bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Fluoride Intake by Children: When to Use a Fluoride Toothpaste?
Authors: Casaglia Adriano , Cassini Maria Antonietta , Condò Roberta , Iaculli Flavia , Cerroni Loredana
Published: May 2021

Fluoride is recommended for its cariostatic effect, but excessive fluoride intake may have health risks. Increased prevalence of dental fluorosis in areas with low fluoride content in drinking water has been attributed to the inappropriate excessive intake of fluoride supplements (tablets and drops) and toothpaste ingestion. The aim of the present study was to estimate the fluoride intake and the risk of fluorosis in children (6 months–6 years) in the Castelli Romani area (province of Rome, Italy), which is volcanic, therefore with a higher concentration of fluorine. Measurements of the fluoride content in drinking water, mineral waters, vegetables and commercial toothpaste for children were performed. The fluoride concentrations of all samples were determined using a Fluoride Ion Selective Electrode (GLP 22, Crison, Esp). Data were analyzed by descriptive statistics. Differences between samples were determined by Student’s t-test. The fluoride content in tap water samples collected from public sources averaged from 0.35 to 1.11 ppm. The Pavona area showed the highest content of fluoride with respect to the others (p ≤ 0.05). The fluoride content in mineral water samples averaged from 0.07 to 1.50 ppm. The fluoride content of some vegetables showed increased mean values when compared to control vegetables (p ≤ 0.05). Within the limitations of the present study, considerations should be made when prescribing fluoride toothpaste for infants (6 months–4 years) in the areas with high fluoride content, because involuntary ingestion is consistent.
The Japanese Educational System as an International Model for Urban Resilience
Authors: Gavari-Starkie Elisa , Casado-Claro María-Francisca , Navarro-González Inmaculada
Published: May 2021

Global cities in the context of accelerated urbanization have to deal with more diverse risk factors than ever before, which highlights the need for a faster and more creative response capacity. Although it is necessary to strengthen technical systems, since they are surrounded by human systems, individual resilience will help to strengthen the community. The educational system is key to developing the human factor in a world where various systems in global cities are increasingly interconnected, which in turn increases risks. Japan is fostering a culture of disaster risk reduction in both the formal, non-formal, and informal education sectors, in which creativity and autonomy are key competencies. Tokyo is the highest populated metropolitan area globally, and its educational system is the international model for education in disaster risk reduction. Urban areas around the world face similar challenges and experience similar needs. This article addresses the challenges that the human factor faces in large cities and the possibilities of increasing resilience in both individuals and communities through Disaster Resilience Education (DRE), taking the Japanese educational system as a model.
Chemical Contamination Pathways and the Food Safety Implications along the Various Stages of Food Production: A Review
Authors: Lebelo Kgomotso , Malebo Ntsoaki , Mochane Mokgaotsa Jonas , Masinde Muthoni
Published: May 2021

Historically, chemicals exceeding maximum allowable exposure levels have been disastrous to underdeveloped countries. The global food industry is primarily affected by toxic chemical substances because of natural and anthropogenic factors. Food safety is therefore threatened due to contamination by chemicals throughout the various stages of food production. Persistent Organic Pollutants (POPs) in the form of pesticides and other chemical substances such as Polychlorinated Biphenyls (PCBs) have a widely documented negative impact due to their long-lasting effect on the environment. This present review focuses on the chemical contamination pathways along the various stages of food production until the food reaches the consumer. The contamination of food can stem from various sources such as the agricultural sector and pollution from industrialized regions through the air, water, and soil. Therefore, it is imperative to control the application of chemicals during food packaging, the application of pesticides, and antibiotics in the food industry to prevent undesired residues on foodstuffs. Ultimately, the protection of consumers from food-related chemical toxicity depends on stringent efforts from regulatory authorities both in developed and underdeveloped nations.
mHealth Interventions to Address Physical Activity and Sedentary Behavior in Cancer Survivors: A Systematic Review
Authors: Khoo Selina , Mohbin Najihah , Ansari Payam , Al-Kitani Mahfoodha , Müller Andre Matthias
Published: May 2021

This review aimed to identify, evaluate, and synthesize the scientific literature on mobile health (mHealth) interventions to promote physical activity (PA) or reduce sedentary behavior (SB) in cancer survivors. We searched six databases from 2000 to 13 April 2020 for controlled and non-controlled trials published in any language. We conducted best evidence syntheses on controlled trials to assess the strength of the evidence. All 31 interventions included in this review measured PA outcomes, with 10 of them also evaluating SB outcomes. Most study participants were adults/older adults with various cancer types. The majority (n = 25) of studies implemented multicomponent interventions, with activity trackers being the most commonly used mHealth technology. There is strong evidence for mHealth interventions, including personal contact components, in increasing moderate-to-vigorous intensity PA among cancer survivors. However, there is inconclusive evidence to support mHealth interventions in increasing total activity and step counts. There is inconclusive evidence on SB potentially due to the limited number of studies. mHealth interventions that include personal contact components are likely more effective in increasing PA than mHealth interventions without such components. Future research should address social factors in mHealth interventions for PA and SB in cancer survivors.
A Qualitative Study to Explore the Barriers for Nonadherence to Referral to Hospital Births by Women with High-Risk Pregnancies in Nepal
Authors: Rajbanshi Sushma , Norhayati Mohd Noor , Nik Hazlina Nik Hussain
Published: May 2021

Maternal and neonatal morbidity and mortality tend to decrease if referral advice during pregnancy is utilized appropriately. This study explores the reasons for nonadherence to referral advice among high-risk pregnant women. A qualitative study was conducted in Morang District, Nepal. A phenomenological inquiry was used. Fourteen participants were interviewed in-depth. High-risk women who did not comply with the referral to have a hospital birth were the study participants. Participants were chosen purposively until data saturation was achieved. The data were generated using thematic analysis. Preference of homebirth, women’s diminished autonomy and financial dependence, conditional factors, and sociocultural factors were the four major themes that hindered hospital births. Women used antenatal check-ups to reaffirm normalcy in their current pregnancies to practice homebirth. For newly-wed young women, information barriers such as not knowing where to seek healthcare existed. The poorest segments and marginalized women did not adhere to referral hospital birth advice even when present with high-risk factors in pregnancy. Multiple factors, including socioeconomic and sociocultural factors, affect women’s decision to give birth in the referral hospital. Targeted interventions for underprivileged communities and policies to increase facility-based birth rates are recommended.
Depression among the Non-Native International Undergraduate Students Studying Dentistry in Bangladesh
Authors: Kabir Russell , Isha Samia Naz , Chowdhury Mohammad Tawfique Hossain , Siddika Nazeeba , Jahan Shah Saif , Saha Arup Kumar , Nath Sujan Kanti , Jahan Mohammed Shahed , Sivasubramanian Madhini , Mahmud Ilias , Hoque Apu Ehsanul
Published: May 2021

Background: Bangladesh has been attracting international students with interests in various subjects recently. Every year students from different parts of the world come to study undergraduate and postgraduate courses, mostly at private universities in Bangladesh. This study evaluates the depression status among international students who are studying dentistry in Bangladesh. Methods: This cross-sectional survey was conducted among International undergraduate dental students who enrolled in the Bachelor of Dental Surgery program in nine public and private dental colleges in Bangladesh. Participants were selected using a convenience sampling method. A total of 206 students completed the survey where 78.5% of them were female students and 21.5% students were male, and a CES-D 10-item Likert scale questionnaire was used for data collection. The Cronbach alpha for the 10-item CES-D scale for this population is 0.812. Results: The majority of the students (79.5%) are below 24 years of age with a mean age of 23.22 years and standard deviation of 2.3, and are students who cannot communicate well in Bengali (Bangla), about 60% of them have experienced depression. About 77.3% (p < 0.00) of the international students having financial difficulties exhibited depression. The international students who went through financial problems were two times more likely to suffer from depression (OR = 2.38; p-value < 0.01). Conclusion: This study tried to highlight the struggles faced by international students in Bangladesh studying dentistry. It is evident from the findings that several factors influence students’ mental well-being during demanding dental education years.
How Risk Signaling Influences Binge Drinking Impression Formation: An Evolutionary Experimental Approach
Authors: Boudesseul Jordane , Zerhouni Oulmann , Bègue Laurent
Published: May 2021

Background. Evolutionary theory-driven alcohol prevention programs for adolescents are lacking. This study introduced a binge drinking impression formation paradigm to test whether emphasizing sexual dysfunction induced by alcohol abuse lowers positive attitudes and expectancies related to binge drinking when compared with cognitive or long-term health consequences. Method. In a between-subjects experiment, 269 French high school students (age, M = 15.94, SD = 0.93, 63.20% women) watched professional-quality videos emphasizing sexual impotence (n = 60), cognitive impairment (n = 72), or long-term effects (cancer, cardiovascular disease, n = 68) induced by alcohol and then had to evaluate a drinking scene. We predicted that the video on impotence would be the most impactful when compared with the other videos. Results. Results showed that women evaluated the target as less attractive after viewing the cognitive video compared with the video on impotence. Men were more willing to play sports against the target after viewing the cognitive video, compared with the video on impotence. Conclusions. These results showed that evolutionary meaning might shape impressions formed by participants depending on the context. This study calls for further replications using the same design and materials.
Maternal Ambient Exposure to Atmospheric Pollutants during Pregnancy and Offspring Term Birth Weight in the Nationwide ELFE Cohort
Authors: Ouidir Marion , Seyve Emie , Rivière Emmanuel , Bernard Julien , Cheminat Marie , Cortinovis Jérôme , Ducroz François , Dugay Fabrice , Hulin Agnès , Kloog Itai , Laborie Anne , Launay Ludivine , Malherbe Laure , Robic Pierre-Yves , Schwartz Joel , Siroux Valérie , Virga Jonathan , Zaros Cécile , Charles Marie-Aline , Slama Rémy , Lepeule Johanna
Published: May 2021

Background: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study. Methods: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM2.5, PM10 (particles < 2.5 µm and <10 µm) and NO2 (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW. Results: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, −26.8, −7.3) and by 18.0 g (−26.6, −9.4) for each 5 µg/m3 increase in PM2.5 and PM10, respectively, and by 15.9 g (−27.6, −4.2) for each 10 µg/m3 increase in NO2. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (−58.1, −38.0) for PM2.5, 38.1 g (−46.7, −29.6) for PM10 and 14.7 g (−25.3, −4.0) for NO2. Effects of pollutants on TBW were larger in rural areas. Conclusions: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.
Malaysian Health Literacy: Scorecard Performance from a National Survey
Authors: Jaafar Norrafizah , Perialathan Komathi , Krishnan Manimaran , Juatan Nurashma , Ahmad Masitah , Mien Teresa Yong Sui , Salleh Kamarul Zaman , Isa Affendi , Mohamed Suraiya Syed , Hanit Nor Hanizah Abu , Hasani Wan Shakira Rodzlan , Mohamad Emma Mirza Wati , Johari Mohammad Zabri
Published: May 2021

Health literacy is an indicator of a society’s ability to make better health judgements for themselves and the people around them. This study investigated the prevalence of health literacy among Malaysian adults and provided an overall picture of the society’s current health literacy status, which has not been previously assessed. The study also highlighted socio-demographic markers of communities with limited health literacy that may warrant future intervention. A population-based self-administered survey using the Health Literacy Survey Malaysian Questionnaire18 (HLS-M-Q18) instrument was conducted as part of the National Health Morbidity Survey 2019 in Malaysia. The nationwide survey utilized a two-staged stratified random sampling method. A sample of 9478 individuals aged 18 and above, drawn from the living quarter list, participated in the study. The health literacy score was divided into three levels; limited, sufficient, and excellent. Findings showed a majority of the Malaysian population had a sufficient health literacy level in all three domains—healthcare, diseases prevention and health promotion (49.1%, 44.2%, and 47.5%, respectively)—albeit leaning towards the lower end of the category with an average score of 35.5. The limited health literacy groups were prevalent among respondents with older age (68%), lower education level (64.8%), and lower household income (49.5%). The overall health literacy status for Malaysia was categorized at a lower sufficiency level. Future health literacy improvements should focus on communities with a limited health literacy level to improve the overall score.
Structural, Personal and Socioenvironmental Determinants of HIV Transmission among Transgender Women in Indonesia
Authors: Fauk Nelsensius Klau , Merry Maria Silvia , Siri Theodorus Asa , Mwanri Lillian , Ward Paul Russell
Published: May 2021

Transgender populations are considered as a highly vulnerable group to HIV infection. This study aimed to understand structural, personal and socioenvironmental factors and the mechanisms through which these factors facilitate HIV transmission among transgender women (waria) in Yogyakarta, Indonesia. A qualitative inquiry using one-on-one in-depth interviews was employed to collect data from participants (n = 29). Thematic analysis was used to guide data analysis. Findings showed that poverty in families, a sense of responsibility to support family necessities, limited employment options and low education attainment were the structural factors driving participants’ engagement in sex work practices and unprotected anal intercourse, which facilitated HIV transmission among them. Personal need fulfilment and the desire for savings were personal factors driving their engagement in these high-risk practices that supported HIV transmission. Social relationships, social influence and the participants’ living environment were socioenvironmental factors that also supported sex work practices and HIV transmission among the participants. The findings indicate the need for capacity building in terms of knowledge and skills for waria populations to prepare and enable them to gain meaningful employment to prevent the vicious cycle of HIV transmission among them. As structural factors seemed to be the main drivers predisposing waria to HIV acquisition, further studies to explore effective HIV/AIDS interventions that address economic aspects of waria in Yogyakarta and other similar settings in Indonesia are recommended.
Online Videos as a Source of Physiotherapy Exercise Tutorials for Patients with Lumbar Disc Herniation—A Quality Assessment
Authors: Heisinger Stephan , Huber Dominikus , Matzner Michael Paul , Hasenoehrl Timothy , Palma Stefano , Sternik Julia , Trost Carmen , Treiber Michael , Crevenna Richard , Grohs Josef Georg
Published: May 2021

Background: During the last few decades the prevalence of lumbar disc herniation has been increasing constantly, thereby imposing a significant socioeconomic burden. Physiotherapy plays a crucial role in both surgical and conservative treatment of lumbar disc herniation, consequently the current COVID-19 pandemic with concomitant lockdowns has led to a shortage of physiotherapeutical care. In the light of these recent events publicly available physiotherapy tutorials may be a useful tool to address this problem. Aim: The main aim of this study was to assess the quality of online physiotherapy exercise tutorials for lumbar disc herniation. Materials & Methods: With YouTube being a widely known and used platform we screened 240 of the most viewed videos. A total of 76 videos met the inclusion criteria and were statistically analyzed. The videos were assessed using Global Quality Score, DISCERN Score and JAMA benchmark criteria and in regard to their applicability. Results: They displayed a wide range of views (44,969 to 5,448,717), likes (66 to 155,079) and dislikes (6 to 2339). The videos were assessed using Global Quality Score, DISCERN Score and JAMA benchmark criteria and in regard to their applicability. Neither the number of “Views”, “Likes”, nor “Dislikes” was found to have a significant association with any of the quality measures used in this study. Conclusion: Overall quality grade was determined as “moderate”. Based on the data examined in this study, the use of YouTube videos as a source of therapy advice for lumbar spine disc herniation cannot be recommended universally.
‘I Was Smoking a Lot More during Lockdown Because I Can’: A Qualitative Study of How UK Smokers Responded to the Covid-19 Lockdown
Authors: O’Donnell Rachel , Eadie Douglas , Stead Martine , Dobson Ruaraidh , Semple Sean
Published: May 2021

This study explored how Covid-19 lockdown restrictions affected people’s daily smoking routines and behaviours, including adherence and modifications to pre-established smoking restrictions in the home. Semi-structured telephone interviews were conducted with smokers and non-smokers from smoking households 19 to 27 weeks after the first full UK lockdown ended in May 2020. A non-probability purposive sample representing 25 adults aged 21 or over living in households with at least 1 smoker were recruited to the study. A quota sampling strategy was used, according to age, gender, smoking status, family status, household composition, householder access to outdoor space, and change to work-life status. Most participants found lockdown increased the amount of time spent at home, where stresses associated with confinement, curtailment of social routines, removal of barriers and distractions to smoking due to home working, and feelings of boredom all contributed to increased smoking. Fewer factors were identified as reducing smoking during lockdown. Prominent examples included disruption to habitual smoking patterns and distraction from smoking associated with spending more time doing outdoor activities. Pressures placed on physical space and lack of privacy due to the confinement at home were responsible for displacement of smoking within the home, leading to breaking of smoke-free rules and family tensions, and in some cases to greater awareness amongst parents that their children smoked. Changes in daily routines associated with lockdown affected and displaced smoking behaviour both positively and negatively. Health improvement interventions could seek to harness positive changes in smoking associated with any future lockdown approaches. New home-working norms highlight the need for employers to support staff to reduce their smoking and to remain smoke-free.
The Impact of COVID 19 on University Staff and Students from Iberoamerica: Online Learning and Teaching Experience
Authors: Jojoa Mario , Lazaro Esther , Garcia-Zapirain Begonya , Gonzalez Marino J. , Urizar Elena
Published: May 2021

(1) Background: The COVID-19 pandemic has created a great impact on mental health in society. Considering the little attention paid by scientific studies to either students or university staff during lockdown, the current study has two aims: (a) to analyze the evolution of mental health and (b) to identify predictors of educational/professional experience and online learning/teaching experience. (2) Methods: 1084 university students and 554 staff in total from four different countries (Spain, Colombia, Chile and Nicaragua) participated in the study, affiliated with nine different universities, four of them Spanish and one of which was online. We used an online survey known as LockedDown, which consists of 82 items, analyzed with classical multiple regression analyses and machine learning techniques. (3) Results: Stress level and feelings of anxiety and depression of students and staff either increased or remained over the weeks. A better online learning experience for university students was associated with the age, perception of the experience as beneficial and support of the university. (4) Conclusions: The study has shown evidence of the emotional impact and quality of life for both students and staff. For students, the evolution of feelings of anxiety and depression, as well as the support offered by the university affected the educational experience and online learning. For staff who experienced a positive professional experience, with access to services and products, the quality-of-life levels were maintained.
Maintaining Medical Resources to Treat Paediatric Injuries during COVID-19 Lockdown Is Essential—An Epidemiological Analysis of a Level 1 Trauma Centre in Central Europe
Authors: Payr Stephan , Schuller Andrea , Dangl Theresia , Scheider Philipp , Sator Thomas , Chocholka Britta , Jaindl Manuela , Schwendenwein Elisabeth , Tiefenboeck Thomas M.
Published: May 2021

Background: This study examined the effect of the COVID-19 pandemic and the resulting decrease in the incidence of various categories of injuries, with the main focus on fractures and mild traumatic brain injuries in a paediatric population. Methods: This retrospective cohort study evaluated all children from 0 to 18 years of age presenting with an injury at the level 1 trauma centre of the University Clinic of Orthopaedics and Trauma Surgery in Vienna during the lockdown from 16 March to 29 May 2020 compared to records over the same timeframe from 2015 to 2019. Results: In total, 14,707 patients with injuries were included. The lockdown did not lead to a significant decrease in fractures but, instead, yielded a highly significant increase in mild traumatic brain injuries when compared to all injuries that occurred (p = 0.082 and p = 0.0001) as well as acute injuries (excluding contusions, distortions and miscellaneous non-acute injuries) (p = 0.309 and p = 0.034). Conclusions: The percentage of paediatric fractures did not decrease at the level 1 trauma centre, and a highly significant proportional increase in paediatric patients with mild traumatic brain injuries was observed during the COVID-19 lockdown. Therefore, medical resources should be maintained to treat paediatric trauma patients and provide neurological monitoring during pandemic lockdowns.
The Moderating Role of Corporate Social Responsibility in the Association of Internal Corporate Governance and Profitability; Evidence from Pakistan
Authors: Lu Jihai , Javeed Sohail Ahmad , Latief Rashid , Jiang Tao , Ong Tze San
Published: May 2021

At present, climate and other environmental problems are arising because of the development of the industrial sector at a large level. The industrial sector is supposed to be a major cause of climate change problems that lead to global warming. Therefore, corporate social responsibility (CSR) with the help of corporate governance is an imperative approach to control these social problems. Consequently, in the context of the organizational and management theory, agency theory, and the stakeholder theory, this study focuses on important factors of internal corporate governance such as chief executive officer (CEO) power, the board size, independence, ownership concentration, managerial ownership, and audit quality for improving the profitability of firms. Moreover, this study considers corporate social responsibility as a controlling and moderating factor for firm performance and internal corporate governance. We employed ordinary least square (OLS) for endogeneity testing, fixed effect (FE), generalized method of moments (GMM), and feasible generalized least square (FGLS) on data of Pakistani firms for the period of 2010–2019. The results of this study demonstrate the following outcomes: firstly, all internal corporate governance factors are positively linked with firm performance; secondly, corporate social responsibility (CSR) is the most valuable tool for improving profitability. Importantly, this study suggests that all internal corporate governance factors are positively linked with firm performance because of the interactive role of corporate social responsibility (CSR). This study practically contributes to the literature by suggesting the imperative role of corporate social responsibility (CSR) for internal corporate governance, which may help to reduce climate and social problems.
Wellbeing of Indigenous Peoples in Canada, Aotearoa (New Zealand) and the United States: A Systematic Review
Authors: Gall Alana , Anderson Kate , Howard Kirsten , Diaz Abbey , King Alexandra , Willing Esther , Connolly Michele , Lindsay Daniel , Garvey Gail
Published: May 2021

Despite the health improvements afforded to non-Indigenous peoples in Canada, Aotearoa (New Zealand) and the United States, the Indigenous peoples in these countries continue to endure disproportionately high rates of mortality and morbidity. Indigenous peoples’ concepts and understanding of health and wellbeing are holistic; however, due to their diverse social, political, cultural, environmental and economic contexts within and across countries, wellbeing is not experienced uniformly across all Indigenous populations. We aim to identify aspects of wellbeing important to the Indigenous people in Canada, Aotearoa and the United States. We searched CINAHL, Embase, PsycINFO and PubMed databases for papers that included key Indigenous and wellbeing search terms from database inception to April 2020. Papers that included a focus on Indigenous adults residing in Canada, Aotearoa and the United States, and that included empirical qualitative data that described at least one aspect of wellbeing were eligible. Data were analysed using the stages of thematic development recommended by Thomas and Harden for thematic synthesis of qualitative research. Our search resulted in 2669 papers being screened for eligibility. Following full-text screening, 100 papers were deemed eligible for inclusion (Aotearoa (New Zealand) n = 16, Canada n = 43, United States n = 41). Themes varied across countries; however, identity, connection, balance and self-determination were common aspects of wellbeing. Having this broader understanding of wellbeing across these cultures can inform decisions made about public health actions and resources.
Use of Respiratory Protection Devices by Medical Students during the COVID-19 Pandemic
Authors: Shashina Ekaterina A. , Makarova Valentina V. , Shcherbakov Denis V. , Isiutina-Fedotkova Tatiana S. , Zabroda Nadezhda N. , Ermakova Nina A. , Skopin Anton Yu. , Mitrokhin Oleg V.
Published: May 2021

The use of face masks has assumed a leading spot among nonspecific prevention measures during the coronavirus pandemic. The effectiveness of this protective measure depends on the specifics of individual use. The purpose of our study was to analyze the use of respiratory protective equipment (RPE) by medical students during the COVID-19 pandemic. The evaluation of face mask use was based on the results of a survey of medical students at Sechenov University. There were 988 participants in the study: 97.5% used RPE during the pandemic, 89.1% used disposable medical and hygienic face masks, 27.4% used reusable cloth face masks, and 13.2% used respirators. The majority of respondents (75.2%) were found to wear face masks correctly. However, 17.0% of the respondents were found to cover only their mouths with a face mask, while 7.8% reported often shifting their face mask under the chin due to perceived discomfort. Only 25.1% of respondents changed their disposable face mask after 2–3 h of wearing, while 13.0% decontaminated and used it several times. Most cloth face mask users (93.7%) decontaminated their marks, but only 55.7% of respondents did so daily. Face masks were most often worn in medical organizations (91.5%), and 1.4% of respondents did not use respiratory protection anywhere. In conclusion, we consider it necessary to introduce a special module on nonspecific prevention in the discipline of hygiene.
Hijacked Immune Cells in the Tumor Microenvironment: Molecular Mechanisms of Immunosuppression and Cues to Improve T Cell-Based Immunotherapy of Solid Tumors
Authors: Balta Emre , Wabnitz Guido H. , Samstag Yvonne
Published: May 2021

The understanding of the tumor microenvironment (TME) has been expanding in recent years in the context of interactions among different cell types, through direct cell–cell communication as well as through soluble factors. It has become evident that the development of a successful antitumor response depends on several TME factors. In this context, the number, type, and subsets of immune cells, as well as the functionality, memory, and exhaustion state of leukocytes are key factors of the TME. Both the presence and functionality of immune cells, in particular T cells, are regulated by cellular and soluble factors of the TME. In this regard, one fundamental reason for failure of antitumor responses is hijacked immune cells, which contribute to the immunosuppressive TME in multiple ways. Specifically, reactive oxygen species (ROS), metabolites, and anti-inflammatory cytokines have central roles in generating an immunosuppressive TME. In this review, we focused on recent developments in the immune cell constituents of the TME, and the micromilieu control of antitumor responses. Furthermore, we highlighted the current challenges of T cell-based immunotherapies and potential future strategies to consider for strengthening their effectiveness.
The Organization of the Golgi Structures during Drosophila Male Meiosis Requires the Citrate Lyase ATPCL
Authors: Morciano Patrizia , Di Giorgio Maria Laura , Tullo Liliana , Cenci Giovanni
Published: May 2021

During spermatogenesis, the Golgi apparatus serves important roles including the formation of the acrosome, which is a sperm-specific organelle essential for fertilization. We have previously demonstrated that D. melanogaster ATP-dependent Citrate Lyase (ATPCL) is required for spindle organization, cytokinesis, and fusome assembly during male meiosis, mainly due to is activity on fatty acid biosynthesis. Here, we show that depletion of DmATPCL also affects the organization of acrosome and suggest a role for this enzyme in the assembly of Golgi-derived structures during Drosophila spermatogenesis.
Fine-Tuning Phylogenetic Alignment and Haplogrouping of mtDNA Sequences
Authors: Dür Arne , Huber Nicole , Parson Walther
Published: May 2021

In this paper, we present a new algorithm for alignment and haplogroup estimation of mitochondrial DNA (mtDNA) sequences. Based on 26,011 vetted full mitogenome sequences, we refined the 5435 original haplogroup motifs of Phylotree Build 17 without changing the haplogroup nomenclature. We adapted 430 motifs (about 8%) and added 966 motifs for yet undetermined subclades. In summary, this led to an 18% increase of haplogroup defining motifs for full mitogenomes and a 30% increase for the mtDNA control region that is of interest for a variety of scientific disciplines, such as medical, population and forensic genetics. The new algorithm is implemented in the EMPOP mtDNA database and is freely accessible.
The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression
Authors: Zou Tingting , Lin Zhenghong
Published: May 2021

The cell cycle is a collection of events by which cellular components such as genetic materials and cytoplasmic components are accurately divided into two daughter cells. The cell cycle transition is primarily driven by the activation of cyclin-dependent kinases (CDKs), which activities are regulated by the ubiquitin-mediated proteolysis of key regulators such as cyclins, CDK inhibitors (CKIs), other kinases and phosphatases. Thus, the ubiquitin-proteasome system (UPS) plays a pivotal role in the regulation of the cell cycle progression via recognition, interaction, and ubiquitination or deubiquitination of key proteins. The illegitimate degradation of tumor suppressor or abnormally high accumulation of oncoproteins often results in deregulation of cell proliferation, genomic instability, and cancer occurrence. In this review, we demonstrate the diversity and complexity of the regulation of UPS machinery of the cell cycle. A profound understanding of the ubiquitination machinery will provide new insights into the regulation of the cell cycle transition, cancer treatment, and the development of anti-cancer drugs.
Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening in Saccharomyces cerevisiae
Authors: Kipanga Purity N. , Demuyser Liesbeth , Vrijdag Johannes , Eskes Elja , D’hooge Petra , Matasyoh Josphat , Callewaert Geert , Winderickx Joris , Van Dijck Patrick , Luyten Walter
Published: May 2021

Polygodial is a “hot” peppery-tasting sesquiterpenoid that was first described for its anti-feedant activity against African armyworms. Using the haploid deletion mutant library of Saccharomyces cerevisiae, a genome-wide mutant screen was performed to shed more light on polygodial’s antifungal mechanism of action. We identified 66 deletion strains that were hypersensitive and 47 that were highly resistant to polygodial treatment. Among the hypersensitive strains, an enrichment was found for genes required for vacuolar acidification, amino acid biosynthesis, nucleosome mobilization, the transcription mediator complex, autophagy and vesicular trafficking, while the resistant strains were enriched for genes encoding cytoskeleton-binding proteins, ribosomal proteins, mitochondrial matrix proteins, components of the heme activator protein (HAP) complex, and known regulators of the target of rapamycin complex 1 (TORC1) signaling. WE confirm that polygodial triggers a dose-dependent vacuolar alkalinization and that it increases Ca2+ influx and inhibits glucose-induced Ca2+ signaling. Moreover, we provide evidence suggesting that TORC1 signaling and its protective agent ubiquitin play a central role in polygodial resistance, suggesting that they can be targeted by polygodial either directly or via altered Ca2+ homeostasis.
Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies
Authors: Owen Manon D. , Baker Bernadette C. , Scott Eleanor M. , Forbes Karen
Published: May 2021

Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.
Protease Inhibition—An Established Strategy to Combat Infectious Diseases
Authors: Sojka Daniel , Šnebergerová Pavla , Robbertse Luïse
Published: May 2021

Therapeutic agents with novel mechanisms of action are urgently needed to counter the emergence of drug-resistant infections. Several decades of research into proteases of disease agents have revealed enzymes well suited for target-based drug development. Among them are the three recently validated proteolytic targets: proteasomes of the malarial parasite Plasmodium falciparum, aspartyl proteases of P. falciparum (plasmepsins) and the Sars-CoV-2 viral proteases. Despite some unfulfilled expectations over previous decades, the three reviewed targets clearly demonstrate that selective protease inhibitors provide effective therapeutic solutions for the two most impacting infectious diseases nowadays—malaria and COVID-19.
Integration of the Microbiome, Metabolome and Transcriptomics Data Identified Novel Metabolic Pathway Regulation in Colorectal Cancer
Authors: Bisht Vartika , Nash Katrina , Xu Yuanwei , Agarwal Prasoon , Bosch Sofie , Gkoutos Georgios V. , Acharjee Animesh
Published: May 2021

Integrative multiomics data analysis provides a unique opportunity for the mechanistic understanding of colorectal cancer (CRC) in addition to the identification of potential novel therapeutic targets. In this study, we used public omics data sets to investigate potential associations between microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing datasets. We identified multiple potential interactions, for example 5-aminovalerate interacting with Adlercreutzia; cholesteryl ester interacting with bacterial genera Staphylococcus, Blautia and Roseburia. Using public single cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the ACAT1 gene that indirectly regulates the esterification of cholesterol. These findings demonstrate that the integration of multiomics data sets from diverse populations can help us in untangling the colorectal cancer pathogenesis as well as postulate the disease pathology mechanisms and therapeutic targets.
Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
Authors: Chandrasekaran Arun Pandian , Woo Sang Hyeon , Sarodaya Neha , Rhie Byung Ho , Tyagi Apoorvi , Das Soumyadip , Suresh Bharathi , Ko Na Re , Oh Seung Jun , Kim Kye-Seong , Ramakrishna Suresh
Published: May 2021

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.
Challenging Safety and Efficacy of Retinal Gene Therapies by Retinogenesis
Authors: Marrocco Elena , Maritato Rosa , Botta Salvatore , Esposito Marianna , Surace Enrico Maria
Published: May 2021

Gene-expression programs modulated by transcription factors (TFs) mediate key developmental events. Here, we show that the synthetic transcriptional repressor (TR; ZF6-DB), designed to treat Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP), does not perturb murine retinal development, while maintaining its ability to block Rho expression transcriptionally. To express ZF6-DB into the developing retina, we pursued two approaches, (i) the retinal delivery (somatic expression) of ZF6-DB by Adeno-associated virus (AAV) vector (AAV-ZF6-DB) gene transfer during retinogenesis and (ii) the generation of a transgenic mouse (germ-line transmission, TR-ZF6-DB). Somatic and transgenic expression of ZF6-DB during retinogenesis does not affect retinal function of wild-type mice. The P347S mouse model of RHO-adRP, subretinally injected with AAV-ZF6-DB, or crossed with TR-ZF6-DB or shows retinal morphological and functional recovery. We propose the use of developmental transitions as an effective mode to challenge the safety of retinal gene therapies operating at genome, transcriptional, and transcript levels.
Calpastatin-Mediated Inhibition of Calpain Ameliorates Skin Scar Formation after Burn Injury
Authors: Seo Cheong Hoon , Cui Hui Song , Kim June-Bum
Published: May 2021

Hypertrophic scars, the most common complication of burn injuries, are characterized by excessive deposition of fibroblast-derived extracellular matrix proteins. Calpain, a calcium-dependent protease, is involved in the fibroblast proliferation and extracellular matrix production observed in certain fibrotic diseases. However, its role in the formation of post-burn hypertrophic skin scars remains largely unknown. Here, calpain expression and activity were assessed in skin fibroblasts obtained directly from patients with third-degree burns, who consequently developed post-burn hypertrophic scars. Furthermore, the antifibrotic effect of calpastatin, an endogenous calpain inhibitor, was evaluated in human fibroblasts and a murine burn model. The activity, mRNA levels, and protein levels of calpain were markedly higher in fibroblasts from the burn wounds of patients than in normal cells. Selective calpain inhibition by calpastatin markedly reduced not only the proliferation of burn-wound fibroblasts but also the mRNA and protein expression of calpain, transforming growth factor-beta 1, α-smooth muscle actin, type I and type III collagens, fibronectin, and vimentin in burn-wound fibroblasts. The anti-scarring effects of calpastatin were validated using a murine burn model by molecular, histological, and visual analyses. This study demonstrates the pathological role of calpain and the antifibrotic effect of calpastatin via calpain inhibition in post-burn hypertrophic scar formation.
Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain
Authors: Ozen Maide , Kitase Yuma , Vasan Vikram , Burkhardt Christopher , Ramachandra Sindhu , Robinson Shenandoah , Jantzie Lauren L.
Published: May 2021

Chorioamnionitis (CHORIO), placental insufficiency, and preterm birth are well-known antecedents of perinatal brain injury (PBI). Heme-oxygenase-1 (HO-1) is an important inducible enzyme in oxidative and inflammatory conditions. In the brain, HO-1 and the iron regulatory receptor, transferrin receptor-1 (TfR1), are known to be involved in iron homeostasis, oxidative stress, and cellular adaptive mechanisms. However, the role of HO pathway in the pathophysiology of PBI has not been previously studied. In this study, we set out to define the ontogeny of the HO pathway in the brain and determine if CHORIO changed its normal developmental regulation. We also aimed to determine the role of HO-1/TfR1 in CHORIO-induced neuroinflammation and peripheral inflammation in a clinically relevant rat model of PBI. We show that HO-1, HO-2, and TfR1 expression are developmentally regulated in the brain during the perinatal period. CHORIO elevates HO-1 and TfR1 mRNA expression in utero and in the early postnatal period and results in sustained increase in HO-1/TfR1 ratios in the brain. This is associated with neuroinflammatory and peripheral immune phenotype supported by a significant increase in brain mononuclear cells and peripheral blood double negative T cells suggesting a role of HO-1/TfR1 pathway dysregulation in CHORIO-induced neuroinflammation.
Macrophages/Microglia in the Glioblastoma Tumor Microenvironment
Authors: Ma Jun , Chen Clark C. , Li Ming
Published: May 2021

The complex interaction between glioblastoma and its microenvironment has been recognized for decades. Among various immune profiles, the major population is tumor-associated macrophage, with microglia as its localized homolog. The present definition of such myeloid cells is based on a series of cell markers. These good sentinel cells experience significant changes, facilitating glioblastoma development and protecting it from therapeutic treatments. Huge, complicated mechanisms are involved during the overall processes. A lot of effort has been dedicated to crack the mysterious codes in macrophage/microglia recruiting, activating, reprogramming, and functioning. We have made our path. With more and more key factors identified, a lot of new therapeutic methods could be explored to break the ominous loop, to enhance tumor sensitivity to treatments, and to improve the prognosis of glioblastoma patients. However, it might be a synergistic system rather than a series of clear, stepwise events. There are still significant challenges before the light of truth can shine onto the field. Here, we summarize recent advances in this field, reviewing the path we have been on and where we are now.