bluuebunny/crossref_metadata_2025 huggingface dataset:
Competitive Development Tools in Identifying Efficient Educational Interventions for Improving Pro-Environmental and Recycling Behavior
Authors: Popescu Sorin , Rusu Diana , Dragomir Mihai , Popescu Daniela , Nedelcu Șerban
Published: December 2019

Daily life in today’s dynamic world requires fast adaptation of people’s behavior to new challenges emerged from environmental, health, urban housing, transportation, etc. problems. A strong and complex tool in changing behaviors, education consumes significant resources and requires time for effective impact. The present study proposes a roadmap, integrating advanced methods for industrial competitive development (QFD) in configuring efficient educational interventions for changing people’s behavior on special thematic areas, such as environment and recycling. A literature review on applicable behavioral theories led to more than 30 behavioral factors (constructs) targetable by education, their specific impact evaluation being the subject of a survey among education professionals. Finally, to reach a mapping of efficient interventions with low costs, high impact and fast results criteria, educational interventions and behavioral factors were correlated by the QFD method on three dimensions addressing: teachers and trainers, contents and tools, respectively the national & institutional level. The current research results are focused particularly on changing recycling behaviors, but the overall concept and methodology can be expanded to incorporate any preoccupation in the areas of environment and health, as long-term drivers of public well-being.
Erratum: Sierra-Diaz, E.; Celis-de la Rosa, A.J.; Lozano-Kasten, F.; Trasande, L.; Peregrina-Lucano, A.A.; Sandoval-Pinto, E.; Gonzalez-Chavez, H. Urinary Pesticide Levels in Children and Adolescents Residing in Two Agricultural Communities in Mexico. Int. J. Environ. Res. Public Health 2019, 16, 562
Authors: Sierra-Diaz Erick , Celis-de la Rosa Alfredo de Jesus , Lozano-Kasten Felipe , Trasande Leonardo , Peregrina-Lucano Alejandro Aarón , Sandoval-Pinto Elena , Gonzalez-Chavez Humberto
Published: December 2019

The authors would like to update some important data in the manuscript [...]
Effect of 12-Week Functional Training Intervention on the Speed of Young Footballers
Authors: Baron Jakub , Bieniec Anna , Swinarew Andrzej S. , Gabryś Tomasz , Stanula Arkadiusz
Published: December 2019

The aim of the research was to verify the functional state of young football players using selected tests of the Functional Movement Screen (FMS) protocol, as well as the impact of the 12 weeks of functional training on the speed parameters. The research was conducted on 20 highly competitive young (U17) football players. Research project was conducted in two stages: in the first part of the study, the functional assessment was made by using the FMS test, then the measurement of the speed parameters was done with the Microgate photocells system. Results showed a significant improvement in the functional state of young football players: FMS 1 (45.2% of difference, p = 0.004), FMS 2 (24.3% of difference, p = 0.012), FMS 3 (48.5% of difference, p = 0.001). After the functional training program, there was also an improvement in the parameters of the acceleration and velocity: acceleration between 5–10 m and speed between 10–30 m shows significant improvement (expressed during covering a given distance) of the footballers, amounting to 0.02 s (2.4%) and 0.04 s (1.5%). But there was no improvement in acceleration between 0–5 m. An appropriate training schedule, based on FMS results, should be adopted in the annual training program to improve basic motor skills of the football players and minimize their injuries.
Characterization of the Inhibitory Effect of Gastrodigenin and Gastrodin on M-type K+ Currents in Pituitary Cells and Hippocampal Neurons
Authors: Yang Chih-Sheng , Lai Ming-Chi , Liu Ping-Yen , Lo Yi-Ching , Huang Chin-Wei , Wu Sheng-Nan
Published: December 2019

Gastrodigenin (HBA) and gastrodin (GAS) are phenolic ingredients found in Gastrodia elata Blume (GEB), a traditional Chinese herbal medicine. These compounds have been previously used to treat cognitive dysfunction, convulsion, and dizziness. However, at present, there is no available information regarding their potential ionic effects in electrically excitable cells. In the current study, the possible effects of HBA and GAS on different ionic currents in pituitary GH3 cells and hippocampal mHippoE-14 neurons were investigated using the patch-clamp technique. The addition of HBA or GAS resulted in the differential inhibition of the M-type K+ current (IK(M)) density in a concentration-dependent manner in GH3 cells. HBA resulted in a slowing of the activation time course of IK(M), while GAS elevated it. HBA also mildly suppressed the density of erg-mediated or the delayed-rectifier K+ current in GH3 cells. Neither GAS nor HBA (10 µM) modified the voltage-gated Na+ current density, although they suppressed the L-type Ca2+ current density at the same concentration. In hippocampal mHippoE-14 neurons, HBA was effective at inhibiting IK(M) density as well as slowing the activation time course. Taken together, the present study provided the first evidence that HBA or GAS could act on cellular mechanisms, and could therefore potentially have a functional influence in various neurologic disorders.
Comparative Proteomic Analysis Reveals the Regulatory Effects of H2S on Salt Tolerance of Mangrove Plant Kandelia obovata
Authors: Liu Yi-Ling , Shen Zhi-Jun , Simon Martin , Li Huan , Ma Dong-Na , Zhu Xue-Yi , Zheng Hai-Lei
Published: December 2019

As a dominant mangrove species, Kandelia obovata is distributed in an intertidal marsh with an active H2S release. Whether H2S participates in the salt tolerance of mangrove plants is still ambiguous, although increasing evidence has demonstrated that H2S functions in plant responses to multiple abiotic stresses. In this study, NaHS was used as an H2S donor to investigate the regulatory mechanism of H2S on the salt tolerance of K. obovata seedlings by using a combined physiological and proteomic analysis. The results showed that the reduction in photosynthesis (Pn) caused by 400 mM of NaCl was recovered by the addition of NaHS (200 μM). Furthermore, the application of H2S enhanced the quantum efficiency of photosystem II (PSII) and the membrane lipid stability, implying that H2S is beneficial to the survival of K. obovata seedlings under high salinity. We further identified 37 differentially expressed proteins by proteomic approaches under salinity and NaHS treatments. Among them, the proteins that are related to photosynthesis, primary metabolism, stress response and hormone biosynthesis were primarily enriched. The physiological and proteomic results highlighted that exogenous H2S up-regulated photosynthesis and energy metabolism to help K. obovata to cope with high salinity. Specifically, H2S increased photosynthetic electron transfer, chlorophyll biosynthesis and carbon fixation in K. obovata leaves under salt stress. Furthermore, the abundances of other proteins related to the metabolic pathway, such as antioxidation (ascorbic acid peroxidase (APX), copper/zinc superoxide dismutase (CSD2), and pancreatic and duodenal homeobox 1 (PDX1)), protein synthesis (heat-shock protein (HSP), chaperonin family protein (Cpn) 20), nitrogen metabolism (glutamine synthetase 1 and 2 (GS2), GS1:1), glycolysis (phosphoglycerate kinase (PGK) and triosephosphate isomerase (TPI)), and the ascorbate–glutathione (AsA–GSH) cycle were increased by H2S under high salinity. These findings provide new insights into the roles of H2S in the adaptations of the K. obovata mangrove plant to high salinity environments.
Interaction of Osteoarthritis and BMI on Leptin Promoter Methylation in Taiwanese Adults
Authors: Yang Tzi-Peng , Chen Hsiao-Mei , Hu Chao-Chin , Chen Li-Yuan , Shih Fen-Fen , Tantoh Disline Manli , Lee Kuan-Jung , Liaw Yi-Chia , Tsai Rong-Tzong , Liaw Yung-Po
Published: December 2019

Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30–70 years were retrieved from the Taiwan Biobank Database (2008–2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (β = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.
Cardiovascular Disease Prevention: The Earlier the Better? A Review of Plant Sterol Metabolism and Implications of Childhood Supplementation
Authors: Scolaro Bianca , Andrade Leticia F.S. de , Castro Inar A.
Published: December 2019

Atherosclerosis is the underlying cause of major cardiovascular events. The development of atherosclerotic plaques begins early in life, indicating that dietary interventions in childhood might be more effective at preventing cardiovascular disease (CVD) than treating established CVD in adulthood. Although plant sterols are considered safe and consistently effective in lowering plasma cholesterol, the health effects of early-life supplementation are unclear. Studies suggest there is an age-dependent effect on plant sterol metabolism: at a younger age, plant sterol absorption might be increased, while esterification and elimination might be decreased. Worryingly, the introduction of low-cholesterol diets in childhood may unintentionally favor a higher intake of plant sterols. Although CVD prevention should start as early as possible, more studies are needed to better elucidate the long-term effects of plant sterol accumulation and its implication on child development.
Overexpression of ThMYC4E Enhances Anthocyanin Biosynthesis in Common Wheat
Authors: Zhao Shuo , Xi Xingyuan , Zong Yuan , Li Shiming , Li Yun , Cao Dong , Liu Baolong
Published: December 2019

The basic helix-loop helix (bHLH) transcription factor has been inferred to play an important role in blue and purple grain traits in common wheat, but to date, its overexpression has not been reported. In this study, the bHLH transcription factor ThMYC4E, the candidate gene controlling the blue grain trait from Th. Ponticum, was transferred to the common wheat JW1. The positive transgenic lines displayed higher levels of purple anthocyanin pigments in their grains, leaves and glumes. Stripping the glumes (light treatment) caused white grains to become purple in transgenic lines. RNA-Seq and qRT-PCR analysis demonstrated that the transcript levels of structural genes associated with anthocyanin biosynthesis were higher in transgenic wheat than the wild-type (WT), which indicated that ThMYC4E activated anthocyanin biosynthesis in the transgenic lines. Correspondingly, the anthocyanin contents in grains, roots, stems, leaves and glumes of transgenic lines were higher than those in the WT. Metabolome analysis demonstrated that the anthocyanins were composed of cyanidin and delphinidin in the grains of the transgenic lines. Moreover, the transgenic lines showed higher antioxidant activity, in terms of scavenging DPPH radicals, in the ethanol extracts of their grains. The overexpression of ThMYC4E sheds light on the traits related to anthocyanin biosynthesis in common wheat and provide a new way to improve anthocyanin content.
AtKATANIN1 Modulates Microtubule Depolymerization and Reorganization in Response to Salt Stress in Arabidopsis
Authors: Yang Jie , An Bang , Luo Hongli , He Chaozu , Wang Qiannan
Published: December 2019

The microtubule cytoskeleton is a dynamic system that plays vital roles in fundamental cellular processes and in responses to environmental stumili. Salt stress induced depolymerization and reorganization of microtubules are believed to function in the promotion of survival in Arabidopsis. Microtubule-severing enzyme ATKATANIN1 (AtKTN1) is recognized as a MAP that help to maintain organized microtubule structure. To date, whether AtKTN1 is involved in response to salt stress in Arabidopsis remains unknown. Here, our phenotypic analysis showed that the overexpression of AtKTN1 decreased tolerance to salt stress, whereas the knock-out of AtKTN1 increased salt tolerance in the early stage but decreased salt tolerance in the later stage. Microscopic analysis revealed that microtubule organization and dynamics are distorted in both overexpression and mutant cells which, in turn, resulted in an abnormal disassembly and reorganization under salt stress. Moreover, qRT analysis revealed that stress-responsive genes were down-regulated in overexpression and mutant cells compared to WT cells under salt stress. Taken together, our results indicated roles of AtKTN1 in modulating microtubule organization, salt-stress induced microtubule disruption and recovery, and its involvement in stress-related signaling pathways.
Exploiting RAS Nucleotide Cycling as a Strategy for Drugging RAS-Driven Cancers
Authors: Mattox Tyler E. , Chen Xi , Maxuitenko Yulia Y. , Keeton Adam B. , Piazza Gary A.
Published: December 2019

Oncogenic mutations in RAS genes result in the elevation of cellular active RAS protein levels and increased signal propagation through downstream pathways that drive tumor cell proliferation and survival. These gain-of-function mutations drive over 30% of all human cancers, presenting promising therapeutic potential for RAS inhibitors. However, many have deemed RAS “undruggable” after nearly 40 years of failed drug discovery campaigns aimed at identifying a RAS inhibitor with clinical activity. Here we review RAS nucleotide cycling and the opportunities that RAS biochemistry presents for developing novel RAS inhibitory compounds. Additionally, compounds that have been identified to inhibit RAS by exploiting various aspects of RAS biology and biochemistry will be covered. Our current understanding of the biochemical properties of RAS, along with reports of direct-binding inhibitors, both provide insight on viable strategies for the discovery of novel clinical candidates with RAS inhibitory activity.
The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations
Authors: Yang Nae-Cherng , Cho Yu-Hung , Lee Inn
Published: December 2019

Calorie restriction can extend lifespan by increasing intracellular nicotinamide adenine dinucleotide (NAD+), thereby upregulating the activity of sirtuins (Caenorhabditis elegans Sir-2.1; human SIRT1). Nicotinic acid (NA) can be metabolized to NAD+; however, the calorie restriction mimetic (CRM) potential of NA is unclear. This study explored the ability and mechanism of NA to extend the lifespan of human Hs68 cells and C. elegans. We found that NA can efficiently increase the intracellular NAD+ levels in Hs68 cells and C. elegans; however, NA was only able to extend the lifespan of C. elegans. The steady-state NAD+ level in C. elegans was approximately 55 μM. When intracellular NAD+ was increased by a mutation of pme-1 (poly (ADP-ribose) metabolism enzyme 1) or by pretreatment with NAD+ in the medium, the lifespan extension ability of NA disappeared. Additionally, the saturating concentration of NAD+ required by SIRT1 was approximately 200 μM; however, the steady-state concentration of NAD+ in Hs68 cells reached up to 460 μM. These results demonstrate that the lifespan extension ability of NA depends on whether the intracellular level of NAD+ is lower than the sirtuin-saturating concentration in Hs68 cells and in C. elegans. Thus, the CRM potential of NA should be limited to individuals with lower intracellular NAD+.
Gene Copy Number and Post-Transductional Mechanisms Regulate TRAP1 Expression in Human Colorectal Carcinomas
Authors: Pietrafesa Michele , Maddalena Francesca , Possidente Luciana , Condelli Valentina , Zoppoli Pietro , Li Bergolis Valeria , Rodriquenz Maria Grazia , Aieta Michele , Vita Giulia , Esposito Franca , Landriscina Matteo
Published: December 2019

Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone overexpressed in 60–70% human colorectal carcinomas (CRCs) and the co-upregulation of TRAP1 and associated 6-related proteins identifies metastatic CRCs with poor prognosis. Since the molecular mechanisms responsible for TRAP1 regulation are still unknown, the significance of TRAP1 gene copy number (CN) and the role of post-transductional protein modifications were addressed. TRAP1 gene aneuploidy accounted for 34.5% of cases in a cohort of 58 human CRCs and TRAP1 CN correlated with its mRNA and protein expression, suggesting that transcriptional mechanisms are responsible for TRAP1 upregulation. Furthermore, the analysis of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium/The Cancer Genome Atlas (CPTAC/TCGA) CRC database showed that TRAP1 polysomy significantly correlates with lymph node involvement. However, a subgroup of tumors showed TRAP1 protein levels independent from its CN. Of note, a direct correlation was observed between TRAP1 protein levels and the expression of S-nitrosoglutathione reductase (GSNOR), a denitrosylase involved in the regulation of protein S-nitrosylation. Furthermore, CRC cell lines exposed to hypoxia or dichloroacetate treatment showed the downregulation of TRAP1 upon GSNOR silencing and this resulted in increased TRAP1 mono/polyubiquitination. These data suggest that transcriptional and post-transductional mechanisms account for TRAP1 expression in human CRCs and GSNOR protects TRAP1 from S-nitrosylation and consequent proteasome degradation mostly in conditions of stress.
Polyphenols: Modulators of Platelet Function and Platelet Microparticle Generation?
Authors: Ed Nignpense Borkwei , Chinkwo Kenneth A. , Blanchard Christopher L. , Santhakumar Abishek B.
Published: December 2019

Platelets and platelet microparticles (PMPs) play a key role in the pathophysiology of vascular disorders such as coronary artery disease and stroke. In atherosclerosis, for example, the disruption of the plaque exposes endogenous agonists such as collagen, which activates platelets. Platelet hyper-activation and the high levels of PMPs generated in such situations pose a thrombotic risk that can lead to strokes or myocardial infarctions. Interestingly, dietary polyphenols are gaining much attention due to their potential to mimic the antiplatelet activity of treatment drugs such as aspirin and clopidogrel that target the glycoprotein VI (GPVI)–collagen and cyclooxygenease-1 (COX-1)–thromboxane platelet activation pathways respectively. Platelet function tests such as aggregometry and flow cytometry used to monitor the efficacy of antiplatelet drugs can also be used to assess the antiplatelet potential of dietary polyphenols. Despite the low bioavailability of polyphenols, several in vitro and dietary intervention studies have reported antiplatelet effects of polyphenols. This review presents a summary of platelet function in terms of aggregation, secretion, activation marker expression, and PMP release. Furthermore, the review will critically evaluate studies demonstrating the impact of polyphenols on aggregation and PMP release.
On-Membrane Dynamic Interplay between Anti-GM1 IgG Antibodies and Complement Component C1q
Authors: Yanaka Saeko , Yogo Rina , Watanabe Hiroki , Taniguchi Yuki , Satoh Tadashi , Komura Naoko , Ando Hiromune , Yagi Hirokazu , Yuki Nobuhiro , Uchihashi Takayuki , Kato Koichi
Published: December 2019

Guillain–Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness, is often preceded by Campylobacter jejuni infection. Molecular mimicry exists between the bacterial lipo-oligosaccharide and human ganglioside. Such C. jejuni infection induces production of immunoglobulin G1 (IgG1) autoantibodies against GM1 and causes complement-mediated motor nerve injury. For elucidating the molecular mechanisms linking autoantigen recognition and complement activation, we characterized the dynamic interactions of anti-GM1 IgG autoantibodies on ganglioside-incorporated membranes. Using high-speed atomic force microscopy, we found that the IgG molecules assemble into a hexameric ring structure on the membranes depending on their specific interactions with GM1. Complement component C1q was specifically recruited onto these IgG rings. The ring formation was inhibited by an IgG-binding domain of staphylococcal protein A bound at the cleft between the CH2 and CH3 domains. These data indicate that the IgG assembly is mediated through Fc–Fc interactions, which are promoted under on-membrane conditions due to restricted translational diffusion of IgG molecules. Reduction and alkylation of the hinge disulfide impaired IgG ring formation, presumably because of an increase in conformational entropic penalty. Our findings provide mechanistic insights into the molecular processes involved in Guillain–Barré syndrome and, more generally, into antigen-dependent interplay between antibodies and complement components on membranes.
Transcriptomic and Proteomic Analyses Reveal the Potential Mode of Action of Chondrocyte Sheets in Hyaline Cartilage Regeneration
Authors: Toyoda Eriko , Sato Masato , Takahashi Takumi , Maehara Miki , Okada Eri , Wasai Shiho , Iijima Hiroshi , Nonaka Ken , Kawaguchi Yuka , Watanabe Masahiko
Published: December 2019

Chondrocyte sheet transplantation is a novel and promising approach to treating patients who have cartilage defects associated with osteoarthritis. Hyaline cartilage regeneration by autologous chondrocyte sheets has already been demonstrated in clinical research. In this study, the efficacy of polydactyly-derived chondrocyte sheets (PD sheets) as an allogeneic alternative to standard chondrocyte sheets was examined using an orthotopic xenogeneic transplantation model. In addition, the expression of genes and the secreted proteins in the PD sheets was analyzed using a microarray and a DNA aptamer array. The efficacy of PD sheets with respect to cartilage defects was assessed using histological scores, after which the expressions of genes and proteins exhibiting a correlation to efficacy were identified. Enrichment analysis of efficacy-correlated genes and proteins showed that they were associated with extracellular matrices, skeletal development, and angiogenesis. Eight genes (ESM1, GREM1, SERPINA3, DKK1, MIA, NTN4, FABP3, and PDGFA) exhibited a positive correlation with the efficacy of PD sheets, and three genes (RARRES2, APOE, and PGF) showed a negative correlation for both transcriptomic and proteomic analyses. Among these, MIA, DKK1, and GREM1 involved in skeletal development pathways and ESM1 involved in the angiogenesis pathway exhibited a correlation between the amount of secretion and efficacy. These results suggest that these secreted factors may prove useful for predicting PD sheet efficacy and may therefore contribute to hyaline cartilage regeneration via PD sheets.
Transcriptome Analysis Identifies Candidate Genes and Functional Pathways Controlling the Response of Two Contrasting Barley Varieties to Powdery Mildew Infection
Authors: Li Yingbo , Guo Guimei , Zhou Longhua , Chen Yunyun , Zong Yingjie , Huang Jianhua , Lu Ruiju , Liu Chenghong
Published: December 2019

Powdery mildew caused by Blumeria graminis f. sp. hordei (Bgh) is one of the most serious diseases in barley. The numerous barley varieties across China provide valuable genetic resources to screen the resistant germplasm and to discover the primary genes of resistance to powdery mildew. In this study, Chinese barley variety Feng 7 was identified as a highly resistant genotype which limited Bgh colonization by cell apoptosis using leaf staining assay, while another variety Hua 30 showed high susceptibility. The performance of high resistance to Bgh in F1 plants from the two varieties suggested dominant gene(s) controlled the resistance to powdery mildew in Feng 7. To understand the host transcriptional response to Bgh infection, these two barley varieties Feng 7 and Hua 30 were inoculated with Bgh, and their transcriptional profiling using RNA sequencing (RNA-seq) at four time points (12 h post-inoculation (hpi), 24 hpi, 48 hpi, and 72 hpi) were compared. 4318 differentially expressed genes (DEGs), including 2244 upregulated and 2074 downregulated genes, were detected in Feng 7, compared with Hua 30 at 12 hpi. 4907 DEGs (2488 upregulated and 2419 downregulated) were detected at 24 hpi. 4758 DEGs (2295 upregulated and 2463 downregulated) were detected at 48 hpi. 3817 DEGs (2036 upregulated and 1781 downregulated) were detected at 72 hpi. The results showed the number of DEGs between two varieties peaked at 24 hpi (for the upregulated) or 48 hpi (for the downregulated), which is matched with the processing of Bgh infection. In addition, the number of upregulated DEGs involved in the functional pathways of plant defense (mitogen-activated protein kinase (MAPK) pathway and plant hormone signal transduction) is elevated remarkably at 24 hpi. Six candidate genes (PR13, glutaredoxin, alcohol dehydrogenase, and cytochrome P450) were identified in Feng 7. All of them present continuous expression at higher levels upon Bgh infection, compared with the performance in Hua 30, which revealed the potential contribution to Feng 7 mediate resistance to Bgh. In conclusion, the candidate genes and relevant pathways provided key information towards understanding the defense of barley to Bgh attack and the molecular mechanisms of different genetic resistance to powdery mildew.
External Human–Machine Interfaces: The Effect of Display Location on Crossing Intentions and Eye Movements
Authors: Eisma Y. B. , van Bergen S. , ter Brake S. M. , Hensen M. T. T. , Tempelaar W. J. , de Winter J. C. F.
Published: December 2019

In the future, automated cars may feature external human–machine interfaces (eHMIs) to communicate relevant information to other road users. However, it is currently unknown where on the car the eHMI should be placed. In this study, 61 participants each viewed 36 animations of cars with eHMIs on either the roof, windscreen, grill, above the wheels, or a projection on the road. The eHMI showed ‘Waiting’ combined with a walking symbol 1.2 s before the car started to slow down, or ‘Driving’ while the car continued driving. Participants had to press and hold the spacebar when they felt it safe to cross. Results showed that, averaged over the period when the car approached and slowed down, the roof, windscreen, and grill eHMIs yielded the best performance (i.e., the highest spacebar press time). The projection and wheels eHMIs scored relatively poorly, yet still better than no eHMI. The wheels eHMI received a relatively high percentage of spacebar presses when the car appeared from a corner, a situation in which the roof, windscreen, and grill eHMIs were out of view. Eye-tracking analyses showed that the projection yielded dispersed eye movements, as participants scanned back and forth between the projection and the car. It is concluded that eHMIs should be presented on multiple sides of the car. A projection on the road is visually effortful for pedestrians, as it causes them to divide their attention between the projection and the car itself.
Practical Methodology for the Design of Educational Serious Games
Authors: Silva Frutuoso G. M.
Published: December 2019

Educational serious games are primarily intended to teach about or train on a subject. However, a serious game must also be catchy for the player to want to play it multiple times and thus learn while playing. The design of educational serious games includes game experts and pedagogical experts that must be able to efficiently communicate to produce a product that is both educationally efficient and fun to play. Although there are some design frameworks to help with this communication, they are usually more conceptual and do not distinguish the fun factor from the learning contents well, making communication difficult. In this paper, a new practical methodology is presented to support the design process of this kind of digital games. This methodology is more all-encompassing because it identifies all the main steps that are needed to define the learning mechanisms in an educational serious game, from topic choice to user experience. It also separates the game’s learning contents from other mechanics used to keep the game fun to play. Finally, some practical examples are shown, illustrating the use of this methodology.
Atrial Fibrillation Progression Is Associated with Cell Senescence Burden as Determined by p53 and p16 Expression
Authors: Jesel Laurence , Abbas Malak , Park Sin-Hee , Matsushita Kensuke , Kindo Michel , Hasan Hira , Auger Cyril , Sato Chisato , Ohlmann Patrick , Mazzucotelli Jean-Philippe , Toti Florence , Kauffenstein Gilles , Schini-Kerth Valérie , Morel Olivier
Published: December 2019

Background: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear. Aims: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR). Methods: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis. Results: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, p = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, p = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, p = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, p = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. Conclusions: The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.
Prediction of the Clinical Severity of Progressive Supranuclear Palsy by Diffusion Tensor Imaging
Authors: Chen Yao-Liang , Zhao Xiang-An , Ng Shu-Hang , Lu Chin-Song , Lin Yu-Chun , Cheng Jur-Shan , Tsai Chih-Chien , Wang Jiun-Jie
Published: December 2019

Progressive supranuclear palsy (PSP) is characterized by a rapid and progressive clinical course. A timely and objective image-based evaluation of disease severity before standard clinical assessments might increase the diagnostic confidence of the neurologist. We sought to investigate whether features from diffusion tensor imaging of the entire brain with a machine learning algorithm, rather than a few pathogenically involved regions, may predict the clinical severity of PSP. Fifty-three patients who met the diagnostic criteria for probable PSP were subjected to diffusion tensor imaging. Of them, 15 underwent follow-up imaging. Clinical severity was assessed by the neurological examinations. Mean diffusivity and fractional anisotropy maps were spatially co-registered, normalized, and parcellated into 246 brain regions from the human Brainnetome atlas. The predictors of clinical severity from a stepwise linear regression model were determined after feature reduction by the least absolute shrinkage and selection operator. Performance estimates were obtained using bootstrapping, cross-validation, and through application of the model in the patients who underwent repeated imaging. The algorithm confidently predicts the clinical severity of PSP at the individual level (adjusted R2: 0.739 and 0.892, p < 0.001). The machine learning algorithm for selection of diffusion tensor imaging-based features is accurate in predicting motor subscale of unified Parkinson’s disease rating scale and postural instability and gait disturbance of PSP.
Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn’s Disease: A Pilot Study (ACROHNEM)
Authors: Capron Monique , Béghin Laurent , Leclercq Céline , Labreuche Julien , Dendooven Arnaud , Standaert Annie , Delbeke Marie , Porcherie Adeline , Nachury Maria , Boruchowicz Arnaud , Dupas Jean-Louis , Fumery Mathurin , Paupard Thierry , Catteau Sylviane , Deplanque Dominique , Colombel Jean-Frederic , Desreumaux Pierre
Published: December 2019

Despite the development of novel therapies, inflammatory bowel diseases remain an innovative treatment challenge. Helminth therapy is a new promising approach, and a key issue is the identification of helminth-derived anti-inflammatory mediators. P28 glutathione-S-transferase (P28GST), a protein derived from schistosomes, a trematode parasitic helminth, was shown to reduce intestinal inflammation in experimental colitis by down-regulating the Th1/Th17 response. In this multicenter, open-label, pilot Phase 2a study, we evaluated the safety of P28GST administered to patients with mild Crohn’s disease (CD). We enrolled 10 patients with a baseline Crohn’s disease activity index (CDAI) value <220. Eight patients received two to three subcutaneous injections of recombinant P28GST with adjuvant. This three-month treatment was followed by a nine-month monitoring period. The primary endpoints were the monthly rate and seriousness of adverse events (AEs). Secondary endpoints were clinical recurrence, assessed with the CDAI as well as the levels of immunologic and inflammatory blood and tissue markers. The most common AEs were local or regional events at the injection site and gastrointestinal disorders. At three months after the first injection, CDAI scores and blood calprotectin levels decreased in parallel. These results indicate that P28GST showed promise as a safe and new therapeutic option for treating CD.
Surgical Treatment for the Ankle and Foot in Patients with Rheumatoid Arthritis: A Systematic Review
Authors: Ortega-Avila Ana Belen , Moreno-Velasco Antonio , Cervera-Garvi Pablo , Martinez-Rico Magdalena , Chicharro-Luna Esther , Gijon-Noqueron Gabriel
Published: December 2019

The aim was to identify effective surgical treatments for patients with rheumatoid arthritis in the foot and/or ankle. A systematic review of the literature was conducted via a data search of the PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PROSPERO databases, from their inception until June 2019. Only non-randomized controlled trials and cohort studies were included in this review. Two of the present authors independently assessed the quality of each study and extracted the relevant data. A quality assessment of all articles was performed using the methodological index for non-randomized studies criteria. In addition, the Newcastle Ottawa scale was used for cohort studies. Thirteen studies met the inclusion criteria (five cohort studies and eight NRCTs). The total population considered was 923 patients (570 patients had RA), with a mean age of 58.8 years. Regarding the risk of bias, both the NRCTs and the cohort studies had a moderate level of quality. Despite the relatively low quality of these studies, surgical treatment for the foot and/or ankle is shown to reduce pain and improve functionality in patients with RA, in the short term (6–12 months).
Influence of the Digital Mock-Up and Experience on the Ability to Determine the Prosthetically Correct Dental Implant Position during Digital Planning: An In Vitro Study
Authors: O’Connor Esteban Miriam , Riad Deglow Elena , Zubizarreta-Macho Álvaro , Hernández Montero Sofía
Published: December 2019

The purpose of this study was to analyze the influence of the digital mock-up and operator experience on the dental implant planning position. A total of 200 dental implants were planned, which were distributed into two study groups: A. dental implant planning by dental surgeons with 5–10 years of experience (n = 80); and B. dental implant planning by dental surgery students without experience (n = 120). Operators were required to plan eight dental implants in the same maxillary edentulous case uploaded in 3D implant-planning software, before and after using the digital mock-up. Deviations between the dental implant planning positions before and after using the digital mock-up were analyzed at platform, apical and angular levels, and were analyzed using a 3D implant-planning software using Student’s t test. The paired t-test revealed statistically significant differences between the deviation levels of participants with 5–10 years’ experience and no experience at the platform, apical and angular levels. Digital mock-ups allow for more accurate dental implant planning regardless of the experience of the operator. Nevertheless, they are more useful for operators without dental surgery experience.
The Systemic Redox Status Is Maintained in Non-Smoking Type 2 Diabetic Subjects Without Cardiovascular Disease: Association with Elevated Triglycerides and Large VLDL
Authors: van Dijk Peter R. , Abdulle Amaal Eman , Bulthuis Marian L.C. , Perton Frank G. , Connelly Margery A. , van Goor Harry , Dullaart Robin P.F.
Published: December 2019

Decreased circulating levels of free thiols (R-SH, sulfhydryl groups) reflect enhanced oxidative stress, which plays an important role in the pathogenesis of cardiometabolic diseases. Since hyperglycemia causes oxidative stress, we questioned whether plasma free thiols are altered in patients with type 2 diabetes mellitus (T2DM) without cardiovascular disease or renal function impairment. We also determined their relationship with elevated triglycerides and very low density lipoproteins (VLDL), a central feature of diabetic dyslipidemia. Fasting plasma free thiols (colorimetric method), lipoproteins, VLDL (nuclear magnetic resonance spectrometry), free fatty acids (FFA), phospholipid transfer protein (PLTP) activity and adiponectin were measured in 79 adult non-smoking T2DM subjects (HbA1c 51 ± 8 mmol/mol, no use of insulin or lipid lowering drugs), and in 89 non-smoking subjects without T2DM. Plasma free thiols were univariately correlated with glucose (r = 0.196, p < 0.05), but were not decreased in T2DM subjects versus non-diabetic subjects (p = 0.31). Free thiols were higher in subjects with (663 ± 84 µmol/L) versus subjects without elevated triglycerides (619 ± 91 µmol/L; p = 0.002). Age- and sex-adjusted multivariable linear regression analysis demonstrated that plasma triglycerides were positively and independently associated with free thiols (β = 0.215, p = 0.004), FFA (β = 0.168, p = 0.029) and PLTP activity (β = 0.228, p = 0.002), inversely with adiponectin (β = −0.308, p < 0.001) but not with glucose (β = 0.052, p = 0.51). Notably, the positive association of free thiols with (elevated) triglycerides appeared to be particularly evident in men. Additionally, large VLDL were independently associated with free thiols (β = 0.188, p = 0.029). In conclusion, circulating free thiols are not decreased in this cohort of non-smoking and generally well-controlled T2DM subjects. Paradoxically, higher triglycerides and more large VLDL particles are likely associated with higher plasma levels of thiols, reflecting lower systemic oxidative stress.
Application of Impedance-Based Techniques in Hepatology Research
Authors: Morgan Katie , Gamal Wesam , Samuel Kay , Morley Steven D. , Hayes Peter C. , Bagnaninchi Pierre , Plevris John N.
Published: December 2019

There are a variety of end-point assays and techniques available to monitor hepatic cell cultures and study toxicity within in vitro models. These commonly focus on one aspect of cell metabolism and are often destructive to cells. Impedance-based cellular assays (IBCAs) assess biological functions of cell populations in real-time by measuring electrical impedance, which is the resistance to alternating current caused by the dielectric properties of proliferating of cells. While the uses of IBCA have been widely reported for a number of tissues, specific uses in the study of hepatic cell cultures have not been reported to date. IBCA monitors cellular behaviour throughout experimentation non-invasively without labelling or damage to cell cultures. The data extrapolated from IBCA can be correlated to biological events happening within the cell and therefore may inform drug toxicity studies or other applications within hepatic research. Because tight junctions comprise the blood/biliary barrier in hepatocytes, there are major consequences when these junctions are disrupted, as many pathologies centre around the bile canaliculi and flow of bile out of the liver. The application of IBCA in hepatology provides a unique opportunity to assess cellular polarity and patency of tight junctions, vital to maintaining normal hepatic function. Here, we describe how IBCAs have been applied to measuring the effect of viral infection, drug toxicity/IC50, cholangiopathies, cancer metastasis and monitoring of the gut-liver axis. We also highlight key areas of research where IBCAs could be used in future applications within the field of hepatology.
Risk Assessment Methodology for Vessel Traffic in Ports by Defining the Nautical Port Risk Index
Authors: Bellsolà Olba Xavier , Daamen Winnie , Vellinga Tiedo , Hoogendoorn Serge P.
Published: December 2019

Ports represent a key element in the maritime transportation chain. Larger vessels and higher traffic volumes in ports might result in higher risks at the navigational level. Thus, the dire need for a comprehensive and efficient risk assessment method for ports is felt. Many methodologies have been proposed so far, but their application to aggregated vessel traffic risks for the overall assessment of ports is not developed yet. Hence, the development of an approach for the appraisal of the vessel traffic risks is still a challenging issue. This research aims to develop an assessment methodology to appraise the potential risk of accident occurrence in port areas at an aggregated level by creating a ‘Nautical Port Risk Index’ (NPRI). After identifying the main nautical risks in ports, the Analytic Network Process (ANP) is used to derive the risk perception (RP) weights for each criterion from data collected through surveys to expert navigators. The consequences related to each nautical risk are identified in consultation with risk experts. By combining the RP values and the consequence of each criterion for a time period, the NPRI is calculated. The risks in the Port of Rotterdam are presented in a case study, and the method has been validated by checking the results with experts in assessing nautical port risks from the Port of Rotterdam Authority. This method can be used to assess any new port design, the performance of different vessel traffic management measures, changes in the fleet composition, or existent ports using the Automatic Identification System (AIS) data.
Numerical Investigation into the Effect of Damage Openings on Ship Hydrodynamics by the Overset Mesh Technique
Authors: Zhang Xinlong , Lin Zhuang , Mancini Simone , Li Ping , Liu Dengke , Liu Fei , Pang Zhanwei
Published: December 2019

Damage stability is difficult to assess due to the complex hydrodynamic phenomena regarding interactions between fluid and structures. Therefore, a detailed analysis of the flooding progression and motion responses is important for improving ship safety. In this paper, numerical simulations are performed on the damaged DTMB 5415 ship at zero speed. All calculation are carried out using CD Adapco Star CCM + software, investigating the effect of damage openings on ship hydrodynamics, including the side damage and the bottom damage. The computational domain is modelled by the overset mesh and solved using the unsteady Reynold-average Navier-Stokes (URANS) solver. An implicit solver is used to find the field of all hydrodynamics unknown quantities, in conjunction with an iterative solver to solve each time step. The Volume of Fluid (VOF) method is applied to visualize the flooding process and capture the complex hydrodynamics behaviors. The simulation results indicated that two damage locations produce the characteristic flooding processes, and the motion responses corresponding to the hydrodynamic behaviors are different. Through comparative analysis, due to the difference between the horizontal impact on the longitudinal bulkhead and the vertical impact on the bottom plate, the bottom damage scenario always has a larger heel angle than the side damage scenario in the same period. However, the pitch motions are basically consistent. Generally, the visualization of the flooding process is efficient to explain the causes of the motion responses. Also, when the damage occurs, regardless of the bottom damage or the side damage, the excessive heel angle due to asymmetric flooding is often a threat to ship survivability with respect to the pitch angle.
Numerical Investigation of the Semi-Active Flapping Foil of the Wave Glider
Authors: Qi Zhanfeng , Zou Bo , Lu Huiqiang , Shi Jian , Li Guofu , Qin Yufeng , Zhai Jingsheng
Published: December 2019

A numerical investigation is conducted to study the propulsive performance of the semi-active flapping foil of the wave glider, where the heaving smotion is fully prescribed, and the pitching motion is determined by the hydrodynamic force and torsion spring. A mesh for two-dimensional NACA0012 foil with the Reynolds number Re = 42000 is produced, and a dynamic mesh and sliding interface are used in the computation. The influences of reduced frequency, spring stiffness, and critical pitching amplitude on the hydrodynamic characteristics of semi-active flapping foil are systematically investigated. We find that there is a critical reduced frequency: When the reduced frequency is lower than the critical value, the propulsive performance of flapping foil can be improved exponentially, and when the reduced frequency is higher than the critical value, the semi-active flapping foil cannot provide an effective thrust. For a greater reduced frequency, there is an optimal spring stiffness value, which corresponds to the maximum value of the output power coefficient. For a lower reduced frequency, the mean value of the output power coefficient monotonically decreases as the spring stiffness increases. We also notice that the propulsive efficiency of flapping foil monotonically decreases as the spring stiffness increases. Finally, we find that the appropriate critical pitching amplitude can improve the propulsive performance of semi-active flapping foil, especially for greater heaving amplitudes.