bluuebunny/crossref_metadata_2025 huggingface dataset:
Smokers Are More Likely to Smoke More after the COVID-19 California Lockdown Order
Authors: Gonzalez Mariaelena , Epperson Anna E. , Halpern-Felsher Bonnie , Halliday Deanna M. , Song Anna V.
Published: March 2021

To determine if cigarette smoking, electronic cigarette use, and rate of consumption of these products differed before and after a pandemic lockdown order, two convenience samples of adults in Central California were recruited and surveyed before (March 2020) and after (May 2020) COVID-19 lockdown orders were implemented in California (n = 2571). Multivariable logistic and negative binomial regression models tested the association between adults recruited pre- or post-California lockdown and past month cigarette use, past month electronic cigarette use, past month cigarette consumption, and past month e-cigarette consumption among current users, controlling for demographic differences. Adults pre- and post-lockdown had equal odds of using cigarettes during the past month. Cigarette users who responded post-lockdown had higher cigarette consumption rates compared to cigarette users who responded pre-lockdown (IRR = 1.13, 95% CI = 1.15, 1.23). Adults who responded post-lockdown had lower odds of using electronic cigarettes during the past month compared to participants surveyed before the order (OR = 0.66, 95% CI: 0.55, 0.78). Cigarette users may be using more cigarettes during the state mandated lockdown. Possible causes for this increase in cigarette use may include increased stress, the change in workplace smokefree protections coverage, and increased opportunities for smoking or vaping.
Firm Growth as a Driver of Sustainable Product Innovation: Mediation and Moderation Analysis. Evidence from Manufacturing Firms
Authors: Labella-Fernández Ana , Serrano-Arcos M. Mar , Payán-Sánchez Belén
Published: March 2021

Facing worldwide environmental and social concerns, manufacturing firms are trying to adopt effective environmentally friendly actions to mitigate their environmental impacts. Although the existent literature has provided many insights about the drivers of sustainable product innovation, little is known about the impact of firm growth. Thus, we intend to contribute to this gap in the literature by examining the impact that firm growth can have on sustainable product innovation. To achieve this goal, the partial least square (PLS) modeling technique was used to analyze a dataset of 3250 manufacturing firms from 39 different countries. The results reveal that firm growth exerts a positive effect on sustainable product innovation and that the relationship is partially mediated by the adoption of environmental practices. The findings also indicate that managerial barriers lessen the effectiveness of the adoption of environmental practices in facilitating the development of sustainable product innovation, while improving labor conditions increases it. However, operational barriers do not exert a significant moderating effect between the adoption of environmental practices and sustainable product innovation. These results prompt interesting insights related to theory development in environmental management and sustainable product innovation research.
Microbiological Health Risk Assessment of Water Conservation Strategies: A Case Study in Amsterdam
Authors: Kusumawardhana Agung , Zlatanovic Ljiljana , Bosch Arne , van der Hoek Jan Peter
Published: March 2021

The aim of this study was to assess the health risks that may arise from the implementation of greywater reuse and rainwater harvesting for household use, especially for toilet flushing. In addition, the risk of cross connections between these systems and the drinking water system was considered. Quantitative microbial risk assessment (QMRA) is a method that uses mathematical modelling to estimate the risk of infection when exposure to pathogens happens and was used in this study to assess the health risks. The results showed that using rainwater without prior treatment for toilet flushing poses an annual infection risk from L. pneumophila at 0.64 per-person-per-year (pppy) which exceeds the Dutch standard of 10−4 pppy. The use of untreated greywater showed a risk that is below the standard. However, treatment is recommended due to the ability of P. aeruginosa to grow in the reuse system. Moreover, showering and drinking with cross-connected water has a high annual infection risk that exceeds the standard due to contact with Staphylococcus aureus and E. coli O157:H7. Several measures can be implemented to mitigate the risks such as treating the greywater and rainwater with a minimum of 5-log removal, closing the toilet lid while flushing, good design of greywater and rainwater collection systems, and rigorous plumbing installation procedures.
How Are Consensual, Non-Consensual, and Pressured Sexting Linked to Depression and Self-Harm? The Moderating Effects of Demographic Variables
Authors: Wachs Sebastian , Wright Michelle F. , Gámez-Guadix Manuel , Döring Nicola
Published: March 2021

Sexting among adolescents has triggered controversial debates among scholars and the general public. However, questions regarding the associations between different types of sexting, namely consensual, non-consensual, and pressured sexting, depressive symptoms, and non-suicidal self-harm remain. In addition, little attention has been given to whether demographic variables (i.e., gender, ethnicity, disability, sexual minority) might influence these associations. To fill these gaps in the literature, the present study was conducted. Participants were 2506 adolescents (ages 13–16 years old; Mage = 15.17; SDage = 0.89) from eight high schools located in the suburbs of a large Midwestern city in the United States. Adolescents self-identified as female (50%), Caucasian (57%), approximately 15% reported that they had a disability they received school accommodation for, and 18% self-identified as a sexual minority. They completed self-report questionnaires on their sexting behaviors, depressive symptoms, and non-suicidal self-harm. Findings revealed that non-consensual and pressured sexting were positively related to depressive symptoms and non-suicidal self-harm, whereas consensual sexting was unrelated to these outcomes. Boys engaged in more non-consensual sexting compared with girls, girls were more pressured to send sexts compared with boys, and sexual minority adolescents reported greater consensual sexting compared with non-sexual minority adolescents. Moderating effects revealed that girls, non-minority adolescents, and non-sexual minority adolescents experienced greater depressive symptoms and non-suicidal self-harm when they experienced pressured sexting. These findings underscore the importance of considering various types of sexting and adolescents’ demographic variables when examining the negative outcomes of sexting. Disentangling the relationships among different types of sexting, depressive symptoms, and self-harm aids in the development of evidence-based recommendations for sexting harm prevention and sexual education programs.
Looking for Commensality: On Culture, Health, Heritage, and the Mediterranean Diet
Authors: Medina Francesc-Xavier
Published: March 2021

The concept of the Mediterranean Diet has substantially evolved in the last decade and a half. From a model focused uniquely on nutrition and public health, in recent years, and after its registration as Intangible Heritage of the Humanity by the United Nations Educational, Scientific and Cultural Organization (UNESCO), its conception incorporated important elements related to society, culture, and sustainability. In this regard, the use of concepts such as commensality (or conviviality around food, or eating together), linked to a more cultural vision of food, began to be one object of attention. The aim of this article is to reflect on the role of these “new” elements regarding the actual definitions of the Mediterranean diet and, particularly, its relationship with other significant discourses inside this concept, as the preponderant of health, or the emergence of sustainability.
French Public Familiarity and Attitudes toward Clinical Research during the COVID-19 Pandemic
Authors: Schultz Émilien , Ward Jeremy K. , Atlani-Duault Laëtitia , Holmes Seth M. , Mancini Julien
Published: March 2021

The COVID-19 pandemic put clinical research in the media spotlight globally. This article proposes a first measure of familiarity with and attitude toward clinical research in France. Drawing from the “Health Literacy Survey 2019” (HLS19) conducted online between 27 May and 5 June 2020 on a sample of the French adult population (N = 1003), we show that a significant proportion of the French population claimed some familiarity with clinical trials (64.8%) and had positive attitudes (72%) toward them. One of the important findings of this study is that positive attitudes toward clinical research exist side by side with a strong distancing from the pharmaceutical industry. While respondents acknowledged that the pharmaceutical industry plays an important role in clinical research (68.3%), only one-quarter indicated that they trust the industry (25.7%). Positive attitudes toward clinical trials were associated with familiarity with clinical trials (Odds Ratio, OR 2.97 [1.90–4.63]), financial difficulties (OR 0.63 [0.46–0.85]), as well as mistrust of doctors (0.48 [0.27–0.85]) and of scientists (OR 0.62 [0.38–0.99]). Although the French media provided a great deal of information on how clinical research works during the first months of the pandemic, there remains profound mistrust of the pharmaceutical industry in France. This suspicion can undermine crisis management, especially in the areas of vaccine development and preparation for future pandemics.
Adaptation and Psychometric Analysis of the Test of Mobile Phone Dependence—Brief Version in Italian Adolescents
Authors: Cerutti Rita , Presaghi Fabio , Spensieri Valentina , Fontana Andrea , Amendola Simone
Published: March 2021

Since the diffusion of recent models of mobile phones, anyone with an internet connection can communicate continuously and search for information. This raises some questions about the possible consequences of problematic mobile phone use (PMPU) in a complex life phase such as adolescence. Therefore, we performed a psychometric analysis of the brief version of the Test of Mobile Phone Dependence (TMD) in Italy. The sample comprised 575 Italian adolescents aged 11 to 18 years. Data were collected using the TMD-brief, the Personality Inventory for the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form. Regarding test dimensionality, the best-fit measurement model included four factors: “Abstinence”; “Abuse and interference with other activities”; “Tolerance”; and “Lack of control” (Satorra–Bentler χ2 (48) = 185.96, p < 0.01; robust root mean square error of approximation (RMSEA) = 0.079 (90% confidence interval (CI): 0.067; 0.091); robust TLI = 0.904; robust comparative fit index (CFI) = 0.930). The Italian version of the TMD-brief was found to have good reliability and psychometric properties, and a four-factorial structure. PMPU predicted significant sleep disturbances and this relationship was moderated by clinical personality traits. Findings from this study support the use of the Italian version of the TMD-brief as a screening tool to investigate PMPU in Italian adolescents.
Process of Work Disability: From Determinants of Sickness Absence Trajectories to Disability Retirement in a Long-Term Follow-Up of Municipal Employees
Authors: Leino-Arjas Päivi , Seitsamo Jorma , Nygård Clas-Håkan , K.C. Prakash , Neupane Subas
Published: March 2021

Work disability may originate early during work history and involve sickness absences (SA) and eventually permanent disability. We studied this process over 15 years. Questionnaire data collected in 1981 on health, working conditions, and lifestyle of Finnish municipal employees aged 44–58 years (n = 6257) were linked with registers on SA (≥10 workdays), disability pension, and death from the period 1986–1995. Trajectory analysis was used to assess development in SA (days/year) over 5 years (1981–1985). We analyzed determinants of the trajectories with multinomial regression, while trajectory membership was used as a predictor of disability pension (DP) during the subsequent 10 years in survival analysis. Three SA trajectories emerged: increasing (women: 6.8%; men: 10.2%), moderate (21.2%; 22.7%), and low. In a mutually adjusted model, the increasing trajectory in women was associated with baseline musculoskeletal (MSD), mental and respiratory disorders, injuries, obesity, sleep problems, and low exercise (effect sizes OR > 2), and in men with MSD, sleep problems, smoking, low exercise, and non-satisfaction with management. The moderate trajectory associated with MSD, ‘other somatic disorders’, sleep problems, and awkward work postures in both genders; in women, also overweight, cardiovascular and respiratory morbidity, and (inversely) knowledge-intensive work, and in men, smoking and mental disorders were thus associated. Ten-year risks of DP contrasting increasing vs. low SA were more than 10-fold in both genders and contrasting moderate vs. low SA 3-fold in women and 2-fold in men. These findings emphasize the need for early identification of workers with short-term problems of work ability and interventions regarding lifestyle, health, and working conditions, to help prevent permanent disability.
Perception of Attitudes of the General Population toward Homosexuality in Taiwan: Roles of Demographic Factors, Mental Health, and Social Debates on Legalizing Same-Sex Marriage
Authors: Lin Huang-Chi , Chen Yi-Lung , Ko Nai-Ying , Chang Yu-Ping , Lu Wei-Hsin , Yen Cheng-Fang
Published: March 2021

The aims of this online survey study were to examine the associations of demographic characteristics (gender, age, and sexual orientation), mental health status, and point in time of the survey (i.e., the beginning of the social debates on legalizing same-sex marriage vs. the end of the social debates) with people’s perception of the attitudes of the general population in Taiwan toward homosexuality. A two-wave internet survey was conducted using Facebook to gather information regarding people’s perception of the population’s attitudes toward homosexuality among 4562 participants. The five-item Brief Symptom Rating Scale was used for assessing mental health status. The results indicated that participants perceived the population as having a lower acceptance at the end of the social debates on legalizing same-sex marriage than at the beginning of the social debates; gender moderated the decline in perceived acceptance. The results also indicated that poor mental health and heterosexual orientation were significantly associated with a lower perception of the population’s homosexuality acceptance in both waves of the survey. The factors related to perceived homosexuality acceptance need to be considered in developing programs to increase the population’s homosexuality acceptance.
Psychosocial Effects and Use of Communication Technologies during Home Confinement in the First Wave of the COVID-19 Pandemic in Italy and The Netherlands
Authors: Bastoni Sofia , Wrede Christian , Ammar Achraf , Braakman-Jansen Annemarie , Sanderman Robbert , Gaggioli Andrea , Trabelsi Khaled , Masmoudi Liwa , Boukhris Omar , Glenn Jordan M. , Bouaziz Bassem , Chtourou Hamdi , van Gemert-Pijnen Lisette
Published: March 2021

(1) Background: The COVID-19 pandemic forced people from all around the globe to strongly modify their daily routines, putting a significant strain on the social aspects of daily lives. While the first wave of the pandemic was a very challenging time in all countries, it is still uncertain whether various lockdown intensities and infection rates differed regarding their psychosocial impact. This work therefore aimed to investigate (i) the psychosocial effects of home confinement in two European countries that underwent different lockdown intensities: Italy and the Netherlands and (ii) the role of communication technology in relation to feelings of loneliness. (2) Methods: A cross-sectional online survey inquiring about different psychosocial variables and the use of and satisfaction towards communication technology was circulated among the general public during the first wave of the COVID-19 pandemic. In total, 629 participants (66% female, 68% from the Netherlands) answered each question twice, referring to “before” and “during” the pandemic. (3) Results: We found significant negative effects of COVID-19 home confinement on depressive feelings (p < 0.001, %∆ = +54%), loneliness (p < 0.001, %∆ = +37.3%), life satisfaction (p < 0.001, %∆ = −19.8%) and mental wellbeing (p < 0.001, %∆ = −10.6%) which were accompanied with a significantly increased need for psychosocial support (p < 0.001, %∆ = +17.3%). However, the magnitude of psychosocial impact did not significantly differ between residents undergoing a more intense (Italy) versus a less intense (Netherlands) lockdown, although the decrease in social participation was found to be significantly different for both countries (z = −7.714, p < 0.001). Furthermore, our findings demonstrate that the increase in loneliness was associated with the adoption of new digital communication tools (r = 0.21, p < 0.001), and significantly higher for individuals who started to adopt at least one new digital communication tool during confinement than for those who did not (z = −4.252, p < 0.001). (4) Conclusions: This study highlights that, although COVID-19 home confinement significantly impacted psychosocial wellbeing during the first wave of the pandemic, this impact did not differ based on lockdown intensity. Recognizing the increasing adoption of digital communication technology in an attempt to reduce lockdown loneliness, future studies should investigate what is needed from the technology to achieve this effect.
Insecticide Filtration Efficiency of Respiratory Protective Equipment Commonly Worn by Farmers in Thailand
Authors: Sapbamrer Ratana , Hongsibsong Surat , Naksata Manoch , Naksata Wimol
Published: March 2021

Farmers are at a high risk of inhalation exposure when handling pesticides. Thai farmers usually protect themselves against pesticide exposure by wearing commercial respiratory protective equipment (RPE) available from rural community markets. However, scientific data regarding the pesticide filtration efficiency of RPE commonly worn by farmers is limited. Thus, this study aimed to investigate the efficiency of insecticide filtration of various RPE commonly worn by farmers in Thailand. The half facepiece respirator was used as a control to compare the results with other RPE. Ten types of RPE were selected for testing. The filtration efficiency of each RPE against insecticides was tested in a laboratory. The remarkable findings were that a surgical mask demonstrated the least filtration efficiency of all tested insecticides, with a range of 25.7–61.5%. The RPE available in rural markets of Thailand had a filtration efficiency within a range of 64.9–95.4%, whereas a half facepiece respirator was the most efficient in filtering insecticides, with a range of 96.5–98.9%. Therefore, our results suggest that the RPE most frequently worn by farmers may not provide adequate protection when compared with the respirator. However, considerations around RPE use in low-and middle-income countries and tropical climate conditions should be based on pesticide toxicity and practical use, ensuring balance between the risks from pesticide exposure and acceptance of PPE use.
Inuit Country Food and Health during Pregnancy and Early Childhood in the Circumpolar North: A Scoping Review
Authors: Caughey Amy B. , Sargeant Jan M. , Møller Helle , Harper Sherilee L.
Published: March 2021

Inuit communities in the Circumpolar North have experienced a nutrition transition characterized by the decreased intake of culturally important, nutrient-rich traditional food (country food), and an increased intake of market food, resulting in concerns over reduced diet quality and emerging chronic diseases. Nutrition in early life is critical for development, may influence health risks in later life, and is an important concern for Inuit community health. The goal of this scoping review was to characterize the nature, extent, and range of the published literature on Inuit country food and health in pregnancy and childhood. A search string was developed and applied to three databases, followed by title and abstract screening and full text review. Articles published between 1995 and 2019 were included, and data were extracted and summarized descriptively. The number of articles generally increased over time, despite the unequal geographic distribution of articles. The majority of the articles focused on environmental contaminants, and one-quarter described nutrient adequacy. Few articles described food security or food safety in pregnancy, and the most utilized quantitative methods. Gaps in understanding of country food use in pregnancy and early childhood highlight areas of future research to support public health policy for this population. Given the critical role of good nutrition in early life and the important contribution country food makes to diet quality for Inuit, further understanding of this interface is warranted.
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease
Authors: Zefferino Roberto , Piccoli Claudia , Di Gioia Sante , Capitanio Nazzareno , Conese Massimo
Published: March 2021

Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.
Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells
Authors: Venugopal Sathvika , Galano Melanie , Chan Rachel , Sanyal Esha , Issop Leeyah , Lee Sunghoon , Taylor Lorne , Kaur Pushwinder , Daly Edward , Papadopoulos Vassilios
Published: March 2021

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. cAMP stimulation also increased the movement of cholesterol from the PM compared to untreated cells, which was partially inhibited when ATPase family AAA-domain containing protein 3 A (ATAD3A), which functions in ER and mitochondria interactions, was knocked down. Mitochondria, ER, cytoplasm, PM, PM-associated membranes (PAMs), and mitochondria-associated membranes (MAMs) were isolated from control and hormone-stimulated cells. Lipidomic analyses revealed that each isolated compartment had a unique lipid composition, and the induction of steroidogenesis caused the significant remodeling of its lipidome. cAMP-induced changes in lipid composition included an increase in phosphatidylserine and cardiolipin levels in PAM and PM compartments, respectively; an increase in phosphatidylinositol in the ER, mitochondria, and MAMs; and a reorganization of phosphatidic acid, cholesterol ester, ceramide, and phosphatidylethanolamine. Abundant lipids, such as phosphatidylcholine, were not affected by hormone treatment. Our data suggested that PM–ER–mitochondria tethering may be involved in lipid trafficking between organelles and indicated that hormone-induced acute steroid production involves extensive organelle remodeling.
Genetic Regulation of Physiological Reproductive Lifespan and Female Fertility
Authors: McGrath Isabelle M. , Mortlock Sally , Montgomery Grant W.
Published: March 2021

There is substantial genetic variation for common traits associated with reproductive lifespan and for common diseases influencing female fertility. Progress in high-throughput sequencing and genome-wide association studies (GWAS) have transformed our understanding of common genetic risk factors for complex traits and diseases influencing reproductive lifespan and fertility. The data emerging from GWAS demonstrate the utility of genetics to explain epidemiological observations, revealing shared biological pathways linking puberty timing, fertility, reproductive ageing and health outcomes. The observations also identify unique genetic risk factors specific to different reproductive diseases impacting on female fertility. Sequencing in patients with primary ovarian insufficiency (POI) have identified mutations in a large number of genes while GWAS have revealed shared genetic risk factors for POI and ovarian ageing. Studies on age at menopause implicate DNA damage/repair genes with implications for follicle health and ageing. In addition to the discovery of individual genes and pathways, the increasingly powerful studies on common genetic risk factors help interpret the underlying relationships and direction of causation in the regulation of reproductive lifespan, fertility and related traits.
The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung
Authors: Ruaro Barbara , Salton Francesco , Braga Luca , Wade Barbara , Confalonieri Paola , Volpe Maria Concetta , Baratella Elisa , Maiocchi Serena , Confalonieri Marco
Published: March 2021

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.
Understanding the Pathophysiology of Thrombotic APS through Animal Models
Authors: Gandhi Alex A. , Estes Shanea K. , Rysenga Christine E. , Knight Jason S.
Published: March 2021

Antiphospholipid syndrome (APS) is a leading acquired cause of thrombotic events, with a notable tendency to promote thrombosis in vascular beds of all sizes, including both arterial and venous circuits. While pathogenic antiphospholipid antibodies circulate at relatively stable levels in blood, thrombosis tends to manifest as discrete and acute events, suggesting the requirement for a “second hit.” While this two-hit model is generally accepted, much remains to be learned about exactly how antiphospholipid antibodies predispose to thrombosis in vivo and exactly how this predisposition interacts with the second hit. To this end, investigators have turned to animal models. Numerous approaches for modeling APS in animals have been described to date, each with potential advantages and disadvantages. This review will attempt to describe the most common APS models employed so far while discussing some pros and cons of each. Mechanisms of thrombotic APS that have thus far been explored in animal models will also be briefly addressed.
Autoimmune Diseases in Patients with Premature Ovarian Insufficiency—Our Current State of Knowledge
Authors: Szeliga Anna , Calik-Ksepka Anna , Maciejewska-Jeske Marzena , Grymowicz Monika , Smolarczyk Katarzyna , Kostrzak Anna , Smolarczyk Roman , Rudnicka Ewa , Meczekalski Blazej
Published: March 2021

Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4–30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave’s disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto’s type thyroid antibodies and has a prevalence of 10–40%. 21OH-Antibodies in Addison’s disease (AD) can develop in association to APS-2.
Sex-Related Differences in Chronic Myeloid Neoplasms: From the Clinical Observation to the Underlying Biology
Authors: Karantanos Theodoros , Jain Tania , Moliterno Alison R. , Jones Richard J. , DeZern Amy E.
Published: March 2021

Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. Different groups have highlighted that men have overall worse survival and higher incidence of transformation to acute leukemia compared to women across neoplasms such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap neoplasms, and CML. More recent studies evaluating the genomic profile of patients with these neoplasms demonstrated a male predominance for mutations in high-risk genes including ASXL1, U2AF1, SRSF2 and ZRSR2. The understanding of the underlying biology is limited but a number of hypotheses have been developed and are currently being investigated. This review summarizes the current knowledge about sex-related differences in the clinical outcomes and genomic profile of patients with chronic myeloid neoplasms and discusses the hypothesized biologic mechanisms as an attempt to explain these observations.
CFTR Cooperative Cis-Regulatory Elements in Intestinal Cells
Authors: Collobert Mégane , Bocher Ozvan , Le Nabec Anaïs , Génin Emmanuelle , Férec Claude , Moisan Stéphanie
Published: March 2021

About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions of CREs, described as “cis-ruptions” have been identified as being involved in various genetic diseases. Thanks to the development of chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory elements were identified, but the regulatory mechanisms of the CFTR gene have yet to be fully elucidated. The aim of this work is to improve our knowledge of the CFTR gene regulation, and to identity factors that could impact the CFTR gene expression, and potentially account for the variability of the clinical presentation of cystic fibrosis as well as CFTR-related disorders. Here, we apply the robust GWAS3D score to determine which of the CFTR introns could be involved in gene regulation. This approach highlights four particular CFTR introns of interest. Using reporter gene constructs in intestinal cells, we show that two new introns display strong cooperative effects in intestinal cells. Chromatin immunoprecipitation analyses further demonstrate fixation of transcription factors network. These results provide new insights into our understanding of the CFTR gene regulation and allow us to suggest a 3D CFTR locus structure in intestinal cells. A better understand of regulation mechanisms of the CFTR gene could elucidate cases of patients where the phenotype is not yet explained by the genotype. This would thus help in better diagnosis and therefore better management. These cis-acting regions may be a therapeutic challenge that could lead to the development of specific molecules capable of modulating gene expression in the future.
5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells
Authors: Damiano Simona , La Rosa Giuliana , Sozio Concetta , Cavaliere Gina , Trinchese Giovanna , Raia Maddalena , Paternò Roberto , Mollica Maria Pina , Avvedimento Vittorio Enrico , Santillo Mariarosaria
Published: March 2021

Inside the adult CNS, oligodendrocyte progenitor cells (OPCS) are able to proliferate, migrate and differentiate into mature oligodendrocytes (OLs) which are responsible for the production of myelin sheet and energy supply for neurons. Moreover, in demyelinating diseases, OPCs are recruited to the lesion areas where they undergo differentiation and myelin synthesis. Serotonin (5-hydroxytryptamine, 5-HT) is involved in OLs’ development and myelination, but so far the molecular mechanisms involved or the effects of 5-HT on mitochondria function have not yet been well documented. Our data show that 5-HT inhibits migration and proliferation committing cells toward differentiation in an immortalized human oligodendrocyte precursor cell line, M03-13. Migration blockage is mediated by reactive oxygen species (ROS) generation since antioxidants, such as Vit C and Cu-Zn superoxide dismutase, prevent the inhibitory effects of 5-HT on cell migration. 5-HT inhibits OPC migration and proliferation and increases OL phenotypic markers myelin basic protein (MBP) and Olig-2 via protein kinase C (PKC) activation since the inhibitor of PKC, bis-indolyl-maleimide (BIM), counteracts 5-HT effects. NOX inhibitors as well, reverse the effects of 5-HT, indicating that 5-HT influences the maturation process of OPCs by NOX-dependent ROS production. Finally, 5-HT increases mitochondria function and antioxidant activity. The identification of the molecular mechanisms underlying the effects of 5-HT on maturation and energy metabolism of OPCs could pave the way for the development of new treatments for autoimmune demyelinating diseases such as Multiple Sclerosis where oligodendrocytes are the primary target of immune attack.
Drug Discovery in Liver Disease Using Kinome Profiling
Authors: Yu Bingting , Mamedov Ruslan , Fuhler Gwenny M. , Peppelenbosch Maikel P.
Published: March 2021

The liver is one of the most important organs, playing critical roles in maintaining biochemical homeostasis. Accordingly, disease of the liver is often debilitating and responsible for untold human misery. As biochemical nexus, with kinases being master regulators of cellular biochemistry, targeting kinase enzymes is an obvious avenue for treating liver disease. Development of such therapy, however, is hampered by the technical difficulty of obtaining comprehensive insight into hepatic kinase activity, a problem further compounded by the often unique aspects of hepatic kinase activities, which makes extrapolations from other systems difficult. This consideration prompted us to review the current state of the art with respect to kinome profiling approaches towards the hepatic kinome. We observe that currently four different approaches are available, all showing significant promise. Hence we postulate that insight into the hepatic kinome will quickly increase, leading to rational kinase-targeted therapy for different liver diseases.
Sitosterolemia: Twenty Years of Discovery of the Function of ABCG5ABCG8
Authors: Williams Kori , Segard Allison , Graf Gregory A.
Published: March 2021

Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either ABCG5 or ABCG8. ABCG5 ABCG8 encodes a pair of ABC half transporters that form a heterodimer (G5G8), which then traffics to the surface of hepatocytes and enterocytes and promotes the secretion of cholesterol and xenosterols into the bile and the intestinal lumen. We review the literature from the initial description of the disease, the discovery of its genetic basis, current therapy, and what has been learned from animal, cellular, and molecular investigations of the transporter in the twenty years since its discovery. The genomic era has revealed that there are far more carriers of loss of function mutations and likely pathogenic variants of ABCG5 ABCG8 than previously thought. The impact of these variants on G5G8 structure and activity are largely unknown. We propose a classification system for ABCG5 ABCG8 mutants based on previously published systems for diseases caused by defects in ABC transporters. This system establishes a framework for the comprehensive analysis of disease-associated variants and their impact on G5G8 structure–function.
Complex Concentrated Alloys for Substitution of Critical Raw Materials in Applications for Extreme Conditions
Authors: Mitrica Dumitru , Badea Ioana Cristina , Serban Beatrice Adriana , Olaru Mihai Tudor , Vonica Denisa , Burada Marian , Piticescu Radu-Robert , Popov Vladimir V.
Published: March 2021

The paper is proposing a mini-review on the capability of the new complex concentrated alloys (CCAs) to substitute or reduce the use of critical raw materials in applications for extreme conditions. Aspects regarding the regulations and expectations formulated by the European Union in the most recent reports on the critical raw materials were presented concisely. A general evaluation was performed on the CCAs concept and the research directions. The advantages of using critical metals for particular applications were presented to acknowledge the difficulty in the substitution of such elements with other materials. In order to establish the level of involvement of CCAs in the reduction of critical metal in extreme environment applications, a presentation was made of the previous achievements in the field and the potential for the reduction of critical metal content through the use of multi-component compositions.
Characterizing Mat Formation of Bamboo Fiber Composites: Horizontal Density Distribution
Authors: Hu Yu’an , He Mei , Semple Kate , Chen Meiling , Pineda Hugo , Zhou Chenli , Dai Chunping
Published: March 2021

Bamboo fiber composite (BFC) is a unidirectional and continuous bamboo fiber composite manufactured by consolidation and gluing of flattened, partially separated bamboo culm strips into thick and dense panels. The composite mechanical properties are primarily influenced by panel density, its variation and uniformity. This paper characterized the horizontal density distribution (HDD) within BFC panels and its controlling factors. It revealed that HDD follows a normal distribution, with its standard deviation (SD) strongly affected by sampling specimen size, panel thickness and panel locations. SD was lowest in the thickest (40 mm) panel and largest-size (150 × 150-mm2) specimens. There was also a systematic variation along the length of the BFC due to the tapering effect of bamboo culm thickness. Density was higher along panel edges due to restraint from the mold edges during hot pressing. The manual BFC mat forming process is presented and found to effectively minimize the density variation compared to machine-formed wood composites. This study provides a basic understanding of and a quality control guide to the formation uniformity of BFC products.
The Effect of Void Arrangement on the Pattern Transformation of Porous Soft Solids under Biaxial Loading
Authors: Qiu Hai , Li Ying , Guo Tianfu , Tang Shan , Xie Zhaoqian , Guo Xu
Published: March 2021

Structural topology and loading condition have important influences on the mechanical behaviors of porous soft solids. The porous solids are usually set to be under uniaxial tension or compression. Only a few studies have considered the biaxial loads, especially the combined loads of tension and compression. In this study, porous soft solids with oblique and square lattices of circular voids under biaxial loadings were studied through integrated experiments and numerical simulations. For the soft solids with oblique lattices of circular voids, we found a new pattern transformation under biaxial compression, which has alternating elliptic voids with an inclined angle. This kind of pattern transformation is rarely reported under uniaxial compression. Introducing tensile deformation in one direction can hamper this kind of pattern transformation under biaxial loading. For the soft solids with square lattices of voids, the number of voids cannot change their deformation behaviors qualitatively, but quantitatively. In general, our present results demonstrate that void morphology and biaxial loading can be harnessed to tune the pattern transformations of porous soft solids under large deformation. This discovery offers a new avenue for designing the void morphology of soft solids for controlling their deformation patterns under a specific biaxial stress-state.
Selected Properties of Formaldehyde-Free Polymer-Straw Boards Made from Different Types of Thermoplastics and Different Kinds of Straw
Authors: Mirski Radosław , Banaszak Aleksandra , Bekhta Pavlo
Published: March 2021

This research investigated the effects of different thermoplastics types and different kinds of straw on selected properties of polymer-straw boards. Polyethylene, polyethylene, and polystyrene of virgin and of recycled origin were used for bonding the boards. Three kinds of straw were used: rape (Brassica napus L. var. napus), triticale (Triticosecale Witt b m.), and rye (Secale L.). Five-layer polymer-straw boards were produced. The obtained boards differed in both the materials they were made of and the moisture content (7, 25, and 2% for the core, the middle, and the face layers, respectively), and 30% of straw particles were substituted with thermoplastics added to the face layers. It was found that properties of polymer-straw boards strongly depend on both the kind of straw and the type of polymer used. The best mechanical properties were obtained for rye straw and polystyrene or recycled polymers, whereas the best hydrophobic properties were observed for rape straw combined with recycled polyethylene or polypropylene. Although recycled polymers improved the hydrophobic properties of the boards, they impaired their mechanical properties in comparison with the reference ones. However, in terms of bending strength, they still met the requirements for heavy duty load-bearing boards for use in humid conditions (20 MPa for P7 boards according to EN 312).
The Sclerometrical, Mechanical, and Wear Behavior of Mg-Y-Nd Magnesium Alloy after Deep Cryogenic Treatment Combined with Heat Treatment
Authors: Barylski Adrian , Aniołek Krzysztof , Dercz Grzegorz , Kupka Marian , Matuła Izabela , Kaptacz Sławomir
Published: March 2021

The paper investigates changes in the structure, microhardness, and sclerometrical and tribological properties of a Mg-Y-Nd alloy under the influence of deep cryogenic treatment (DCT) in combination with heat treatment. The solution treatment was carried out at 545 °C for 8 h, aging was carried out at 250 °C for 24 h, and the deep cryogenic treatment applied at different treatment stages was performed at −196 °C. Tests showed a significant increase in the number of β-phase precipitates identified as Mg46.1Y6.25RE3.45 in the alloy subjected to DCT after solution treatment followed by aging. In addition, an approximately 20% reduction of the grain size was observed. Changes in the structure in the precipitation process strengthened the alloy and resulted in an increase of its hardness. At the same time, sclerometric tests allowed the micromechanism of wear and the coefficient of resistance to abrasive wear to be determined. Tribological tests showed a three-fold reduction in the volumetric wear and a considerable reduction of the friction coefficient, with the main mechanism observed during friction being abrasive wear. The most favorable properties of the alloy were obtained after precipitation hardening combined with DCT, resulting in a large increase in resistance to abrasive wear. Additionally, the formation of deep scratches in the examined material was reduced. The introduction of sub-zero treatment reduces the precipitation hardening time, and the results obtained indicate that the service life of the Mg-Y-Nd alloy can be extended.
Visco-Hyperelastic Characterization of the Equine Immature Zona Pellucida
Authors: Ficarella Elisa , Minooei Mohammad , Santoro Lorenzo , Toma Elisabetta , Trentadue Bartolomeo , De Spirito Marco , Papi Massimiliano , Pruncu Catalin I. , Lamberti Luciano
Published: March 2021

This article presents a very detailed study on the mechanical characterization of a highly nonlinear material, the immature equine zona pellucida (ZP) membrane. The ZP is modeled as a visco-hyperelastic soft matter. The Arruda–Boyce constitutive equation and the two-term Prony series are identified as the most suitable models for describing the hyperelastic and viscous components, respectively, of the ZP’s mechanical response. Material properties are identified via inverse analysis based on nonlinear optimization which fits nanoindentation curves recorded at different rates. The suitability of the proposed approach is fully demonstrated by the very good agreement between AFM data and numerically reconstructed force–indentation curves. A critical comparison of mechanical behavior of two immature ZP membranes (i.e., equine and porcine ZPs) is also carried out considering the information on the structure of these materials available from electron microscopy investigations documented in the literature.