bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations for Individual-Level Versus Whole-School Physical Activity Interventions: Stakeholder Perspectives
Authors: Tibbitts Byron , Willis Kathryn , Reid Tom , Sebire Simon J. , Campbell Rona , Kipping Ruth R. , Kandiyali Rebecca , Jago Russell
Published: July 2021

Strategies to address declining physical activity levels among children and adolescents have focused on ‘individual-level’ approaches which often fail to demonstrate impact. Recent attention has been on an alternative ‘whole-school’ approach to increasing physical activity that involves promoting physical activity throughout all aspects of the school environment. There is, however, a lack of evidence on how whole-school physical activity approaches could be implemented in the UK. This qualitative study explored perspectives of key stakeholders on potential reasons for the lack of impact of individual-level school-based interventions on children’s physical activity, and key considerations for adopting a whole-school approach. Nineteen semi-structured interviews were conducted with a range of stakeholders involved in the implementation of physical activity programmes in UK schools. Data were analysed using an inductive approach. Respondents suggested that individual-level school-based interventions to increase physical activity often failed to consult end users in the design and were typically implemented in environments unsupportive of long-term change. They subsequently outlined specific barriers and key facilitators for the adoption and implementation of whole-school approaches in UK settings and recommended a shift in research foci towards building an evidence base around educational outcomes and whole-school implementation insights.
Emotional Competence of Early Childhood Educators and Child Socio-Emotional Wellbeing
Authors: Arace Angelica , Prino Laura Elvira , Scarzello Donatella
Published: July 2021

Background: Early childhood educators are attachment figures for babies and play an important role in emotion socialization. This study aims to analyze the role of educators as emotional socializers and its relationship with infants’ social competence and attachment security, considering various characteristics of educators (age, years of experience, level of knowledge of development and parenting) and the context (day-care center–family communication). Methods: 563 infants attending day-care centers (age: M = 25.98 months SD = 5.41) and their 223 early childhood educators (age: M = 42.61 SD = 11.02) took part in this study. The educators completed: CEESQ—Crèche Educator Emotional Style Questionnaire, Information Sources Questionnaire, two sub-scales of KIDI—Knowledge of Infant Development Inventory, QRS-F—Questionnaire on the Relationship between Services and Families, QPI—Questionnaire on Peer Interactions, and AQS—Attachment-Q-Sort. Results: Results showed that the educator’s coaching style has a relationship with attachment security and social skills and is positively correlated with the educators’ emotional self-efficacy and with the level of communication between day-care centers and families, while the correlation with knowledge of parenting is weak. Conclusions: These findings highlight the importance of enhancing not only educators’ knowledge about educative strategies, but above all their emotional competence to promote children adaptation to day-care centers.
Development of Machine Learning Models for Prediction of Osteoporosis from Clinical Health Examination Data
Authors: Ou Yang Wen-Yu , Lai Cheng-Chien , Tsou Meng-Ting , Hwang Lee-Ching
Published: July 2021

Osteoporosis is treatable but often overlooked in clinical practice. We aimed to construct prediction models with machine learning algorithms to serve as screening tools for osteoporosis in adults over fifty years old. Additionally, we also compared the performance of newly developed models with traditional prediction models. Data were acquired from community-dwelling participants enrolled in health checkup programs at a medical center in Taiwan. A total of 3053 men and 2929 women were included. Models were constructed for men and women separately with artificial neural network (ANN), support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), and logistic regression (LoR) to predict the presence of osteoporosis. Area under receiver operating characteristic curve (AUROC) was used to compare the performance of the models. We achieved AUROC of 0.837, 0.840, 0.843, 0.821, 0.827 in men, and 0.781, 0.807, 0.811, 0.767, 0.772 in women, for ANN, SVM, RF, KNN, and LoR models, respectively. The ANN, SVM, RF, and LoR models in men, and the ANN, SVM, and RF models in women performed significantly better than the traditional Osteoporosis Self-Assessment Tool for Asians (OSTA) model. We have demonstrated that machine learning algorithms improve the performance of screening for osteoporosis. By incorporating the models in clinical practice, patients could potentially benefit from earlier diagnosis and treatment of osteoporosis.
“My Life during the Lockdown”: Emotional Experiences of European Adolescents during the COVID-19 Crisis
Authors: Forte Alberto , Orri Massimiliano , Brandizzi Martina , Iannaco Cecilia , Venturini Paola , Liberato Daniela , Battaglia Claudia , Nöthen-Garunja Isabel , Vulcan Maria , Brusìc Asja , Quadrana Lauro , Cox Olivia , Fabbri Sara , Monducci Elena
Published: July 2021

This study investigates, using an online self-report questionnaire, adolescents’ emotional reactions during the lockdown in a sample of 2105 secondary school students (aged 14–19) in Italy, Romania, and Croatia. We used a self-reported online questionnaire (answers on a 5-point scale or binary), composed of 73 questions investigating the opinions, feelings, and emotions of teenagers, along with sociodemographic information and measures of the exposure to lockdown. The survey was conducted online through a web platform in Italy (between 27 April and 15 June 2020), Romania, and Croatia (3 June and 2 July 2020). Students aged >14 years, living in a small flat, and not spending time outside were more likely to report anger, sadness, boredom/emptiness, and anxiety. Boys were significantly less likely than girls to report all measured emotional reactions. Those who lost someone from COVID-19 were more than twice as likely to experience anger compared to those who did not. Our findings may help identifying adolescents more likely to report negative emotional reactions during the COVID-19 pandemic and inform public health strategies for improving mental health among adolescents during/after the COVID-19 crisis.
Sedentary Lifestyle Matters as Past Sedentariness, Not Current Sedentariness, Predicts Cognitive Inhibition Performance among College Students: An Exploratory Study
Authors: Magnon Valentin , Vallet Guillaume T. , Dutheil Frédéric , Auxiette Catherine
Published: July 2021

Background: Currently, sedentariness is assessed over a short period of time, thus it is difficult to study its cognitive implications. To investigate the cognitive consequences of a sedentary lifestyle, the past level (i.e., the sedentary time accumulated over the years) and current level of sedentariness should be considered. This pilot study aimed to investigate the negative association between a sedentary lifestyle and cognition by considering both the current and past sedentariness. It was expected that the physical activity level moderates the potential negative association between sedentariness and cognition. Methods: 52 college students (Mage = 20.19, SDage = 2; 36 women) participated in the study. Current sedentariness (ratio of sedentary time in the last year), past sedentariness (ratio of sedentary time accumulated in previous years), and physical activity (ratio of time spent in physical activity in years) were assessed using a questionnaire. Cognitive inhibition, cognitive flexibility, and working memory updating were measured through three specific tests. Results: Past sedentariness significantly explained the inhibition performance when controlled for physical activity, whereas current sedentariness did not. More precisely, past sedentariness only negatively predicted cognitive inhibition when the physical activity level was low (β = −3.15, z(48) = −2.62, p = 0.01). Conclusions: The impact of sedentariness on cognitive functioning might only be revealed when past sedentariness and physical activity are controlled.
LSTM Networks to Improve the Prediction of Harmful Algal Blooms in the West Coast of Sabah
Authors: Yussof Fatin Nadiah , Maan Normah , Md Reba Mohd Nadzri
Published: July 2021

Harmful algal bloom (HAB) events have alarmed authorities of human health that have caused severe illness and fatalities, death of marine organisms, and massive fish killings. This work aimed to perform the long short-term memory (LSTM) method and convolution neural network (CNN) method to predict the HAB events in the West Coast of Sabah. The results showed that this method could be used to predict satellite time series data in which previous studies only used vector data. This paper also could identify and predict whether there is HAB occurrence in the region. A chlorophyll a concentration (Chl-a; mg/L) variable was used as an HAB indicator, where the data were obtained from MODIS and GEBCO bathymetry. The eight-day dataset interval was from January 2003 to December 2018. The results obtained showed that the LSTM model outperformed the CNN model in terms of accuracy using RMSE and the correlation coefficient r as the statistical criteria.
Revenge in Couple Relationships and Their Relation to the Dark Triad
Authors: Clemente Miguel , Espinosa Pablo
Published: July 2021

Background: This research examines how, when a romantic partner commits a perceived transgression that leads to couple break up, vengeful reactions are predicted by the type of transgression and the Dark Triad of personality. Methods: An incidental sample of 2142 participants, half male and half female aged 18 to 70, completed a questionnaire developed by the authors to assess how they had reacted after being the perceived victims of a transgression committed by their partner and a measure of the Dark Triad. Results: Results show half of the people who feel as though they are victims of a partner transgression show revenge reactions. These reactions are more emotional than rational and do not usually anticipate their consequences or success. Moreover, revenge is related primarily to psychopathy and to a lesser extent to Machiavellianism. Psychopathy is the best predictor for revenge thoughts and actions, whereas narcissism does not predict revenge when controlling for other dark traits. Conclusions: This study contributes to the explanation of revenge reactions in couple relationships in relation to the type of transgression perceived and the Dark Triad. Conflicts that arise out of revenge may have long-lasting consequences for both the perceived aggressor and victim, and our results may be useful for assessing risks, monitoring, and preventing negative consequences for partners or ex-partners.
Recurrent Home Flooding in Detroit, MI 2012–2020: Results of a Household Survey
Authors: Larson Peter S. , Gronlund Carina , Thompson Lyke , Sampson Natalie , Washington Ramona , Steis Thorsby Jamie Steis , Lyon Natalie , Miller Carol
Published: July 2021

Household flooding has wide ranging social, economic and public health impacts particularly for people in resource poor communities. The determinants and public health outcomes of recurrent home flooding in urban contexts, however, are not well understood. A household survey was used to assess neighborhood and household level determinants of recurrent home flooding in Detroit, MI. Survey activities were conducted from 2012 to 2020. Researchers collected information on past flooding, housing conditions and public health outcomes. Using the locations of homes, a “hot spot” analysis of flooding was performed to find areas of high and low risk. Survey data were linked to environmental and neighborhood data and associations were tested using regression methods. 4803 households participated in the survey. Flooding information was available for 3842 homes. Among these, 2085 (54.26%) reported experiencing pluvial flooding. Rental occupied units were more likely to report flooding than owner occupied homes (Odd ratio (OR) 1.72 [95% Confidence interval (CI) 1.49, 1.98]). Housing conditions such as poor roof quality and cracks in basement walls influenced home flooding risk. Homes located in census tracts with increased percentages of owner occupied units (vs. rentals) had a lower odds of flooding (OR 0.92 [95% (CI) 0.86, 0.98]). Household factors were found the be more predictive of flooding than neighborhood factors in both univariate and multivariate analyses. Flooding and housing conditions associated with home flooding were associated with asthma cases. Recurrent home flooding is far more prevalent than previously thought. Programs that support recovery and which focus on home improvement to prevent flooding, particularly by landlords, might benefit the public health. These results draw awareness and urgency to problems of urban flooding and public health in other areas of the country confronting the compounding challenges of aging infrastructure, disinvestment and climate change.
Characteristics and Injury Patterns of Road Traffic Injuries in Urban and Rural Uganda—A Retrospective Medical Record Review Study in Two Hospitals
Authors: Temizel Selin , Wunderlich Robert , Leifels Mats
Published: July 2021

In the ongoing Second Decade of Action for Road Safety, road traffic crashes pose a considerable threat especially in low-income countries. Uganda shows a vast burden of non-fatal injuries and resides at the top range of countries with the highest death rates due to unsafe roads. However, little is known about the differences in road traffic associated injuries between urban and rural areas and potential influence factors. Here, we used a cross-sectional study conducted by a retrospective medical record review from trauma cases admitted in 2016 to hospitals in rural and urban areas in Uganda. Injury severity scores were calculated and descriptive analysis was carried out while multivariate logistic regression was applied to assess significant covariates. According to the 1683 medical records reviewed, the mean age of trauma patients in the dataset under investigation was 30.8 years with 74% male. The trauma in-hospital mortality was 4% while prevalence of traumatic injuries is 56.4%. Motorcycle users (49.6%) and pedestrians (33.7%) were identified as the most vulnerable groups in both urban and rural setting while mild injuries of extremities (61.6%) and the head/neck-region (42.0%) were registered most. The frequency of road traffic injuries was homogenous in the urban and rural hospitals investigated in this study; interventions should therefore be intensified ubiquitously. The identification of significant differences in road traffic crash and injury characteristics provides the opportunity for specific programmes to decrease the socio-economic and health burden of unsafe roads. In addition to law enforcement and introduction of a Systems Thinking approach to road safety including infrastructural and educational concepts, the strengthening of trauma care and health resources is recommended.
Qualitative Study on the Observations of Emissions, Transport, and the Influence of Climatic Factors from Sugarcane Burning: A South African Perspective
Authors: Shikwambana Lerato , Ncipha Xolile , Sangeetha Sivakumar Kandasami , Sivakumar Venkataraman , Mhangara Paidamwoyo
Published: July 2021

There are two methods of harvesting sugarcane—manual or mechanical. Manual harvesting requires the burning of the standing sugarcane crop. Burning of the crop results in the emission of aerosols and harmful trace gases into the atmosphere. This work makes use of a long-term dataset (1980–2019) to study (1) the atmospheric spatial and vertical distribution of pollutants; (2) the spatial distribution and temporal change of biomass emissions; and (3) the impact/influence of climatic factors on temporal change in atmospheric pollutant loading and biomass emissions over the Mpumalanga and KwaZulu Natal provinces in South Africa, where sugarcane farming is rife. Black carbon (BC) and sulfur dioxide (SO2) are two dominant pollutants in the JJA and SON seasons due to sugarcane burning. Overall, there was an increasing trend in the emissions of BC, SO2, and carbon dioxide (CO2) from 1980 to 2019. Climatic conditions, such as warm temperature, high wind speed, dry conditions in the JJA, and SON season, favor the intensity and spread of the fire, which is controlled. The emitted pollutants are transported to neighboring countries and can travel over the Atlantic Ocean, as far as ~6600 km from the source site.
The Bidirectional Relationship between Body Weight and Depression across Gender: A Simultaneous Equation Approach
Authors: Zhang Jun
Published: July 2021

Purpose: This study investigates the bidirectional relationship between body weight and depression for both males and females in the U.S. Methods: Data are drawn from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), and a simultaneous ordered probability system is estimated with maximum likelihood estimation (MLE) to accommodate the two-way causality between depression and body weight categories. The variable of depression is measured by individuals’ past depressive records and current mental health status. Results: Depression and body weight are found to affect each other positively for both males and females on average. In a randomized population, the results of average treatment effects suggest significant body weight differences between depressed and non-depressed individuals. Age and other sociodemographic factors affect body weight differently between genders and between the people with depression and those without. Conclusion: The positive bidirectional relationship between body weight and depression is found. The effect of depression on body weight is significant among both males and females in a randomized population, and females who experience depression are most likely to be obese and less likely to have normal weight compared to females without depression. The risks of overweight and obesity are high among people who are less educated or unable, who have poor health statuses, and who had high blood pressure.
Absence of Association between Previous Mycoplasma pneumoniae Infection and Subsequent Myasthenia Gravis: A Nationwide Population-Based Matched Cohort Study
Authors: Chen Kuan , Wei James Cheng-Chung , Yip Hei-Tung , Chou Mei-Chia , Chang Renin
Published: July 2021

Mycoplasma pneumoniae (M. pneumoniae) is not only one of the most common pathogenic bacteria for respiratory infection but also a trigger for many autoimmune diseases. Its infection process shared many similarities with the pathogenesis of myasthenia gravis (MG) at cellular and cytokine levels. Recent case reports demonstrated patients present with MG after M. pneumoniae infection. However, no epidemiological studies ever looked into the association between the two. Our study aimed to investigate the relationship between M. pneumoniae infection and subsequent development of MG. In this population-based retrospective cohort study, the risk of MG was analyzed in patients who were newly diagnosed with M. pneumoniae infection between 2000 and 2013. A total of 2428 M. pneumoniae patients were included and matched with the non-M. pneumoniae control cohort at a 1:4 ratio by age, sex, and index date. Cox proportional hazards regression analysis was applied to analyze the risk of MG development after adjusting for sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The incidence rates of MG in the non-M. pneumoniae and M. pneumoniae cohorts were 0.96 and 1.97 per 10,000 person-years, respectively. Another case–control study of patients with MG (n = 515) was conducted to analyze the impact of M. pneumoniae on MG occurrence as a sensitivity analysis. The analysis yielded consistent absence of a link between M. pneumoniae and MG. Although previous studies have reported that M. pneumoniae infection and MG may share associated immunologic pathways, we found no statistical significance between M. pneumoniae infection and subsequent development of MG in this study.
A GeoSPARQL Compliance Benchmark
Authors: Jovanovik Milos , Homburg Timo , Spasić Mirko
Published: July 2021

GeoSPARQL is an important standard for the geospatial linked data community, given that it defines a vocabulary for representing geospatial data in RDF, defines an extension to SPARQL for processing geospatial data, and provides support for both qualitative and quantitative spatial reasoning. However, what the community is missing is a comprehensive and objective way to measure the extent of GeoSPARQL support in GeoSPARQL-enabled RDF triplestores. To fill this gap, we developed the GeoSPARQL compliance benchmark. We propose a series of tests that check for the compliance of RDF triplestores with the GeoSPARQL standard, in order to test how many of the requirements outlined in the standard a tested system supports. This topic is of concern because the support of GeoSPARQL varies greatly between different triplestore implementations, and the extent of support is of great importance for different users. In order to showcase the benchmark and its applicability, we present a comparison of the benchmark results of several triplestores, providing an insight into their current GeoSPARQL support and the overall GeoSPARQL support in the geospatial linked data domain.
Semantic Relation Model and Dataset for Remote Sensing Scene Understanding
Authors: Li Peng , Zhang Dezheng , Wulamu Aziguli , Liu Xin , Chen Peng
Published: July 2021

A deep understanding of our visual world is more than an isolated perception on a series of objects, and the relationships between them also contain rich semantic information. Especially for those satellite remote sensing images, the span is so large that the various objects are always of different sizes and complex spatial compositions. Therefore, the recognition of semantic relations is conducive to strengthen the understanding of remote sensing scenes. In this paper, we propose a novel multi-scale semantic fusion network (MSFN). In this framework, dilated convolution is introduced into a graph convolutional network (GCN) based on an attentional mechanism to fuse and refine multi-scale semantic context, which is crucial to strengthen the cognitive ability of our model Besides, based on the mapping between visual features and semantic embeddings, we design a sparse relationship extraction module to remove meaningless connections among entities and improve the efficiency of scene graph generation. Meanwhile, to further promote the research of scene understanding in remote sensing field, this paper also proposes a remote sensing scene graph dataset (RSSGD). We carry out extensive experiments and the results show that our model significantly outperforms previous methods on scene graph generation. In addition, RSSGD effectively bridges the huge semantic gap between low-level perception and high-level cognition of remote sensing images.
Molecular Mechanisms of Lipid Metabolism Disorders in Infectious Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Kotlyarov Stanislav , Kotlyarova Anna
Published: July 2021

Exacerbations largely determine the character of the progression and prognosis of chronic obstructive pulmonary disease (COPD). Exacerbations are connected with changes in the microbiological landscape in the bronchi due to a violation of their immune homeostasis. Many metabolic and immune processes involved in COPD progression are associated with bacterial colonization of the bronchi. The objective of this review is the analysis of the molecular mechanisms of lipid metabolism and immune response disorders in the lungs in COPD exacerbations. The complex role of lipid metabolism disorders in the pathogenesis of some infections is only beginning to be understood, however, there are already fewer and fewer doubts even now about its significance both in the pathogenesis of infectious exacerbations of COPD and in general in the progression of the disease. It is shown that the lipid rafts of the plasma membranes of cells are involved in many processes related to the detection of pathogens, signal transduction, the penetration of pathogens into the cell. Smoking disrupts the normally proceeded processes of lipid metabolism in the lungs, which is a part of the COPD pathogenesis.
Gene Therapy in Hemophilia: Recent Advances
Authors: Rodríguez-Merchán E. Carlos , De Pablo-Moreno Juan Andres , Liras Antonio
Published: July 2021

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.
Editorial to Radiation in Multimodal Tumor Immune Therapies—Mechanisms and Application
Authors: Frey Benjamin , Gaipl Udo S.
Published: July 2021

The understanding and the application of radiation-induced immune modulation has become more and more relevant in the therapy of malignant, but also benign diseases [...]
Breast Cancer and Anaesthesia: Genetic Influence
Authors: Raigon Ponferrada Aida , Guerrero Orriach Jose Luis , Molina Ruiz Juan Carlos , Romero Molina Salvador , Gómez Luque Aurelio , Cruz Mañas Jose
Published: July 2021

Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical and morphological heterogeneity of the different types of breast tumors has led to a diversity of staging and classification systems. Thus, these tumors show wide variability in genetic expression and prognostic biomarkers. Surgical treatment is essential in the management of these patients. However, the perioperative period has been found to significantly influence survival and cancer recurrence. There is growing interest in the pro-tumoral effect of different anaesthetic and analgesic agents used intraoperatively and their relationship with metastatic progression. There is cumulative evidence of the influence of anaesthetic techniques on the physiopathological mechanisms of survival and growth of the residual neoplastic cells released during surgery. Prospective randomized clinical trials are needed to obtain quality evidence on the relationship between cancer and anaesthesia. This document summarizes the evidence currently available about the effects of the anaesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction.
Microbial Toxins in Insect and Nematode Pest Biocontrol
Authors: Chalivendra Subbaiah
Published: July 2021

Invertebrate pests, such as insects and nematodes, not only cause or transmit human and livestock diseases but also impose serious crop losses by direct injury as well as vectoring pathogenic microbes. The damage is global but greater in developing countries, where human health and food security are more at risk. Although synthetic pesticides have been in use, biological control measures offer advantages via their biodegradability, environmental safety and precise targeting. This is amply demonstrated by the successful and widespread use of Bacillusthuringiensis to control mosquitos and many plant pests, the latter by the transgenic expression of insecticidal proteins from B. thuringiensis in crop plants. Here, I discuss the prospects of using bacterial and fungal toxins for pest control, including the molecular basis of their biocidal activity.
X Chromosome Inactivation in Carriers of Fabry Disease: Review and Meta-Analysis
Authors: Viggiano Emanuela , Politano Luisa
Published: July 2021

Anderson-Fabry disease is an X-linked inborn error of glycosphingolipid catabolism caused by a deficiency of α-galactosidase A. The incidence ranges between 1: 40,000 and 1:117,000 of live male births. In Italy, an estimate of incidence is available only for the north-western Italy, where it is of approximately 1:4000. Clinical symptoms include angiokeratomas, corneal dystrophy, and neurological, cardiac and kidney involvement. The prevalence of symptomatic female carriers is about 70%, and in some cases, they can exhibit a severe phenotype. Previous studies suggest a correlation between skewed X chromosome inactivation and symptoms in carriers of X-linked disease, including Fabry disease. In this review, we briefly summarize the disease, focusing on the clinical symptoms of carriers and analysis of the studies so far published in regards to X chromosome inactivation pattern, and manifesting Fabry carriers. Out of 151 records identified, only five reported the correlation between the analysis of XCI in leukocytes and the related phenotype in Fabry carriers, in particular evaluating the Mainz Severity Score Index or cardiac involvement. The meta-analysis did not show any correlation between MSSI or cardiac involvement and skewed XCI, likely because the analysis of XCI in leukocytes is not useful for predicting the phenotype in Fabry carriers.
Effects of Brain Size on Adult Neurogenesis in Shrews
Authors: Bartkowska Katarzyna , Turlejski Krzysztof , Tepper Beata , Rychlik Leszek , Vogel Peter , Djavadian Ruzanna
Published: July 2021

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.
Response of Wheat DREB Transcription Factor to Osmotic Stress Based on DNA Methylation
Authors: Wang Huihui , Zhu Yanqiu , Yuan Ping , Song Shanglin , Dong Tianyu , Chen Peilei , Duan Zhikun , Jiang Lina , Lu Longdou , Duan Hongying
Published: July 2021

Dehydration-responsive element-binding protein (DREB) plays an important role in response to osmotic stress. In this study, DREB2, DREB6 and Wdreb2 are isolated from wheat AK58, yet they belong to different types of DREB transcription factors. Under osmotic stress, the transcript expression of DREB2, DREB6 and Wdreb2 has tissue specificity and is generally higher in leaves, but their expression trends are different along with the increase of osmotic stress. Furthermore, some elements related to stresses are found in their promoters, promoters of DREB2 and Wdreb2 are slightly methylated, but DREB6’s promoter is moderately methylated. Compared with the control, the level of promoter methylation in Wdreb2 is significantly lower under osmotic stress and is also lower at CG site in DREB2, yet is significantly higher at CHG and CHH sites in DREB2, which is also found at a CHG site in DREB6. The status of promoter methylation in DREB2, DREB6 and Wdreb2 also undergoes significant changes under osmotic stress; further analysis showed that promoter methylation of Wdreb2 is negatively correlated with their expression. Therefore, the results of this research suggest the different functions of DREB2, DREB6 and Wdreb2 in response to osmotic stress and demonstrate the effects of promoter methylation on the expression regulation of Wdreb2.
Every Beat You Take—The Wilms′ Tumor Suppressor WT1 and the Heart
Authors: Wagner Nicole , Wagner Kay-Dietrich
Published: July 2021

Nearly three decades ago, the Wilms’ tumor suppressor Wt1 was identified as a crucial regulator of heart development. Wt1 is a zinc finger transcription factor with multiple biological functions, implicated in the development of several organ systems, among them cardiovascular structures. This review summarizes the results from many research groups which allowed to establish a relevant function for Wt1 in cardiac development and disease. During development, Wt1 is involved in fundamental processes as the formation of the epicardium, epicardial epithelial-mesenchymal transition, coronary vessel development, valve formation, organization of the cardiac autonomous nervous system, and formation of the cardiac ventricles. Wt1 is further implicated in cardiac disease and repair in adult life. We summarize here the current knowledge about expression and function of Wt1 in heart development and disease and point out controversies to further stimulate additional research in the areas of cardiac development and pathophysiology. As re-activation of developmental programs is considered as paradigm for regeneration in response to injury, understanding of these processes and the molecules involved therein is essential for the development of therapeutic strategies, which we discuss on the example of WT1.
Metformin Affects Cardiac Arachidonic Acid Metabolism and Cardiac Lipid Metabolite Storage in a Prediabetic Rat Model
Authors: Miklankova Denisa , Markova Irena , Hüttl Martina , Zapletalova Iveta , Poruba Martin , Malinska Hana
Published: July 2021

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids—triglycerides, cholesteryl esters and the lipotoxic intermediates—diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.
Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis
Authors: Al-Roub Areej , Akhter Nadeem , Al-Sayyar Amnah , Wilson Ajit , Thomas Reeby , Kochumon Shihab , Al-Rashed Fatema , Al-Mulla Fahd , Sindhu Sardar , Ahmad Rasheed
Published: July 2021

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.
Sympatholytic Mechanisms for the Beneficial Cardiovascular Effects of SGLT2 Inhibitors: A Research Hypothesis for Dapagliflozin’s Effects in the Adrenal Gland
Authors: Lymperopoulos Anastasios , Borges Jordana I. , Cora Natalie , Sizova Anastasiya
Published: July 2021

Heart failure (HF) remains the leading cause of morbidity and death in the western world, and new therapeutic modalities are urgently needed to improve the lifespan and quality of life of HF patients. The sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed and mainly indicated for diabetes mellitus treatment, have been increasingly shown to ameliorate heart disease, and specifically HF, in humans, regardless of diabetes co-existence. Indeed, dapagliflozin has been reported to reduce cardiovascular mortality and hospitalizations in patients with HF and reduced ejection fraction (HFrEF). This SGLT2 inhibitor demonstrates these benefits also in non-diabetic subjects, indicating that dapagliflozin’s efficacy in HF is independent of blood glucose control. Evidence for the effectiveness of various SGLT2 inhibitors in providing cardiovascular benefits irrespective of their effects on blood glucose regulation have spurred the use of these agents in HFrEF treatment and resulted in FDA approvals for cardiovascular indications. The obvious question arising from all these studies is, of course, which molecular/pharmacological mechanisms underlie these cardiovascular benefits of the drugs in diabetics and non-diabetics alike. The fact that SGLT2 is not significantly expressed in cardiac myocytes (SGLT1 appears to be the dominant isoform) adds even greater perplexity to this answer. A variety of mechanisms have been proposed over the past few years and tested in cell and animal models and prominent among those is the potential for sympatholysis, i.e., reduction in sympathetic nervous system activity. The latter is known to be high in HF patients, contributing significantly to the morbidity and mortality of the disease. The present minireview first summarizes the current evidence in the literature supporting the notion that SGLT2 inhibitors, such as dapagliflozin and empagliflozin, exert sympatholysis, and also outlines the main putative underlying mechanisms for these sympatholytic effects. Then, we propose a novel hypothesis, centered on the adrenal medulla, for the sympatholytic effects specifically of dapagliflozin. Adrenal medulla is responsible for the production and secretion of almost the entire amount of circulating epinephrine and of a significant percentage of circulating norepinephrine in the human body. If proven true experimentally, this hypothesis, along with other emerging experimental evidence for sympatholytic effects in neurons, will shed new light on the pharmacological effects that mediate the cardiovascular benefits of SGLT2 inhibitor drugs, independently of their blood glucose-lowering effects.
Antibacterial Poly(ε-CL)/Hydroxyapatite Electrospun Fibers Reinforced by Poly(ε-CL)-b-poly(ethylene phosphoric acid)
Authors: Nifant’ev Ilya , Gavrilov Dmitry , Tavtorkin Alexander , Chinova Maria , Besprozvannykh Victoria , Komarov Pavel , Zaitsev Vladimir , Podoprigora Irina , Ivchenko Pavel
Published: July 2021

In bone surgery and orthopedics, bioresorbable materials can be helpful in bone repair and countering post-op infections. Explicit antibacterial activity, osteoinductive and osteoconductive effects are essential to achieving this objective. Nonwoven electrospun (ES) fibers are receiving the close attention of physicians as promising materials for wound dressing and tissue engineering; potentially, in high contrast with dense materials, ES mats hamper regeneration of the bone extracellular matrix to a lesser extent. The use of the compositions of inherently biodegradable polyesters (poly(ε-caprolactone) PCL, poly(lactoglycolide), etc.), calcium phosphates and antibiotics is highly prospective, but the task of forming ES fibers from such compositions is complicated by the incompatibility of the main organic and inorganic ingredients, polyesters and calcium phosphates. In the present research we report the synthesis of hydroxyapatite (HAp) nanoparticles with uniform morphology, and demonstrate high efficiency of the block copolymer of PCL and poly(ethylene phosphoric acid) (PEPA) as an efficient compatibilizer for PCL/HAp mixtures that are able to form ES fibers with improved mechanical characteristics. The materials obtained in the presence of vancomycin exhibited incremental drug release against Staphylococcus aureus (St. aureus).
Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions
Authors: Guglielmi Chiara , Scarpitta Rosa , Gambino Gaetana , Conti Eleonora , Bellè Francesca , Tancredi Mariella , Cervelli Tiziana , Falaschi Elisabetta , Cosini Cinzia , Aretini Paolo , Congregati Caterina , Marino Marco , Patruno Margherita , Pilato Brunella , Spina Francesca , Balestrino Luisa , Tenedini Elena , Carnevali Ileana , Cortesi Laura , Tagliafico Enrico , Tibiletti Maria Grazia , Tommasi Stefania , Ghilli Matteo , Vivanet Caterina , Galli Alvaro , Caligo Maria Adelaide
Published: July 2021

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.