon energy or by reducing recombination losses of photogenerated charge carriers, for which fabrication of nanocomposite structure with carbon materials is an optional selection. Among various nanocarbons, graphene (G), graphene oxide (GO), and reduced graphene oxide (rGO) are more favorable as the counterpart materials because they can provide availability of both obverse and reverse surface, thus doubling effective sites for adsorption, loading of nanoparticles, and interfacial interaction with the loaded nanoparticles. Composition of G/GO with titania, therefore, is a hopeful strategy for achieving synergy or cooperative effect in photocatalysis. In this personal account, we focus on the background and methodology of several soft chemical approaches that we have utilized up to date to fabricate nanocomposites of G/GO and titania, aiming to shed light on the importance of designing of nanocomposite structure for enhancing photocatalysis. In addition, we emphasize the role of interfacial interaction between carbon and titania by exemplifying a hybridized photocatalyst based on inexpensive biomass‐derived carbon sphere (CS), and demonstrate that it is a crucial influential factor underlying an enhanced visible light photocatalysis. CS can be a better selection as a counterpart component than G/GO, whose core‐shell composing structure with titania (TiO2@CS) can efficiently induce charge transfer so as to achieve a much higher photocatalytic performance under visible light illumination as compared to the composite of rGO and titania.
Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers
Authors: Lascano Santiago , Lopez Marie , Arimondo Paola B. 
Published: December 2018

AbstractDNA methylation and histone acetylation are widely studied epigenetic modifications. They are involved in numerous pathologies such as cancer, neurological disease, inflammation, obesity, etc. Since the discovery of the epigenome, numerous compounds have been developed to reverse DNA methylation and histone acetylation aberrant profile in diseases. Among them several were inspired by Nature and have a great interest as therapeutic molecules. In the quest of finding new ways to target epigenetic mechanisms, the use of chemical tools is a powerful strategy to better understand epigenetic mechanisms in biological systems. In this review we will present natural products reported as DNMT or HDAC inhibitors for anticancer treatments. We will then discuss the use of chemical tools that have been used in order to explore the epigenome.