bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels of Physical Activity and Mental Health in Adolescents in Ireland
Authors: Molcho Michal , Gavin Aoife , Goodwin Devon
Published: February 2021

The benefits of physical activity for the physical health of individuals are well documented. Less is known about the benefits of physical activity for mental health. This paper explores the associations between physical activity and positive mental health and mental health problems. The paper utilises data collected from a representative sample of 10–17-year-old adolescents in Ireland. Physical activity in the study is measured using moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA). Mental health was measured using the Cantril Leader of Life Satisfaction, the WHO-5 index, Mental Health Inventory (MHI-5) and the Health Behaviour in School-Aged Children (HBSC) Symptom Checklist (HBSC-SCL). Data were analysed using bivariate (Pearson Correlation, t-test, one-way ANOVA) and multivariate (two-way ANOVA, ordinary least squares (OLS) regressions) analyses. In total, 8636 adolescents were included in this analysis. Higher participation in physical activity was associated with higher scores on the positive mental health indicators and lower scores on the mental health problems indicators. When modelled together, VPA was a stronger predictor of mental health than MVPA, especially in girls. For example, standardised beta coefficients for predicting MHI-5 were −0.09 for MVPA (p < 0.001) and −0.13 for VPA (p < 0.001) To our knowledge, this is the first study that looks at levels of physical activity as well as both positive mental health and mental health problems. The study highlights the need to encourage and enable adolescents, and especially girls, to participate in vigorous exercising as way of promoting positive mental health.
A Preliminary Research Study for Distribution Characteristics and Sources of Indoor Air Pollutants in the Valuable Archive of the National Library of Korea
Authors: Lee Hye-Won , Jeon Jeong-In , Lim Hui-Been , Lee Kwi-Bok , Park So-Yeon , Lee Cheol-Min
Published: February 2021

Important records can be damaged directly and indirectly. Their restoration, if possible, is difficult as it is very time-consuming and costly. Although measures have been taken to permanently preserve records, most studies focus on preventing short-term damage from physical or biological factors and not on preventive measures against chemical damage from long-term polluted air exposure. This study investigated the types, concentrations, and distribution characteristics of hazardous chemicals present in the valuable archive of the National Library of Korea (NLK) and identified the sources of these pollutants. Mean SO2, NOX, CO, CO2, and total volatile organic compound (TVOC) concentrations were 1.49 ± 0.44 ppb, 30.52 ± 19.70 ppb, 0.75 ± 0.21 ppm, 368.91 ± 32.23 ppm, and 320.03 ± 44.20 µg/m3, respectively, meeting the Ministry of the Interior and Safety (MOIS) of Korea standards. Toluene (66.43 ± 10.69 µg/m3) and acetaldehyde (157.23 ± 6.43 µg/m3) were present at the highest concentrations, respectively. Two principal components were extracted via a principal component analysis; the primary component (66%) was closely related to outdoor pollution sources and the secondary component (33%) to indoor sources. Results contribute to establishing air quality standards and management measures for preservation of this archive.
Prevalence and Risk Factors of Metabolic Syndrome among the Homeless in Taipei City: A Cross-Sectional Study
Authors: Gu Ming , Lu Chi-Jie , Lee Tian-Shyug , Chen Mingchih , Liu Chih-Kuang , Chen Ching-Lin
Published: February 2021

The safety and health of homeless people are important social issues. Metabolic syndrome (MetS) is a sub-health-risk phenomenon that has been severely aggravated worldwide in recent years. The purpose of this study was to investigate the prevalence and risk factors of MetS among the homeless in Taipei City, Taiwan. In this study, a convenience sampling was conducted at homeless counseling agencies in Taipei City from April 2018 to September 2018. A total of 297 homeless participants were recruited, from whom clinical indicators and questionnaire information were collected. Through statistical verification, analysis of variance (ANOVA), and logistic regression, we found the following main conclusions for homeless adults in Taipei: (1) The prevalence of MetS was estimated to be 53%, with 50% meeting four or more diagnostic conditions. (2) Dyslipidemia (high-density lipoprotein (HDL) deficiency and elevated triglyceride (TG)) showed the strongest association with the prevalence of MetS; more than 83% of people with HDL deficiency or hypertriglyceridemia had MetS. For the patient groups meeting more MetS diagnostic conditions, the values of high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) increased significantly. (3) The deterioration of MetS was significantly related to the high prevalence of hyperlipidemia (HL). (4) The homeless who were divorced, separated or widowed were more likely to suffer from MetS.
Challenges in the Prevention of Cervical Cancer in Romania
Authors: Todor Raluca Dania , Bratucu Gabriel , Moga Marius Alexandru , Candrea Adina Nicoleta , Marceanu Luigi Geo , Anastasiu Costin Vlad
Published: February 2021

Approximately every two hours, a Romanian woman is diagnosed with cervical cancer as the country ranks first in the EU in terms of its mortality rate. This paper aims to identify the main reasons that have led to this situation. First, a study based on secondary data was conducted in order to identify measures taken by the Romanian Ministry of Health for the prevention of this type of cancer. Second, a quantitative study was conducted to evaluate the impact that exposure to information and awareness campaigns has on women’s behavior regarding cervical cancer prevention through screening. The results of the research show an increased percentage of the women understanding the importance of screening and the benefits of early diagnosis, but also shows that a high percentage of women postpone the routine checks due to lack of time and financial resources. The research results also indicate that the only free screening program implemented in Romania during 2012–2017 was a failure due to poor procedures, low number of women tested, underfunding and the lack of promotion. Our conclusion is that the Romanian Ministry of Health has to take immediate action by conducting major awareness campaigns and also by implementing functional screening programs.
Relationship between Mortality and Oral Function of Older People Requiring Long-Term Care in Rural Areas of Japan: A Four-Year Prospective Cohort Study
Authors: Morishita Shiho , Ohara Yuki , Iwasaki Masanori , Edahiro Ayako , Motokawa Keiko , Shirobe Maki , Furuya Junichi , Watanabe Yutaka , Suga Takeo , Kanehisa Yayoi , Ohuchi Akitugu , Hirano Hirohiko
Published: February 2021

Oral ingestion influences the life sustenance, quality of life, and dignity of older adults. Thus, it is an important issue in medical care and the welfare of older adults. The purpose of this four-year prospective cohort study was to investigate the relationship between mortality and oral function among older adults who required long-term care and were living in different settings in a rural area of Japan. This study included 289 participants aged 65 and older who required long-term care and lived in the former Omorimachi area in Yokote City, Akita Prefecture, located in northern Japan. Following the baseline survey, mortality data were collected over four years; 102 participants (35.3%) died during that time. A significant difference was noted in the overall survival rates between the groups with good and deterioration of oral function such as oral dryness, rinsing ability, swallowing function, and articulation, based on Log-rank test results. After adjusting for various potential confounders using Cox proportional-hazards regression, oral dryness (HR: 1.83, 95% confidence interval: 1.12−3.00) was significantly associated with mortality within four years. This study revealed that oral dryness influences the life prognosis of older adults who receive long-term care in different settings.
Defining Attachment and Bonding: Overlaps, Differences and Implications for Music Therapy Clinical Practice and Research in the Neonatal Intensive Care Unit (NICU)
Authors: Ettenberger Mark , Bieleninik Łucja , Epstein Shulamit , Elefant Cochavit
Published: February 2021

Preterm birth and the subsequent hospitalization in the Neonatal Intensive Care Unit (NICU) is a challenging life event for parents and babies. Stress, anxiety, and depressive symptoms, limitations in holding or touching the baby, and medical complications during the NICU stay can negatively affect parental mental health. This can threaten the developing parent-infant relationship and might adversely impact child development. Music therapy in the NICU is an internationally growing field of clinical practice and research and is increasingly applied to promote relationship building between parents and babies. The two most commonly used concepts describing the early parent-infant relationship are ‘attachment’ and ‘bonding’. While frequently used interchangeably in the literature, they are actually not the same and describe distinctive processes of the early relationship formation. Thus, it is important to discuss the overlaps and differences between attachment and bonding and the implications for music therapy clinical practice and research. Whereas providing examples and possible scenarios for music therapists working on either bonding or attachment, the distinction between both concepts is relevant for many health care professionals concerned with early parenting interventions in the NICU. This will hopefully lead to a more precise use of theory, and ultimately, to a more informed clinical practice and research.
Symptom Profiles, Health-Related Quality of Life, and Clinical Blood Markers among Korean Community-Dwelling Older Adults Living with Chronic Conditions
Authors: Park Jongmin , Lukkahatai Nada , Perrin Nancy , Kim Yoonju , Saligan Leorey N. , Won Chang Won
Published: February 2021

Older adults suffer from multiple symptoms, which negatively affects their health-related quality of life. The single-symptom management approach has been less than effective. The data of 2362 Korean community-dwelling older adults aged 70 and above were analyzed in the Korean Frailty and Aging Cohort Study (KFACS) study. A cluster analysis, correlation analysis, and logistic regression were used to analyze the data. We found three symptom clusters: high symptom burden (HSB, n = 1032); pain and fatigue group (PAF, n = 566); and the sleep deprivation group (SDP, n = 764). Participants in the HSB group are more likely to be of old age (OR = 1.1), be female (OR = 2.4), live in a rural area (OR = 1.4), have low physical activity (OR = 0.9), and have multiple chronic conditions (OR = 1.5). The clinical blood markers analysis showed a negative relationship among the physical health, free T4 (r = −0.083, p < 0.01) and insulin (r = −0.084, p < 0.01). The sex-specific blood markers analysis showed differences among three clusters. While free testosterone (male: r = 0.124, female: r = 0.110, p < 0.05) and dehydroepiandrosterone (DHEA) (male: r = 0.352 and female: r = 0.134, p < 0.05) were associated with physical health in the HSB group, only free testosterone was associated with mental health (male: r = −0.093, and female: r = −0.116, p < 0.05) in the SDP group. These findings suggest the potential role of the patient’s sex and sex hormones in symptoms of Korean community-dwelling older adults. Understanding the symptom profiles and impact of biopsychosocial factors may enhance precision symptom management.
Crisis Brings Innovative Strategies: Collaborative Empathic Teleintervention for Children with Disabilities during the COVID-19 Lockdown
Authors: Schiariti Verónica , McWilliam Robin A.
Published: February 2021

Background: While coronavirus disease 2019 (COVID-19) continues to spread across the globe, public health strategies—including the social distancing measures that many countries have implemented— have caused disruptions to daily routines. For children with disabilities and their families, such measures mean a lack of access to the resources they usually have through schools and habilitation or rehabilitation services. Health emergencies, like the current COVID-19 pandemic, require innovative strategies to ensure continuity of care. The objective of this perspective paper is to propose the adoption of two innovative strategies for teleintervention. Methods: The novel strategies include: (1) to apply the principles of the Routines-Based Model beyond the early years of development, and (2) to adopt My Abilities First—which is a novel educational tool promoting an abilities-oriented approach in healthcare encounters. Results: In the context of COVID-19, and using accessible language, the content of the paper highlights what is important for families and individuals with disabilities, and how the proposed novel strategies could be useful delivering remote support. Conclusions: The principles of the Routines-Based Model and My Abilities First are universal and facilitate collaborative, empathic, family-centered teleintervention for children and youth with disabilities during and post the COVID-19 lockdown.
A Mobile App to Optimize Social Participation for Individuals with Physical Disabilities: Content Validation and Usability Testing
Authors: Kairy Dahlia , Mostafavi Mir Abolfazl , Blanchette-Dallaire Catherine , Belanger Eva , Corbeil Andrea , Kandiah Meena , Wu Tian Qiang , Mazer Barbara
Published: February 2021

Background: Social participation is beneficial for individuals’ health. However, people with disabilities that may lead to mobility limitations tend to experience lower levels of social participation. Information and communication technologies such as the OnRoule mobile application (app) can help promote social participation. Objectives: To obtain potential users’ perceptions on the usability and content of the OnRoule app for providing information on accessibility, as well as its potential to optimize social participation. Materials and Methods: Cross-sectional user-centered design study. Individuals with physical disabilities (n = 18) were recruited through community organizations and interviewed using a semi-structured guide. Interviews were recorded, transcribed, and analyzed using thematic analysis. Results: Three main themes were identified: (1) “user-friendliness”; (2) “balance between the amount and relevance of information”; and (3) “potential use of the app”. Discussion and Conclusion: Findings from this study indicated that the app was easy to use, had pertinent information, and enabled a positive experience of finding information. However, several areas of improvement were identified, such as the clarity of specific elements, organization and amount of information, optimization of features, and inclusiveness. Apps such as OnRoule could optimize social participation by facilitating the process of finding resources in the community and building a sense of connectedness between users.
Mortality Risk Factors for Individuals Experiencing Homelessness in Catalonia (Spain): A 10-Year Retrospective Cohort Study
Authors: Calvo Fran , Turró-Garriga Oriol , Fàbregas Carles , Alfranca Rebeca , Calvet Anna , Salvans Mercè , Giralt Cristina , Castillejos Sandra , Rived-Ocaña Mercè , Calvo Paula , Castillo Paz , Garre-Olmo Josep , Carbonell Xavier
Published: February 2021

(1) Background: Current evidence suggests that mortality is considerably higher in individuals experiencing homelessness. The aim of this study was to analyze the mortality rate and the mortality risk factors in a sample of individuals experiencing homelessness in the city of Girona over a ten-year period. (2) Methods: We retrospectively examined the outcomes of 475 people experiencing homelessness with the available clinical and social data. Our sample was comprised of 84.4% men and 51.8% foreign-born people. Cox’s proportional hazard models were used to identify mortality risk factors between origin groups. (3) Results: 60 people died during the ten-year period. The average age of death was 49.1 years. After adjusting for demographic characteristics and the duration of homelessness, the risk factors for mortality were origin (people born in Spain) (HR = 4.34; 95% CI = 1.89–10.0), type 2 diabetes (HR = 2.9; 95% CI = 1.62–5.30), alcohol use disorder (HR = 1.9; 95% CI = 1.12–3.29), and infectious diseases (HR = 1.6; 95% CI = 1.09–2.39). Our results show a high prevalence of infectious and chronic diseases. Type 2 diabetes emerges as an important risk factor in homelessness. The average age of death of individuals experiencing homelessness was significantly lower than the average age of death in the general population (which is greater than 80 years). (4) Conclusions: Foreign-born homeless people were generally younger and healthier than Spanish-born homeless people. Chronic diseases were controlled better in Spanish-born people, but this group showed an increased risk of mortality.
Comparison of Learning Transfer Using Simulation Problem-Based Learning and Demonstration: An Application of Papanicolaou Smear Nursing Education
Authors: Lee Jeongim , Son Hae Kyoung
Published: February 2021

The purpose of this study was to compare the effects of simulation problem-based learning (S-PBL), a type of learning that reflects various clinical situations, and demonstration-based learning, a conventional type of learning that shows clinical skill performance, of Papanicolaou smear education on the self-confidence, learner satisfaction, and critical thinking of nursing students. A quasi-experimental control group pretest-posttest design was used. Nursing students who were classified as advanced beginners were randomly allocated to the control group (n = 53) or the experimental group (n = 52). Students in the control group participated in a conventional demonstration of a Papanicolaou smear, while students in the experimental group participated in S-PBL. The students’ self-confidence, learner satisfaction, and critical thinking were measured via a self-reported questionnaire. Compared with the control group, self-confidence, learner satisfaction, and critical thinking increase significantly more (p < 0.001) in the experimental group. S-PBL was found to be an effective strategy for improving learning transfer, applying learned nursing knowledge to simulated nursing situations. Thus, S-PBL is recommended to improve training in nursing education.
The Psychological and Physical Effects of Forests on Human Health: A Systematic Review of Systematic Reviews and Meta-Analyses
Authors: Stier-Jarmer Marita , Throner Veronika , Kirschneck Michaela , Immich Gisela , Frisch Dieter , Schuh Angela
Published: February 2021

Background: The aim of this systematic review of systematic reviews was to identify, summarise, and synthesise the available evidence of systematic reviews (SRs) and meta-analyses (MAs) on the preventative and therapeutic psychological and physical effects of forest-based interventions. Methods: Both bibliographic databases and grey literature sources were searched for SRs and MAs published until May 2020. Eight databases were searched for relevant articles: MEDLINE, Embase, Web of Science, Cochrane Library, PsycInfo, CiNii, EBSCO, and Scopus. Grey literature was sourced from Google Scholar and other web-based search tools. SRs and MAs that included randomised controlled (RCT), non-randomised controlled (NRCT), and non-controlled trials (NCT) on health-related effects of forest-based interventions were eligible if they had searched at least two databases. The methodological quality of eligible reviews was assessed by AMSTAR-2. Results: We evaluated 11 systematic reviews covering 131 different primary intervention studies, mostly from Asian countries, three of which included supplementary meta-analyses. The quality assessment resulted in moderate confidence in the results of two reviews, low confidence in six, and critically low confidence in three. The results of the eight moderate and low-rated reviews indicated that forest-based interventions are beneficial to the cardiovascular system, immune system, and mental health (in the areas of stress, depression, anxiety, and negative emotions). Evidence for the effectiveness of forest-based interventions on metabolic parameters in adults, the severity of atopic dermatitis in children and adolescents, and social skills and sociality in healthy primary school children was weak. Discussion/Conclusions: Evidence suggests beneficial therapeutic effects of forest-based interventions on hypertension, stress, and mental-health disorders, such as depression and anxiety. Changes in immunological and inflammatory parameters after forest therapy should be verified in bio-geographically native forests. In the future, more attention should be paid to careful planning, implementation, and reporting of primary studies and to systematic reviews on the effects of forest-based interventions.
Infodemic and Fake News in Spain during the COVID-19 Pandemic
Authors: Fernández-Torres María Jesús , Almansa-Martínez Ana , Chamizo-Sánchez Rocío
Published: February 2021

Internet, new technologies and social networks have changed the consumption and dissemination of information. The world is witnessing the proliferation of so-called false news, especially since the beginning of 2020, when COVID-19 became the main issue on the global agenda. Alleged government actions, remedies, advice, etc., are the cause of a multitude of messages that are often false. Through surveys (1115 responses were obtained) and a review of the literature, we explore how the proliferation of COVID-19’s false news affects and impacts public opinion in Spain. We also examine how citizens are being informed about the pandemic, identify the main channels of communication used and discover the impact of misinformation. The main conclusions are that, in Spain, citizens are interested in information related to the coronavirus, but there is a lack of media credibility and reliability; the social networks and instant messaging are considered the channels that transmit the greatest amount of false news.
Metabolic Alterations in Myotonic Dystrophy Type 1 and Their Correlation with Lipin
Authors: Mateus Tiago , Martins Filipa , Nunes Alexandra , Herdeiro Maria Teresa , Rebelo Sandra
Published: February 2021

Myotonic dystrophy type 1 (DM1) is an autosomal dominant hereditary and multisystemic disease, characterized by progressive distal muscle weakness and myotonia. Despite huge efforts, the pathophysiological mechanisms underlying DM1 remain elusive. In this review, the metabolic alterations observed in patients with DM1 and their connection with lipin proteins are discussed. We start by briefly describing the epidemiology, the physiopathological and systemic features of DM1. The molecular mechanisms proposed for DM1 are explored and summarized. An overview of metabolic syndrome, dyslipidemia, and the summary of metabolic alterations observed in patients with DM1 are presented. Patients with DM1 present clinical evidence of metabolic alterations, namely increased levels of triacylglycerol and low-density lipoprotein, increased insulin and glucose levels, increased abdominal obesity, and low levels of high-density lipoprotein. These metabolic alterations may be associated with lipins, which are phosphatidate phosphatase enzymes that regulates the triacylglycerol levels, phospholipids, lipid signaling pathways, and are transcriptional co-activators. Furthermore, lipins are also important for autophagy, inflammasome activation and lipoproteins synthesis. We demonstrate the association of lipin with the metabolic alterations in patients with DM1, which supports further clinical studies and a proper exploration of lipin proteins as therapeutic targets for metabolic syndrome, which is important for controlling many diseases including DM1.
Coping with COVID-19: The Strategies Adapted by Pakistani Students to Overcome Implications
Authors: Baloch Gul Muhammad , Kamaludin Kamilah , Chinna Karuthan , Sundarasen Sheela , Nurunnabi Mohammad , Khoshaim Heba Bakr , Hossain Syed Far Abid , Sukayt Areej Al , Baloch Laareb Gul
Published: February 2021

COVID-19 has speedily immersed the globe with 72+ million cases and 1.64 million deaths, in a span of around one year, disturbing and deteriorating almost every sphere of life. This study investigates how students in Pakistan have coped with the COVID-19. Zung’s self-rating anxiety scale (SAS) was used for measuring anxiety and the coping strategies were measured on four strategies i.e., seeking social support, humanitarian, acceptance, and mental disengagement. Among 494 respondents, 61% were females and 77.3% of the students were in the age group of 19–25 years. The study findings indicate that approximately 41 percent of students are experiencing some level of anxiety, including 16% with severe to extreme levels. Seeking social support seemed to be the least preferred coping strategy and that female students seek social support, humanitarian, and acceptance coping strategies more than males. Students used both emotion-based and problem-based coping strategies. The variables of gender, age, ethnicity, level and type of study, and living arrangement of the students were associated with usage of coping strategies. Findings showing that students do not prefer to seek social support. The study outcomes will provide basic data for university policies in Pakistan and the other countries with same cultural contexts to design and place better mental health provisions for students.
Population Aging, Health Investment and Economic Growth: Based on a Cross-Country Panel Data Analysis
Authors: Yang Yingzhu , Zheng Rong , Zhao Lexiang
Published: February 2021

With the economic development of various countries and the deepening of population aging, health plays an increasingly important role in the macro-economy. How to meet the growing health needs as well as promote the economy has captured the attention of the world. Therefore, whether health investment can promote economic growth is an important theoretical and practical issue. An extended Mankiw–Romer–Weil model (MRW) with human health capital and population aging is employed to examine the impact on economic growth from population aging and health investment. On the basis of the theoretical model, this paper uses the LSDV and TSLS methods to carry out an empirical study based on cross-country panel data during the period 2000–2016. The empirical results show that health investment plays a significant role in promoting economic growth, and there is an inverted U-shaped relationship between population aging and economic growth. The impacts on economic growth from health investment and population aging can weaken each other. In addition, this paper also finds that health investment structure and the proportion of government health investment to total government spending can affect economic growth.
The Use of Social Networking Sites and Pro-Environmental Behaviors: A Mediation and Moderation Model
Authors: Shah Zakir , Wei Lu , Ghani Usman
Published: February 2021

Climate change poses a huge threat. Social networking sites (SNSs) have become sources of human–environment interactions and shaped the societal perception of climate change and its effect on society. This study, based on the extended parallel process model, aims to examine the effect of exposure to climate change-related information on SNSs on the pro-environmental behaviors of individuals. The study examines the mediation effect of fear of victimization from climate change between the exposure to climate change-related information on SNSs and pro-environmental behaviors, including the moderation effect of attention deficit and decision-making self-efficacy with the help of appropriate instruments. A total sample of 406 reliable questionnaires were collected from students using SNSs in China, and data were analyzed through SPSS and AMOS. Results indicate that the exposure to climate change-related information on SNSs has a direct positive effect on users’ pro-environmental behaviors (β = 0.299, p < 0.01). Fear of victimization from climate change also mediates the relationship between exposure to climate change-related information on SNSs and pro-environmental behaviors (β = 0.149, SE = 0.029, p < 0.01). In addition, attention deficit moderates the relationship of exposure to climate change-related information on SNSs with fear of victimization from climate change (β = −0.090, p ≤ 0.01) and pro-environmental behaviors (β = −0.090, p ≤ 0.05). Similarly, the relationship between fear of victimization from climate change and pro-environmental behaviors is moderated by decision-making self-efficacy (β = 0.267, p ≤ 0.01). The findings offer implications for media organizations and government policy makers, who should post or spread environmental information through the most trustworthy media, with trustworthy sources, in an effective manner, and without exaggerated adverse impacts.
Label-Free Quantitative Phosphoproteomics of the Fission Yeast Schizosaccharomyces pombe Using Strong Anion Exchange- and Porous Graphitic Carbon-Based Fractionation Strategies
Authors: Sivakova Barbara , Jurcik Jan , Lukacova Veronika , Selicky Tomas , Cipakova Ingrid , Barath Peter , Cipak Lubos
Published: February 2021

The phosphorylation of proteins modulates various functions of proteins and plays an important role in the regulation of cell signaling. In recent years, label-free quantitative (LFQ) phosphoproteomics has become a powerful tool to analyze the phosphorylation of proteins within complex samples. Despite the great progress, the studies of protein phosphorylation are still limited in throughput, robustness, and reproducibility, hampering analyses that involve multiple perturbations, such as those needed to follow the dynamics of phosphoproteomes. To address these challenges, we introduce here the LFQ phosphoproteomics workflow that is based on Fe-IMAC phosphopeptide enrichment followed by strong anion exchange (SAX) and porous graphitic carbon (PGC) fractionation strategies. We applied this workflow to analyze the whole-cell phosphoproteome of the fission yeast Schizosaccharomyces pombe. Using this strategy, we identified 8353 phosphosites from which 1274 were newly identified. This provides a significant addition to the S. pombe phosphoproteome. The results of our study highlight that combining of PGC and SAX fractionation strategies substantially increases the robustness and specificity of LFQ phosphoproteomics. Overall, the presented LFQ phosphoproteomics workflow opens the door for studies that would get better insight into the complexity of the protein kinase functions of the fission yeast S. pombe.
Human Induced Pluripotent Stem Cell-Derived Exosomes as a New Therapeutic Strategy for Various Diseases
Authors: Wang Aline Yen Ling
Published: February 2021

Recently, an increasing number of studies have demonstrated that induced pluripotent stem cells (iPSCs) and iPSC-derived cells display therapeutic effects, mainly via the paracrine mechanism in addition to their transdifferentiation ability. Exosomes have emerged as an important paracrine factor for iPSCs to repair injured cells through the delivery of bioactive components. Animal reports of iPSC-derived exosomes on various disease models are increasing, such as in heart, limb, liver, skin, bone, eye and neurological disease and so forth. This review aims to summarize the therapeutic effects of iPSC-derived exosomes on various disease models and their properties, such as angiogenesis, cell proliferation and anti-apoptosis, with the hopes of improving their potential role in clinical applications and functional restoration.
Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats
Authors: Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Shimizu Kana , Miyazaki Yusuke , Sari Nurmila , Shimizu Satoshi , Mori Kiyoshi , Wada Hiromichi , Hasegawa Koji , Morimoto Tatsuya
Published: February 2021

Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy or in heart failure. The acetylation of H3K9 on the promoter of the hypertrophic response gene was significantly increased in the left ventricular hypertrophy stage, whereas the acetylation of H3K122 did not increase in the left ventricular hypertrophy stage but did significantly increase in the heart failure stage. Interestingly, the interaction between the chromatin remodeling factor BRG1 and p300 was significantly increased in the heart failure stage, but not in the left ventricular hypertrophy stage. This study demonstrates that stage-specific acetylation of the histone tail and globular domains occurs during the development and progression of heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes.
Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy
Authors: Pishavar Elham , Luo Hongrong , Bolander Johanna , Atala Antony , Ramakrishna Seeram
Published: February 2021

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.
Prolyl Oligopeptidase Regulates Dopamine Transporter Oligomerization and Phosphorylation in a PKC- and ERK-Independent Manner
Authors: Julku Ulrika H. , Jäntti Maria , Svarcbahs Reinis , Myöhänen Timo T.
Published: February 2021

Prolyl oligopeptidase (PREP) is a serine protease that binds to alpha-synuclein (aSyn) and induces its aggregation. PREP inhibitors have been shown to have beneficial effects in Parkinson’s disease models by enhancing the clearance of aSyn aggregates and modulating striatal dopamine. Additionally, we have shown that PREP regulates phosphorylation and internalization of dopamine transporter (DAT) in mice. In this study, we clarified the mechanism behind this by using HEK-293 and PREP knock-out HEK-293 cells with DAT transfection. We tested the effects of PREP, PREP inhibition, and alpha-synuclein on PREP-related DAT regulation by using Western blot analysis and a dopamine uptake assay, and characterized the impact of PREP on protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) by using PKC assay and Western blot, respectively, as these kinases regulate DAT phosphorylation. Our results confirmed our previous findings that a lack of PREP can increase phosphorylation and internalization of DAT and decrease uptake of dopamine. PREP inhibition had a variable impact on phosphorylation of ERK dependent on the metabolic state of cells, but did not have an effect on phosphorylation or function of DAT. PREP modifications did not affect PKC activity either. Additionally, a lack of PREP elevated a DAT oligomerization that is associated with intracellular trafficking of DAT. Our results suggest that PREP-mediated phosphorylation, oligomerization, and internalization of DAT is not dependent on PKC or ERK.
Origin and Fates of TERT Gene Copies in Polyploid Plants
Authors: Fajkus Petr , Peška Vratislav , Fajkus Jiří , Sýkorová Eva
Published: February 2021

The gene coding for the telomerase reverse transcriptase (TERT) is essential for the maintenance of telomeres. Previously we described the presence of three TERT paralogs in the allotetraploid plant Nicotiana tabacum, while a single TERT copy was identified in the paleopolyploid model plant Arabidopsis thaliana. Here we examine the presence, origin and functional status of TERT variants in allotetraploid Nicotiana species of diverse evolutionary ages and their parental genome donors, as well as in other diploid and polyploid plant species. A combination of experimental and in silico bottom-up analyses of TERT gene copies in Nicotiana polyploids revealed various patterns of retention or loss of parental TERT variants and divergence in their functions. RT–qPCR results confirmed the expression of all the identified TERT variants. In representative plant and green algal genomes, our synteny analyses show that their TERT genes were located in a conserved locus that became advantageous after the divergence of eudicots, and the gene was later translocated in several plant groups. In various diploid and polyploid species, translocation of TERT became fixed in target loci that show ancient synapomorphy.
Mass Spectrometry-Based Redox and Protein Profiling of Failing Human Hearts
Authors: Tomin Tamara , Schittmayer Matthias , Sedej Simon , Bugger Heiko , Gollmer Johannes , Honeder Sophie , Darnhofer Barbara , Liesinger Laura , Zuckermann Andreas , Rainer Peter P. , Birner-Gruenberger Ruth
Published: February 2021

Oxidative stress contributes to detrimental functional decline of the myocardium, leading to the impairment of the antioxidative defense, dysregulation of redox signaling, and protein damage. In order to precisely dissect the changes of the myocardial redox state correlated with oxidative stress and heart failure, we subjected left-ventricular tissue specimens collected from control or failing human hearts to comprehensive mass spectrometry-based redox and quantitative proteomics, as well as glutathione status analyses. As a result, we report that failing hearts have lower glutathione to glutathione disulfide ratios and increased oxidation of a number of different proteins, including constituents of the contractile machinery as well as glycolytic enzymes. Furthermore, quantitative proteomics of failing hearts revealed a higher abundance of proteins responsible for extracellular matrix remodeling and reduced abundance of several ion transporters, corroborating contractile impairment. Similar effects were recapitulated by an in vitro cell culture model under a controlled oxygen atmosphere. Together, this study provides to our knowledge the most comprehensive report integrating analyses of protein abundance and global and peptide-level redox state in end-stage failing human hearts as well as oxygen-dependent redox and global proteome profiles of cultured human cardiomyocytes.
Therapeutic Targeting of Fumaryl Acetoacetate Hydrolase in Hereditary Tyrosinemia Type I
Authors: Gil-Martínez Jon , Macias Iratxe , Unione Luca , Bernardo-Seisdedos Ganeko , Lopitz-Otsoa Fernando , Fernandez-Ramos David , Lain Ana , Sanz-Parra Arantza , Mato José M , Millet Oscar
Published: February 2021

Fumarylacetoacetate hydrolase (FAH) is the fifth enzyme in the tyrosine catabolism pathway. A deficiency in human FAH leads to hereditary tyrosinemia type I (HT1), an autosomal recessive disorder that results in the accumulation of toxic metabolites such as succinylacetone, maleylacetoacetate, and fumarylacetoacetate in the liver and kidney, among other tissues. The disease is severe and, when untreated, it can lead to death. A low tyrosine diet combined with the herbicidal nitisinone constitutes the only available therapy, but this treatment is not devoid of secondary effects and long-term complications. In this study, we targeted FAH for the first-time to discover new chemical modulators that act as pharmacological chaperones, directly associating with this enzyme. After screening several thousand compounds and subsequent chemical redesign, we found a set of reversible inhibitors that associate with FAH close to the active site and stabilize the (active) dimeric species, as demonstrated by NMR spectroscopy. Importantly, the inhibitors are also able to partially restore the normal phenotype in a newly developed cellular model of HT1.
Signatures of Dermal Fibroblasts from RDEB Pediatric Patients
Authors: Beilin Arkadii K. , Evtushenko Nadezhda A. , Lukyanov Daniil K. , Murashkin Nikolay N. , Ambarchian Eduard T. , Pushkov Alexander A. , Savostyanov Kirill V. , Fisenko Andrey P. , Rogovaya Olga S. , Vasiliev Andrey V. , Vorotelyak Ekaterina A. , Gurskaya Nadya G.
Published: February 2021

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored. The mutations in the COL7A1 gene, described here, were found in the DEB register. Among them, two homozygous mutations and two cases of compound heterozygous mutations were identified. We created the panel of primary patient-specific RDEB fibroblast lines (FEB) and compared it with control fibroblasts from healthy donors (FHC). The set of morphological features and the contraction capacity of the cells distinguished FEB from FHC. We also report the relationships between the mutations and several phenotypic traits of the FEB. Based on the analysis of the available RNA-seq data of RDEB fibroblasts, we performed an RT-qPCR gene expression analysis of our cell lines, confirming the differential status of multiple genes while uncovering the new ones. We anticipate that our panels of cell lines will be useful not only for studying RDEB signatures but also for investigating the overall mechanisms involved in disease progression.
Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation
Authors: Dangoumau Audrey , Marouillat Sylviane , Coelho Roxane , Wurmser François , Brulard Céline , Haouari Shanez , Laumonnier Frédéric , Corcia Philippe , Andres Christian R. , Blasco Hélène , Vourc’h Patrick
Published: February 2021

Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations.
Increased Bone Resorption during Lactation in Pycnodysostosis
Authors: Jansen Ineke D.C. , Papapoulos Socrates E. , Bravenboer Nathalie , de Vries Teun J. , Appelman-Dijkstra Natasha M.
Published: February 2021

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.
A Toxic Synergy between Aluminium and Amyloid Beta in Yeast
Authors: Mcdonald Jamieson B. , Dhakal Sudip , Macreadie Ian
Published: February 2021

Alzheimer’s disease (AD), the most prevalent, age-related, neurodegenerative disease, is associated with the accumulation of amyloid beta (Aβ) and oxidative stress. However, the sporadic nature of late-onset AD has suggested that other factors, such as aluminium may be involved. Aluminium (Al3+) is the most ubiquitous neurotoxic metal on earth, extensively bioavailable to humans. Despite this, the link between Al3+ and AD has been debated for decades and remains controversial. Using Saccharomyces cerevisiae as a model organism expressing Aβ42, this study aimed to examine the mechanisms of Al3+ toxicity and its interactions with Aβ42. S. cerevisiae cells producing Aβ42 treated with varying concentrations of Al3+ were examined for cell viability, growth inhibition, and production of reactive oxygen species (ROS). Al3+ caused a significant reduction in cell viability: cell death in yeast producing green fluorescent protein tagged with Aβ42 (GFP–Aβ42) was significantly higher than in cells producing green fluorescent protein (GFP) alone. Additionally, Al3+ greatly inhibited the fermentative growth of yeast producing GFP–Aβ42, which was enhanced by ferric iron (Fe3+), while there was negligible growth inhibition of GFP cells. Al3+- induced ROS levels in yeast expressing native Aβ42 were significantly higher than in empty vector controls. These findings demonstrate Al3+ has a direct, detrimental toxic synergy with Aβ42 that can be influenced by Fe3+, causing increased oxidative stress. Thus, Al3+ should be considered as an important factor, alongside the known characteristic hallmarks of AD, in the development and aetiology of the disease.