bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dimorphism of Heart Rate Variability in Adolescence: A Case-Control Study on Depression, Anxiety, Stress Levels, Body Composition, and Heart Rate Variability in Adolescents with Impaired Fasting Glucose
Authors: Stefanaki Charikleia , Michos Athanasios , Latsios George , Tousoulis Dimitrios , Peppa Melpomeni , Zosi Paraskevi , Boschiero Dario , Bacopoulou Flora
Published: April 2020

Prediabetes in the form of impaired fasting glucose, impaired glucose tolerance, or both is considered as a preliminary stage for the onset of diabetes and diabetic complications. Hormonal fluctuations in adolescence are accompanied by body composition modifications, which are associated with insulin resistance and subclinical inflammation. Bioimpedance (BIA) accurately evaluates body composition, and heart rate variability (HRV) assesses cardiac autonomic function, which are frequently afflicted by insulin resistance. We aimed at evaluating the effect of glycemic status on mental stress, anxiety, and depression status in adolescents with impaired fasting glucose, body composition, and HRV parameters. This is a case-control study to evaluate the effect of the hyperglycemia on depression, anxiety, and stress levels (DASS21 questionnaire), body composition (BIA-ACC—BIOTEKNA©), and HRV (PPG Stress Flow—BIOTEKNA©), between euglycemic adolescents (euglycemic group) and adolescents with impaired fasting glucose (prediabetic group), aged 12–20 years. No differences were found between the prediabetic (n = 13) and the euglycemic (n = 16) groups in the outcome measures, possibly due to the number of participants. Interestingly, females, irrespective of their glycemic status, exhibited altered sympathovagal function as revealed by impaired HRV. In the euglycemic group, HRV parameters were significantly correlated and in line with the DASS21 scores, but in the prediabetic group, similarities to those of adults were observed. Impaired fasting glucose had no impact on mental health, body composition, or HRV parameters in adolescents. HRV parameters were impaired in females, irrespective of their glycemic status. This finding implies that females seem to be more prone to stress disorders, even from a young age. Future studies are needed to confirm these findings.
Sociodemographic Determinants for the Health-Related Quality of Life of Patients with Vascular Amputations as Determined with the Prosthesis Evaluation Questionnaire
Authors: Benavent José Vicente , Tenías José María , Pellin Ana , Casaña Mohedo Jorge , Cabellos-García Ana Cristina , Gea-Caballero Vicente
Published: April 2020

Background: To identify the sociodemographic variables independently related to the different dimensions of the Prosthesis Evaluation Questionnaire (PEQ). Methods: An observational, cross-sectional study was conducted, with a sample of 61 Spanish vascular amputees (Valencia, Spain). Included in this study are the results of the PEQ and explanatory-sociodemographic variables, as well as a descriptive and analytic analysis. Results: Gender differences were observed in “appearance” and “perception of appearance” (significantly higher levels for men). Older patients tended to have worse scores in “utility”, “frustration”, “social burden” and “deambulation”. More favorable scores were obtained for those residing in rural areas in “social burden” and “deambulation”. Educational level had a positive correlation with scores. Conclusion: Gender, age, place of residence, and educational level could be considered determinants of the quality of health related to prosthesis adaptation in vascular amputees. Clinical relevance: Knowing the influential variables in the process of prosthetization will allow better adaptation and an improvement in the quality of life.
Built Environment and Childhood Weight Status: A Multi-Level Study Using Population-Based Data in the City of Hannover, Germany
Authors: Zhou Yusheng , Buck Christoph , Maier Werner , von Lengerke Thomas , Walter Ulla , Dreier Maren
Published: April 2020

In recent years, built environmental characteristics have been linked to childhood overweight, but the results remain inconsistent across studies. The present study examines associations between several built environmental features and body weight status (BMI) z-score among a large sample of preschool children in the city of Hannover, Germany. Walkability (Index), green space availability, and playground availability related to preschool children’s home environments were measured using data from OpenStreetMap (OSM). These built environment characteristics were linked to the data from the 2010–2014 school entry examinations in the Hannover city (n = 22,678), and analysed using multilevel linear regression models to examine associations between the built environment features and the BMI z-score of these children (4–8 years old). No significant associations of built environmental factors on children’s BMI were detected, but the effect between green space availability and BMI was modified by the parental educational level. In children with lower compared to higher educated parents, a higher spatial availability of greenspace was significantly associated with reduced body weight. Future research should continue to monitor the disparities in diverse built environment features and how these are related to children’s health.
Inequalities in Rotavirus Vaccine Uptake in Ethiopia: A Decomposition Analysis
Authors: Wondimu Abrham , van der Schans Jurjen , van Hulst Marinus , Postma Maarten J.
Published: April 2020

A previous study in Ethiopia reported significant variation in rotavirus vaccine uptake across socioeconomic strata. This study aims to quantify socioeconomic inequality of rotavirus vaccine uptake in Ethiopia and to identify the contributing factors for the inequality. The concentration curve (CC) and the Erreygers Normalized Concentration Index (ECI) were used to assess the socioeconomic related inequality in rotavirus vaccine uptake using data from the 2016 Ethiopian Demographic and Health Survey. Decomposition analysis was conducted to identify the drivers of inequalities. The CC for rotavirus vaccine uptake lay below the line of equality and the ECI was 0.270 (p < 0.001) indicating that uptake of rotavirus vaccine in Ethiopia was significantly concentrated among children from families with better socioeconomic status. The decomposition analysis showed that underlining inequalities in maternal health care services utilization, including antenatal care use (18.4%) and institutional delivery (8.1%), exposure to media (12.8%), and maternal educational level (9.7%) were responsible for the majority of observed inequalities in the uptake of rotavirus vaccine. The findings suggested that there is significant socioeconomic inequality in rotavirus vaccine uptake in Ethiopia. Multi-sectoral actions are required to reduce the inequalities, inclusive increasing maternal health care services, and educational attainments among economically disadvantaged mothers.
Visitors’ Motives for Attending a Healthy Food Exhibition
Authors: Bi Yahua , Choi Sooyoung , Kim Insin
Published: April 2020

Environmental issues (i.e., food safety and environmental pollution) have increased concerns about individuals’ health as well as global environment. These concerns drive awareness for the influences of healthy foods, and eventually lead them to visit healthy food exhibitions. This research aims to understand the attendees’ motives for participating in a healthy food exhibition. Specific objectives are to identify crucial visitors’ motives influencing satisfaction with the healthy food exhibition and to verify whether visitors’ satisfaction with the exhibition enhances their memory for the experience in the exhibition. The survey was conducted by targeting visitors who participated in the Busan International Food Expo, and the data collected from 363 attendees were analyzed using the SPSS and AMOS statistical programs. The analysis results revealed that three dimensions of healthy food exhibition motives, namely perceived healthiness, perceived hedonism and perceived food safety, increase visitors’ satisfaction with the healthy food exhibition, and that satisfaction with the healthy food exhibition further had a positive impact on the visitors’ memory for the exhibition experience.
Demographic and Risk-Factor Differences between Users and Non-Users of Unscheduled Healthcare among Pediatric Outpatients with Persistent Asthma
Authors: Rangachari Pavani , Griffin Dixie D. , Ghosh Santu , May Kathleen R.
Published: April 2020

This study assesses differences between users and non-users of unscheduled healthcare for persistent childhood asthma, with regard to select demographic and risk factors. The objectives are to provide important healthcare utilization information and a foundation for future research on self-management effectiveness (SME), informed by a recently developed “holistic framework” for measuring SME in childhood asthma. An 18-month retrospective chart review was conducted on 59 pediatric outpatients with persistent asthma—mild, moderate, or severe, to obtain data on various demographic and risk factors, and healthcare use for each child. The study examined five types of “unscheduled” healthcare use. Users had non-zero encounters (at least one) in any of the five types; non-users had zero encounters (not even one) in all five types. Differences between users and non-users were assessed using contingency table and logistic regression analysis. There were 25 users and 34 non-users of unscheduled healthcare. Each severity category contained users and non-users. The only statistically significant finding was that the mild persistent category had fewer users than severe persistent (p < 0.05). There were no significant differences between users and non-users for any other demographic or risk factor examined. After adjusting for asthma severity, there were no other significant differences between users and non-users of unscheduled healthcare. This is a crucial finding which suggests that something else is driving unscheduled healthcare use in these children, given there were users and non-users in each asthma severity category. These results provide impetus for future research on the role of other aspects of the "holistic framework" in explaining differences in uses of unscheduled healthcare in persistent childhood asthma.
Sleep Quality and Mental Disorder Symptoms among Canadian Public Safety Personnel
Authors: Angehrn Andréanne , Teale Sapach Michelle J. N. , Ricciardelli Rosemary , MacPhee Renée S. , Anderson Gregory S. , Carleton R. Nicholas
Published: April 2020

Poor sleep quality is associated with numerous mental health concerns and poorer overall physical health. Sleep disturbances are commonly reported by public safety personnel (PSP) and may contribute to the risk of developing mental disorders or exacerbate mental disorder symptoms. The current investigation was designed to provide estimates of sleep disturbances among PSP and explore the relationship between sleep quality and mental health status. PSP completed screening measures for sleep quality and diverse mental disorders through an online survey. Respondents (5813) were grouped into six categories: communications officials, correctional workers, firefighters, paramedics, police officers, and Royal Canadian Mounted Police (RCMP). Many PSP in each category reported symptoms consistent with clinical insomnia (49–60%). Rates of sleep disturbances differed among PSP categories (p < 0.001, ω = 0.08). Sleep quality was correlated with screening measures for post-traumatic stress disorder (PTSD), depression, anxiety, social anxiety disorder, panic disorder, and alcohol use disorder for all PSP categories (r = 0.18–0.70, p < 0.001). PSP who screened positive for insomnia were 3.43–6.96 times more likely to screen positive for a mental disorder. All PSP reported varying degrees of sleep quality, with the lowest disturbances found among firefighters and municipal/provincial police. Sleep appears to be a potentially important factor for PSP mental health.
How Perceived Quality of Care and Job Satisfaction Are Associated with Intention to Leave the Profession in Young Nurses and Physicians
Authors: Koch Peter , Zilezinski Max , Schulte Kevin , Strametz Reinhard , Nienhaus Albert , Raspe Matthias
Published: April 2020

German hospitals are now confronted with major challenges from both shortages and fluctuations in the numbers of physicians and nurses. This makes it even more important that physicians and nurses do not prematurely leave patient care. The objective of the present study was to improve our understanding of the factors that trigger intentions to leave the profession. For this purpose, data from 1060 young physicians and nurses in hospital care were analysed. Intentions to leave the profession was assessed with the Copenhagen Psychosocial Questionnaire (COPSOQ). In the first step, the association was determined between intention to leave the profession and the factors of perceived quality of care and job satisfaction. In a second step, a mediation analysis was performed to determine the effect of perceived quality of care after correction for the possible mediator of job satisfaction. There were statistically significant negative associations between perceived quality of care and intention to leave the profession (beta: −2.9, 95% CI: −4.48–−1.39) and job satisfaction and intention to leave the profession (beta: −0.5, 95% CI: −0.64–−0.44). The effect of perceived quality of care on intention to leave the profession was partially mediated by job satisfaction. Thus, high perceived quality of care and high job satisfaction are both important factors that tend to prevent young physicians and nurses from leaving their professions.
Role of Type and Volume of Recreational Physical Activity on Heart Rate Variability in Men
Authors: Alkahtani Shaea , Flatt Andrew A. , Kanas Jawad , Aldyel Abdulaziz , Habib Syed Shahid
Published: April 2020

The aim of this study was to investigate the effect of recreational aerobic physical activity (PA) type and volume on heart rate variability (HRV) in Arab men. This was a retrospective, cross-sectional study, and included men (n = 75, age = 37.6 ± 7.1 years, body mass index (BMI) = 26.7 ± 3.1 kg/m2) who were members of a walking group, cycling group, or were inactive controls. Monthly distances from the past three months were obtained from walking and cycling groups, and the volume of PA was classified into three subgroups (high, moderate, low). HRV was measured using a computerized electrocardiographic data acquisition device. R–R interval recordings were performed while participants rested in a motionless supine position. RR intervals were recorded for 15 minutes, and a five-minute segment with minimal ectopic beats and artifacts was selected for HRV analysis. Time-domain parameters included the mean R–R interval, standard deviation of the mean R–R interval (SDNN), and root-mean-squared difference of successive RR intervals (RMSSD). The frequency-domain parameters included high-frequency power (HF), low-frequency power (LF), and LF to HF ratio (LF/HF). Results showed that there were no significant differences between walking, cycling, and control groups for all HRV parameters. Time-domain analyses based on PA volume showed that age-adjusted SDNN for the high-active group was greater than the low-active group (P = 0.03), and RMSSD for the moderate-active group was greater than the control group (P = 0.009). For the frequency domain, LF for the high-active group was greater than the low-active and control groups (P = 0.006), and HF for the moderate-active group was greater than the low-active group (P = 0.04). These data indicate that walking >150 km per month, or cycling >100 km per month at a speed >20 km/h may be necessary to derive cardiac autonomic benefits from PA among Arab men.
The Study of Health-Related Fitness Normative Scores for Nepalese Older Adults
Authors: Kim Jung Kyu , Son Won Il , Sim Ye Jung , Lee Ju Sung , Oli Saud Kamala
Published: April 2020

Physical fitness tests are important to maintain and promote the health status of people. The purpose of this study was to develop health-related fitness evaluation norms according to the age and gender of Nepalese older adults. One thousand nine subjects (449 males, 560 females) above 60 years, residing in 19 wards (rural and urban) of Dhangadhi Sub-Metropolitan City participated in this study. The test included the PAR-Q (Physical Activity Readiness Questionnaire), social aspects questionnaire, blood pressure test, height, weight, BMI (body mass index), percent body fat, and four physical fitness components (grip strength, 1-minute sit-to-stand, sit and reach, and 2-minute step tests). Mean, SD, and fitness evaluation norms for each component were obtained after the main test and statistical analyses. This study showed higher BMI and percent body fat in female age groups than in male age groups. Grip strength, relative grip strength, sit-to-stand, and 2-minute steps scores were better in male age groups than in female age groups, but in contrast, flexibility was better in female age groups. This study may help the related sectors to assess physical fitness, identify fitness levels, and develop appropriate physical activities or exercise programs for older adults based on age.
The Intensity of Simulated Grazing Modifies Costs and Benefits of Physiological Integration in a Rhizomatous Clonal Plant
Authors: Liu Jushan , Chen Chen , Pan Yao , Zhang Yang , Gao Ying
Published: April 2020

Clonal plants in grasslands are special species with physiological integration which can enhance their ability to tolerate herbivory stress especially in heterogeneous environments. However, little is known about how grazing intensity affects the trade-off between the benefits and costs of physiological integration, and the mechanism by which physiological integration improves compensatory growth in response to herbivory stress. We examined the effects of simulated grazing intensity on compensatory growth and physiological integration in a clonal species Leymus chinensis with a greenhouse experiment. This experiment was conducted in a factorial design involving nutrient heterogeneity (high-high, high-low, low-high, low-low), simulated grazing by clipping (0%, 25%, 50% or 75% shoot removal) and rhizome connection (intact versus severed) treatments. Compensatory indexes at 25% and 50% clipping levels were higher than that at 75% clipping level except in low-low nutrient treatments. Physiological integration decreased and increased compensatory indexes when the target-ramets worked as exporter and importer, respectively. Generally, clipping increased both benefits and costs of physiological integration, but its net benefits (benefits minus costs) changed with clipping intensity. Physiological integration optimized compensatory growth at light and moderate clipping intensity, and its net benefits determined the high capacity of compensatory growth. Grassland managements such as grazing or mowing at light and moderate intensity would maximize the profit of physiological integration and improve grassland sustainability.
Identification and Characterization of microRNAs in the Developing Seed of Linseed Flax (Linum usitatissimum L.)
Authors: Zhang Tianbao , Li Zhen , Song Xiaxia , Han Lida , Wang Limin , Zhang Jianping , Long Yan , Pei Xinwu
Published: April 2020

Seed development plays an important role during the life cycle of plants. Linseed flax is an oil crop and the seed is a key organ for fatty acids synthesis and storage. So it is important to understand the molecular mechanism of fatty acid biosynthesis during seed development. In this study, four small RNA libraries from early seeds at 5, 10, 20 and 30 days after flowering (DAF) were constructed and used for high-throughput sequencing to identify microRNAs (miRNAs). A total of 235 miRNAs including 114 known conserved miRNAs and 121 novel miRNAs were identified. The expression patterns of these miRNAs in the four libraries were investigated by bioinformatics and quantitative real-time polymerase chain reaction (qPCR) analysis. It was found that several miRNAs, including Lus-miRNA156a was significantly correlated with seed development process. In order to confirm the actual biological function of Lus-miRNA156a, over-expression vector was constructed and transformed to Arabidopsis. The phenotypes of homozygous transgenic lines showed decreasing of oil content and most of the fatty acid content in seeds as well as late flowering time. The results provided a clue that miRNA156a participating the fatty acid biosynthesis pathway and the detailed molecular mechanism of how it regulates the pathway needs to be further investigated.
Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review
Authors: Muhammad Sajjad , Chaudhry Shafqat Rasul , Kahlert Ulf Dietrich , Lehecka Martin , Korja Miikka , Niemelä Mika , Hänggi Daniel
Published: April 2020

Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for “subarachnoid hemorrhage” in combination with “HMGB1”. Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.
Skeletal Dysplasias Caused by Sulfation Defects
Authors: Paganini Chiara , Gramegna Tota Chiara , Superti-Furga Andrea , Rossi Antonio
Published: April 2020

Proteoglycans (PGs) are macromolecules present on the cell surface and in the extracellular matrix that confer specific mechanical, biochemical, and physical properties to tissues. Sulfate groups present on glycosaminoglycans, linear polysaccharide chains attached to PG core proteins, are fundamental for correct PG functions. Indeed, through the negative charge of sulfate groups, PGs interact with extracellular matrix molecules and bind growth factors regulating tissue structure and cell behavior. The maintenance of correct sulfate metabolism is important in tissue development and function, particularly in cartilage where PGs are fundamental and abundant components of the extracellular matrix. In chondrocytes, the main sulfate source is the extracellular space, then sulfate is taken up and activated in the cytosol to the universal sulfate donor to be used in sulfotransferase reactions. Alteration in each step of sulfate metabolism can affect macromolecular sulfation, leading to the onset of diseases that affect mainly cartilage and bone. This review presents a panoramic view of skeletal dysplasias caused by mutations in genes encoding for transporters or enzymes involved in macromolecular sulfation. Future research in this field will contribute to the understanding of the disease pathogenesis, allowing the development of targeted therapies aimed at alleviating, preventing, or modifying the disease progression.
Prior Toxoplasma Gondii Infection Ameliorates Liver Fibrosis Induced by Schistosoma Japonicum through Inhibiting Th2 Response and Improving Balance of Intestinal Flora in Mice
Authors: Xu Fei , Cheng Ruitang , Miao Sunhan , Zhu Yuwei , Sun Ze , Qiu Liying , Yang Junqi , Zhou Yonghua
Published: April 2020

Schistosomiasis is an immunopathogenic disease in which a T helper (Th) cell type 2-like response plays vital roles. Hepatic fibrosis is its main pathologic manifestations, which is the leading cause of hepatic cirrhosis. Co-infections of Schistosoma japonicum (Sj) with other pathogens are frequently encountered but are easily ignored in clinical studies, and effective therapeutic interventions are lacking. In this study, we explored the effect of Toxoplasma gondii (Tg) prior infection on Th1/Th2 response, community shifts in gut microbiome (GM), and the pathogenesis of schistosomiasis in murine hosts. Mice were prior infected with Tg before Sj infection. The effects of co-infection on Th1/Th2 response and hepatic fibrosis were analyzed. Furthermore, we investigated this issue by sequencing 16S rRNA from fecal specimens to define the GM profiles during co-infection. Tg prior infection markedly reduced the granuloma size and collagen deposit in livers against Sj infection. Prior infection promoted a shift toward Th1 immune response instead of Th2. Furthermore, Tg infection promoted the expansion of preponderant flora and Clostridiaceae was identified as a feature marker in the GM of the co-infection group. Redundancy analysis (RDA)/canonical correspondence analysis (CCA) results showed that liver fibrosis, Th1/Th2 cytokines were significantly correlated (P < 0.05) with the GM compositions. Tg infection inhibits hepatic fibrosis by downregulating Th2 immune response against Sj infection, and further promotes the GM shifts through “gut–liver axis” in the murine hosts. Our study may provide insights into potential anti-fibrosis strategies in co-infection individuals.
Genotypes and Phenotypes: A Search for Influential Genes in Diabetic Retinopathy
Authors: Cabrera Andrea P. , Mankad Rushi N. , Marek Lauren , Das Ryan , Rangasamy Sampath , Monickaraj Finny , Das Arup
Published: April 2020

Although gene–environment interactions are known to play an important role in the inheritance of complex traits, it is still unknown how a genotype and the environmental factors result in an observable phenotype. Understanding this complex interaction in the pathogenesis of diabetic retinopathy (DR) remains a big challenge as DR appears to be a disease with heterogenous phenotypes with multifactorial influence. In this review, we examine the natural history and risk factors related to DR, emphasizing distinct clinical phenotypes and their natural course in retinopathy. Although there is strong evidence that duration of diabetes and metabolic factors play a key role in the pathogenesis of DR, accumulating new clinical studies reveal that this disease can develop independently of duration of diabetes and metabolic dysfunction. More recently, studies have emphasized the role of genetic factors in DR. However, linkage analyses, candidate gene studies, and genome-wide association studies (GWAS) have not produced any statistically significant results. Our recently initiated genomics study, the Diabetic Retinopathy Genomics (DRGen) Study, aims to examine the contribution of rare and common variants in the development DR, and how they can contribute to clinical phenotype, rate of progression, and response to available therapies. Our preliminary findings reveal a novel set of genetic variants associated with proangiogenic and inflammatory pathways that may contribute to DR pathogenesis. Further investigation of these variants is necessary and may lead to development of novel biomarkers and new therapeutic targets in DR.
Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
Authors: André Saudade , P. Nunes Sandra , Silva Fernanda , Henrique Rui , Félix Ana , Jerónimo Carmen
Published: April 2020

Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.
RX-3117 (Fluorocyclopentenyl-Cytosine)-Mediated Down-Regulation of DNA Methyltransferase 1 Leads to Protein Expression of Tumor-Suppressor Genes and Increased Functionality of the Proton-Coupled Folate Carrier
Authors: Sarkisjan Dzjemma , Julsing Joris R. , El Hassouni Btissame , Honeywell Richard J. , Kathmann Ietje , Matherly Larry H. , Lee Young B. , Kim Deog J. , Peters Godefridus J.
Published: April 2020

(1) Background: RX-3117 (fluorocyclopentenyl-cytosine) is a cytidine analog that inhibits DNA methyltransferase 1 (DNMT1). We investigated the mechanism and potential of RX-3117 as a demethylating agent in several in vitro models. (2) Methods: we used western blotting to measure expression of several proteins known to be down-regulated by DNA methylation: O6-methylguanine-DNA methyltransferase (MGMT) and the tumor-suppressor genes, p16 and E-cadherin. Transport of methotrexate (MTX) mediated by the proton-coupled folate transporter (PCFT) was used as a functional assay. (3) Results: RX-3117 treatment decreased total DNA-cytosine-methylation in A549 non-small cell lung cancer (NSCLC) cells, and induced protein expression of MGMT, p16 and E-cadherin in A549 and SW1573 NSCLC cells. Leukemic CCRF-CEM cells and the MTX-resistant variant (CEM/MTX, with a deficient reduced folate carrier) have a very low expression of PCFT due to promoter hypermethylation. In CEM/MTX cells, pre-treatment with RX-3117 increased PCFT-mediated MTX uptake 8-fold, and in CEM cells 4-fold. With the reference hypomethylating agent 5-aza-2′-deoxycytidine similar values were obtained. RX-3117 also increased PCFT gene expression and PCFT protein. (4) Conclusion: RX-3117 down-regulates DNMT1, leading to hypomethylation of DNA. From the increased protein expression of tumor-suppressor genes and functional activation of PCFT, we concluded that RX-3117 might have induced hypomethylation of the promotor.
Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling
Authors: Sabol Rachel A. , Villela Vidal A. , Denys Alexandra , Freeman Benjamin T. , Hartono Alifiani B. , Wise Rachel M. , Harrison Mark A. A. , Sandler Maxwell B. , Hossain Fokhrul , Miele Lucio , Bunnell Bruce A.
Published: April 2020

Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads to higher mortality rates for obese women who develop breast cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, the effects of obesity-altered ASCs (obASCs) on estrogen receptor positive breast cancer cell’s (ER+BCCs) response to radiotherapy (RT) were evaluated. We determined that BCCs had a decreased apoptotic index and increased surviving fraction following RT when co-cultured with obASCs compared to lnASCs or non-co-cultured cells. Further, obASCs reduced oxidative stress and induced IL-6 expression in co-cultured BCCs after radiation. obASCs produce increased levels of leptin relative to ASCs from normal-weight individuals (lnASCs). obASCs upregulate the expression of IL-6 compared to non-co-cultured BCCs, but BCCs co-cultured with leptin knockdown obASCs did not upregulate IL-6. The impact of shLeptin obASCs on radiation resistance of ER+BCCs demonstrate a decreased radioprotective ability compared to shControl obASCs. Key NOTCH signaling players were enhanced in ER+BBCs following co-culture with shCtrl obASCs but not shLep obASCs. This work demonstrates that obesity-altered ASCs, via enhanced secretion of leptin, promote IL-6 and NOTCH signaling pathways in ER+BCCs leading to radiation resistance.
Single-Cell Gene Profiling Reveals Social Status-Dependent Modulation of Nuclear Hormone Receptors in GnRH Neurons in a Male Cichlid Fish
Authors: Ogawa Satoshi , Parhar Ishwar S.
Published: April 2020

Gonadotropin-releasing hormone (GnRH) is essential for the initiation and maintenance of reproductive functions in vertebrates. To date, three distinct paralogue lineages, GnRH1, GnRH2, and GnRH3, have been identified with different functions and regulatory mechanisms. Among them, hypothalamic GnRH1 neurons are classically known as the hypophysiotropic form that is regulated by estrogen feedback. However, the mechanism of action underlying the estrogen-dependent regulation of GnRH1 has been debated, mainly due to the coexpression of low levels of estrogen receptor (ER) genes. In addition, the role of sex steroids in the modulation of GnRH2 and GnRH3 neurons has not been fully elucidated. Using single-cell real-time PCR, we revealed the expression of genes for estrogen, androgen, glucocorticoid, thyroid, and xenobiotic receptors in GnRH1, GnRH2, and GnRH3 neurons in the male Nile tilapia Oreochromis niloticus. We further quantified expression levels of estrogen receptor genes (ERα, ERβ, and ERγ) in three GnRH neuron types in male tilapia of two different social statuses (dominant and subordinate) at the single cell level. In dominant males, GnRH1 mRNA levels were positively proportional to ERγ mRNA levels, while in subordinate males, GnRH2 mRNA levels were positively proportional to ERβ mRNA levels. These results indicate that variations in the expression of nuclear receptors (and possibly steroid sensitivities) among individual GnRH cells may facilitate different physiological processes, such as the promotion of reproductive activities through GnRH1 neurons, and the inhibition of feeding and sexual behaviors through GnRH2 neurons.
Dextran Sodium Sulfate-Induced Impairment of Protein Trafficking and Alterations in Membrane Composition in Intestinal Caco-2 Cell Line
Authors: Toutounji Mohamad , Wanes Dalanda , El-Harakeh Mohammad , El-Sabban Marwan , Rizk Sandra , Naim Hassan Y.
Published: April 2020

A key morphological feature of inflammatory bowel disease (IBD) is the loss of the barrier function of intestinal epithelial cells. The present study investigates endoplasmic reticulum (ER) stress in addition to alterations in protein and membrane trafficking in a dextran sulfate sodium (DSS)-induced IBD-like phenotype of intestinal Caco-2 cells in culture. DSS treatment significantly reduced the transepithelial electric resistance (TEER) and increased the epithelial permeability of Caco-2 cells, without affecting their viability. This was associated with an alteration in the expression levels of inflammatory factors in addition to an increase in the expression of the ER stress protein markers, namely immunoglobulin-binding protein (BiP), C/EBP homologous protein (CHOP), activation transcription factor 4 (ATF4), and X-box binding protein (XBP1). The DSS-induced ER-stress resulted in impaired intracellular trafficking and polarized sorting of sucrase-isomaltase (SI) and dipeptidyl peptidase-4 (DPPIV), which are normally sorted to the apical membrane via association with lipid rafts. The observed impaired sorting was caused by reduced cholesterol levels and subsequent distortion of the lipid rafts. The data presented confirm perturbation of ER homeostasis in DSS-treated Caco-2 cells, accompanied by impairment of membrane and protein trafficking resulting in altered membrane integrity, cellular polarity, and hence disrupted barrier function.
Carbohydrate-Active Enzymes: Structure, Activity, and Reaction Products
Authors: Benini Stefano
Published: April 2020

Carbohydrate-active enzymes are responsible for both the biosynthesis and breakdown of carbohydrates and glycoconjugates [...]
Pro-Apoptotic Function Analysis of the Reaper Homologue IBM1 in Spodoptera frugiperda
Authors: Shu Benshui , Zhang Jingjing , Veeran Sethuraman , Zhong Guohua
Published: April 2020

As an important type of programmed cell death, apoptosis plays a critical role in lepidopteran insects in response to various internal and external stresses. It is controlled by a network of genes such as those encoding the inhibitor of apoptosis proteins. However, there are few studies on apoptosis-related genes in Spodoptera frugiperda. In this study, an orthologue to the Drosophila reaper gene, named Sf-IBM1, was identified from S. frugiperda, and a full-length sequence was obtained by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends PCR (RACE-PCR). The expression pattern of Sf-IBM1 was determined in different developmental stages and various tissues. Apoptotic stimuli including azadirachtin, camptothecin, and ultraviolet radiation (UV) induced the expression of Sf-IBM1 at both transcript and protein levels. Overexpression of Sf-IBM1 induced apoptosis in Sf9 cells, and the Sf-IBM1 protein was localized in mitochondria. The apoptosis induced by Sf-IBM1 could be blocked by the caspase universal inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) and Sf-IAP1. Our results provide valuable information that should contribute to a better understanding of the molecular events that lead to apoptosis in lepidopterans.
Molecular Mechanisms of Brassinosteroid-Mediated Responses to Changing Environments in Arabidopsis
Authors: Lv Minghui , Li Jia
Published: April 2020

Plant adaptations to changing environments rely on integrating external stimuli into internal responses. Brassinosteroids (BRs), a group of growth-promoting phytohormones, have been reported to act as signal molecules mediating these processes. BRs are perceived by cell surface receptor complex including receptor BRI1 and coreceptor BAK1, which subsequently triggers a signaling cascade that leads to inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Recent studies in the model plant Arabidopsis demonstrated that BR biosynthesis and signal transduction, especially the regulatory components BIN2 and BES1/BZR1, are finely tuned by various environmental cues. Here, we summarize these research updates and give a comprehensive review of how BR biosynthesis and signaling are modulated by changing environments and how these changes regulate plant adaptive growth or stress tolerance.
Ensemble Deep Learning Models for Heart Disease Classification: A Case Study from Mexico
Authors: Baccouche Asma , Garcia-Zapirain Begonya , Castillo Olea Cristian , Elmaghraby Adel
Published: April 2020

Heart diseases are highly ranked among the leading causes of mortality in the world. They have various types including vascular, ischemic, and hypertensive heart disease. A large number of medical features are reported for patients in the Electronic Health Records (EHR) that allow physicians to diagnose and monitor heart disease. We collected a dataset from Medica Norte Hospital in Mexico that includes 800 records and 141 indicators such as age, weight, glucose, blood pressure rate, and clinical symptoms. Distribution of the collected records is very unbalanced on the different types of heart disease, where 17% of records have hypertensive heart disease, 16% of records have ischemic heart disease, 7% of records have mixed heart disease, and 8% of records have valvular heart disease. Herein, we propose an ensemble-learning framework of different neural network models, and a method of aggregating random under-sampling. To improve the performance of the classification algorithms, we implement a data preprocessing step with features selection. Experiments were conducted with unidirectional and bidirectional neural network models and results showed that an ensemble classifier with a BiLSTM or BiGRU model with a CNN model had the best classification performance with accuracy and F1-score between 91% and 96% for the different types of heart disease. These results are competitive and promising for heart disease dataset. We showed that ensemble-learning framework based on deep models could overcome the problem of classifying an unbalanced heart disease dataset. Our proposed framework can lead to highly accurate models that are adapted for clinical real data and diagnosis use.
Do Development and Diet Determine the Degree of Cannibalism in Insects? To Eat or Not to Eat Conspecifics
Authors: Fernandez Francisco J. , Gamez Manuel , Garay Jozsef , Cabello Tomas
Published: April 2020

Cannibalism in insects plays an important role in ecological relationships. Nonetheless, it has not been studied as extensively as in other arthropods groups (e.g., Arachnida). From a theoretical point of view, cannibalism has an impact on the development of more realistic stage-structure mathematical models. Additionally, it has a practical application for biological pest control, both in mass-rearing and out in the field through inoculative releases. In this paper, the cannibalistic behavior of two species of predatory bugs was studied under laboratory conditions—one of them a generalist predator (strictly carnivorous), Nabis pseudoferus, and the other a true omnivore (zoophytophagous), Nesidiocoris tenuis—and compared with the intraguild predation (IGP) behavior. The results showed that cannibalism in N. pseudoferus was prevalent in all the developmental stages studied, whereas in N. tenuis, cannibalism was rarely observed, and it was restricted mainly to the first three nymphal stages. Cannibalism and intraguild predation had no linear relationship with the different cannibal–prey size ratios, as evaluated by the mortality rates and survival times, although there were variations in cannibalism between stages, especially for N. pseudoferus. The mathematical model’s implications are presented and discussed.
Concanavalin A Toxicity Towards Potato Psyllid and Apoptosis Induction in Midgut Cells
Authors: Tang Xiao-Tian , Ibanez Freddy , Tamborindeguy Cecilia
Published: April 2020

Concanavalin A (ConA), a legume lectin, has been drawing increasing attention in recent years concerning its toxicity against insects and its potential application in pest management. In an attempt to evaluate the effect of ConA on potato psyllid (Bactericera cockerelli), an economically important pest of solanaceous crops, the effect of ConA on potato psyllid survival, psyllid gut nuclear morphology, and expression of psyllid caspase genes were evaluated. Our results determined that artificial diet-feeding assays using ConA had deleterious effects on potato psyllids, resulting in significant psyllid mortality following ingestion. We also found that an apoptotic response was induced by ConA in psyllid midgut cells, which was demonstrated by the DNA fragmentation and abnormal nuclear architecture in the midgut cells. Following ConA ingestion, there was also upregulation of caspase genes in the psyllid midguts. Therefore, a key mechanism behind ConA toxicity towards potato psyllid probably involves the induction of apoptosis in midgut cells. This study could provide a better understanding of the mechanisms underlying ConA toxicity in insects and be a stepping stone towards the development of new psyllid control strategies based on plant lectins.
Where Have All the Spiders Gone? Observations of a Dramatic Population Density Decline in the Once Very Abundant Garden Spider, Araneus diadematus (Araneae: Araneidae), in the Swiss Midland
Authors: Nyffeler Martin , Bonte Dries
Published: April 2020

Aerial web-spinning spiders (including large orb-weavers), as a group, depend almost entirely on flying insects as a food source. The recent widespread loss of flying insects across large parts of western Europe, in terms of both diversity and biomass, can therefore be anticipated to have a drastic negative impact on the survival and abundance of this type of spider. To test the putative importance of such a hitherto neglected trophic cascade, a survey of population densities of the European garden spider Araneus diadematus—a large orb-weaving species—was conducted in the late summer of 2019 at twenty sites in the Swiss midland. The data from this survey were compared with published population densities for this species from the previous century. The study verified the above-mentioned hypothesis that this spider’s present-day overall mean population density has declined alarmingly to densities much lower than can be expected from normal population fluctuations (0.7% of the historical values). Review of other available records suggested that this pattern is widespread and not restricted to this region. In conclusion, the decline of this once so abundant spider in the Swiss midland is evidently revealing a bottom-up trophic cascade in response to the widespread loss of flying insect prey in recent decades.
Sequential Combination of FIB-4 Followed by M2BPGi Enhanced Diagnostic Performance for Advanced Hepatic Fibrosis in an Average Risk Population
Authors: Kim Mimi , Jun Dae Won , Park Huiyul , Kang Bo-Kyeong , Sumida Yoshio
Published: April 2020

The fibrosis-4 (FIB-4) index is the most widely used estimated formula to screen for advanced hepatic fibrosis; however, it has a considerable intermediate zone. Here, we propose an algorithm to reduce the intermediate zone and improve the diagnostic performance of screening for advanced liver fibrosis by incorporating Mac-2-binding protein glycan isomer (M2BPGi) into a FIB-4 based screening strategy in an average risk group. Four-hundred eighty-eight healthy and chronic liver disease subjects were analyzed using a 1:1 propensity score matched for age and sex. Advanced liver fibrosis (≥F3) was defined by magnetic resonance elastography (MRE, ≥3.6 kPa). Classification tree analysis was employed to improve diagnostic performance using a combination of the FIB-4 index and M2BPGi. The median serum M2BPGi levels of healthy subjects, patients without advanced fibrosis, and those with the condition were 0.48, 0.94, and 2.93, respectively. The area under the receiver operating characteristic (AUROC) curve of M2BPGi (0.918) for advanced fibrosis was the highest compared to those of the FIB-4 index (0.887), APRI (0.873), and AST/ALT ratio (0.794). When M2BPGi was incorporated following the FIB-4 index, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.1%, 82.5%, 54.0%, and 96.4%, respectively. Moreover, 74.3% (133/179) of cases in the intermediate zone of the FIB-4 index avoided unnecessary referrals. Two-step pathway (FIB-4 followed by M2BPGi) could reduce unnecessary referrals and/or liver biopsies in an average-risk population.