bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet Dental Care Needs among Korean National Health Insurance Beneficiaries Based on Income Inequalities: Results from Five Waves of a Population-Based Panel Study
Authors: Sohn Minsung , Che Xianhua , Park Hee-Jung
Published: May 2020

This study investigates whether self-employed beneficiaries experience greater difficulties in accessing dental care than insured employees based on their income level. This analysis uses 2011–2015 data from the Korea Health Panel, a population-based and nationally representative sample, covering 7083 participants aged 18 years and older. We measured barriers to dental access based on unmet needs or the inability to receive necessary dental care owing to the past year’s economic burdens. The type of health insurance and household income are considered independent variables. We applied multiple panel logistic regressions and two-panel logistic regression models with a fixed-effects approach to analyze the data. Self-employed beneficiaries were 1.16 times (95% confidence interval (CI) = 1.08–1.24) more likely to experience unmet dental needs than were insured employees. Insured employees and self-employed beneficiaries belonging to the lowest income bracket were 1.76 times (95% CI = 1.53–2.03) and 2.33 times (95% CI = 1.89–2.87) more likely to have unmet needs than those in the highest income bracket. Self-employed beneficiaries were 1.31 times (95% CI = 1.21–1.43) more likely to experience unmet dental needs caused by economic burdens than are insured employees. Insured employees of the lowest income quintile were 4.15 times (95% CI = 3.41–5.05) more likely to experience unmet needs caused by economic burdens, while the odds ratio for self-employed beneficiaries was 5.47 (95% CI = 4.05–7.39). Our findings indicate gaps in unmet dental needs between self-employed beneficiaries and insured employees. The government should adopt strategies to reduce unmet needs among marginalized groups and redefine the role of national health insurance.
Soil Odor as An Extra-Official Criterion for Qualifying Remediation Projects of Crude Oil-Contaminated Soil
Authors: López-Aguilar Saúl , Adams Randy H. , Domínguez-Rodríguez Verónica Isidra , Gaspar-Génico José A. , Zavala-Cruz Joel , Hernández-Natarén Edith
Published: May 2020

Unfortunately, many property owners in southeastern Mexico do not trust environmental authorities, and the de facto method they use to evaluate the progress in environmental remediation projects is soil smell. This criterion was evaluated to determine if it was reliable to assess soil fertility and toxicity. Three soils (Fluvisol, Gleysol, and Arenosol), were contaminated with 2% medium or heavy crude oil (30.2, 17.1°API, respectively), and treated for 18 months to simulate bioremediation or natural attenuation. Every two months, field capacity, water repellency, hydrocarbon concentration, acute toxicity and soil odor were measured. Odor was measured in controlled conditions with a group of unexperienced panelists. During remediation, the Fluvisol and Gleysol were perceived to have an odor intensity between slight to low, and were considered acceptable. Meanwhile, in the Arenosol, the odor intensity was between low to medium and was considered unacceptable. After treatment, the hydrocarbon concentration was reduced to low levels, very near Mexican norm, and all the soils, including the Arenosol, were perceived to have an intensity between neutral to slightly agreeable, were considered acceptable, and no toxicity was observed in the earthworm bioassay (no false positives). However, in various soil samples from the Fluvisol and Arenosol, important risks were present with respect to field capacity and water repellency. Due to these observations, even though soil smell may be a trustworthy guide to soil toxicity, it does not ensure that the remediated soil’s fertility has been restored.
Validation of the Index for Inclusion Questionnaire for Parents of Non-University Education Students
Authors: Fernández-Archilla José A. , Aguilar-Parra José M. , Álvarez-Hernández Joaquín F. , Luque de la Rosa Antonio , Echeita Gerardo , Trigueros Rubén
Published: May 2020

The perspective from the parents of non-university students is essential in determining inclusive education in a school. The Index of Inclusion is one of the most widely used self-assessment tools and strategies to help teaching teams self-assess their political cultures and practices from the perspective of the values and principles of educational inclusion worldwide. For this reason, the present study intends to show evidence of validity of the Index for Inclusion questionnaire for parents of non-university education students, in a quantitative way, through a confirmatory factor analysis (CFA). In this study, 108 fathers and 500 mothers took part, aged between 21 and 62 years (M = 43.59; SD = 6.64), whose children belonged to educational institutions throughout Spain. The results revealed adequate adjustment rates, showing invariant structure with respect to sex. The Index for Inclusion for families of non-university education students was shown to be a robust and adequate psychometric instrument to assess the degree of development of inclusive education in educational institutions from the perspective of the parents of said student body. The family is a basic pillar in the education of children and a reference for them. In addition, parents of non-university education students are configured as fundamental participatory elements of the child’s educational institution thus; making the family a fundamental element that favors inclusive education. Precisely because of all this, the future administration of this questionnaire (to the parents of these students) is recommended.
Spatial Characteristics of Urban Green Spaces and Human Health: An Exploratory Analysis of Canonical Correlation
Authors: Yeh Chia-Tsung , Cheng Ya-Yun , Liu Tsai-Yun
Published: May 2020

In highly urbanized areas, urban green spaces (UGSs) are important natural and cultural entities. Previous studies have shown some evidence of positive relationships between UGSs and human health. Most of these studies relied on self-reported health data and often used institutional quantitative measures of UGSs instead of the spatial characteristics of UGSs. This study analyzed the relationships between the spatial characteristics of UGSs and morbidity of diseases, which were considered variables of human health in the Taipei Metro. The Longitudinal Health Insurance Database of Taiwan was applied as the source of morbidity of diseases. A canonical correlation analysis was performed by using the six variables of spatial characteristics of UGSs as predictors and three variables of morbidity as criterion variables to evaluate the multivariate shared relationships between the two variable sets. The results found a strong canonical correlation between the spatial characteristics of UGSs and human health. Furthermore, the results revealed that living in districts with a higher area percentage of green spaces and denser vegetation cover, as well as exposure to more aggregative and irregular-shape green spaces, can reduce the morbidity of diseases.
Handgrip Strength Asymmetry and Weakness Are Differentially Associated with Functional Limitations in Older Americans
Authors: Collins Kyle , Johnson Nathaniel , Klawitter Lukus , Waldera Roman , Stastny Sherri , Kraemer William J. , Christensen Bryan , McGrath Ryan
Published: May 2020

Background: Handgrip strength (HGS) is a convent measure of strength capacity and associated with several age-related health conditions such as functional disability. Asymmetric strength between limbs has been linked to diminished function. Therefore, both HGS asymmetry and weakness could be associated with functional disability. We examined the associations of HGS asymmetry and weakness on functional limitations in a nationally representative sample of older Americans. Methods: Data were analyzed from 2689 adults ≥ 60 years who participated in the 2011–2012 and 2013–2014 waves of the National Health and Nutrition Examination Survey. Weakness was defined as HGS < 26 kg for men and < 16 kg for women. Asymmetry was determined from the ratio of the dominant and non-dominant HGS. Those with HGS ratio 0.9–1.1 were considered as having HGS symmetry, and those outside this range had asymmetry. Results: Compared to those with symmetric HGS and were not weak, those with weakness alone, and both weakness and HGS asymmetry had 2.47 (95% confidence interval [CI]: 1.14–5.35) and 3.93 (CI: 1.18–13.07) greater odds for functional limitations, respectively. However, HGS asymmetry alone was not associated with functional limitations (odds ratio: 0.80; CI: 0.62–1.03). Conclusion: The use of HGS asymmetry in protocols could improve the prognostic value of handgrip dynamometers.
Evaluation of the Stomatognathic System before and after Osteopathic Manipulative Treatment in 120 Healthy People by Using Surface Electromyography
Authors: Manzotti Andrea , Viganoni Chiara , Lauritano Dorina , Bernasconi Silvia , Paparo Alice , Risso Rachele , Nanussi Alessandro
Published: May 2020

Objective: To investigate the action of osteopathic manipulative treatment on the muscular activity of the stomatognathic apparatus by using surface electromyography (sEMG). Material and Methods: Surface electromyography (sEMG) was performed on the masseter and anterior temporalis muscles of 120 subjects (73 F; 47 M), both at time T0 and T2. The sample was divided into three randomized groups of 40 subjects each: control, placebo, and osteopathic manipulative treatment (OMT). In the T1 interval between the two evaluations, the control group was not treated, the placebo group underwent a placebo treatment, and the OMT group underwent manipulative treatment. The mean value of each measurement and its coefficient of variation, between time T0 and T2, were calculated for both the intragroup (OMT, placebo, control) and the intergroup (OMT-placebo, OMT-control). Outcomes: In 40% of the subjects, statistically significant improvements were highlighted in the OMT. Whereas, the statistically significant results of the placebo and control groups were 7.5% and 17.5%, respectively, of which more than 75% moved away from the physiological range, showing a worsening of the muscular activity. This analysis showed statistically significant variations (p ≤ 0.05) in the OMT group compared to the placebo and the control groups. Conclusions: OMT determines variations of the activity of masticatory muscles.
Physical Fitness, Body Composition, and Adherence to the Mediterranean Diet in Young Football Players: Influence of the 20 mSRT Score and Maturational Stage
Authors: Manzano-Carrasco Samuel , Felipe Jose Luis , Sanchez-Sanchez Javier , Hernandez-Martin Antonio , Gallardo Leonor , Garcia-Unanue Jorge
Published: May 2020

This study aimed to analyze the differences in physical fitness variables, body composition, and adherence to the Mediterranean diet according to the cardiorespiratory fitness and the maturational stage in young football players. A total of 194 male football players (aged 8–16) from three football sport schools participated in this study. Data on cardiorespiratory fitness (the 20-m shuttle run test), anthropometric measurements, handgrip strength, respiratory capacity (forced spirometry), and adherence to the Mediterranean diet (KIDMED questionnaire) were collected. Players were divided into two groups depending on their maturational stage (prepubertal n = 127 and pubertal n = 67). The results show a direct relationship between low levels of cardiorespiratory fitness and body mass index, as well as body fat and leg fat. Similarly, players with lower cardiorespiratory fitness presented higher values of handgrip strength in the prepubertal state. On the other hand, improvements in respiratory values were observed in the pubertal state with the rest of the parameters when the cardiorespiratory fitness was increased. Therefore, the promotion of recreational football that encourage and develop cardiorespiratory fitness is a key factor and can be used as an effective sport activity to promote physical fitness and healthy habits in children and adolescents as well as within the population that is already physically active.
Comet Test in Saliva Leukocytes of Pre-School Children Exposed to Air Pollution in North Italy: The Respira Study
Authors: Zani Claudia , Ceretti Elisabetta , Zerbini Ilaria , Viola Gaia Claudia Viviana , Donato Francesco , Gelatti Umberto , Feretti Donatella
Published: May 2020

Air pollution is a well-known problem for human health, especially for children living in highly polluted urban areas. This study aimed to assess the relationship between airborne pollutants concentration and biomarkers of DNA damage in the buccal mucosa cells of pre-school children. DNA damage was investigated with comet test in saliva leukocytes taken from sputum of 3- to 6-year-old children living in Brescia, Northern Italy, collected during two consecutive winter seasons (2012–2013). The daily levels of PM10, PM2.5, NO2, CO, SO2, benzene and O3 in urban air were collected for the whole period. A questionnaire filled in by the children’s parents was used to evaluate indoor and outdoor exposure. DNA damage in saliva leukocytes was evaluated in 152 children and the means of tail intensity and visual score as DNA damage were 6.2 ± 4.3 and 182.1 ± 30.9, respectively. No demographic and indoor or outdoor exposure variable was associated with the two measures of DNA damage. No significant association between air pollution and DNA damage in children’s buccal leukocytes was found. In this study, the comet assay does not appear to be a valuable biomarker to detect DNA damage in children exposed to high levels of air pollutants, such as PM10, PM2.5 and NO2.
Systematic Review and Meta-Analysis of the Occurrence of ESKAPE Bacteria Group in Dogs, and the Related Zoonotic Risk in Animal-Assisted Therapy, and in Animal-Assisted Activity in the Health Context
Authors: Santaniello Antonio , Sansone Mario , Fioretti Alessandro , Menna Lucia Francesca
Published: May 2020

Animal-assisted interventions are widely implemented in different contexts worldwide. Particularly, animal-assisted therapies and animal-assisted activities are often implemented in hospitals, rehabilitation centers, and other health facilities. These interventions bring several benefits to patients but can also expose them to the risk of infection with potentially zoonotic agents. The dog is the main animal species involved used in these interventions. Therefore, we aimed at collecting data regarding the occurrence of the pathogens ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) in dogs, in order to draft guidelines concerning the possible monitoring of dogs involved in animal-assisted therapies and animal-assisted activities in healthcare facilities. We performed a literature search using the PRISMA guidelines to examine three databases: PubMed, Web of Science, and Scopus. Out of 2604 records found, 52 papers were identified as eligible for inclusion in the review/meta-analysis. Sixteen papers reported data on E. faecium; 16 on S. aureus; nine on K. pneumoniae; four on A. baumannii; eight on P. aeruginosa; and six on Enterobacter spp. This work will contribute to increased awareness to the potential zoonotic risks posed by the involvement of dogs in animal-assisted therapies, and animal-assisted activities in healthcare facilities.
Assessment of Groundwater Contamination by Terbuthylazine Using Vadose Zone Numerical Models. Case Study of Valencia Province (Spain)
Authors: Rodrigo-Ilarri Javier , Rodrigo-Clavero María-Elena , Cassiraga Eduardo , Ballesteros-Almonacid Leticia
Published: May 2020

Terbuthylazine is commonly used as an herbicide to control weeds and prevent non-desirable grow of algae, fungi and bacteria in many agricultural applications. Despite its highly negative effects on human health, environmental modeling of this kind of pesticide in the vadose zone till reaching groundwater is still not being done on a regular basis. This work shows results obtained by two mathematical models (PESTAN and PRZM-GW) to explain terbuthylazine behavior in the non-saturated zone of a vertical soil column. One of the models use a one-dimensional analytical formulation to simulate the movement of terbuthylazine through the non-saturated soil to the phreatic surface. The second and more complex model uses a whole set of parameters to solve a modified version of the mass transport equation considering the combined effect of advection, dispersion and reactive transport processes. Both models have been applied as a case-study on a particular location in South Valencia Aquifer (Spain). A whole set of simulation scenarios have been designed to perform a parameter sensitivity analysis. Despite both models leading to terbuthylazine’s concentration values, numerical simulations show that PRZM-GW is able to reproduce concentration observations leading to much more accurately results than those obtained using PESTAN.
Safety in Wine Production: A Pilot Study on the Quality Evaluation of Prosecco Wine in the Framework of UE Regulation
Authors: Marcotrigiano Vincenzo , Cinquetti Sandro , Flamini Riccardo , De Rosso Mirko , Ferraro Luca , Petrilli Saverio , Poggi Matilde , Dettori Alessandro , De Polo Anna , De Giglio Osvalda , Orsi Giovanni Battista , Montagna Maria Teresa , Napoli Christian
Published: May 2020

In Italy, wine production is considered a sector of excellence, where the wines’ appreciable sensory features are favored by environmental factors, including weather and climate conditions, which benefit territories with a specific vocation. The whole chain involves many economic and agri-food sector operators, and requires an in-depth assessment of specific risks for identifying critical points, keeping the entire production process under control, and ensuring product traceability. This article describes the results of a pilot study conducted in the Prosecco DOCG (Designations of Controlled and Guaranteed Origin) area, concerning the detection of residues of plant protection products in fifty wine bottles. Although considerably below the maximum residue levels, all the samples tested were positive, ranging from two to five active substances detected in each sample. In addition to the provisions of the European Community legislation, this paper critically evaluates some best practices models that are already used by the Wine Federations of Italy, with the aim of identifying advantages of and areas for improvement in production methods, applicable to raw materials reception, rasping, storage, and bottling phases, in order to guarantee product safety and quality.
Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women
Authors: Abd Aziz Nor Haslinda , Yazid Noor Azyani , Abd Rahman Rahana , Abd Rashid Norhashima , Wong Sok Kuan , Mohamad Nur Vaizura , Lim Pei Shan , Chin Kok-Yong
Published: May 2020

Information on the role of 25-hydroxyvitamin D (25(OH)D) in preventing adverse pregnancy/neonatal outcomes is limited in Malaysia. This study aims to determine the relationship between the level of maternal 25(OH)D in the first trimester of pregnant women and their pregnancy/neonatal outcomes. A total of 60 pregnant women in the first trimester were recruited and followed until the end of their pregnancy. The occurrence of any antenatal, delivery, and neonatal complications was recorded. Their blood was collected in the first trimester for total serum 25(OH)D determination using enzyme-linked immunosorbent assay. Overall, 10% of the women had vitamin D deficiency, while 57% had vitamin D insufficiency in their first trimester. No statistically significant difference in 25(OH)D level/status was observed between women with or without antenatal and delivery complications (p > 0.05). No difference in maternal serum 25(OH)D level and vitamin D status was observed between neonates with or without complications (p > 0.05). In conclusion, there is a high prevalence of vitamin D insufficiency among Malaysian pregnant women, but it is not associated with adverse maternal and neonatal outcomes. More comprehensive studies should be planned to verify this relationship.
Boosting Computational Effectiveness in Big Spatial Flow Data Analysis with Intelligent Data Reduction
Authors: Tao Ran , Gong Zhaoya , Ma Qiwei , Thill Jean-Claude
Published: May 2020

One of the enduring issues of spatial origin-destination (OD) flow data analysis is the computational inefficiency or even the impossibility to handle large datasets. Despite the recent advancements in high performance computing (HPC) and the ready availability of powerful computing infrastructure, we argue that the best solutions are based on a thorough understanding of the fundamental properties of the data. This paper focuses on overcoming the computational challenge through data reduction that intelligently takes advantage of the heavy-tailed distributional property of most flow datasets. We specifically propose the classification technique of head/tail breaks to this end. We test this approach with representative algorithms from three common method families, namely flowAMOEBA from flow clustering, Louvain from network community detection, and PageRank from network centrality algorithms. A variety of flow datasets are adopted for the experiments, including inter-city travel flows, cellphone call flows, and synthetic flows. We propose a standard evaluation framework to evaluate the applicability of not only the selected three algorithms, but any given method in a systematic way. The results prove that head/tail breaks can significantly improve the computational capability and efficiency of flow data analyses while preserving result quality, on condition that the analysis emphasizes the “head” part of the dataset or the flows with high absolute values. We recommend considering this easy-to-implement data reduction technique before analyzing a large flow dataset.
Protected Areas from Space Map Browser with Fast Visualization and Analytical Operations on the Fly. Characterizing Statistical Uncertainties and Balancing Them with Visual Perception
Authors: Masό Joan , Zabala Alaitz , Pons Xavier
Published: May 2020

Despite huge progress in applying Earth Observation (EO) satellite data to protected areas, managers still lack the right tools or skills to analyze the data and extract the necessary knowledge. In this paper a set of EO products are organized in a visualization and analysis map browser that lowers usage barriers and provides functionalities comparable to raster-based GIS. Normally, web map servers provide maps as pictorial representations at screen resolution. The proposal is to use binary arrays with actual values, empowering the JavaScript web client to operate with the data in many ways. Thanks to this approach, the user can analyze big data by performing queries and spatial filters, changing image contrast or color palettes or creating histograms, time series profiles and complex calculations. Since the analysis is made at screen resolution, it minimizes bandwidth while maintaining visual quality. The paper explores the limitations of the approach and quantifies the statistical validity of some resampling methods that provide different visual perceptions. The results demonstrate that the methods known for having good visual perception, the mode for categorical values and the median for continuous values, have admissible statistical uncertainties.
Multi-Scale Representation of Ocean Flow Fields Based on Feature Analysis
Authors: Ai Bo , Sun Decheng , Liu Yanmei , Li Chengming , Yang Fanlin , Yin Yong , Tian Huibo
Published: May 2020

When it comes to feature retention in multi-scale representations of ocean flow fields, not all data points are equal. Therefore, this paper proposes a method of selecting data points based on their importance. First, an autocorrelation analysis is performed on flow speed and the rate of change in flow direction. Then, the magnitude of speed and variation in the rate of change in flow direction are classified. Feature regions are determined according to autocorrelation aggregation and classification analysis. Then, rough set theory and evidence theory are applied, using these results to determine the weights of different points. Finally, these weights are used to construct multi-scale representations of ocean flow fields, which effectively retain flow-field characteristics.
Assessing Equity in the Accessibility to Urban Green Spaces According to Different Functional Levels
Authors: Iraegui Edorta , Augusto Gabriela , Cabral Pedro
Published: May 2020

Accessibility of urban residents to different services and amenities is a growing concern for policy makers. Urban green spaces (UGS) provide services and benefits that are particularly important for people having less mobility, such as children, the elderly or the poor. Practical experience has led to the classification of UGS in hierarchic systems reflecting the type and degree of benefits and services or functions they provide to users, which vary, primarily with their size. It is therefore necessary to ensure equity in the spatial distribution of different classes of UGS in the urban areas. In this work, we explore a methodology based in geographical information systems (GIS) to assess equity of access by different population groups to UGS according to its functional levels in the City of Barcelona, Spain, using a spatial clustering method. Results did not support the existence of overall inequalities in the access to UGS by the different groups of the population. However, indicators of spatial association revealed insufficiencies concerning accessibility to nearby UGS by seniors, children and the less wealthy in some parts of the city. This methodology may be used to inform urban planners dealing with the provision of UGS in an equitable manner to different socioeconomic groups of the resident population.
Lipids: Key Players That Modulate α-Synuclein Toxicity and Neurodegeneration in Parkinson’s Disease
Authors: Mori Akio , Imai Yuzuru , Hattori Nobutaka
Published: May 2020

Parkinson’s disease (PD) is the second most common neurodegenerative disease; it is characterized by the loss of dopaminergic neurons in the midbrain and the accumulation of neuronal inclusions, mainly consisting of α-synuclein (α-syn) fibrils in the affected regions. The prion-like property of the pathological forms of α-syn transmitted via neuronal circuits has been considered inherent in the nature of PD. Thus, one of the potential targets in terms of PD prevention is the suppression of α-syn conversion from the functional form to pathological forms. Recent studies suggested that α-syn interacts with synaptic vesicle membranes and modulate the synaptic functions. A series of studies suggest that transient interaction of α-syn as multimers with synaptic vesicle membranes composed of phospholipids and other lipids is required for its physiological function, while an α-syn-lipid interaction imbalance is believed to cause α-syn aggregation and the resultant pathological α-syn conversion. Altered lipid metabolisms have also been implicated in the modulation of PD pathogenesis. This review focuses on the current literature reporting the role of lipids, especially phospholipids, and lipid metabolism in α-syn dynamics and aggregation processes.
The Role of Gut Microbiome in Psoriasis: Oral Administration of Staphylococcus aureus and Streptococcus danieliae Exacerbates Skin Inflammation of Imiquimod-Induced Psoriasis-Like Dermatitis
Authors: Okada Karin , Matsushima Yoshiaki , Mizutani Kento , Yamanaka Keiichi
Published: May 2020

Psoriasis is one of the common chronic inflammatory skin diseases in which inflammatory cytokines such as IL-17 and TNF-α play critical roles. Skin microbiome of psoriasis patients is reported to have elevated Staphylococcus and Streptococcus genus. There are controversial reports about gut microbiome of psoriasis patients, and whether the diversity of bacteria in genus level is decreased or not is still unclear. Moreover, it is not yet known if these gut bacteria would be the cause of the inflammation or the result of the inflammation. We analyzed the gut microbiome of the inflammatory skin model mouse (keratinocyte-specific caspase-1 transgenic (Kcasp1Tg) mouse), by analyzing the 16S rRNA gene. Staphylocuccus aureus and Streptococcus danieliae were abundant in Kcasp1Tg mouse fecal microbiome. These dominant bacteria as well as recessive control bacteria were orally administrated to antibiotic-treated wild type mice, and set up imiquimod-induced psoriasis-like skin inflammation model. The skin inflammation including ear thickness and histopathological findings was analyzed. The exacerbated skin lesions with the elevated levels of TNF-α, IL-17A, IL-17F, and IL-22 were observed in Staphylocuccus aureus and Streptococcus danieliae administrated groups. Our finding suggests that there is affinity between skin inflammation severity and certain gut bacteria leading to a vicious cycle: skin inflammation populates certain gut bacteria which itself worsens the skin inflammation. This is the first report on Staphylocuccus aureus and Streptococcuus danieliae effects in vivo. Not only treating the skin lesion but also treating the gut microbiome could be the future key treatment for inflammatory skin disease such as psoriasis.
The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis
Authors: Winslow James W.W. , Limesand Kirsten H. , Zhao Ningning
Published: May 2020

As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.
The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor
Authors: Astolfi Annalisa , Pantaleo Maria Abbondanza , Indio Valentina , Urbini Milena , Nannini Margherita
Published: May 2020

Gastrointestinal stromal tumors (GIST) are rare neoplasms of mesenchymal origin arising in the gastrointestinal tract. The vast majority are characterized by mutually exclusive activating mutations in KIT or Platelet-derived growth factor alpha (PDGFRA) receptors, or less frequently by succinate dehydrogenase complex (SDH) or NF1 inactivation, with very rare cases harboring mutant BRAF or RAS alleles. Approximately 5% of GISTs lack any of such mutations and are called quadruple wild-type (WT) GISTs. Recently, deregulated Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling emerged as a relevant pathway driving oncogenic activity in different molecular subgroups of GISTs. This review summarizes all the current evidences supporting the key role of the FGF/FGFR pathway activation in GISTs, whereby either activating mutations, oncogenic gene fusions, or autocrine/paracrine signaling have been detected in quadruple WT, SDH-deficient, or KIT-mutant GISTs.
Biochemical Convergence of Mitochondrial Hsp70 System Specialized in Iron–Sulfur Cluster Biogenesis
Authors: Kleczewska Malgorzata , Grabinska Aneta , Jelen Marcin , Stolarska Milena , Schilke Brenda , Marszalek Jaroslaw , Craig Elizabeth A. , Dutkiewicz Rafal
Published: May 2020

Mitochondria play a central role in the biogenesis of iron–sulfur cluster(s) (FeS), protein cofactors needed for many cellular activities. After assembly on scaffold protein Isu, the cluster is transferred onto a recipient apo-protein. Transfer requires Isu interaction with an Hsp70 chaperone system that includes a dedicated J-domain protein co-chaperone (Hsc20). Hsc20 stimulates Hsp70′s ATPase activity, thus stabilizing the critical Isu–Hsp70 interaction. While most eukaryotes utilize a multifunctional mitochondrial (mt)Hsp70, yeast employ another Hsp70 (Ssq1), a product of mtHsp70 gene duplication. Ssq1 became specialized in FeS biogenesis, recapitulating the process in bacteria, where specialized Hsp70 HscA cooperates exclusively with an ortholog of Hsc20. While it is well established that Ssq1 and HscA converged functionally for FeS transfer, whether these two Hsp70s possess similar biochemical properties was not known. Here, we show that overall HscA and Ssq1 biochemical properties are very similar, despite subtle differences being apparent - the ATPase activity of HscA is stimulated to a somewhat higher levels by Isu and Hsc20, while Ssq1 has a higher affinity for Isu and for Hsc20. HscA/Ssq1 are a unique example of biochemical convergence of distantly related Hsp70s, with practical implications, crossover experimental results can be combined, facilitating understanding of the FeS transfer process.
NLRC4, ASC and Caspase-1 Are Inflammasome Components That Are Mediated by P2Y2R Activation in Breast Cancer Cells
Authors: Jin Hana , Kim Hye Jung
Published: May 2020

The inflammasomes are reported to be associated with tumor progression. In our previous study, we determined that extracellular ATP enhances invasion and tumor growth by inducing inflammasome activation in a P2Y purinergic receptor 2 (P2Y2R)-dependent manner. However, it is not clear which inflammasome among the diverse complexes is associated with P2Y2R activation in breast cancer. Thus, in this study, we determined which inflammasome components are regulated by P2Y2R activation and are involved in tumor progression in breast cancer cells and radiotherapy-resistant (RT-R)-breast cancer cells. First, we found that NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3); NLR family caspase activation and recruitment domain (CARD) containing 4 (NLRC4); apoptosis-associated speck-like protein containing a CARD complex (ASC); and caspase-1 mRNA levels were upregulated in RT-R-MDA-MB-231 cells compared to MDA-MB-231 cells, whereas tumor necrosis factor-α (TNF-α) or ATP treatment induced NLRC4, ASC, and caspase-1 but not NLRP3 protein levels. Moreover, TNF-α or ATP increased protein levels of NLRC4, ASC, and caspase-1 in a P2Y2R-dependent manner in MDA-MB-231 and RT-R-MDA-MB-231 cells. In addition, P2Y2R activation by ATP induced the secretion of IL-1β and VEGF-A, as well as invasion, in MDA-MB-231 and RT-R-MDA-MB-231 cells, which was inhibited by NLRC4, ASC, and caspase-1 small interfering RNA (siRNA). Taken together, this report suggests that P2Y2R activation by ATP induces tumor invasion and angiogenesis through inflammasome activation, specifically by regulating the inflammasome components NLRC4, ASC, and caspase-1.
A Diverse Data Augmentation Strategy for Low-Resource Neural Machine Translation
Authors: Li Yu , Li Xiao , Yang Yating , Dong Rui
Published: May 2020

One important issue that affects the performance of neural machine translation is the scale of available parallel data. For low-resource languages, the amount of parallel data is not sufficient, which results in poor translation quality. In this paper, we propose a diversity data augmentation method that does not use extra monolingual data. We expand the training data by generating diversity pseudo parallel data on the source and target sides. To generate diversity data, the restricted sampling strategy is employed at the decoding steps. Finally, we filter and merge origin data and synthetic parallel corpus to train the final model. In the experiment, the proposed approach achieved 1.96 BLEU points in the IWSLT2014 German–English translation tasks, which was used to simulate a low-resource language. Our approach also consistently and substantially obtained 1.0 to 2.0 BLEU improvement in three other low-resource translation tasks, including English–Turkish, Nepali–English, and Sinhala–English translation tasks.
Functional Role of Natriuretic Peptides in Risk Assessment and Prognosis of Patients with Mitral Regurgitation
Authors: Gallo Giovanna , Forte Maurizio , Stanzione Rosita , Cotugno Maria , Bianchi Franca , Marchitti Simona , Berni Andrea , Volpe Massimo , Rubattu Speranza
Published: May 2020

The management of mitral valve regurgitation (MR), a common valve disease, represents a challenge in clinical practice, since the indication for either surgical or percutaneous valve replacement or repair are guided by symptoms and by echocardiographic parameters which are not always feasible. In this complex scenario, the use of natriuretic peptide (NP) levels would serve as an additive diagnostic and prognostic tool. These biomarkers contribute to monitoring the progression of the valve disease, even before the development of hemodynamic consequences in a preclinical stage of myocardial damage. They may contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations, thus requiring surgical management rather than a conservative approach. This article provides a comprehensive overview of the available evidence on the role of NPs in the management, risk evaluation, and prognostic assessment of patients with MR both before and after surgical or percutaneous valve repair. Despite largely positive evidence, a series of controversial findings exist on this relevant topic. Recent clinical trials failed to assess the role of NPs following the interventional procedure. Future larger studies are required to enable the introduction of NP levels into the guidelines for the management of MR.
Estimation of Unreported Novel Coronavirus (SARS-CoV-2) Infections from Reported Deaths: A Susceptible–Exposed–Infectious–Recovered–Dead Model
Authors: Maugeri Andrea , Barchitta Martina , Battiato Sebastiano , Agodi Antonella
Published: May 2020

In the midst of the novel coronavirus (SARS-CoV-2) epidemic, examining reported case data could lead to biased speculations and conclusions. Indeed, estimation of unreported infections is crucial for a better understanding of the current emergency in China and in other countries. In this study, we aimed to estimate the unreported number of infections in China prior to the 23 January 2020 restrictions. To do this, we developed a Susceptible–Exposed–Infectious–Recovered–Dead (SEIRD) model that estimated unreported infections from the reported number of deaths. Our approach relied on the fact that observed deaths were less likely to be affected by ascertainment biases than reported infections. Interestingly, we estimated that the basic reproductive number (R0) was 2.43 (95%CI = 2.42–2.44) at the beginning of the epidemic and that 92.9% (95%CI = 92.5%–93.1%) of total cases were not reported. Similarly, the proportion of unreported new infections by day ranged from 52.1% to 100%, with a total of 91.8% (95%CI = 91.6%–92.1%) of infections going unreported. Agreement between our estimates and those from previous studies proves that our approach is reliable for estimating the prevalence and incidence of undocumented SARS-CoV-2 infections. Once it has been tested on Chinese data, our model could be applied to other countries with different surveillance and testing policies.
Perioperative Chemotherapy in Poorly Differentiated Neuroendocrine Neoplasia of the Bladder: A Multicenter Analysis
Authors: Lamberti Giuseppe , Brizzi Maria Pia , Pusceddu Sara , Gelsomino Fabio , Di Meglio Giovanni , Massari Francesco , Badalamenti Giuseppe , Riccardi Ferdinando , Ibrahim Toni , Ciccarese Chiara , Buti Sebastiano , Carnaghi Carlo , Prinzi Natalie , Panzuto Francesco , Campana Davide
Published: May 2020

There is scant evidence about optimal management of poorly differentiated neuroendocrine carcinoma of the bladder (BNEC). We performed a multicenter retrospective study on BNEC patients from 13 Italian neuroendocrine-dedicated centers to analyze strategies associated with better outcomes. Mixed adeno-neuroendocrine carcinomas (MANEC) were included. We analyzed overall survival (OS) in the overall cohort, relapse-free survival (RFS) in radically operated patients and progression-free survival (PFS) in patients who received chemotherapy for metastatic disease. Fifty-one BNEC patients were included (male: 46, median age: 70 years). Overall, median OS was 16.0 months, radical tumor resection was performed in 37 patients (72.5%) and 11 of these (29.7%) also received peri-operative platinum-etoposide chemotherapy. Median OS was longer in patients with better performance status (PS) and in those with stage I–III disease at diagnosis compared to stage IV. Among patients who underwent radical tumor resection (N = 37), RFS was longer in patients with better PS and showed a trend towards a longer RFS in those treated with peri-operative chemotherapy than with surgery alone (11 vs. 6 months; p = 0.078). Among 28 patients receiving chemotherapy for metastatic disease, PFS was 5.0 months and there was a trend towards improved PFS in patients receiving carboplatin-etoposide chemotherapy compared to other regimens. A multivariate model unmasked a significant association between carboplatin-etoposide chemotherapy and risk for disease progression or death (HR: 0.39 (95%CI: 0.16–0.96) p = 0.040). Performance status might be associated with improved RFS in radically operated patients, while type of chemotherapy might affect PFS in patients receiving chemotherapy for metastatic BNEC.
Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology
Authors: Gringeri Enrico , Gambato Martina , Sapisochin Gonzalo , Ivanics Tommy , Lynch Erica Nicola , Mescoli Claudia , Burra Patrizia , Cillo Umberto , Russo Francesco Paolo
Published: May 2020

Cholangiocarcinoma (CCA) arises from the biliary tract epithelium and accounts for 10–15% of all hepatobiliary malignancies. Depending on anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). The best treatment option for pCCA is liver resection and when a radical oncological surgery is obtained, 5-year survival rate are around 20–40%. In unresectable patients, following a specific protocol, liver transplantation (LT) for pCCA showed excellent long-term disease-free survival rates. Fewer data are available for iCCA in LT setting. Nevertheless, patients with very early unresectable iCCA appear to achieve excellent outcomes after LT. This review aims to evaluate existing evidence to define the current role of LT in the management of patients with CCA.
Acute Myocardial Infarction among Hospitalizations for Heat Stroke in the United States
Authors: Bathini Tarun , Thongprayoon Charat , Chewcharat Api , Petnak Tananchai , Cheungpasitporn Wisit , Boonpheng Boonphiphop , Prasitlumkum Narut , Chokesuwattanaskul Ronpichai , Vallabhajosyula Saraschandra , Kaewput Wisit
Published: May 2020

Background: This study aimed to assess the risk factors and impact of acute myocardial infarction on in-hospital treatments, complications, outcomes, and resource utilization in hospitalized patients for heat stroke in the United States. Methods: Hospitalized patients with a principal diagnosis of heat stroke were identified in the National Inpatient Sample dataset from the years 2003 to 2014. Acute myocardial infarction was identified using the hospital International Classification of Diseases, Ninth Revision (ICD-9), diagnosis of 410.xx. Clinical characteristics, in-hospital treatment, complications, outcomes, and resource utilization between patients with and without acute myocardial infarction were compared. Results: A total of 3372 heat stroke patients were included in the analysis. Of these, acute myocardial infarction occurred in 225 (7%) admissions. Acute myocardial infarction occurred more commonly in obese female patients with a history of chronic kidney disease, but less often in male patients aged <20 years with a history of hypothyroidism. The need for mechanical ventilation, blood transfusion, and renal replacement therapy were higher in patients with acute myocardial infarction. Acute myocardial infarction was associated with rhabdomyolysis, metabolic acidosis, sepsis, gastrointestinal bleeding, ventricular arrhythmia or cardiac arrest, renal failure, respiratory failure, circulatory failure, liver failure, neurological failure, and hematologic failure. Patients with acute myocardial infarction had 5.2-times greater odds of in-hospital mortality than those without myocardial infarction. The length of hospital stay and hospitalization cost were also higher when an acute myocardial infarction occurred while hospitalized. Conclusion: Acute myocardial infarction was associated with worse outcomes and higher economic burden among patients hospitalized for heat stroke. Obesity and chronic kidney disease were associated with increased risk of acute myocardial infarction, while young male patients and hypothyroidism were associated with decreased risk.
A Single-Arm, Prospective, Exploratory Study to Preliminarily Test Effectiveness and Safety of Skin Electrical Stimulation for Leber Hereditary Optic Neuropathy
Authors: Kurimoto Takuji , Ueda Kaori , Mori Sotaro , Kamada Seiko , Sakamoto Mari , Yamada-Nakanishi Yuko , Matsumiya Wataru , Nakamura Makoto
Published: May 2020

Leber hereditary optic neuropathy (LHON) is an intractable disease associated with mitochondrial DNA (mtDNA) mutations. In this preliminary, single-arm, prospective, open-label exploratory trial, we investigated the effectiveness and safety of skin electrical stimulation (SES) for cases of LHON harboring the mtDNA 11,778 mutation. Of the 11 enrolled patients, 10 completed six sessions of SES once every two weeks over a 10-week period. The primary outcome measure was the change in logarithm of the minimum angle of resolution (logMAR)-converted best-corrected visual acuity (BCVA) at one week after the last session of SES. The main secondary outcome measures were the logMAR BCVA at four and eight weeks and Humphrey visual field test sensitivities at one, four, and eight weeks. At all follow-up points, the logMAR BCVA had improved significantly from baseline, [1.80 (1.70–1.80) at baseline, 1.75 (1.52–1.80) at one week, 1.75 (1.50–1.80) at four weeks, and 1.75 (1.52–1.80) at eight weeks; p < 0.05]. At eight weeks of follow-up, five patients showed >2-fold increase in the summed sensitivity at 52 measurement points from baseline. No adverse effects were observed. In conclusion, SES could be a viable treatment option for patients with LHON in the chronic phase harboring the mtDNA 11,778 mutation.