bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of Factors Related to Ocean Literacy Based on Gender-Invariance Measurement
Authors: Tsai Liang-Ting , Lin Yen-Ling , Chang Cheng-Chieh
Published: September 2019

This study sought to gain a more comprehensive understanding of how the factors of parental education level and student attitude toward the ocean influence the ocean literacy of students in Taiwan after establishing measurement invariance across genders. The analyzed data were collected from self-reported questionnaires filled out by students aged 16–18 years old. The students’ ocean literacy was used as the outcome variable, while parental education level and student attitude toward the ocean were employed as the independent variables. The effects of parental education level and student attitude toward the ocean on ocean literacy were estimated with a multi-group structural equation model. Of the final total of 945 valid respondents in this study, 58.1% were male and 41.9% were female. The results from the multiple-group analysis supported measurement invariance across the genders. After establishing gender invariance, it was further found that higher degrees of parental education level and student attitude toward the ocean were positively related to ocean literacy. A considerable contribution was detected between parental education level and ocean literacy that was indirectly related through student attitude toward the ocean in the female student.
Monitoring Work Ability Index During a Two-Year Period Among Portuguese Municipality Workers
Authors: Cotrim Teresa Patrone , Ribeiro Camila , Teles Júlia , Reis Vítor , Guerreiro Maria João , Janicas Ana Sofia , Candeias Susana , Costa Margarida
Published: September 2019

In Portugal, little is known about the work ability profiles of municipal workers and their changes during working life. In order to characterize and understand the changes in work ability among municipal workers, a prospective study was designed to begin in 2015 in the municipality of Sintra, in the surroundings of Lisbon, and to collect data every two years. The present paper aims at characterizing the changes in the work ability of those workers between 2015 and 2017 and to identify the main predictors. Data collection was based on a questionnaire that encompassed socio-demographic data, the Copenhagen Psychosocial Questionnaire II (COPSOQ II), the Nordic questionnaire adapted, and the Work Ability Index (WAI). In this two-year period, the work ability of municipal workers decreased and the main predictive factors were age, lower-back pain, negative health perception, the presence of burnout, and making manual efforts. Still, there were factors that act as positive predictors of an excellent work ability, such as having training in the previous two years, a good sense of community at work, and a favorable meaning of work. In summary, the intervention strategies in the work field should take into consideration the main predictors of work ability that are relevant for each organization.
The Risk Factors Related to Voice Disorder in Teachers: A Systematic Review and Meta-Analysis
Authors: Byeon Haewon
Published: September 2019

Background and Objectives: Identifying the risk factors of teachers’ voice disorders is very important for preventing voice disorders and the recurrence of them. This meta-study identified risk factors associated with teachers’ voice disorders through systematic review and meta-analysis and provided basic data for preventing them. Materials and Methods: This study collected literature on the risk factors of teachers’ voice disorders using six databases (i.e., CINAHL, EBSCO, PUBMED, SCOPUS, Web of Science, and Springer Link). Search was limited to studies published between 1 January 2000 and 15 October 2018, and a total of 16 publications were selected for the analysis of this study. The quality of selected literature was assessed using the “Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields”. The effect size was analyzed by odds ratio and 95% confidence interval. Results: The results of the quality assessment ranged from 20 to 24 points with six strong studies and ten good studies. The meta-analysis showed that gender, upper airway problems, caffeine consumption, speaking loudly, number of classes per week, and resignation experience due to voice problems were the major risk factors of teachers’ voice disorders. On the other hand, age, number of children, drinking, physical activity, smoking, water intake, singing habits, duration of teaching, perception of noise inside the school, number of classes per day, noise assessment inside the classroom, and perception of technology and instruments inside the workplace were not significantly related to voice disorders. Conclusions: Longitudinal studies should be conducted in the future to confirm causality between voice disorders and risk factors based on the results of this study.
Effects of Bacillus thuringiensis HC-2 Combined with Biochar on the Growth and Cd and Pb Accumulation of Radish in a Heavy Metal-Contaminated Farmland under Field Conditions
Authors: Li Zigang , Wang Peng , Yue Xiaoyu , Wang Jingtao , Ren Baozeng , Qu Lingbo , Han Hui
Published: September 2019

The objective of this study was to explore the effect of heavy metal-resistant bacteria and biochar (BC) on reducing heavy metal accumulation in vegetables and the underlying mechanism. We tested Bacillus thuringiensis HC-2, BC, and BC+HC-2 for their ability to immobilize Cd and Pb in culture solution. We also studied the effects of these treatments on the dry weight and Cd and Pb uptake of radish in metal-contaminated soils under field conditions and the underlying mechanism. Treatment with HC-2, BC, and BC+HC-2 significantly reduced the water-soluble Cd (34–56%) and Pb (31–54%) concentrations and increased the pH and NH4+ concentration in solution compared with their vales in a control. These treatments significantly increased the dry weight of radish roots (18.4–22.8%) and leaves (37.8–39.9%) and decreased Cd (28–94%) and Pb (22–63%) content in the radish roots compared with the control. Treatment with HC-2, BC, and BC+HC-2 also significantly increased the pH, organic matter content, NH4+ content, and NH4+/NO3− ratio of rhizosphere soils, and decreased the DTPA-extractable Cd (37–58%) and Pb (26–42%) contents in rhizosphere soils of radish. Furthermore, BC+HC-2 had higher ability than the other two treatments to protect radish against Cd and Pb toxicity and increased radish biomass. Therefore, Bacillus thuringiensis HC-2 combined with biochar can ensure vegetable safety in situ for the bioremediation of heavy metal-polluted farmland.
Linear Growth in Children and Adolescents with Type 1 Diabetes Mellitus
Authors: Santi Elisa , Tascini Giorgia , Toni Giada , Berioli Maria Giulia , Esposito Susanna
Published: September 2019

Ensuring normal linear growth is one of the major therapeutic aims in the management of type one diabetes mellitus (T1DM) in children and adolescents. Many studies in the literature have shown that pediatric patients with T1DM frequently present some abnormalities in their growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis compared to their healthy peers. Data on the growth of T1DM children and adolescents are still discordant: Some studies have reported that T1DM populations, especially those whose diabetes began in early childhood, are taller than healthy pediatric populations at diagnosis, while other studies have not found any difference. Moreover, many reports have highlighted a growth impairment in T1DM patients of prepubertal and pubertal age, and this impairment seems to be influenced by suboptimal glycemic control and disease duration. However, the most recent data showed that children treated with modern intensive insulin therapies reach a normal final adult height. This narrative review aims to provide current knowledge regarding linear growth in children and adolescents with T1DM. Currently, the choice of the most appropriate therapeutic regimen to achieve a good insulin level and the best metabolic control for each patient, together with the regular measurement of growth parameters, remains the most important available tool for a pediatric diabetologist. Nevertheless, since new technologies are the therapy of choice in young children, especially those of pre-school age, it would be of great interest to evaluate their effects on the growth pattern of children with T1DM.
Association between Phthalate Metabolites and Risk of Endometriosis: A Meta-Analysis
Authors: Cai Wei , Yang Jule , Liu Yini , Bi Yongyi , Wang Hong
Published: September 2019

Objective: The association between phthalates and endometriosis risk is inconclusive. This meta-analysis aims to evaluate the association between five different phthalate metabolites and endometriosis, based on current evidence. Methods: The literature included PubMed, WOS (web of science), and EMBASE, published until 3 March 2019. We selected the related literature and evaluated the relationship between phthalates exposure and endometriosis risk. All statistical analyses were conducted with STATA version 12.0. Results: Data from eight studies were used in this review. The results of this analysis showed that mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) exposure was potentially associated with endometriosis (OR = 1.246, 95% CI = 1.003–1.549). We have not found positive results in mono(2-ethylhexyl) phthalate (MEHP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) analyses (MEHP: OR = 1.089, 95% CI = 0.858–1.383; MEP: OR = 1.073, 95% CI = 0.899–1.282; MBzP: OR = 0.976, 95% CI = 0.810–1.176; MEOHP: OR = 1.282, 95% CI = 0.874–1.881). In subgroup analyses for regions, the associations were significant between MEHHP and endometriosis in Asia (OR = 1.786, 95% CI = 1.005–3.172, I² = 0%), but not in USA (OR = 1.170, 95% CI = 0.949–1.442, I² = 45.6%). Conclusions: Our findings suggested a potential statistical association between MEHHP exposure and endometriosis, particularly, the exposure of MEHHP might be a potential risk for women with endometriosis in Asia. However, positive associations between the other four Phthalate acid esters (PAEs) and endometriosis was not found. Given the weak strength of the results, well-designed cohort studies, with large sample sizes, should be performed in future.
Association between Health Literacy and Subgroups of Health Risk Behaviors among Chinese Adolescents in Six Cities: A Study Using Regression Mixture Modeling
Authors: Yang Rong , Li Danlin , Hu Jie , Tian Run , Wan Yuhui , Tao Fangbiao , Fang Jun , Zhang Shichen
Published: September 2019

Adolescents engage in health risk behaviors (HRBs) that influence their current and future health status. Health literacy (HL) is defined as how well a person can get and understand the health information and services, and use them to make good health decisions. HL can be used to participate in everyday activities actively and apply new information to the changing circumstances. HRBs commonly co-occur in adolescence, and few researchers have examined how HL predicts multiple HRBs in adolescence. In this study we examined the subgroups of HRBs, and investigated heterogeneity in the effects of HL on the subgroups. In total, 22,628 middle school students (10,990 males and 11,638 females) in six cities were enrolled by multistage stratified cluster sampling from November 2015 to January 2016. The measurement of HL was based on the Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ). Analyses were conducted with regression mixture modeling approach (RMM) by Mplus. By this study we found four latent classes among Chinese adolescents: Low-risk class, moderate-risk class 1 (smoking/alcohol use (AU)/screen time (ST)), moderate-risk class 2 (non-suicidal self-injury (NSSI)/suicidal behaviors (SB)/unintentional injury (UI)), and high-risk class (smoking/AU/ST/NSSI/SB/UI) which were 64.0%, 4.5%, 28.8% and 2.7% of involved students, respectively. Negative correlations were found between HL and HRBs: higher HL accompanied decreased HBRs. Compared to the low-risk class, moderate-risk class 1 (smoking/AU/ST), moderate-risk class 2 (NSSI/SB/UI), and high-risk class (smoking/AU/ST/NSSI/SB/UI) showed OR (95%CI) values of 0.990 (0.982–0.998), 0.981 (0.979–0.983) and 0.965 (0.959–0.970), respectively. Moreover, there was heterogeneity in the profiles of HRBs and HL in different classes. It is important for practitioners to examine HRBs in multiple domains concurrently rather than individually in isolation. Interventions and research should not only target adolescents engaging in high levels of risky behavior but also adolescents who are engaging in lower levels of risky behavior.
Exposure–Response Relationship and Doubling Risk Doses—A Systematic Review of Occupational Workload and Osteoarthritis of the Hip
Authors: Sun Yi , Nold Annette , Glitsch Ulrich , Bochmann Frank
Published: September 2019

In this review, we critically evaluated the evidence of exposure–response relationships between occupational workload and the risk of hip osteoarthritis. The existing evidence was evaluated in order for us to extrapolate possible doubling risk doses for hip osteoarthritis. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases (PubMed, EMBASE, Cochrane Work and Google Scholar) and recent reviews up to February 2019. In total, 85 papers met the preliminary inclusion criteria, and 10 studies indicating an exposure-response relationship between occupational workload and hip osteoarthritis were identified. All studies were assessed on the basis of their study design, defined quality scores and relevant confounders considered. An exposure–response relationship between heavy lifting and the risk of hip osteoarthritis is consistently observed among the male populations but not among the female populations. We quantified the doubling risk doses in two studies in which both an exposure–response relationship and cumulative exposure doses were stated. These two studies provided the highest quality level of all studies published to date. The estimated doubling risk doses in these two studies lie between 14,761 and 18,550 tons (daily lifting 2.2–2.8 tons, 220 days/year for 30 years). These results can be used for workplace interventions to prevent hip osteoarthritis.
The Relationship between Cognitive Impairment and Social Vulnerability among the Elderly: Evidence from an Unconditional Quantile Regression Analysis in China
Authors: Zhao Junkai , Zhang Xinxin , Li Zongmin
Published: September 2019

As the global proportion of the elderly population has been growing rapidly, it has become important to better understand the holistic social factors involved in cognitive impairment in the elderly. To investigate the relationship between social vulnerability and cognitive impairment in the elderly, this study applied an unconditional quantile regression model on open source health survey data in China. It was used to estimate the relationship for full sample and subsamples divided by different levels of a specific covariate. It was found that the cognitive impairment had a positive association with social vulnerability, and this relationship is stronger at the higher cognitive impairment quantiles. The cognitive impairment of females and elderly who took less exercise; had lower self-rated health; had greater incidences of depression, chronic diseases, and physical limitations; and consumed less fruit and vegetables, milk and tea were more related to social vulnerability. These results provide some insights into the strategies that could be used by the elderly to decrease the risk of cognitive impairment.
Spatial Variability in the Effect of High Ambient Temperature on Mortality: An Analysis at Municipality Level within the Greater Athens Area
Authors: Zafeiratou Sofia , Analitis Antonis , Founda Dimitra , Giannakopoulos Christos , Varotsos Konstantinos V. , Sismanidis Panagiotis , Keramitsoglou Iphigenia , Katsouyanni Klea
Published: September 2019

Spatial variability in temperature exists within metropolitan areas but very few studies have investigated intra-urban differentiation in the temperature-mortality effects. We investigated whether local characteristics of 42 Municipalities within the Greater Athens Area lead to modified temperature effects on mortality and if effect modifiers can be identified. Generalized Estimating Equations models were used to assess the effect of high ambient temperature on the total and cause-specific daily number of deaths and meta-regression to investigate effect modification. We found significant effects of daily temperature increases on all-cause, cardiovascular, and respiratory mortality (e.g., for all ages 4.16% (95% CI: 3.73,4.60%) per 1 °C increase in daily temperature (lags 0–3). Heterogeneity in the effect estimates between Municipalities was observed in several outcomes and environmental and socio-economic effect modifying variables were identified, such as % area coverage of buildings, length of roads/km2, population density, % unemployed, % born outside the EU countries and mean daily temperature. To further examine the role of temperature, we alternatively used modelled temperature per Municipality and calculated the effects. We found that heterogeneity was reduced but not eliminated. It appears that there are socioeconomic status and environmental determinants of the magnitude of heat-related effects on mortality, which are detected with some consistency and should be further investigated.
A Relief Dependent Evaluation of Digital Elevation Models on Different Scales for Northern Chile
Authors: Kramm Tanja , Hoffmeister Dirk
Published: September 2019

Many geoscientific computations are directly influenced by the resolution and accuracy of digital elevation models (DEMs). Therefore, knowledge about the accuracy of DEMs is essential to avoid misleading results. In this study, a comprehensive evaluation of the vertical accuracy of globally available DEMs from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), Shuttle Radar Topography Mission (SRTM), Advanced Land Observing Satellite (ALOS) World 3D and TanDEM-X WorldDEM™ was conducted for a large region in Northern Chile. Additionally, several very high-resolution DEM datasets were derived from Satellite Pour l’Observation de la Terre (SPOT) 6/7 and Pléiades stereo satellite imagery for smaller areas. All datasets were evaluated with three reference datasets, namely elevation points from both Ice, Cloud, and land Elevation (ICESat) satellites, as well as very accurate high-resolution elevation data derived by unmanned aerial vehicle (UAV)-based photogrammetry and terrestrial laser scanning (TLS). The accuracy was also evaluated with regard to the existing relief by relating the accuracy results to slope, terrain ruggedness index (TRI) and topographic position index (TPI). For all datasets with global availability, the highest overall accuracies are reached by TanDEM-X WorldDEM™ and the lowest by ASTER Global DEM (GDEM). On the local scale, Pléiades DEMs showed a slightly higher accuracy as SPOT imagery. Generally, accuracy highly depends on topography and the error is rising up to four times for high resolution DEMs and up to eight times for low-resolution DEMs in steeply sloped terrain compared to flat landscapes.
Exploring Housing Rent by Mixed Geographically Weighted Regression: A Case Study in Nanjing
Authors: Zhang Shiwei , Wang Lin , Lu Feng
Published: September 2019

In China, the housing rent can clearly reveal the actual utility value of a house due to its low capital premium. However, few studies have examined the spatial variability of housing rent. Accordingly, this study attempted to determine the utility value of houses based on housing rent data. In this study, we applied mixed geographically weighted regression (MGWR) to explore the residential rent in Nanjing, the largest city in Jiangsu Province. The results show that the distribution of residential rent has a multi-center group pattern. Commercial centers, primary and middle schools, campuses, subways, expressways, and railways are the most significant influencing factors of residential rent in Nanjing, and each factor has its own unique characteristics of spatial differentiation. In addition, the MGWR has a better fit with housing rent than geographically weighted regression (GWR). These research results provide a scientific basis for local real estate management and urban planning departments.
The Americas’ Spatial Data Infrastructure
Authors: Merodio Gómez Paloma , Pérez García Macarena , García Seco Gabriela , Ramírez Santiago Andrea , Tapia Johnson Catalina
Published: September 2019

During the last decade, the production of geospatial information has increased considerably; however, managing and sharing this information has become increasingly difficult for the organizations that produce it, because it comes from different data sources and has a wide variety of users. In this sense, to have a better use of geospatial information, several countries have developed national spatial data infrastructures (SDIs) to improve access, visualization, and integration of their data and in turn, have the need to cooperate with other countries to develop regional SDIs, which allow better decision making with regional impact. However, its design and development plan requires, as a starting point, to knowing the level of development of the national SDIs to identify the strengths and gaps that exist in the region. This document presents the methodology developed and the results obtained from the evaluation of the status of implementation of the SDI components in each of the member countries of the Regional Committee of United Nations on Global Geospatial Information Management for the Americas (UN-GGIM: Americas), which will contribute to the equal development of SDIs in an integrated and collaborative way in the Americas.
Dynamic Recommendation of POI Sequence Responding to Historical Trajectory
Authors: Huang Jianfeng , Liu Yuefeng , Chen Yue , Jia Chen
Published: September 2019

Point-of-Interest (POI) recommendation is attracting the increasing attention of researchers because of the rapid development of Location-based Social Networks (LBSNs) in recent years. Differing from other recommenders, who only recommend the next POI, this research focuses on the successive POI sequence recommendation. A novel POI sequence recommendation framework, named Dynamic Recommendation of POI Sequence (DRPS), is proposed, which models the POI sequence recommendation as a Sequence-to-Sequence (Seq2Seq) learning task, that is, the input sequence is a historical trajectory, and the output sequence is exactly the POI sequence to be recommended. To solve this Seq2Seq problem, an effective architecture is designed based on the Deep Neural Network (DNN). Owing to the end-to-end workflow, DRPS can easily make dynamic POI sequence recommendations by allowing the input to change over time. In addition, two new metrics named Aligned Precision (AP) and Order-aware Sequence Precision (OSP) are proposed to evaluate the recommendation accuracy of a POI sequence, which considers not only the POI identity but also the visiting order. The experimental results show that the proposed method is effective for POI sequence recommendation tasks, and it significantly outperforms the baseline approaches like Additive Markov Chain, LORE and LSTM-Seq2Seq.
Genome-Wide CpG Island Methylation Profiles of Cutaneous Skin with and without HPV Infection
Authors: AL-Eitan Laith N. , Alghamdi Mansour A. , Tarkhan Amneh H. , Al-Qarqaz Firas A.
Published: September 2019

HPV infection is one of the most commonly transmitted diseases among the global population. While it can be asymptomatic, non-genital HPV infection often gives rise to cutaneous warts, which are benign growths arising from the epidermal layer of the skin. This study aimed to produce a global analysis of the ways in which cutaneous wart formation affected the CpG island methylome. The Infinium MethylationEPIC BeadChip microarray was utilized in order to quantitatively interrogate CpG island methylation in genomic DNA extracted from 24 paired wart and normal skin samples. Differential methylation analysis was carried out by means of assigning a combined rank score using RnBeads. The 1000 top-ranking CpG islands were then subject to Locus Overlap Analysis (LOLA) for enrichment of genomic ranges, while signaling pathway analysis was carried out on the top 100 differentially methylated CpG islands. Differential methylation analysis illustrated that the most differentially methylated CpG islands in warts lay within the ITGB5, DTNB, RBFOX3, SLC6A9, and C2orf27A genes. In addition, the most enriched genomic region sets in warts were Sheffield’s tissue-clustered DNase hypersensitive sites, ENCODE’s segmentation and transcription factor binding sites, codex sites, and the epigenome sites from cistrome. Lastly, signaling pathway analysis showed that the GRB2, GNB1, NTRK1, AXIN1, and SKI genes were the most common regulators of the genes associated with the top 100 most differentially methylated CpG islands in warts. Our study shows that HPV-induced cutaneous warts have a clear CpG island methylation profile that sets them apart from normal skin. Such a finding could account for the temporary nature of warts and the capacity for individuals to undergo clinical remission.
Membrane Transporters in Human Parotid Gland-Targeted Proteomics Approach
Authors: Lapczuk-Romanska Joanna , Busch Diana , Gieruszczak Ewa , Drozdzik Agnieszka , Piotrowska Katarzyna , Kowalczyk Robert , Oswald Stefan , Drozdzik Marek
Published: September 2019

Salivary glands provide secretory functions, including secretion of xenobiotics and among them drugs. However, there is no published information about protein abundance of drug transporters measured using reliable protein quantification methods. Therefore, mRNA expression and absolute protein content of clinically relevant ABC (n = 6) and SLC (n = 15) family member transporters in the human parotid gland, using the qRT-PCR and liquid chromatography‒tandem mass spectrometry (LC−MS/MS) method, were studied. The abundance of nearly all measured proteins ranged between 0.04 and 0.45 pmol/mg (OCT3 > MRP1 > PEPT2 > MRP4 > MATE1 > BCRP). mRNAs of ABCB1, ABCC2, ABCC3, SLC10A1, SLC10A2, SLC22A1, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLCO1A2, SLCO1B1, SLCO1B3 and SLCO2B1 were not detected. The present study provides, for the first time, information about the protein abundance of membrane transporters in the human parotid gland, which could further be used to define salivary bidirectional transport (absorption and secretion) mechanisms of endogenous compounds and xenobiotics.
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women
Authors: Wu Bohua , Peng Yunhui , Eggert Julia , Alexov Emil
Published: September 2019

This study suggests that two newly discovered variants in the MSH2 gene, which codes for a DNA mismatch repair (MMR) protein, can be associated with a high risk of breast cancer. While variants in the MSH2 gene are known to be linked with an elevated cancer risk, the MSH2 gene is not a part of the standard kit for testing patients for elevated breast cancer risk. Here we used the results of genetic testing of women diagnosed with breast cancer, but who did not have variants in BRCA1 and BRCA2 genes. Instead, the test identified four variants with unknown significance (VUS) in the MSH2 gene. Here, we carried in silico analysis to develop a classifier that can distinguish pathogenic from benign mutations in MSH2 genes taken from ClinVar. The classifier was then used to classify VUS in MSH2 genes, and two of them, p.Ala272Val and p.Met592Val, were predicted to be pathogenic mutations. These two mutations were found in women with breast cancer who did not have mutations in BRCA1 and BRCA2 genes, and thus they are suggested to be considered as new bio-markers for the early detection of elevated breast cancer risk. However, before this is done, an in vitro validation of mutation pathogenicity is needed and, moreover, the presence of these mutations should be demonstrated in a higher number of patients or in families with breast cancer history.
A Molecular Dynamics Study of a Photodynamic Sensitizer for Cancer Cells: Inclusion Complexes of γ-Cyclodextrins with C70
Authors: Raffaini Giuseppina , Ganazzoli Fabio
Published: September 2019

Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes [(γ-CD)2/C70] are investigated analyzing the differences with the analogous C60 complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy. The inclusion complex of γ-CD and C70 has a 2:1 stoichiometry, the same as C60, but is significantly less stable and displays an unlike arrangement. In vacuo, mimicking an apolar solvent, the complex is compact, whereas in water the two γ-CDs encapsulate C70 forming a relatively stable complex by interacting through their primary rims, however exposing part of C70 to the solvent. Other higher-energy complexes with the γ-CDs facing different rims can form in water, but in all cases part of the hydrophobic C70 surface remains exposed to water. The stability and arrangement of these peculiar amphiphilic inclusion complexes having non-covalent interactions in water can be an important key for cancer therapy to enhance both the solubilization and the fullerene insertion into liposomes or cell membranes.
Micro RNA Transcriptome Profile in Canine Oral Melanoma
Authors: Rahman Md. Mahfuzur , Lai Yu-Chang , Husna Al Asmaul , Chen Hui-wen , Tanaka Yuiko , Kawaguchi Hiroaki , Miyoshi Noriaki , Nakagawa Takayuki , Fukushima Ryuji , Miura Naoki
Published: September 2019

MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dogs is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MiRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor miRNAs, we report 30 oncogenic miRNAs in COM. The expressions of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had a significant negative correlation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors with respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA’s profile in COM which will be a useful resource for developing therapeutic interventions in both species.
Differential Role of TGF-β in Extracellular Matrix Regulation During Trypanosoma cruzi-Host Cell Interaction
Authors: Silva Tatiana Araújo , Ferreira Luis Felipe de Carvalho , Pereira Mirian Claudia de Souza , Calvet Claudia Magalhães
Published: September 2019

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of Trypanosoma cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF), and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF, and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1 h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 was less stimulated in CF than CM and L6E9. T. cruzi infection resulted in localized FN disorganization in CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.
Perioperative Cardioprotection by Remote Ischemic Conditioning
Authors: Cho Youn Joung , Kim Won Ho
Published: September 2019

Remote ischemic conditioning has been investigated for cardioprotection to attenuate myocardial ischemia/reperfusion injury. In this review, we provide a comprehensive overview of the current knowledge of the signal transduction pathways of remote ischemic conditioning according to three stages: Remote stimulus from source organ; protective signal transfer through neuronal and humoral factors; and target organ response, including myocardial response and coronary vascular response. The neuronal and humoral factors interact on three levels, including stimulus, systemic, and target levels. Subsequently, we reviewed the clinical studies evaluating the cardioprotective effect of remote ischemic conditioning. While clinical studies of percutaneous coronary intervention showed relatively consistent protective effects, the majority of multicenter studies of cardiac surgery reported neutral results although there have been several promising initial trials. Failure to translate the protective effects of remote ischemic conditioning into cardiac surgery may be due to the multifactorial etiology of myocardial injury, potential confounding factors of patient age, comorbidities including diabetes, concomitant medications, and the coadministered cardioprotective general anesthetic agents. Given the complexity of signal transfer pathways and confounding factors, further studies should evaluate the multitarget strategies with optimal measures of composite outcomes.
4-Mercaptobenzoic Acid Labeled Gold-Silver-Alloy-Embedded Silica Nanoparticles as an Internal Standard Containing Nanostructures for Sensitive Quantitative Thiram Detection
Authors: Pham Xuan-Hung , Hahm Eunil , Huynh Kim-Hung , Son Byung Sung , Kim Hyung-Mo , Jeong Dae Hong , Jun Bong-Hyun
Published: September 2019

In this study, SiO2@Au@4-MBA@Ag (4-mercaptobenzoic acid labeled gold-silver-alloy-embedded silica nanoparticles) nanomaterials were investigated for the detection of thiram, a pesticide. First, the presence of Au@4-MBA@Ag alloys on the surface of SiO2 was confirmed by the broad bands of ultraviolet-visible spectra in the range of 320–800 nm. The effect of the 4-MBA (4-mercaptobenzoic acid) concentration on the Ag shell deposition and its intrinsic SERS (surface-enhanced Raman scattering) signal was also studied. Ag shells were well coated on SiO2@Au@4-MBA in the range of 1–1000 µM. The SERS intensity of thiram-incubated SiO2@Au@4-MBA@Ag achieved the highest value by incubation with 500 µL thiram for 30 min, and SERS was measured at 200 µg/mL SiO2@Au@4-MBA@Ag. Finally, the SERS intensity of thiram at 560 cm−1 increased proportionally with the increase in thiram concentration in the range of 240–2400 ppb, with a limit of detection (LOD) of 72 ppb.
Overexpression of GmCAMTA12 Enhanced Drought Tolerance in Arabidopsis and Soybean
Authors: Noman Muhammad , Jameel Aysha , Qiang Wei-Dong , Ahmad Naveed , Liu Wei-Can , Wang Fa-Wei , Li Hai-Yan
Published: September 2019

Fifteen transcription factors in the CAMTA (calmodulin binding transcription activator) family of soybean were reported to differentially regulate in multiple stresses; however, their functional analyses had not yet been attempted. To characterize their role in stresses, we first comprehensively analyzed the GmCAMTA family in silico and thereafter determined their expression pattern under drought. The bioinformatics analysis revealed multiple stress-related cis-regulatory elements including ABRE, SARE, G-box and W-box, 10 unique miRNA (microRNA) targets in GmCAMTA transcripts and 48 proteins in GmCAMTAs’ interaction network. We then cloned the 2769 bp CDS (coding sequence) of GmCAMTA12 in an expression vector and overexpressed in soybean and Arabidopsis through Agrobacterium-mediated transformation. The T3 (Transgenic generation 3) stably transformed homozygous lines of Arabidopsis exhibited enhanced tolerance to drought in soil as well as on MS (Murashige and Skoog) media containing mannitol. In their drought assay, the average survival rate of transgenic Arabidopsis lines OE5 and OE12 (Overexpression Line 5 and Line 12) was 83.66% and 87.87%, respectively, which was ~30% higher than that of wild type. In addition, the germination and root length assays as well as physiological indexes such as proline and malondialdehyde contents, catalase activity and leakage of electrolytes affirmed the better performance of OE lines. Similarly, GmCAMTA12 overexpression in soybean promoted drought-efficient hairy roots in OE chimeric plants as compare to that of VC (Vector control). In parallel, the improved growth performance of OE in Hoagland-PEG (polyethylene glycol) and on MS-mannitol was revealed by their phenotypic, physiological and molecular measures. Furthermore, with the overexpression of GmCAMTA12, the downstream genes including AtAnnexin5, AtCaMHSP, At2G433110 and AtWRKY14 were upregulated in Arabidopsis. Likewise, in soybean hairy roots, GmELO, GmNAB and GmPLA1-IId were significantly upregulated as a result of GmCAMTA12 overexpression and majority of these upregulated genes in both plants possess CAMTA binding CGCG/CGTG motif in their promoters. Taken together, we report that GmCAMTA12 plays substantial role in tolerance of soybean against drought stress and could prove to be a novel candidate for engineering soybean and other plants against drought stress. Some research gaps were also identified for future studies to extend our comprehension of Ca-CaM-CAMTA-mediated stress regulatory mechanisms.
Application of the Movable Type Free Energy Method to the Caspase-Inhibitor Binding Affinity Study
Authors: Xue Song , Liu Hao , Zheng Zheng
Published: September 2019

Many studies have provided evidence suggesting that caspases not only contribute to the neurodegeneration associated with Alzheimer’s disease (AD) but also play essential roles in promoting the underlying pathology of this disease. Studies regarding the caspase inhibition draw researchers’ attention through time due to its therapeutic value in the treatment of AD. In this work, we apply the “Movable Type” (MT) free energy method, a Monte Carlo sampling method extrapolating the binding free energy by simulating the partition functions for both free-state and bound-state protein and ligand configurations, to the caspase-inhibitor binding affinity study. Two test benchmarks are introduced to examine the robustness and sensitivity of the MT method concerning the caspase inhibition complexing. The first benchmark employs a large-scale test set including more than a hundred active inhibitors binding to caspase-3. The second benchmark includes several smaller test sets studying the relative binding free energy differences for minor structural changes at the caspase-inhibitor interaction interfaces. Calculation results show that the RMS errors for all test sets are below 1.5 kcal/mol compared to the experimental binding affinity values, demonstrating good performance in simulating the caspase-inhibitor complexing. For better understanding the protein-ligand interaction mechanism, we then take a closer look at the global minimum binding modes and free-state ligand conformations to study two pairs of caspase-inhibitor complexes with (1) different caspase targets binding to the same inhibitor, and (2) different polypeptide inhibitors targeting the same caspase target. By comparing the contact maps at the binding site of different complexes, we revealed how small structural changes affect the caspase-inhibitor interaction energies. Overall, this work provides a new free energy approach for studying the caspase inhibition, with structural insight revealed for both free-state and bound-state molecular configurations.
Prediction Model with High-Performance Constitutive Androstane Receptor (CAR) Using DeepSnap-Deep Learning Approach from the Tox21 10K Compound Library
Authors: Matsuzaka Yasunari , Uesawa Yoshihiro
Published: September 2019

The constitutive androstane receptor (CAR) plays pivotal roles in drug-induced liver injury through the transcriptional regulation of drug-metabolizing enzymes and transporters. Thus, identifying regulatory factors for CAR activation is important for understanding its mechanisms. Numerous studies conducted previously on CAR activation and its toxicity focused on in vivo or in vitro analyses, which are expensive, time consuming, and require many animals. We developed a computational model that predicts agonists for the CAR using the Toxicology in the 21st Century 10k library. Additionally, we evaluate the prediction performance of novel deep learning (DL)-based quantitative structure-activity relationship analysis called the DeepSnap-DL approach, which is a procedure of generating an omnidirectional snapshot portraying three-dimensional (3D) structures of chemical compounds. The CAR prediction model, which applies a 3D structure generator tool, called CORINA-generated and -optimized chemical structures, in the DeepSnap-DL demonstrated better performance than the existing methods using molecular descriptors. These results indicate that high performance in the prediction model using the DeepSnap-DL approach may be important to prepare suitable 3D chemical structures as input data and to enable the identification of modulators of the CAR.
Nitrogen Starvation Differentially Influences Transcriptional and Uptake Rate Profiles in Roots of Two Maize Inbred Lines with Different NUE
Authors: Mascia Maria , Sega Davide , Zamboni Anita , Varanini Zeno
Published: September 2019

Nitrogen use efficiency (NUE) of crops is estimated to be less than 50%, with a strong impact on environment and economy. Genotype-dependent ability to cope with N shortage has been only partially explored in maize and, in this context, the comparison of molecular responses of lines with different NUE is of particular interest in order to dissect the key elements underlying NUE. Changes in root transcriptome and NH4+/NO3− uptake rates during growth (after 1 and 4 days) without N were studied in high (Lo5) and low (T250) NUE maize inbred lines. Results suggests that only a small set of transcripts were commonly modulated in both lines in response to N starvation. However, in both lines, transcripts linked to anthocyanin biosynthesis and lateral root formation were positively affected. On the contrary, those involved in root elongation were downregulated. The main differences between the two lines reside in the ability to modulate the transcripts involved in the transport, distribution and assimilation of mineral nutrients. With regard to N mineral forms, only the Lo5 line responded to N starvation by increasing the NH4+ fluxes as supported by the upregulation of a transcript putatively involved in its transport.
ILC2 Activation by Protozoan Commensal Microbes
Authors: Burrows Kyle , Ngai Louis , Wong Flora , Won David , Mortha Arthur
Published: September 2019

Group 2 innate lymphoid cells (ILC2s) are a member of the ILC family and are involved in protective and pathogenic type 2 responses. Recent research has highlighted their involvement in modulating tissue and immune homeostasis during health and disease and has uncovered critical signaling circuits. While interactions of ILC2s with the bacterial microbiome are rather sparse, other microbial members of our microbiome, including helminths and protozoans, reveal new and exciting mechanisms of tissue regulation by ILC2s. Here we summarize the current field on ILC2 activation by the tissue and immune environment and highlight particularly new intriguing pathways of ILC2 regulation by protozoan commensals in the intestinal tract.
STAT3 Regulates the Type I IFN-Mediated Antiviral Response by Interfering with the Nuclear Entry of STAT1
Authors: Wang Huanru , Yuan Meng , Wang Shuaibo , Zhang Li , Zhang Rui , Zou Xue , Wang Xiaohui , Chen Deyan , Wu Zhiwei
Published: September 2019

Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin α family member Karyopherin-α1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.
Recent Advances in Our Understanding of the Link between the Intestinal Microbiota and Systemic Lupus Erythematosus
Authors: Kim Ji-Won , Kwok Seung-Ki , Choe Jung-Yoon , Park Sung-Hwan
Published: September 2019

Systemic lupus erythematosus (SLE) is an autoimmune disease featuring enhanced expression of type I interferon (IFN) and autoantibody production triggering inflammation of, and damage to, multiple organs. Continuing research efforts focus on how gut microbes trigger systemic autoimmunity and SLE. The gut microbial communities of mice and humans with lupus have been investigated via high-throughput sequencing. The Firmicutes-to-Bacteroidetes ratio is consistently reduced in SLE patients, regardless of ethnicity. The relative abundance of Lactobacillus differs from the animal model used (MRL/lpr mice or NZB/W F1 mice). This may indicate that interactions between gut microbes and the host, rather than the enrichment of certain gut microbes, are especially significant in terms of SLE development. Enterococcus gallinarum and Lactobacillus reuteri, both of which are possible gut pathobionts, become translocated into systemic tissue if the gut epithelial barrier is impaired. The microbes then interact with the host immune systems, activating the type I IFN pathway and inducing autoantibody production. In addition, molecular mimicry may critically link the gut microbiome to SLE. Gut commensals of SLE patients share protein epitopes with the Ro60 autoantigen. Ruminococcus gnavus strain cross-reacted with native DNA, triggering an anti-double-stranded DNA antibody response. Expansion of R. gnavus in SLE patients paralleled an increase in disease activity and lupus nephritis. Such insights into the link between the gut microbiota and SLE enhance our understanding of SLE pathogenesis and will identify biomarkers predicting active disease.