bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot Spot TERT Promoter Mutations Are Rare in Sporadic Pancreatic Neuroendocrine Neoplasms and Associated with Telomere Length and Epigenetic Expression Patterns
Authors: Posch Alexandra , Hofer-Zeni Sarah , Klieser Eckhard , Primavesi Florian , Naderlinger Elisabeth , Brandstetter Anita , Filipits Martin , Urbas Romana , Swiercynski Stefan , Jäger Tarkan , Winkelmann Paul , Kiesslich Tobias , Lu Lingeng , Neureiter Daniel , Stättner Stefan , Holzmann Klaus
Published: June 2020

Cancer cells activate a telomere maintenance mechanism like telomerase in order to proliferate indefinitely. Telomerase can be reactivated by gain-of-function Telomerase Reverse Transcriptase (TERT) promoter mutations (TPMs) that occur in several cancer subtypes with high incidence and association with diagnosis, prognosis and epigenetics. However, such information about TPMs in sporadic pancreatic neuroendocrine neoplasms (pNENs) including tumor (pNET) and carcinoma (pNEC) is less well defined. We have studied two hot spot TPMs and telomere length (TL) in pNEN and compared the results with clinicopathological information and proliferation-associated miRNA/HDAC expression profiles. DNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue of 58 sporadic pNEN patients. T allele frequency of C250T and C228T TPM was analyzed by pyrosequencing, relative TL as telomeric content by qPCR. In total, five pNEN cases (9%) including four pNETs and one pNEC were identified with TPMs, four cases with exclusive C250T as predominant TPM and one case with both C250T and C228T. T allele frequencies of DNA isolated from adjacent high tumor cell content FFPE tissue varied considerably, which may indicate TPM tumor heterogeneity. Overall and disease-free survival was not associated with TPM versus wild-type pNEN cases. Binary category analyses indicated a marginally significant relationship between TPM status and longer telomeres (p = 0.086), and changes in expression of miR449a (p = 0.157), HDAC4 (p = 0.146) and HDAC9 (p = 0.149). Future studies with larger patient cohorts are needed to assess the true clinical value of these rare mutations in pNEN.
EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis
Authors: Genna Anthony , Vanwynsberghe Aline M. , Villard Amélie V. , Pottier Charles , Ancel Julien , Polette Myriam , Gilles Christine
Published: June 2020

Epithelial–mesenchymal transitions (EMTs) generate hybrid phenotypes with an enhanced ability to adapt to diverse microenvironments encountered during the metastatic spread. Accordingly, EMTs play a crucial role in the biology of circulating tumor cells (CTCs) and contribute to their heterogeneity. Here, we review major EMT-driven properties that may help hybrid Epithelial/Mesenchymal CTCs to survive in the bloodstream and accomplish early phases of metastatic colonization. We then discuss how interrogating EMT in CTCs as a companion biomarker could help refine cancer patient management, further supporting the relevance of CTCs in personalized medicine.
Metabolic Landscape of a Genetically Engineered Mouse Model of IDH1 Mutant Glioma
Authors: Ruiz-Rodado Victor , Seki Tomohiro , Dowdy Tyrone , Lita Adrian , Zhang Meili , Han Sue , Yang Chunzhang , Cherukuri Murali K. , Gilbert Mark R. , Larion Mioara
Published: June 2020

Understanding the metabolic reprogramming of aggressive brain tumors has potential applications for therapeutics as well as imaging biomarkers. However, little is known about the nutrient requirements of isocitrate dehydrogenase 1 (IDH1) mutant gliomas. The IDH1 mutation involves the acquisition of a neomorphic enzymatic activity which generates D-2-hydroxyglutarate from α-ketoglutarate. In order to gain insight into the metabolism of these malignant brain tumors, we conducted metabolic profiling of the orthotopic tumor and the contralateral regions for the mouse model of IDH1 mutant glioma; as well as to examine the utilization of glucose and glutamine in supplying major metabolic pathways such as glycolysis and tricarboxylic acid (TCA). We also revealed that the main substrate of 2-hydroxyglutarate is glutamine in this model, and how this re-routing impairs its utilization in the TCA. Our 13C tracing analysis, along with hyperpolarized magnetic resonance experiments, revealed an active glycolytic pathway similar in both regions (tumor and contralateral) of the brain. Therefore, we describe the reprogramming of the central carbon metabolism associated with the IDH1 mutation in a genetically engineered mouse model which reflects the tumor biology encountered in glioma patients.
Low-Noble-Metal-Loading Hybrid Catalytic System for Oxygen Reduction Utilizing Reduced-Graphene-Oxide-Supported Platinum Aligned with Carbon-Nanotube-Supported Iridium
Authors: Dembinska Beata , Zlotorowicz Agnieszka , Modzelewska Magdalena , Miecznikowski Krzysztof , Rutkowska Iwona A. , Stobinski Leszek , Malolepszy Artur , Krzywiecki Maciej , Zak Jerzy , Negro Enrico , Di Noto Vito , Kulesza Pawel J.
Published: June 2020

Hybrid systems composed of the reduced graphene oxide-supported platinum and multiwalled carbon nanotube-supported iridium (both noble metals utilized at low loadings on the level of 15 and ≤2 µg cm−2, respectively) were considered as catalytic materials for the reduction of oxygen in acid media (0.5-mol dm−3 H2SO4). The electrocatalytic activity toward reduction of oxygen and formation of hydrogen peroxide intermediate are tested using rotating ring–disk electrode (RRDE) voltammetric experiments. The efficiency of the proposed catalytic systems was also addressed by performing galvanodynamic measurements with gas diffusion electrode (GDE) half-cell at 80 °C. The role of carbon nanotubes is to improve charge distribution at the electrocatalytic interface and facilitate the transport of oxygen and electrolyte in the catalytic systems by lowering the extent of reduced graphene oxide restacking during solvent evaporation. The diagnostic electrochemical experiments revealed that—in iridium-containing systems—not only higher disk currents, but also somehow smaller ring currents are produced (when compared to the Ir-free reduced graphene oxide-supported platinum), clearly implying formation of lower amounts of the undesirable hydrogen peroxide intermediate. The enhancement effect originating from the addition of traces of iridium (supported onto carbon nanotubes) to platinum, utilized at low loading, may originate from high ability of iridium to induce decomposition of the undesirable hydrogen peroxide intermediate.
Synthesis of Valeric Acid by Selective Electrocatalytic Hydrogenation of Biomass-Derived Levulinic Acid
Authors: Du Yan , Chen Xiao , Qi Ji , Wang Pan , Liang Changhai
Published: June 2020

The electrocatalytic hydrogenation (ECH) of biomass-derived levulinic acid (LA) is a promising strategy to synthetize fine chemicals under ambient conditions by replacing the thermocatalytic hydrogenation at high temperature and high pressure. Herein, various metallic electrodes were investigated in the ECH of LA in a H-type divided cell. The effects of potential, electrolyte concentration, reactant concentration, and temperature on catalytic performance and Faradaic efficiency were systematically explored. The high conversion of LA (93%) and excellent “apparent” selectivity to valeric acid (VA) (94%) with a Faradaic efficiency of 46% can be achieved over a metallic lead electrode in 0.5 M H2SO4 electrolyte containing 0.2 M LA at an applied voltage of −1.8 V (vs. Ag/AgCl) for 4 h. The combination of adsorbed LA and adsorbed hydrogen (Hads) on the surface of the metallic lead electrode is key to the formation of VA. Interestingly, the reaction performance did not change significantly after eight cycles, while the surface of the metallic lead cathode became rough, which may expose more active sites for the ECH of LA to VA. However, there was some degree of corrosion for the metallic lead cathode in this strong acid environment. Therefore, it is necessary to improve the leaching-resistance of the cathode for the ECH of LA in future research.
Facile Formation of Anatase Nanoparticles on H-Titanate Nanotubes at Low Temperature for Efficient Visible Light-Driven Degradation of Organic Pollutants
Authors: Fu Weiwei , Shi Zhiqiang , Bai Helong , Dai Jinyu , Lu Zhiming , Lei Feifei , Zhang Deguang , Zhao Lun , Zhang Zongtao
Published: June 2020

Anatase nanoparticles (5–10 nm) generated on H-titanate nanotube surface (H-titanate/anatase) were prepared by an ingenious and simple method. H-titanate tubes were prepared by a hydrothermal reaction of Ti powder in concentrated NaOH solution and an ion exchange process with HNO3 solution. After that, at a relatively low drying temperature (100 °C), a small quantity of anatase nanoparticles were in-situ formed on the H-titanate tubes surface by a surface dehydration reaction. In-situ transformation can form a strong interface coupling between H-titanate and anatase, which is conducive to accelerating charge transfer and improving its photocatalytic activity. In addition, the smaller average crystal size, the large specific surface areas (BET), the nanotubed and layered structure and the synergistic effect of dual phases would be beneficial to improving the photocatalytic efficiency.
Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis
Authors: Auguste Aurélie , Blanc-Durand Félix , Deloger Marc , Le Formal Audrey , Bareja Rohan , Wilkes David C. , Richon Catherine , Brunn Béatrice , Caron Olivier , Devouassoux-Shisheboran Mojgan , Gouy Sébastien , Morice Philippe , Bentivegna Enrica , Sboner Andrea , Elemento Olivier , Rubin Mark A. , Pautier Patricia , Genestie Catherine , Cyrta Joanna , Leary Alexandra
Published: June 2020

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the SMARCA4 gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT. Additional immunohistochemical, Sanger sequencing and functional data are also provided. SCCOHTs showed remarkable genomic stability, with diploid profiles and low mutation load (mean, 5.43 mutations/Mb), including in the three chemotherapy-exposed tumors. All but one SCCOHT cases exhibited 19p13.2-3 copy-neutral LOH. SMARCA4 deleterious mutations were recurrent and accompanied by loss of expression of the SMARCA2 paralog. Variants in a few other genes located in 19p13.2-3 (e.g., PLK5) were detected. Putative therapeutic targets, including MAGEA4, AURKB and CLDN6, were found to be overexpressed in SCCOHT by RNA-seq as compared to benign ovarian tissue. Lastly, we provide additional evidence for sensitivity of SCCOHT to HDAC, DNMT and EZH2 inhibitors. Despite their aggressive clinical course, SCCOHT show remarkable inter-tumor homogeneity and display genomic stability, low mutation burden and few somatic copy number alterations. These findings and preliminary functional data support further exploration of epigenetic therapies in this lethal disease.
Effects of Mutations in the Drosophila melanogaster Rif1 Gene on the Replication and Underreplication of Pericentromeric Heterochromatin in Salivary Gland Polytene Chromosomes
Authors: Kolesnikova Tatyana D. , Kolodyazhnaya Alexandra V. , Pokholkova Galina V. , Schubert Veit , Dovgan Viktoria V. , Romanenko Svetlana A. , Prokopov Dmitry Yu. , Zhimulev Igor F.
Published: June 2020

In Drosophila salivary gland polytene chromosomes, a substantial portion of heterochromatin is underreplicated. The combination of mutations SuURES and Su(var)3-906 results in the polytenization of a substantial fraction of unique and moderately repeated sequences but has almost no effect on satellite DNA replication. The Rap1 interacting factor 1 (Rif) protein is a conserved regulator of replication timing, and in Drosophila, it affects underreplication in polytene chromosomes. We compared the morphology of pericentromeric regions and labeling patterns of in situ hybridization of heterochromatin-specific DNA probes between wild-type salivary gland polytene chromosomes and the chromosomes of Rif1 mutants and SuUR Su(var)3-906 double mutants. We show that, despite general similarities, heterochromatin zones exist that are polytenized only in the Rif1 mutants, and that there are zones that are under specific control of Su(var)3-9. In the Rif1 mutants, we found additional polytenization of the largest blocks of satellite DNA (in particular, satellite 1.688 of chromosome X and simple satellites in chromosomes X and 4) as well as partial polytenization of chromosome Y. Data on pulsed incorporation of 5-ethynyl-2′-deoxyuridine (EdU) into polytene chromosomes indicated that in the Rif1 mutants, just as in the wild type, most of the heterochromatin becomes replicated during the late S phase. Nevertheless, a significantly increased number of heterochromatin replicons was noted. These results suggest that Rif1 regulates the activation probability of heterochromatic origins in the satellite DNA region.
Enhanced Electrochromic Properties by Improvement of Crystallinity for Sputtered WO3 Film
Authors: Xia Zhu-jie , Wang Hong-li , Su Yi-fan , Tang Peng , Dai Ming-jiang , Lin Huai-jun , Zhang Zhi-guo , Shi Qian
Published: June 2020

Tungsten oxide (WO3) is widely used as a functional material for “smart windows” due to its excellent electrochromic properties, however it is difficult to overcome the conflict between its optical modulation and cyclic stability. In this work, WO3 thin films with different crystal structures were prepared by DC reactive magnetron sputtering method. The effects of substrate temperature on the structure, composition, and electrochromic properties of WO3 films were investigated. The results show that the crystallinity of the WO3 film increases with increasing deposition temperature, indicating that temperature plays an important role in controlling the structure of the WO3 film. For WO3 thin films formed at a substrate temperature of 573 K, the film is in an amorphous state to a crystalline transition state. From X-ray diffraction (XRD) analysis, the thin film showed a weak WO3 crystallization peak, which was in the composite structure of amorphous and nanocrystalline. Which has the best electrochromic properties, with modulation amplitude of 73.1% and bleached state with a coloration efficiency of 42.9 cm2/C at a wavelength of 550 nm. Even after 1500 cycles, the optical modulation still contains 65.4%, delivering the best cyclic stability.
Risk Reduction Optimization of Process Systems under Cost Constraint Applying Instrumented Safety Measures
Authors: Moshnikov Aleksandr , Bogatyrev Vladimir
Published: June 2020

This article is devoted to an approach to develop a safety system process according to functional safety standards. With the development of technologies and increasing the specific energy stored in the equipment, the issue of safety during operation becomes more urgent. Adequacy of the decisions on safety measures made during the early stages of planning the facilities and processes contributes to avoiding technological incidents and corresponding losses. A risk-based approach to safety system design is proposed. The approach is based on a methodology for determining and assessing risks and then developing the necessary set of safety measures to ensure that the specified safety indicators are achieved. The classification of safety measures is given, and the model of risk reduction based on deterministic analysis of the process is considered. It is shown that the task of changing the composition of safety measures can be represented as the knapsack discrete optimization problem, and the solution is based on the Monte Carlo method. A numerical example is provided to illustrate the approach. The considered example contains a description of failure conditions, an analysis of the types and consequences of failures that could lead to accidents, and a list of safety measures. Solving the optimization problem used real reliability parameters and the cost of equipment. Based on the simulation results, the optimal composition of the safety measures providing cost minimization is given. This research is relevant to engineering departments, who specialize in planning and designing technological solutions.
Uncovering Potential Roles of Differentially Expressed Genes, Upstream Regulators, and Canonical Pathways in Endometriosis Using an In Silico Genomics Approach
Authors: Mirza Zeenat , Abdel-dayem Umama A.
Published: June 2020

Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological data of endometriosis patients and controls from NCBI’s Gene Expression Omnibus, after a systematic search of multiple independent studies comprising 156 endometriosis patients and 118 controls to identify causative genes, risk factors, and potential diagnostic/therapeutic biomarkers. Comprehensive gene expression meta-analysis, pathway analysis, and gene ontology analysis was done using a bioinformatics-based approach. We identified 1590 unique differentially expressed genes (129 upregulated and 1461 downregulated) mapped by IPA as biologically relevant. The top upregulated genes were FOS, EGR1, ZFP36, JUNB, APOD, CST1, GPX3, and PER1, and the top downregulated ones were DIO2, CPM, OLFM4, PALLD, BAG5, TOP2A, PKP4, CDC20B, and SNTN. The most perturbed canonical pathways were mitotic roles of Polo-like kinase, role of Checkpoint kinase proteins in cell cycle checkpoint control, and ATM signaling. Protein–protein interaction analysis showed a strong network association among FOS, EGR1, ZFP36, and JUNB. These findings provide a thorough understanding of the molecular mechanism of endometriosis, identified biomarkers, and represent a step towards the future development of novel diagnostic and therapeutic options.
A Piston-Swiveling-Cylinder Pair in a High Water-Based Hydraulic Motor with Self-Balanced Distribution Valves
Authors: Zhao Jiyun , Qiu Bingjing , Man Jiaxiang
Published: June 2020

To improve the low viscosity and poor lubrication characteristics of high-water-based hydraulic liquid, the abrasion and leakage problems in hydraulic components need to be addressed. In a high water-based hydraulic motor with self-balanced distribution valve (HWBHM-SDV), there are two key friction pairs: the piston-crankshaft pair and piston-swivelling-cylinder (PSC) pair. To study the working performance of the PSC pair in HWBHM-SDV, we firstly designed the structural parameters. We found that, within the working speed 0–100 rpm, the leakage in the PSC pair is mainly caused by pressure-gradient flow, and the influence of the seal will not be significant when the seal length is 24 mm. Then, the friction coefficients of different matching materials were tested. It was found that the friction coefficient of 316L stainless steel with OVINO-GIC (OVINO-graphite intercalated compound) coating (316L-GIC)/PEEK reinforced with 30% carbon fibre (PEEK-30CF) is about 0.02~0.04, and the friction coefficient of 316L-GIC/316L-GIC is about 0.05–0.07. Finally, the influences of factors (clearance, temperature, pressure, and material) on leakage performance were analysed based on an orthogonal test method considering fluid-structure interaction. It was found that clearance has the most significant influence on leakage, followed by pressure and liquid temperature, and the difference between matching materials 316L-GIC/316L-GIC and 316L-GIC/PEEK-30CF is insignificant when the clearance is less than 8 μm and the working pressure is less than 10 MPa. Moreover, the difference in volume efficiency loss between theoretical analysis and calculated result considering fluid-structure interaction increases with the increase of working pressure and working speed. To ensure good working performance of a PSC pair, matching materials 316L-GIC/PEEK-30CF could be selected for pressures below 15 MPa, while 316L-GIC/316L-GIC could be used at 28 MPa.
Has China’s Oil Investment in Belt and Road Initiative Countries Helped Its Oil Import?
Authors: Shi Benye , Cai Tian
Published: June 2020

Energy cooperation is an important part of the Belt and Road Initiative (BRI). As China’s investment in One Belt One Road countries has increased substantially, a natural question is whether the investment in the BRI countries can contribute to its oil import since it is the most critical part of the national energy security strategy. By employing a dataset that includes the oil import from BRI countries and the oil-related investment in these countries, along with other control variables, an econometric analysis is conducted to investigate the relationship between these two variables. The estimation results provide supporting evidence for the hypothesis that China’s oil investment in BRI countries has helped enhance its oil security. Specifically, investment in BRI countries increases the oil import volume from the host country and diversifies China’s sources of imports. Further analysis also reveals that the effects do not differ by investment mode, e.g., greenfield or mergers and acquisitions (M&A).
Prosumer Response Estimation Using SINDyc in Conjunction with Markov-Chain Monte-Carlo Sampling
Authors: Banis Frederik , Madsen Henrik , Poulsen Niels K. , Guericke Daniela
Published: June 2020

Smart grid operation schemes can integrate prosumers by offering economic rewards in exchange for the desired response. In order to activate prosumers appropriately, such operation schemes require models of the dynamic uncertain price-response relationships. In this study, we combine the system identification of nonlinear dynamics with control (SINDyc) algorithm with Bayesian inference techniques based on Markov-chain Monte-Carlo sampling. We demonstrate this combination of two algorithms on an exemplary system in order to obtain parsimonious models alongside parameter uncertainty estimates. The precision of the identified models depends on the identification experiment and the parameterization of the algorithms. Such models may characterize the prosumer response and its uncertainty, thereby facilitating the integration of such entities into smart grid operation schemes.
A New Wind Turbine CFD Modeling Method Based on a Porous Disk Approach for Practical Wind Farm Design
Authors: Uchida Takanori , Taniyama Yoshihiro , Fukatani Yuki , Nakano Michiko , Bai Zhiren , Yoshida Tadasuke , Inui Masaki
Published: June 2020

In this study, the new computational fluid dynamics (CFD) porous disk (PD) wake model was proposed in order to accurately predict the time-averaged wind speed deficits in the wind turbine wake region formed on the downstream side by the 2-MW wind turbine operating at a wind speed of 10 m/s. We use the concept of forest canopy model as a new CFD PD wake model, which has many research results in the meteorological field. In the forest canopy model, an aerodynamic resistance is added as an external force term to all governing equations (Navier–Stokes equations) in the streamwise, spanwise, and vertical directions. Therefore, like the forest model, the aerodynamic resistance is added to the governing equations in the three directions as an external force term in the CFD PD wake model. In addition, we have positioned the newly proposed the LES using the CFD PD wake model approach as an intermediate method between the engineering wake model (empirical/analytical wake model) and the LES combined with actuator disk (AD) or actuator line (AL) models. The newly proposed model is intended for use in large-scale offshore wind farms (WFs) consisting of multiple wind turbines. In order to verify the validity of the new method, the optimal model parameter CRC was estimated by comparison with the time-averaged wind speed database in the wind turbine wake region with fully resolved geometries, combined with unsteady Reynolds-averaged Navier–Stokes (RANS) equations, implemented using the ANSYS(R) CFX(R) software. Here, product names (mentioned herein) may be trademarks of their respective companies. As a result, in the range from x = 5D of the near wake region to x = 10D of the far wake region, by selecting model parameter CRC, it was clarified that it is possible to accurately evaluate the time-averaged wind speed deficits at those separation distances. We also examined the effect of the spatial grid resolution using the CFD PD wake model that is proposed in the present study, clarifying that the spatial grid resolution has little effect on the simulation results shown here.
Impact of Aqueous Extract of Arbutus unedo Fruits on Limpets (Patella spp.) Pâté during Storage: Proximate Composition, Physicochemical Quality, Oxidative Stability, and Microbial Development
Authors: Pinheiro Joaquina , Rodrigues Sidónio , Mendes Susana , Maranhão Paulo , Ganhão Rui
Published: June 2020

Limpets are molluscs widely used in food diet and much appreciated in many regions. The consumption of fishery products rich in polyunsaturated fatty acids has been increasing through filleted products and restructured products. Since food oxidation is the major cause of nutritional quality deterioration in fish products, the interest in the replacement of synthetic antioxidants with natural sources, namely in the preparation of restructured animal products such as burgers, sausages and pâtés, has been increasing. Phenolic compounds from fruits and vegetables have recognised antioxidant properties and are therefore currently considered as good alternatives to synthetic antioxidants in the food industry. In this study, the effects of the extracts of Arbutus unedo fruits, at two concentration levels (3% and 6%), on proximate composition, physicochemical properties, oxidative stability and safety of limpets pâté, during 90 days at refrigerated storage, were investigated. After processing, the addition of 3% and 6% of A. unedo extracts into limpets pâté contributed to an increase of 18% and 36% in the total phenolic content and 5% and 36% in the antioxidant capacity, respectively. During storage, the enriched limpets pâté with A. unedo fruit extracts at 6% was more efficient as an enhancer of oxidative stability, with 34% inhibition of lipid oxidation, highlighting the potential use of A. unedo fruits as a functional ingredient in the fish industry. Overall, the limpets pâté with 6% of A. unedo fruit extracts proved to be more efficient regarding microbial control, and had the lowest changes in the quality parameters such as in colour, texture and pH during 90 days at refrigerated storage.
Acute Oral Toxicity and Genotoxicity of Polysaccharide Fraction from Young Barley Leaves (Hordeum vulgare L.)
Authors: Cho Chang-Won , Song Young-Ran , Lim Won-Chul , Hwang Youn-Hwan , Rhee Young Kyoung , Choi Jae Woong , Lee Kyung-Tae , Hong Hee-Do
Published: June 2020

Polysaccharides isolated from various plants are considered precious bioactive materials owing to their potent biological activities. Previously, we prepared a polysaccharide fraction (BLE0) isolated from young barley leaves (Hordeum vulgare L.), demonstrating its anti-osteoporotic and immunostimulatory activities. However, data regarding BLE0 toxicity is lacking. To establish its safety, in vitro genotoxicity (chromosomal aberration and bacterial reverse mutation assays) and acute oral toxicity assays were conducted. In the in vitro genotoxicity assays, bacterial reverse mutation and chromosomal aberration assays showed that BLE0 possessed no mutagenicity or clastogenicity. Furthermore, the median lethal dose (LD50) of BLE0 was higher than 5000 mg/kg in female and male Sprague-Dawley (SD) rats and no adverse effects were observed in terms of mortality and abnormal changes in clinical signs (body weight and necropsy). Based on these results, BLE0 was found to be safe with regards to genotoxicity under our test conditions, demonstrating no acute oral toxicity up to 5000 mg/kg in SD rats.
Does High Voltage Electrical Discharge Treatment Induce Changes in Tannin and Fiber Properties of Cocoa Shell?
Authors: Barišić Veronika , Flanjak Ivana , Kopjar Mirela , Benšić Mirta , Jozinović Antun , Babić Jurislav , Šubarić Drago , Miličević Borislav , Doko Kristina , Jašić Midhat , Ačkar Đurđica
Published: June 2020

Cocoa shell is a by-product of the chocolate industry that is rich in dietary fiber and bioactive components. In this research, the influence of high voltage electric discharge (HVED) treatment on chemical and physical characteristics of the cocoa shell, i.e., the effects of applied time and frequencies on grinding ability, water binding capacity (WBC), dietary fibers and tannin content was investigated. HVED had a significant influence on the chemical and physical properties of cocoa shell, all of which could be linked to changes in fiber properties. Along with the fiber content, grinding ability and water binding capacity were increased. These properties have already been linked to fiber content and soluble/insoluble fiber ratio. However, this research implies that change in fiber properties could be linked to tannin formation via complexation of other polyphenolic components. Additional research is needed to verify this effect and to establish mechanisms of tannin formation induced by HVED and its influence on fiber quantification.
Sexual Differentiation Is Coordinately Regulated by Cryptococcus neoformans CRK1 and GAT1
Authors: Liu Kuang-Hung , Shen Wei-Chiang
Published: June 2020

The heterothallic basidiomycetous fungus Cryptococcus neoformans has two mating types, MATa and MATα. Morphological progression of bisexual reproduction in C. neoformans is as follows: yeast to hyphal transition, filament extension, basidium formation, meiosis, and sporulation. C. neoformans Cdk-related kinase 1 (CRK1) is a negative regulator of bisexual mating. In this study, we characterized the morphological features of mating structures in the crk1 mutant and determined the genetic interaction of CRK1 in the regulatory networks of sexual differentiation. In the bilateral crk1 mutant cross, despite shorter length of filaments than in the wild-type cross, dikaryotic filaments and other structures still remained intact during bisexual mating, but the timing of basidium formation was approximately 18 h earlier than in the cross between wild type strains. Furthermore, gene expression analyses revealed that CRK1 modulated the expression of genes involved in the progression of hyphal elongation, basidium formation, karyogamy and meiosis. Phenotypic results showed that, although deletion of C. neoformans CRK1 gene increased the efficiency of bisexual mating, filamentation in the crk1 mutant was blocked by MAT2 or ZNF2 mutation. A bioinformatics survey predicted the C. neoformans GATA transcriptional factor Gat1 as a potential substrate of Crk1 kinase. Our genetic and phenotypic findings revealed that C. neoformans GAT1 and CRK1 formed a regulatory circuit to negatively regulate MAT2 to control filamentation progression and transition during bisexual mating.
Simultaneous Detection of NF1, SPRED1, LZTR1, and NF2 Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients
Authors: Bianchessi Donatella , Ibba Maria Cristina , Saletti Veronica , Blasa Stefania , Langella Tiziana , Paterra Rosina , Cagnoli Giulia Anna , Melloni Giulia , Scuvera Giulietta , Natacci Federica , Cesaretti Claudia , Finocchiaro Gaetano , Eoli Marica
Published: June 2020

Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up.
Phenotypic Variability and Genetic Diversity in a Pinus koraiensis Clonal Trial in Northeastern China
Authors: Kaviriri David Kombi , Zhang Qinhui , Zhang Xinxin , Jiang Luping , Zhang Jinpeng , Wang Jingyuan , Khasa Damase P. , You Xiangling , Zhao Xiyang
Published: June 2020

Combining phenotypic and genetic characteristics in a genetic variation study is of paramount importance to effectively orient the selection of producers’ elite trees in a seed orchard. In total, 28 phenotypic characteristics and 16 microsatellite loci were used to analyze the clonal genetic variation, to characterize the genetic diversity, and to refine the genetic classifications of 110 Pinus koraiensis clones grown in the Naozhi orchard in northeastern China. All clones were significantly different in most traits. Most of the phenotypic characteristics showed great genetic variation among clones, while the genotypic differentiation was weak between the selection sites of clones. The SSR markers showed a relatively high level of genetic diversity (Na = 4.67 ± 0.43, Ne = 2.916 ± 0.18, I = 1.15 ± 0.07, Ho = 0.69 ± 0.04, He = 0.62 ± 0.02, and mean polymorphic information content (PIC) of 0.574), with higher heterozygosity as an indication of a lower probability of inbreeding events in the orchard. Despite weak correlation coefficients between dissimilarity matrices (r(A/B), range equal to 0.022, p-value < 0.001), the genetic and phenotypic classifications congruently subdivided all the clones into three major groups. The patterns of phenotypic trait variations and genetic diversity are valuable to effectively select materials in breeding programs of P. koraiensis.
Design of an Interactive Nostalgic Amusement Device with User-Friendly Tangible Interfaces for Improving the Health of Older Adults
Authors: Wang Chao-Ming , Tseng Shih-Mo , Huang Chen-Siang
Published: June 2020

To help older adults achieve active aging, an interactive device with tangible interfaces is proposed, which combines human–machine interaction techniques and older adults’ life experiences to provide three functions: nostalgia, leisure, and entertainment. Firstly, by a review of related theories and studies, principles for designing a desirable interactive device were established. Accordingly, a prototype device with an interactive game was constructed, which was then tested in a field experiment and improved according to the users’ opinions collected by interviews. Subsequently, in a second experiment the users’ and some experts’ feedback about the system’s usability and user interaction satisfaction was collected and analyzed, and found to be reliable and valid for further evaluations of the effectiveness of the proposed system, resulting in the following findings about the older adults who have played the game: the participants become more willing to use technological devices; involving them in the game creates positive aging effects; participants become more receptive to technology products; the participating older adults’ cognitive abilities are trained and their body exercises increased, creating sensory stimulation and health promotion effects; and considering users with cognitive impairments who have stress and difficulty operating the device, the system needs to be improved in the future.
Access to and Satisfaction with Basic Services in Informal Settlements: Results from a Baseline Assessment Survey
Authors: Mutyambizi Chipo , Mokhele Tholang , Ndinda Catherine , Hongoro Charles
Published: June 2020

Subjective responses of satisfaction with basic services delivery is an indicator of service delivery performance. This study provides an overview of the status of basic service delivery and determines the factors associated with service delivery satisfaction within informal settlements targeted for upgrading in South Africa. A multinomial logistic regression was used to analyze the relationship between satisfaction with basic services of water, sanitation, refuse and electricity with several predictors including individual factors, household factors, community factors and service-related factors. The most common source of drinking water, toilet facility and refuse disposal method were communal tap (55%) pit latrine (53%) and local authorities (34%), respectively. Approximately 52% of the respondents in the study reported not having access to electricity. Results also show that satisfaction in basic services delivery varies and is influenced by service-related factors. Interventions targeted at improving the quality of basic service provided are essential to meet the targets set out in the sustainable development goals.
Evaluation of Inflammation by Cytokine Production Following Combined Exposure to Ultraviolet and Radiofrequency Radiation of Mobile Phones on 3D Reconstructed Human Skin In Vitro
Authors: Szilágyi Zsófia , Németh Zsuzsanna , Bakos József , Necz Péter Pál , Sáfár Anna , Kubinyi Györgyi , Selmaoui Brahim , Thuróczy György
Published: June 2020

The absorption of exposure to radiofrequency (RF) emitted by wireless devices leads to a high specific absorption rate in the skin. Ultraviolet (UV) radiation can induce several damages to the skin. The aim of this study was to examine whether combined, consecutive exposure to solar UV radiation and 1950 MHz RF exposure of third generation (3G) mobile system have any effect on inflammation processes in the skin. Under in vitro experiments, the inflammation process was examined by cytokines (IL-1α, IL-6, and IL-8) and MMP-1 enzyme secretion on 3D full thickness human skin model. The RF exposure was applied before or after UV irradiation, in order to study either the possible cooperative or protective effects of exposure to RF and UV. We did not find changes in cytokines due to exposure to RF alone. The RF exposure did not enhance the effects of UV radiation. There was a statistically not-significant decrease in cytokines when the skin tissues were pre-exposed to RF before being exposed to 4 standard erythemal dose (SED) UV compared to UV exposure alone. We found that RF exposure reduced the previously UV-treated MMP-1 enzyme concentration. This study might support the evaluation of the effects on the skin exposed to microwave radiation of 5G mobile technology.
Effects of Leisure Participation on Life Satisfaction in Older Korean Adults: A Panel Analysis
Authors: Yoon Hyejin , Lee Won Seok , Kim Kyoung-Bae , Moon Joonho
Published: June 2020

South Koreans’ life expectancy has dramatically increased over the last four decades. However, the life satisfaction index of older Korean adults has been in the bottom third globally. The large majority of older Koreans spend most of the day watching television at home. However, concrete evidence regarding the effects of leisure involvement on older adults’ quality of later life is scant. Only a few existing studies have examined the link via cross-sectional survey data. Thus, the purpose of this study was to investigate whether meaningful leisure participation outside the home in older age plays an essential role in improving life satisfaction. To achieve the research aim, nationally representative panel data from the Korea Employment Information Service were used for the data analysis. The results indicated that social and productive leisure participation in religious activity, social gatherings, and volunteering was significantly related to quality of life in older adults. Moreover, frequent participation in travel and cultural activities outside the home were positively related to life satisfaction. These findings suggest that participation in meaningful leisure activities is a critical factor contributing to subjective well-being and good mental health in older Korean adults and should be encouraged.
Implementation of the National Action Plan Health Literacy in Germany—Lessons Learned
Authors: Schaeffer Doris , Gille Svea , Hurrelmann Klaus
Published: June 2020

The promotion of health literacy (HL) has become an important task in public health. In response, in many countries, strategies and action plans to strengthen HL have been developed. Systematic discussion of implementation strategies of action plans on HL is scarce. This paper presents the implementation strategy and the methodical process of its realization of the National Action Plan HL in Germany which was published in 2018. The implementation strategy was based on considerations of implementation science and research. A process consisting of a continuum of various overlapping methodical and strategic steps of diffusion, dissemination and implementation based on collaboration and co-production was chosen. According to this, the Action Plan was widely diffused via various channels, disseminated through numerous publications and presentations, and implemented in several settings by holding workshops with stakeholders from politics, science and practice, as well as by cooperating with the Alliance for Health Literacy. This three-part collaborative and co-productive implementation strategy has helped to place HL and the National Action Plan on the health policy agenda in Germany. Experience demonstrates that implementation should be also considered, systematically planned, and addressed when developing strategies to strengthen HL.
Caregivers’ Experience of Caring for a Family Member with Alzheimer’s Disease: A Content Analysis of Longitudinal Social Media Communication
Authors: Bachmann Pavel
Published: June 2020

Background: The population aging together with an increased incidence of Alzheimer’s disease (AD) should also be accompanied by a growing interest in healthcare research. Therefore, this study examines the nature of the caregiver’s work, its mental and physical demands, experience and questions, and the relationship between the person with AD, the caregiver, and family members. Methods: As social media has become the place where people share family situations, a Facebook private discussion group of caregivers was chosen as the analytical data source. The study documented the daily-life situations of one-hundred dyads based on 2110 posts published during a six-month or longer period. A content analysis classified communication into 35 categories of basic, instrumental, and extended activities of daily livings (ADLs) and newly designed caregiver’s daily issues (CDIs). Results: The frequently discussed topics were related to exhaustion and feelings of “giving up” by caregivers and interpersonal communication and help from family members. The highest support was found for the topics of aging and dying and family events. Conclusion: The communications of caregivers were diverse and rather associated with co-occupational ADLs and CDIs than basic or instrumental ADLs. The support of the group was mainly provided in coping with fundamental life changes.
Diagnostic Precision of Anthropometric Variables for the Detection of Hypertension in Children and Adolescents
Authors: Vaquero-Álvarez Manuel , Molina-Luque Rafael , Fonseca-Pozo Francisco Javier , Molina-Recio Guillermo , López-Miranda José , Romero-Saldaña Manuel
Published: June 2020

Introduction: High blood pressure (HBP) is a health problem the prevalence of which has increased in young populations. Overweight and obesity in early ages have been directly related to its development. Due to the impact of HBP, it is necessary to provide tools that facilitate its early diagnosis, with useful anthropometric variables being those that assess obesity. The objective of this paper was to determine the diagnostic accuracy of anthropometric variables to detect HBP. Methods: A cross-sectional study was conducted on 265 students aged 6–16. The diagnosis of HBP was made following the criteria proposed by the Spanish Association of Pediatrics. Through different statistical methods, the association between anthropometric variables of general obesity with HBP was analyzed. Results: Waist circumference (WC) showed the best diagnostic capacity (area under the receiver operating characteristic curve = 0.729), with a sensitivity and specificity of 72.2% and 76%, respectively, for a cut-off point of 73.5 cm. In the adjusted multivariate analysis, an association was found between HBP and anthropometric variables: WC (odds ratio (OR) = 10.7), body mass index (OR = 7.5), waist-to-height ratio (OR = 5.5) and body fat percentage (OR = 5.3) (p < 0.05). Conclusions: The anthropometric variables studied showed a moderate predictive capacity for HBP, highlighting WC, which showed the strongest association with HBP in the infant and child population.
The Role of Bacterial Colonization of the Suture Thread in Early Identification and Targeted Antibiotic Treatment of Surgical Site Infections: A Prospective Cohort Study
Authors: Iovino Francesco , Calò Federica , Orabona Consiglia , Pizza Alessandra , Fisone Francesca , Caputo Pina , Fusco Alessandra , Macera Margherita , Coppola Nicola
Published: June 2020

Background: The aim of the present study is to investigate the role of the colonization of suture thread to identify patients at risk of developing a surgical site infection (SSI) after clean surgical procedures. Methods: Patients who underwent elective clean surgery procedures at the Surgery Unit of the AOU-University of Campania Luigi Vanvitelli in a 21-month period were prospectively enrolled. For each patient, a synthetic absorbable thread in Lactomer 9-1 was inserted into the surgical site at the end of surgery and microbiologically evaluated after 48 h. Antibiotic prophylaxis was chosen according to international guidelines. Results: A total of 238 patients were enrolled; 208 (87.4%) of them were subjected to clean procedures without the placement of prosthesis, and 30 (12.6%) with prosthesis. Of the 238 patients, 117 (49.2%) underwent an antimicrobial prophylaxis. Overall, 79 (33.2%) patients showed a bacterial colonization of the thread: among the 208 without the implantation of prosthesis, 19 (21.8%) of the 87 with antibiotic prophylaxis and in 58 (47.9%) of the 121 without it; among the 30 patients with the implantation of prosthesis, only two patients showed a colonized thread. The patients with antibiotic prophylaxis developed a colonization of the thread less frequently than those without it (17.9% vs. 47.9%, p < 0.001). SSI was observed in six (2.5%) patients, all of them showing a colonized thread (7.6% vs. 0%, p < 0.001). The bacteria identified in colonized threads were the same as those found in SSIs. Conclusions: Our study presents a new method that is able to precociously assess patients who have undergone clean procedures who may develop SSI, and identify the microorganism involved.