bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma
Authors: Wan Qi , Sang Xuan , Jin Lin , Wang Zhichong
Published: February 2020

Growing evidence has revealed that abnormal alternative splicing (AS) events are closely related to carcinogenic processes. However, the comprehensive study on the prognostic value of splicing events involved in uveal melanoma (UM) is still lacking. Therefore, splicing data of 80 UM patients were obtained from the Cancer Genome Atlas (TCGA) SpliceSeq and RNA sequence data of UM and patient clinical features were downloaded from the Cancer Genome Atlas (TCGA) database to identify survival related splicing events in UM. As a result, a total of 37996 AS events of 17911 genes in UM were detected, among which 5299 AS events of 3529 genes were significantly associated with UM patients’ survival. Functional enrichment analysis revealed that this survival related splicing genes are corelated with mRNA catabolic process and ribosome pathway. Based on survival related splicing events, seven types of prognostic markers and the final overall prognostic signature could independently predict the overall survival of UM patients. Finally, an 11 spliced gene was identified in the final signature. On the basis of these 11 genes, we constructed a Support Vector Machine (SVM) classifier and evaluated it with leave-one-out cross-validation. The results showed that the 11 genes could determine short- and long-term survival with a predicted accuracy of 97.5%. Besides, the splicing factors and alternative splicing events correlation network was constructed to serve as therapeutic targets for UM treatment. Thus, our study depicts a comprehensive landscape of alternative splicing events in the prognosis of UM. The correlation network and associated pathways would provide additional potential targets for therapy and prognosis.
Comparative Genomics and Evolutionary Analysis of RNA-Binding Proteins of Burkholderia cenocepacia J2315 and Other Members of the B. cepacia Complex
Authors: Feliciano Joana R. , Seixas António M. M. , Pita Tiago , Leitão Jorge H.
Published: February 2020

RNA-binding proteins (RBPs) are important regulators of cellular functions, playing critical roles on the survival of bacteria and in the case of pathogens, on their interaction with the host. RBPs are involved in transcriptional, post-transcriptional, and translational processes. However, except for model organisms like Escherichia coli, there is little information about the identification or characterization of RBPs in other bacteria, namely in members of the Burkholderia cepacia complex (Bcc). Bcc is a group of bacterial species associated with a poor clinical prognosis in cystic fibrosis patients. These species have some of the largest bacterial genomes, and except for the presence of two-distinct Hfq-like proteins, their RBP repertoire has not been analyzed so far. Using in silico approaches, we identified 186 conventional putative RBPs in Burkholderia cenocepacia J2315, an epidemic and multidrug resistant pathogen of cystic fibrosis patients. Here we describe the comparative genomics and phylogenetic analysis of RBPs present in multiple copies and predicted to play a role in transcription, protein synthesis, and RNA decay in Bcc bacteria. In addition to the two different Hfq chaperones, five cold shock proteins phylogenetically close to E. coli CspD protein and three distinct RhlE-like helicases could be found in the B. cenocepacia J2315 genome. No RhlB, SrmB, or DeaD helicases could be found in the genomes of these bacteria. These results, together with the multiple copies of other proteins generally involved in RNA degradation, suggest the existence, in B. cenocepacia and in other Bcc bacteria, of some extra and unexplored functions for the mentioned RBPs, as well as of alternative mechanisms involved in RNA regulation and metabolism in these bacteria.
Estimating the Allele-Specific Expression of SNVs From 10× Genomics Single-Cell RNA-Sequencing Data
Authors: N. M. Prashant , Liu Hongyu , Bousounis Pavlos , Spurr Liam , Alomran Nawaf , Ibeawuchi Helen , Sein Justin , Reece-Stremtan Dacian , Horvath Anelia
Published: February 2020

With the recent advances in single-cell RNA-sequencing (scRNA-seq) technologies, the estimation of allele expression from single cells is becoming increasingly reliable. Allele expression is both quantitative and dynamic and is an essential component of the genomic interactome. Here, we systematically estimate the allele expression from heterozygous single nucleotide variant (SNV) loci using scRNA-seq data generated on the 10×Genomics Chromium platform. We analyzed 26,640 human adipose-derived mesenchymal stem cells (from three healthy donors), sequenced to an average of 150K sequencing reads per cell (more than 4 billion scRNA-seq reads in total). High-quality SNV calls assessed in our study contained approximately 15% exonic and >50% intronic loci. To analyze the allele expression, we estimated the expressed variant allele fraction (VAFRNA) from SNV-aware alignments and analyzed its variance and distribution (mono- and bi-allelic) at different minimum sequencing read thresholds. Our analysis shows that when assessing positions covered by a minimum of three unique sequencing reads, over 50% of the heterozygous SNVs show bi-allelic expression, while at a threshold of 10 reads, nearly 90% of the SNVs are bi-allelic. In addition, our analysis demonstrates the feasibility of scVAFRNA estimation from current scRNA-seq datasets and shows that the 3′-based library generation protocol of 10×Genomics scRNA-seq data can be informative in SNV-based studies, including analyses of transcriptional kinetics.
Infection Spread and High-Resolution Detection of Close Contact Behaviors
Authors: Zhang Nan , Su Boni , Chan Pak-To , Miao Te , Wang Peihua , Li Yuguo
Published: February 2020

Knowledge of human behaviors is important for improving indoor-environment design, building-energy efficiency, and productivity, and for studies of infection spread. However, such data are lacking. In this study, we designed a device for detecting and recording, second by second, the 3D indoor positioning and head and body motions of each graduate student in an office. From more than 400 person hours of data. Students spent 92.2%, 4.1%, 2.9%, and 0.8% of their time in their own office cubicles, other office cubicles, aisles, and areas near public facilities, respectively. They spent 9.7% of time in close contact, and each student averagely had 4.0 close contacts/h. Students spent long time on close contact in the office which may lead to high infection risk. The average interpersonal distance during close contact was 0.81 m. When sitting, students preferred small relative face orientation angle. Pairs of standing students preferred a face-to-face orientation during close contact which means this pattern had a lower infection risk via close contact. Probability of close contact decreased exponentially with the increasing distance between two students’ cubicles. Data on human behaviour during close contact is helpful for infection risk analysis and infection control and prevention.
Evaluation and Analysis of Water Quality of Marine Aquaculture Area
Authors: Zhang Xianyu , Zhang Yingqi , Zhang Qian , Liu Peiwu , Guo Rui , Jin Shengyi , Liu Jiawen , Chen Lei , Ma Zhen , Liu Ying
Published: February 2020

In the rapid development of marine aquaculture, the water quality of aquatic environments is regarded as a main limiting factor. Therefore, it is necessary to assess the water quality and environmental conditions in marine aquaculture areas and find out the main influencing factors regarding damage to the water quality environment. In the present research, pond aquaculture and cage aquaculture areas were sampled in May, August and November in 2018. Nine water quality indicators were detected, including pH, temperature, salinity, dissolved oxygen, molybdate-reactive phosphorus, chemical oxygen demand, chlorophyll a, inorganic nitrogen and antibiotic resistance genes (ARGs). Principal component analysis (PCA) was used to analyze the water quality conditions, spatial–temporal changes, and the driving factors in pond and cage aquaculture areas. The results showed that three main components were extracted from the pond aquaculture area, which explained 66.82% of the results, the most relevant factors are salinity, dissolved oxygen and ARGs. For the cage aquaculture area, three main components were extracted which can account for 72.99% of the results, the most relevant factors are chlorophyll a, salinity and dissolved oxygen. The comprehensive scores of the principal components indicated that the heaviest polluted months in pond and aquaculture areas were August and November, respectively. The water quality of the pond aquaculture area is mainly limited by the volume of the pond, while aquaculture activities and seasonality are the main factors for cage aquaculture. ARGs in cage culture areas showed more variety and frequency compared with pond culture areas, which indicated that terrestrial input might be one of the sources for ARGs occurrence. The results would be helpful for the relevant authorities to select water quality monitoring parameters in marine aquaculture areas.
Reliability of 30-s Chair Stand Test with and without Cognitive Task in People with Type-2 Diabetes Mellitus
Authors: Barrios-Fernández Sabina , Pérez-Gómez Jorge , Galán-Arroyo María del Carmen , Señorán-Rivera Jairo , Martín-Carmona Rubén , Mendoza-Muñoz María , García-Gordillo Miguel Ángel , Domínguez-Muñoz Francisco Javier , Adsuar José Carmelo
Published: February 2020

Background: Reliability refers to the precision of an assessment, so it is a critical topic to take the right decisions related to health management. People usually perform several tasks at the same time in their daily life. The aim of this study was to examine the reliability of the 30-s chair stand test in people with type 2 Diabetes Mellitus (T2DM) with test–retest, with and without dual-task (motor + cognitive task). Methods: Twenty-six subjects with T2DM and 30 subjects without T2DM performed the 30-s Chair Stand Test (30sCST) in which they must sit and stand as many times as possible in 30 s. They performed the test in the usual way (30sCST) and also with an additional cognitive task (30sCST-DT). A retest was conducted 7–14 days later. Results: Relative reliability was excellent in both groups (intraclass correlation coefficient > 0.9). In 30sCST-DT, relative reliability was high in the T2DM group (intraclass correlation coefficient > 0.7) and excellent in subjects without T2DM (intraclass correlation coefficient > 0.9). Conclusions: The 30sCST and the 30sCST-DT tests are reliable tools for people with T2DM to measure changes after an intervention. The smallest real difference was 15% and 20% upper in the T2DM group in the 30sCST and 30sCST-DT tests, respectively.
Understanding Barriers and Facilitators of Maternal Health Care Utilization in Central Myanmar
Authors: Milkowska-Shibata Maja Aleksandra , Aye Thin Thin , Yi San Myint , Oo Khin Thein , Khaing Kyi , Than Marlar , Win Thinzar , Myo Su Yi , Toe Su Yi , West Heidi Sierra , Ringstad Kristin Melissa , Galarza Lizeth , Meng Can , Shibata Tomoyuki
Published: February 2020

The study objective was to examine barriers and facilitators of maternal health services utilization in Myanmar with the highest maternal mortality ratio in Southeast Asia. Data for 258 mothers with children under five were extracted from a community health survey administered between 2016 and 2017 in Mandalay, the largest city in central Myanmar, and analyzed for associations between determinants of maternal health care choices and related outcomes. The study showed that late antenatal care was underutilized (41.7%), and antenatal care attendance was significantly associated with geographical setting, household income, education, and access to transportation (p ≤ 0.05). Less than one-third of women gave birth at home and 18.5% of them did so without the assistance of traditional birth attendants. Household education level was a significant predictor for home delivery (p < 0.01). Utilization of postnatal care services was irregular (47.9%–70.9%) and strongly associated with women’s places of delivery (p < 0.01). Efforts geared towards improving maternal health outcomes should focus on supporting traditional birth attendants in their role of facilitating high-quality care and helping women reach traditional health facilities, as well as on maternal health literacy based on culturally appropriate communication.
Palliative Care Symptoms, Outcomes, and Interventions for Chronic Advanced Patients in Spanish Nursing Homes with and without Dementia
Authors: Puente-Fernández Daniel , Campos-Calderón Concepción Petra , -Burgos Ana Alejandra Esteban , Hueso-Montoro César , Roldán-López Concepción Beatriz , Montoya-Juárez Rafael
Published: February 2020

The aim of this study was to compare the symptomatology, palliative care outcomes, therapeutic procedures, diagnostic tests, and pharmacological treatments for people with dementia (PWD) and without dementia (PW/OD) admitted to Spanish nursing homes. Design: This was a cross-sectional study which is part of a long-term prospective follow-up of elderly people performed in nursing homes to measure end-of-life care processes. Participants: 107 nursing home patients with advanced or terminal chronic diseases were selected according to the criteria of the Palliative Care Spanish Society. Setting: Two trained nurses from each nursing home were responsible for participant selection and data collection. They must have treated the residents and had a minimum seniority of 6 months in the nursing home. Measurements: Sociodemographic data; Edmonton Symptom Assessment Scale; Palliative Care Outcome Scale; and prevalence of diagnostic tests, pharmacological treatments, and therapeutic procedures were evaluated. Results: Pain, fatigue, and nausea were found to be significantly higher in the nondementia group and insomnia, poor appetite, and drowsiness were significantly higher in the dementia group. Patient anxiety, support, feeling that life was worth living, self-worth, and practical matters management were higher in the nondementia group. Regarding drugs, use of corticoids was higher in the nondementia group, while use of anxiolytics was higher in the dementia group. Diagnostic procedures such as urine analysis and X-ray were higher in the dementia group. Conclusions: Differences in symptom perception, diagnostic tests, and pharmacological procedures were found between patients with and without dementia. Specific diagnostic tools need to be developed for patients with dementia.
Association between School Performance and Anemia in Adolescents in Mexico
Authors: Mosiño Alejandro , Villagómez-Estrada Karen P. , Prieto-Patrón Alberto
Published: February 2020

In school age children and adolescents, anemia might cause lower cognitive function and attention span, which in turn could diminish human capital accumulation. As children born in low-income households are more likely to be anemic, this may prevent many individuals from overcoming the intergenerational poverty traps. In this paper, we used data from the Mexican National Health and Nutrition Survey 2012 and focused on a sample of adolescents between 12 and 19 years of age to study the relationship between attending school without delay—our proxy for school performance—and anemia. We found a statistically significant association between the two variables. If this relationship is causal, the economic burden linked to the loss of school years could well exceed the costs associated with programs aimed at reducing the prevalence of anemia in vulnerable populations. Our results provide additional support to the existing literature on anemia as a significant barrier to school achievement.
Understanding the Roles of Remoteness and Indigenous Status in Rural and Remote Road Trauma in North Queensland: Using a Mixed-Methods Approach
Authors: Edmonston Colin , Siskind Victor , Sheehan Mary
Published: February 2020

Road trauma is a significant health problem in rural and remote regions of Australia, particularly for Indigenous communities. This study aims to identify and compare the circumstances leading to (proximal causation) and social determinants of (distal causation) crashes of Indigenous and non-Indigenous people in these regions and their relation to remoteness. This is a topic seriously under-researched in Australia. Modelled on an earlier study, 229 persons injured in crashes were recruited from local health facilities in rural and remote North Queensland and interviewed, mainly by telephone, according to a fixed protocol which included a detailed narrative of the circumstances of the crash. A qualitative analysis of these narratives identified several core themes, further explored statistically in this sample, supplemented by participants in the earlier study with compatible questionnaire data, designed to determine which factors were more closely associated with Indigenous status and which with remoteness. Indigenous participants were less often vehicle controllers, more likely to have recently been a drink driver or passenger thereof; to be unemployed, unlicensed, distracted or fatigued before the crash, alcohol dependent and have lower perceived social, but not personal, locus of control in a traffic crash than non-Indigenous persons. Differences between Indigenous and non-Indigenous participants are largely ascribable to hardship and transport disadvantage due to lack of access to licensing and associated limitations on employment opportunities. Based on these findings, a number of policy recommendations relating to educational, enforcement and engineering issues have been made.
Mapping the Spatial–Temporal Distribution and Migration Patterns of Men Who Have Sex with Men in Mainland China: A Web-Based Study
Authors: Huang Dacang , Wang Jinfeng , Yang Tengfei
Published: February 2020

The human immunodeficiency virus (HIV) infection rate for men who have sex with men (MSM) has rapidly increased in recent years in China and the migrant population accounts for a large proportion of this increase. The migration of MSM not only poses difficulties for government departments charged with treating the disease, but also increases the spread of HIV in geographical space, so it is important to understand the geographical distribution and migrant patterns of MSM. We searched the largest dating website in China to obtain open information from all users in the Chinese mainland from January 2006 to August 2017. For the analysis, the datasets were merged according to units of time and administrative regions. In total, 1,356,609 records were obtained for this study. The main users of the website were single males aged 18–35 years old. Most of the users were located in the large and mid-sized cities of East China. The distribution of MSM was strongly associated with the distribution of the development of service industry in geographical space. The main flow of MSM are mainly located inside the province as internal flow. For those MSM who prefer to migrate to other provinces, the Beijing-Tianjin-Hebei area, the Yangtze River Delta, the Pearl River Delta, and Sichuan and Chongqing area were their primary destinations. The interprovincial migration behavior of MSM was closely related to an increased average income. MSM prefer to migrate to cities with developed economies and open cultures. It is important to strengthen the management of migrant MSM and increase their basic understanding of HIV.
Neighborhood Greenery as a Predictor of Outdoor Crimes between Low and High Income Neighborhoods
Authors: Kim Young-Jae , Kim Eun Jung
Published: February 2020

Neighborhood greenery contributes to improving mental, emotional, and physical health and may help to promote neighborhood safety. Several studies have reported positive effects of neighborhood greenery on the improvement of outdoor safety, but little is known about whether the relationship between green vegetation and outdoor safety varies with the income status of neighborhoods. The purpose of this study is to examine neighborhood greenery as a predictor of outdoor crime rates between low and high-income neighborhoods while controlling for the sociodemographic conditions of the neighborhoods. This study used 2010 census block group data and objectively measured natural environment data derived from GIS in Austin, Texas. Comparison t-tests and ordinal least square regressions were conducted as statistical analyses. The t-tests showed that low-income neighborhoods were more socioeconomically disadvantaged and had less greenery than high-income neighborhoods. The final regression models showed that neighborhood greenery had a negative relationship with outdoor crimes for low-income neighborhoods but a positive relationship with crimes for high-income neighborhoods. The results suggest that different strategies may be needed in dealing with neighborhood safety according to neighborhood-level income.
Remediation of Crude Oil-Polluted Soil by the Bacterial Rhizosphere Community of Suaeda Salsa Revealed by 16S rRNA Genes
Authors: Yu Yilei , Zhang Yinghua , Zhao Nana , Guo Jia , Xu Weigang , Ma Muyuan , Li Xiaoxia
Published: February 2020

Crude oil pollution of soil is a serious environmental issue, and bioremediation using plants and microorganisms is a natural and sustainable method for its restoration. Pot incubation of a two-factor randomized block (plants with two levels, and crude oil with three levels) was designed to investigate the rhizosphere bacterial community of Suaeda salsa (L.) Pall. Crude oil contamination of soil was studied at different levels: 2 g/kg (low), 4 g/kg (medium), and 6 g/kg (high) levels. In this study, the physicochemical properties of the collected rhizosphere soil were analyzed. Moreover, the soil bacteria were further identified using the 16S rRNA gene. The effects of S. salsa and crude oil and their interaction on the physiochemical properties of the soil and crude oil degradation were found to be significant. Crude oil significantly influenced the diversity and evenness of bacteria, while the effects of S. salsa and interaction with crude oil were not significant. Proteobacteria were found to be dominant at the phylum level. Meanwhile, at the genera level, Saccharibacteria and Alcanivorax increased significantly in the low and medium contamination treatment groups with S. salsa, whereas Saccharibacteria and Desulfuromonas were prevalent in the high contamination treatment group. High crude oil contamination led to a significant decrease in the bacterial diversity in soil, while the effects of S. salsa and its interaction were not significant. Despite the highest abundance of crude oil degradation bacteria, S. salsa reduced crude oil degradation bacteria and increased bacteria related to sulfur, phosphorus, and nitrogen cycling in the low and high contamination group, whereas the opposite effect was observed for the medium contamination treatment group. The abundance of most crude oil degradation bacteria is negatively correlated with crude oil content. Nitrogen cycling bacteria are sensitive to the total nitrogen, total phosphorus, ammonia nitrogen, and nitrate nitrogen, and pH of the soil. Sulfur cycling bacteria are sensitive to aromatic hydrocarbons, saturated hydrocarbons, and asphaltene in soil. This research is helpful for further studying the mechanism of synergistic degradation by S. salsa and bacteria.
Paediatric Rational Prescribing: A Systematic Review of Assessment Tools
Authors: Corrick Fenella , Conroy Sharon , Sammons Helen , Choonara Imti
Published: February 2020

Rational prescribing criteria have been well established in adult medicine for both research and quality improvement in the appropriate use of medicines. Paediatric rational prescribing has not been as widely investigated. The aims of this review were to identify and provide an overview of all paediatric rational prescribing tools that have been developed for use in paediatric settings. A systematic literature search was made of MEDLINE, Embase, CINAHL and IPA from their earliest records until July 2019 for all published paediatric rational prescribing tools. The characteristics of the tools were recorded including method of development, types of criteria, aspects of rational prescribing assessed, and intended practice setting. The search identified three paediatric rational prescribing tools: the POPI (Pediatrics: Omissions of Prescriptions and Inappropriate Prescriptions) tool, the modified POPI (UK) tool, and indicators of potentially inappropriate prescribing in children (PIPc). PIPc comprises explicit criteria, whereas POPI and the modified POPI (UK) use a mixed approach. PIPc is designed for use in primary care in the UK and Ireland, POPI is designed for use in all paediatric practice settings and is based on French practice standards, and the modified POPI (UK) is based on UK practice standards and is designed for use in all paediatric practice settings. This review describes three paediatric rational prescribing tools and details their characteristics. This will provide readers with information for the use of the tools in quality improvement or research and support further work in the field of paediatric rational prescribing.
Prevalence of Anemia and its Associated Factors among Chinese 9-, 12-, and 14-Year-Old Children: Results from 2014 Chinese National Survey on Students Constitution and Health
Authors: Yang Zhaogeng , Li Yanhui , Hu Peijin , Ma Jun , Song Yi
Published: February 2020

Background: Anemia has been one of the main nutritional challenges around the world. Not enough attention has been paid to this issue in children and adolescents in China. In this study, we aimed to estimate the prevalence of anemia among 9-, 12-, and 14-year old Chinese children and investigate the associated factors of anemia. Methods: Data come from a cross-sectional survey conducted in 26 provinces and 4 municipalities in mainland China. A total of 48,537 children aged 9, 12, and 14 years old were included in data analyses. Anthropometric measurements were conducted to obtain information about height and weight. Capillary blood was collected from the fingertip, and hemoglobin concentration was tested by HemoCue201+. Information about sleep duration, daily consumption of eggs, milk, and breakfast were obtained from a self-administrated questionnaire. The mixed-effects logistic regression model was applied to estimate the association between selected variables and risk of anemia. Results: A total of 8.4% of participants were identified as being anemic; and the prevalence was higher in girls and rural children. Mixed-effects logistic regression analysis showed that children who were overweight, obese, and consumed eggs and milk every day had a lower risk of anemia. Spermarche, overweight/obesity, and having milk every day were associated with lower risk of anemia in boys, while menarche was found to be a risk factor and eating eggs every day to be a protective factor of anemia in girls. Conclusions: Anemia among 9-, 12-, and 14-year-old children is still high. Intervention programs of adding egg and milk into school daily diet might contribute to reducing anemia in Chinese school aged children, especially for those living in rural areas or girls with menarche.
The Administration of 4-Hexylresorcinol Accelerates Orthodontic Tooth Movement and Increases the Expression Level of Bone Turnover Markers in Ovariectomized Rats
Authors: Choi Kwang-Hyo , Kim Dae-Won , Lee Suk Keun , Kim Seong-Gon , Kim Tae-Woo
Published: February 2020

Surgical methods for accelerating orthodontic tooth movement are limited by possible damage to the tooth root and patient discomfort. 4-Hexylresorcinol (4HR) has been shown to increase bone remodeling and may potentially facilitate tooth movement. This study investigated the (1) effect of 4HR administration on osteoblast-like cells and (2) effect of 4HR administration on tooth movement in ovariectomized rats. Saos-2 cells were treated with either 4HR or solvent (control). Protein expression levels were investigated 2, 8, and 24 h after treatment. Thirty ovariectomized Sprague-Dawley rats were divided into two experimental groups (A and B) and one control group. After installation of an orthodontic tooth movement device, groups A and B received subcutaneous weekly injections of 4HR (1.28 and 128 mg/kg). Micro-computerized tomography and histological analyses were performed after 2 weeks of tooth movement. The application of 4HR elevated expression of osteogenic markers in Saos-2 cells. Movement of the first molars was significantly greater in rats administered 4HR. Furthermore, the expression of bone morphogenic protein-2, receptor activator of nuclear factor kappa-B ligand, osteocalcin, and tartrate-resistant acid phosphatase were increased after 4HR administration. 4HR application demonstrated increased expression of osteogenic markers in Saos-2 cells and accelerated orthodontic tooth movement in rats.
Micronucleus Assay: The State of Art, and Future Directions
Authors: Sommer Sylwester , Buraczewska Iwona , Kruszewski Marcin
Published: February 2020

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.
A microRNA Expression Profile as Non-Invasive Biomarker in a Large Arrhythmogenic Cardiomyopathy Cohort
Authors: Bueno Marinas Maria , Celeghin Rudy , Cason Marco , Bariani Riccardo , Frigo Anna Chiara , Jager Joanna , Syrris Petros , Elliott Perry M. , Bauce Barbara , Thiene Gaetano , Corrado Domenico , Basso Cristina , Pilichou Kalliopi
Published: February 2020

Arrhythmogenic Cardiomyopathy (AC) is a clinically and genetically heterogeneous myocardial disease. Half of AC patients harbour private desmosomal gene variants. Although microRNAs (miRNAs) have emerged as key regulator molecules in cardiovascular diseases and their involvement, correlated to phenotypic variability or to non-invasive biomarkers, has been advanced also in AC, no data are available in larger disease cohorts. Here, we propose the largest AC cohort unbiased by technical and biological factors. MiRNA profiling on nine right ventricular tissue, nine blood samples of AC patients, and four controls highlighted 10 differentially expressed miRNAs in common. Six of these were validated in a 90-AC patient cohort independent from genetic status: miR-122-5p, miR-133a-3p, miR-133b, miR-142-3p, miR-182-5p, and miR-183-5p. This six-miRNA set showed high discriminatory diagnostic power in AC patients when compared to controls (AUC-0.995), non-affected family members of AC probands carrying a desmosomal pathogenic variant (AUC-0.825), and other cardiomyopathy groups (Hypertrophic Cardiomyopathy: AUC-0.804, Dilated Cardiomyopathy: AUC-0.917, Brugada Syndrome: AUC-0.981, myocarditis: AUC-0.978). AC-related signalling pathways were targeted by this set of miRNAs. A unique set of six-miRNAs was found both in heart-tissue and blood samples of AC probands, supporting its involvement in disease pathogenesis and its possible role as a non-invasive AC diagnostic biomarker.
Emerging Roles of Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney Injury
Authors: Chen Wei-Yu , Li Lung-Chih , Wu Yi-Hsiu , Yang Jenq-Lin , Tzeng Hong-Tai
Published: February 2020

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses. IL-33 triggers pleiotropic immune functions in multiple types of immune cells, which express the IL-33 receptor, ST2. Recent studies have revealed the potential applications of IL-33 for treating acute kidney injury in preclinical animal models. However, IL-33 and IL-33-responding immune cells are reported to exhibit both detrimental and beneficial roles. The IL-33-mediated immunomodulatory functions have been investigated using loss-of-function approaches, such as IL33-deficient mice, IL-33 antagonists, or administration of exogenous IL-33 recombinant protein. This review will discuss the key findings on IL-33-mediated activation of kidney resident group 2 innate lymphoid cells (ILC2s) and summarize the current understanding of the differential functions of endogenous IL-33 and exogenous IL-33 and their potential implications in treating acute kidney injury.
Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients
Authors: Boldrin Elisa , Curtarello Matteo , Dallan Marco , Alfieri Rita , Realdon Stefano , Fassan Matteo , Saggioro Daniela
Published: February 2020

DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett’s esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring.
Combined Targeting of AKT and mTOR Inhibits Proliferation of Human NF1-Associated Malignant Peripheral Nerve Sheath Tumour Cells In Vitro but not in a Xenograft Mouse Model In Vivo
Authors: Schulte Alexander , Ewald Florian , Spyra Melanie , Smit Daniel J. , Jiang Wei , Salamon Johannes , Jücker Manfred , Mautner Victor-Felix
Published: February 2020

Persistent signalling via the PI3K/AKT/mTOR pathway is a major driver of malignancy in NF1-associated malignant peripheral nerve sheath tumours (MPNST). Nevertheless, single targeting of this pathway is not sufficient to inhibit MPNST growth. In this report, we demonstrate that combined treatment with the allosteric pan-AKT inhibitor MK-2206 and the mTORC1/mTORC2 inhibitor AZD8055 has synergistic effects on the viability of MPNST cell lines in comparison to the treatment with each compound alone. However, when treating animals bearing experimental MPNST with the combined AKT/mTOR regime, no influence on tumour growth was observed. Further analysis of the MPNST xenograft tumours resistant to AKT/mTOR treatment revealed a reactivation of both AKT and mTOR in several tumour samples. Additional targeting of the RAS/RAF/MEK/MAPK pathway with the allosteric MEK1/2 inhibitor AZD6244 showed synergistic effects on the viability of MPNST cell lines in vitro in comparison to the dual AKT/mTOR inhibition. In summary, these data indicate that combined treatment with AKT and mTOR inhibitors is effective on MPNST cells in vitro but tumour resistance can occur rapidly in vivo by restoration of AKT/mTOR signalling. Our data further suggest that a triple treatment with inhibitors against AKT, mTORC1/2 and MEK1/2 may be a promising treatment option that should be further analysed in an experimental MPNST mouse model in vivo.
Remodeling of Intracellular Ca2+ Homeostasis in Rat Hippocampal Neurons Aged In Vitro
Authors: Calvo-Rodriguez Maria , Hernando-Pérez Elena , López-Vázquez Sara , Núñez Javier , Villalobos Carlos , Núñez Lucía
Published: February 2020

Aging is often associated with a cognitive decline and a susceptibility to neuronal damage. It is also the most important risk factor for neurodegenerative disorders, particularly Alzheimer’s disease (AD). AD is related to an excess of neurotoxic oligomers of amyloid β peptide (Aβo); however, the molecular mechanisms are still highly controversial. Intracellular Ca2+ homeostasis plays an important role in the control of neuronal activity, including neurotransmitter release, synaptic plasticity, and memory storage, as well as neuron cell death. Recent evidence indicates that long-term cultures of rat hippocampal neurons, resembling aged neurons, undergo cell death after treatment with Aβo, whereas short-term cultures, resembling young neurons, do not. These in vitro changes are associated with the remodeling of intracellular Ca2+ homeostasis with aging, thus providing a simplistic model for investigating Ca2+ remodeling in aging. In vitro aged neurons show increased resting cytosolic Ca2+ concentration, enhanced Ca2+ store content, and Ca2+ release from the endoplasmic reticulum (ER). Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria is also enhanced. Aged neurons also show decreased store-operated Ca2+ entry (SOCE), a Ca2+ entry pathway related to memory storage. At the molecular level, in vitro remodeling is associated with changes in the expression of Ca2+ channels resembling in vivo aging, including changes in N-methyl-D-aspartate NMDA receptor and inositol 1,4,5-trisphosphate (IP3) receptor isoforms, increased expression of the mitochondrial calcium uniporter (MCU), and decreased expression of Orai1/Stim1, the molecular players involved in SOCE. Additionally, Aβo treatment exacerbates most of the changes observed in aged neurons and enhances susceptibility to cell death. Conversely, the solely effect of Aβo in young neurons is to increase ER–mitochondria colocalization and enhance Ca2+ transfer from ER to mitochondria without inducing neuronal damage. We propose that cultured rat hippocampal neurons may be a useful model to investigate Ca2+ remodeling in aging and in age-related neurodegenerative disorders.
Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy
Authors: Acharya Arpan , Tagny Claude T. , Mbanya Dora , Fonsah Julius Y. , Nchindap Emilienne , Kenmogne Léopoldine , Jihyun Ma , Njamnshi Alfred K. , Kanmogne Georgette D.
Published: February 2020

Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology.
Computational Models in Non-Coding RNA and Human Disease
Authors: Chen Xing , Wang Chun-Chun , Guan Na-Na
Published: February 2020

The central dogma of molecular biology has told that DNA sequences encode proteins through RNAs, which function as an information intermediary [...]
Podocyte Lysosome Dysfunction in Chronic Glomerular Diseases
Authors: Li Guangbi , Kidd Jason , Li Pin-Lan
Published: February 2020

Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.
Transcriptomic Analysis of the Brown Planthopper, Nilaparvata lugens, at Different Stages after Metarhizium anisopliae Challenge
Authors: Peng Yifan , Tang Jifeng , Xie Jiaqin
Published: February 2020

Nilaparvata lugens is one of the major pests of rice and results in substantial yield loss every year. Our previous study found that the entomopathogenic fungus Metarhizium anisopliae showed effective potential for controlling this pest. However, the mechanisms underlying M. anisopliae infection of N. lugens are not well known. In the present study, we further examined the transcriptome of N. lugens at 4 h, 8 h, 16 h, and 24 h after M. anisopliae infection by Illumina deep sequencing. In total, 174.17 Gb of data was collected after sequencing, from which 23,398 unigenes were annotated by various databases, including 3694 newly annotated genes. The results showed that there were 246 vs 75, 275 vs 586, 378 vs 1055, and 638 vs 182 up- and downregulated differentially expressed genes (DEGs) at 4 h, 8 h, 16 h, and 24 h after M. anisopliae infection, respectively. The biological functions and associated metabolic processes of these genes were determined with the Clusters of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The DEGs data were verified using RT-qPCR. These results indicated that the DEGs during the initial fungal infection appropriately reflected the time course of the response to the fungal infection. Taken together, the results of this study provide new insights into the molecular mechanisms underlying the insect host response to fungal infection, especially during the initial stage of infection, and may improve the potential control strategies for N. lugens.
Evidence for Cryptic Diversity in the “Pan-Antarctic” Springtail Friesea antarctica and the Description of Two New Species
Authors: Carapelli Antonio , Greenslade Penelope , Nardi Francesco , Leo Chiara , Convey Peter , Frati Francesco , Fanciulli Pietro Paolo
Published: February 2020

The invertebrate terrestrial fauna of Antarctica is being investigated with increasing interest to discover how life interacts with the extreme polar environment and how millions of years of evolution have shaped their biodiversity. Classical taxonomic approaches, complemented by molecular tools, are improving our understanding of the systematic relationships of some species, changing the nomenclature of taxa and challenging the taxonomic status of others. The springtail Friesea grisea has previously been described as the only species with a “pan-Antarctic” distribution. However, recent genetic comparisons have pointed to another scenario. The latest morphological study has confined F. grisea to the sub-Antarctic island of South Georgia, from which it was originally described, and resurrected F. antarctica as a congeneric species occurring on the continental mainland. Molecular data demonstrate that populations of this taxon, ostensibly occurring across Maritime and Continental Antarctica, as well as on some offshore islands, are evolutionarily isolated and divergent and cannot be included within a single species. The present study, combining morphological with molecular data, attempts to validate this hypothesis and challenges the taxonomic status of F. antarctica, suggesting that two additional new species, described here as Friesea gretae sp. nov. and Friesea propria sp. nov., are present in Continental Antarctica.
Management and Prognosis of Heart Failure in Octogenarians: Final Report from the KorAHF Registry
Authors: Oh Gyu Chul , Cho Hyun-Jai , Lee Sang Eun , Kim Min-Seok , Kim Jae-Joong , Choi Jin-Oh , Jeon Eun-Seok , Hwang Kyung-Kuk , Chae Shung Chull , Baek Sang Hong , Kang Seok-Min , Yoo Byung-Su , Choi Dong-Ju , Ahn Youngkeun , Kim Kye Hun , Cho Myeong-Chan , Oh Byung-Hee , Lee Hae-Young
Published: February 2020

Treatment of heart failure (HF) in the elderly face many difficulties due to lack of robust evidence. We analyzed the outcome of HF in octogenarians using a nationwide HF registry. Among 5625 patients from the Korean Acute Heart Failure (KorAHF) registry, prognosis of octogenarian HF and the association of guideline-directed medical therapy (GDMT) with mortality and readmissions were analyzed. Octogenarian patients (1185, 22.4%) showed a higher mortality, and males were especially at increased risk (HR (hazard ratio) 1.19, 95% CI 1.01–1.40). A J-curve association between blood pressure (BP) and mortality was observed regardless of age, but the nadir value was lower in octogenarians (123.8 vs. 127.9 mmHg for systolic blood pressure (SBP); 67.1 vs. 73.9 mmHg for diastolic blood pressure (DBP), p < 0.001). Use of GDMT in octogenarian patients with HF and reduced ejection fraction (EF) were inadequate (74.3%, 47.1%, and 46.1% in octogenarians vs. 78.4%, 59.8%, and 55.2% in non-elderly for renin-angiotensin system inhibitors, beta-blockers, and aldosterone antagonists, respectively; all p < 0.05). However, those on medications had a significant reduction in 6 month mortality. For octogenarians with HF and preserved EF, angiotensin receptor blocker use reduced hospitalizations for HF in men (HR 0.19, 95% CI 0.04–0.87), but not in women (p-interaction = 0.037). HF in octogenarians were found to have different characteristics compared with the non-elderly. However, adequate use of GDMT was still associated with improved survival, and more attention should be given to prescribing medications with clinical benefits.