bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Childhood Reading in Rural China and Obstacles to Caregiver Investment in Young Children: A Mixed-Methods Analysis
Authors: Li Rui , Rose Nathan , Zheng Yi Ming , Chen Yunwei , Sylvia Sean , Wilson-Smith Henry , Medina Alexis , Dill Sarah-Eve , Rozelle Scott
Published: February 2021

Studies have shown that nearly half of rural toddlers in China have cognitive delays due to an absence of stimulating parenting practices, such as early childhood reading, during the critical first three years of life. However, few studies have examined the reasons behind these low levels of stimulating parenting, and no studies have sought to identify the factors that limit caregivers from providing effective early childhood reading practices (EECRP). This mixed-methods study investigates the perceptions, prevalence, and correlates of EECRP in rural China, as well as associations with child cognitive development. We use quantitative survey results from 1748 caregiver–child dyads across 100 rural villages/townships in northwestern China and field observation and interview data with 60 caregivers from these same sites. The quantitative results show significantly low rates of EECRP despite positive perceptions of early reading and positive associations between EECRP and cognitive development. The qualitative results suggest that low rates of EECRP in rural China are not due to the inability to access books, financial or time constraints, or the absence of aspirations. Rather, the low rate of book ownership and absence of reading to young children is driven by the insufficient and inaccurate knowledge of EECRP among caregivers, which leads to their delayed, misinformed reading decisions with their young children, ultimately contributing to developmental delays.
The Relationship of Sitting Time and Physical Activity on the Quality of Life in Elderly People
Authors: Choi Jung In , Cho Young Hye , Kim Yun Jin , Lee Sang Yeoup , Lee Jeong Gyu , Yi Yu Hyeon , Tak Young Jin , Hwang Hye Rim , Lee Seung Hun , Park Eun Ju , Lee Young In , Ra Young Jin , Lee Su Jin
Published: February 2021

Few studies have shown the combined impact of sitting time and physical activity on quality of life in older people. This cross-sectional study, using data from the 2016–2018 Korean National Health and Nutrition Examination Survey, examines the association between sitting time and physical activity and health-related quality of life (HRQoL) in Korean adults aged ≥ 65 years. HRQoL was assessed using the EuroQol-5 Dimension (EQ-5D, three-level version). We divided subjects into groups based on sitting time and physical activity and analyzed the combined association of sitting time and physical activity with HRQoL. The association between longer sitting time (≥8 h) and HRQoL was analyzed using multiple logistic regression. In total, 4276 participants were included. Prolonged sitting time was associated with all of the EQ-5D dimensions: mobility (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.22–1.68), self-care (OR: 1.65 [95% CI 1.25–2.17]), usual activities (OR: 2.07 [95% CI 1.69–2.52]), pain/discomfort (OR: 1.57 [95% CI 1.34–1.84]), and anxiety/depression (OR: 1.49 [95% CI 1.17–1.91]). The prolonged sitting time/inactive group had higher ORs for all the EQ-5D dimensions than the low sitting time/active group. Prolonged sitting time was associated with low HRQoL in elderly Korean adults; physical activity could weaken the negative influence of prolonged sitting time on HRQoL.
Disclosure in Online vs. Face-to-Face Occupational Health Screenings: A Cross-Sectional Study in Belgian Hospital Employees
Authors: Steel Jonas Stefaan , Godderis Lode , Luyten Jeroen
Published: February 2021

Replacing or supplementing face-to-face health screening by occupational physicians with online surveys can be attractive for various reasons. However, the (cost-)effectiveness of both depends on employees’ willingness to disclose occupational health problems. This article investigates whether employees show a different willingness to disclose information in online surveys compared to face-to-face consultations with an occupational physician. Employees from four Flemish hospitals were asked whether they would disclose a range of typical occupational health problems to either surveys or physicians. The results were analyzed through chi-square tests and multilevel ordinary least squares regression. Of the 776 respondents, 26% indicated that they did not always disclose health problems. Respondents were more inclined to disclose mental health problems to a survey than face-to-face to a physician, whereas the opposite was true for medication misuse. Being male, younger, with lower educational attainment or lower trust in physicians, taking medication, or having a lower risk on alcohol abuse increased the likelihood of a person withholding information. We conclude that this study provides indications that online vs. face-to-face health check-ups have different strengths and weaknesses in this respect. These must be considered when evaluating the need to use online surveys (instead of, or together with, face-to-face contacts) for health screening.
Pain Intensity and Sensory Perception of Tender Points in Female Patients with Fibromyalgia: A Pilot Study
Authors: Úbeda-D'Ocasar Edurne , Valera-Calero Juan Antonio , Hervás-Pérez Juan Pablo , Caballero-Corella Mario , Ojedo-Martín Cristina , Gallego-Sendarrubias Gracia María
Published: February 2021

Fibromyalgia syndrome (FMS) is a condition that courses with chronic pain, fatigue, sleep disturbance, impaired quality of life and daily function. Due to the lack of blood, imaging or histological confirmatory tests, the diagnosis of FMS is based on the presence of widespread pain and presence of tender points (TPs). Our aim was to assess the pain pressure thresholds (PPTs) and subjective pain perception (SPP) of all 18 TPs while applying a normalized pressure in female patients with fibromyalgia. An exploratory descriptive pilot study was conducted in 30 female patients with FMS. Sociodemographic data (e.g., age, height, weight, and body mass index), clinical characteristics (e.g., years with diagnosis and severity of FMS), PPTs (assessed with an algometer), and SPP (assessed with a visual analogue scale) of all 18 TPs were collected. A comparative analysis side-to-side (same TP, left and right sides) and between TPs was conducted. No side-to-side differences were found (p < 0.05). Significant differences between all 18 TPs were found for PPTs (p < 0.0001), and SPP (p < 0.005) scores were found. The most mechanosensitive points were located in the second costochondral junction, the occiput, the trochanteric prominence; the most painful while applying a normalized pressure considering the TP and side were those located in the gluteus, trochanteric prominence, and supraspinatus. The current study describes PPTs and SPP, as assessed with algometry and visual analogue scale, respectively, of all 18 TPs in female patients with FMS. TPs exhibited significant PPTs and SPP differences between TP locations with no side-to-side differences.
Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review
Authors: Amir Saira , Shah Syed Tahir Abbas , Mamoulakis Charalampos , Docea Anca Oana , Kalantzi Olga-Ioanna , Zachariou Athanasios , Calina Daniela , Carvalho Felix , Sofikitis Nikolaos , Makrigiannakis Antonios , Tsatsakis Aristidis
Published: February 2021

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.
The Association between Maternal Experiences of Interpersonal Discrimination and Adverse Birth Outcomes: A Systematic Review of the Evidence
Authors: Larrabee Sonderlund Anders , Schoenthaler Antoinette , Thilsing Trine
Published: February 2021

In the present systematic review, we argue that maternal experiences of interpersonal discrimination at least partially account for the disproportionate rates of adverse birth outcomes in minority populations. Since the 1990s, research in this area has slowly, but steadily increased, shedding more light on the insidious nature of interpersonal discrimination and its toxic health effects. With the aim of bringing this topic to the fore in academic as well as clinical settings, this paper provides a state-of-the-art review of the empirical knowledge on the relationship between maternal experiences of discrimination and birth outcomes. Of 5901 articles retained in the literature search, 28 met the predefined inclusion criteria. Accounting for a range of health and behavioral factors, the vast majority of these studies support the notion that maternal experiences of interpersonal discrimination predict a range of adverse birth outcomes, including preterm birth, low birth weight, and various physiological markers of stress (allostatic load) in both mother and child pre- and postpartum. Several moderators and mediators of this relationship were also identified. These related primarily to the type (first-hand and vicarious), timing (childhood, adolescence, and adulthood), frequency, and pervasiveness of discrimination experienced, as well as to maternal mental health and coping. More research into these factors, however, is required to definitively determine their significance. We discuss these findings as they relate to the general health repercussions of interpersonal discrimination, as well as in terms of applied prenatal care and interventions. Ultimately, we argue that assessing maternal experiences of interpersonal discrimination in prenatal care may represent a considerable asset for mitigating existing majority-minority disparities in adverse birth outcomes.
Communication Experiences in Primary Healthcare with Refugees and Asylum Seekers: A Literature Review and Narrative Synthesis
Authors: Patel Pinika , Bernays Sarah , Dolan Hankiz , Muscat Danielle Marie , Trevena Lyndal
Published: February 2021

Refugee and asylum seeker population numbers are rising in Western countries. Understanding the communication experiences, within healthcare encounters, for this population is important for providing better care and health outcomes. This review summarizes the literature on health consultation communication experiences of refugees and asylum seekers living in Western countries. Seven electronic databases were searched from inception to 31 March 2019. Studies were included if they aimed to improve, assess or report on communication/interaction in the primary health care consultation setting with refugees or asylum seekers, and were conducted in Western countries. A narrative synthesis of the literature was undertaken. Thematic analysis of the 21 included articles, showed that refugees and asylum seekers experience a range of communication challenges and obstacles in primary care consultations. This included practical and relational challenges of organizing and using informal and formal interpreters and cultural understanding of illness and healthcare. Non-verbal and compassionate care aspects of communication emerged as an important factor in helping improve comfort and trust between healthcare providers (HCP) and refugees and asylum seekers during a healthcare encounter. Improvements at the systems level are needed to provide better access to professional interpreters, but also support compassionate and humanistic care by creating time for HCPs to build relationships and trust with patients.
Culturally Sensitive Health Education in the Caribbean Diaspora: A Scoping Review
Authors: Hasan Mashtura , Singh Harmandip , Haffizulla Farzanna
Published: February 2021

Context: The Caribbean diaspora in the United States is a diverse community that is afflicted with high morbidity and mortality due to preventable chronic diseases. Objective: Our goal is to determine which culturally sensitive health and nutrition educational modalities have the highest efficacy for improving general health in the Caribbean diaspora. Methods: A scoping literature review was performed on the MEDLINE, CINAHL, and Web of Science databases using terms related to health and nutrition in the Caribbean population. Original, peer-reviewed research published from 2010 to 2020, which took place in the U.S. and Caribbean countries, were included in our review. Results: We identified a total of nine articles that met our inclusion criteria. Rate differences for individual education program features were calculated to assess the likelihood of a positive impact on diet, physical activity, and diabetes. Conclusion: Our review helps to identify key educational modalities targeting diabetes, diet, and physical activity levels that can be used to meet the health and nutritional needs of the Caribbean diaspora population.
Associations between Socioeconomic Status, Social Participation, and Physical Activity in Older People during the COVID-19 Pandemic: A Cross-Sectional Study in a Northern Japanese City
Authors: Sasaki Sachiko , Sato Akinori , Tanabe Yoshie , Matsuoka Shinji , Adachi Atsuhiro , Kayano Toshiya , Yamazaki Hiroshi , Matsuno Yuichi , Miyake Ann , Watanabe Toshihiro
Published: February 2021

Physical activity (PA) is a key determinant of health in older adults. However, little is known about the effect of social factors on PA among older adults during the coronavirus disease 2019 (COVID-19) pandemic. Therefore, we aimed to clarify the association between socioeconomic status, social participation, and PA during the pandemic. A cross-sectional study was conducted on 999 community-dwelling residents aged 65–90 years. A self-administered questionnaire was used to collect socioeconomic status, social participation, and PA data in August 2020. Multivariable logistic regression analyses were used to calculate the odds ratios (ORs) for the associations between socioeconomic status, social participation, and maintaining PA. For both sexes, PA was reduced by approximately 5–10% after the onset of COVID-19-related distancing restrictions. Men with a low socioeconomic status were less physically active (OR = 0.49, 95% CI: 0.30–0.82). Women who reported social participation had higher odds of maintaining PA (OR = 1.67, 95% CI: 1.13–2.45) during the restrictions. Higher socioeconomic status and social participation levels before the COVID-19 pandemic may have helped older adults to maintain PA during the COVID-19 pandemic. Further research is needed to clarify the potential effects of these factors on the health of older adults.
Educational Attainment and Prevalence of Cardiovascular Health (Life’s Simple 7) in Asian Americans
Authors: Alam Md Towfiqul , Echeverria Sandra E. , DuPont-Reyes Melissa J. , Vasquez Elizabeth , Murillo Rosenda , Gonzalez Tailisha , Rodriguez Fatima
Published: February 2021

Asian Americans have a high burden of cardiovascular disease, yet little is known about the social patterning of cardiovascular health (CVH) in this population. We examined if education (<high school diploma, high school diploma, some college, and college degree+) was associated with CVH and if this varied by time in the United States (U.S.). Our study population included Asian Americans 20+ years of age sampled in the 2011-16 National Health and Nutrition Examination Survey (n = 1634). Ideal cardiovascular health was based on a composite score of adiposity, total cholesterol, blood pressure, blood glucose, smoking, physical activity, and diet. We fit sequential weighted multivariate logistic regression models for all analyses. The prevalence of ideal cardiovascular (CV) health was 17.1% among those living in the U.S. <10 years, 7.1% for those living in the U.S. >10+ years, and 15.9% for the U.S.-born. All models showed that low education compared to high education was associated with lower odds of having ideal CVH. This pattern remained in adjusted models but became non-significant when controlling for nativity (odds ratio = 0.34, 95% confidence interval: 0.10, 1.13). Models stratified by time in the U.S. were less consistent but showed similar education gradients in CVH. Low education is a risk factor for attaining ideal cardiovascular health among Asian Americans, regardless of time in the U.S.
A Framework to Guide the Implementation of Best Practice Clinical Learning Environments in Community General Practice: Australia
Authors: O'Sullivan Belinda , Hickson Helen , Kippen Rebecca , Cohen Donna , Cohen Phil , Wallace Glen
Published: February 2021

Clinical education/training is increasingly being expanded to community general practice settings (primary care clinics led by doctors). This plays an important role in developing a skilled “primary-care ready” workforce. However, there is limited information to guide the implementation of high-quality learning environments suitable for the range of general practices and clinical learners they oversee. We aimed to develop a consensus-based framework to address this. A co-design participatory action research method involved working with stakeholders to agree a project plan, collect and interpret data and endorse a final framework. As a starting point, an initial draft framework was adapted from an existing framework, the Best Practice Clinical Learning Environment (BPCLE) Framework. We gathered feedback about this from a national GP Supervisor Liaison Officer Network (SLON) (experienced GP clinical supervisors) during a 90-minute face-to-face focus group. They rated their agreement with the relevance of objectives and elements, advising on clear terminology and rationale for including/excluding various components. The resulting framework was refined and re-tested with the SLON and wider GP educational stakeholders until a final graphically designed version was endorsed. The resulting “GP Clinical Learning Environment” (GPCLE) Framework is applicable for planning and benchmarking best practice learning environments in general practice.
Wellbeing Literacy: Conceptualization, Measurement, and Preliminary Empirical Findings from Students, Parents and School Staff
Authors: Hou Hanchao , Chin Tan-Chyuan , Slemp Gavin R. , Oades Lindsay G.
Published: February 2021

Aims: Wellbeing literacy is the intentional use of wellbeing relevant vocabulary, knowledge and language skills to maintain or improve the wellbeing of oneself, others and the world. In this study, we operationalize the human aspects of the concept of wellbeing literacy and empirically test its relationship with wellbeing and illbeing. We also assess its incremental variance in wellbeing and illbeing, after controlling for existing and well-established predictors of these constructs within education settings. Methods: We developed and empirically tested the Wellbeing literacy 6-item (Well-Lit 6) scale to assess the concept of wellbeing literacy in the education context. The scale was developed based on a working definition of wellbeing literacy, in combination with the Australian Curriculum, Assessment and Reporting Authority (ACARA)’s definition of literacy. The Well-Lit 6 was administered via a cross-sectional survey to three Australian samples that comprise different elements of Australian education systems: students (N = 1392), parents (N = 584) and school staff (N = 317). Results: Exploratory factor analysis (EFA) suggested the six items of the Well-Lit 6 form an independent construct, empirically distinguishable from other wellbeing-related constructs (e.g., general wellbeing, resilience, and emotion regulation). Convergent analyses showed wellbeing literacy was positively related to wellbeing and negatively related to illbeing. Incremental validity analyses showed wellbeing literacy predicted variance in wellbeing and illbeing after controlling for participant demographics, resilience, and emotion regulation, showing initial evidence of incremental validity. Conclusions: Our results provide preliminary evidence that wellbeing literacy is a distinct construct from wellbeing and illbeing, and it also demonstrates significant unique variance in these constructs over and above resilience and emotion regulation. The Well-Lit 6 is a useful provisional measure of wellbeing literacy, although we suggest a fruitful avenue for future research is to develop a more comprehensive scale of wellbeing literacy that denotes specific facets of communication, allowing a fuller exploration wellbeing literacy, its components, and their antecedents and consequences. We offer further recommendations for future research and discuss limitations with our approach.
Chronic Mental Health Sequelae of Climate Change Extremes: A Case Study of the Deadliest Californian Wildfire
Authors: Silveira Sarita , Kornbluh Mariah , Withers Mathew C. , Grennan Gillian , Ramanathan Veerabhadran , Mishra Jyoti
Published: February 2021

Introduction. Weather-related disasters, such as wildfires exacerbated by a rise in global temperatures, need to be better studied in terms of their mental health impacts. This study focuses on the mental health sequelae of the deadliest wildfire in California to date, the Camp Fire of 2018. Methods. We investigated a sample of 725 California residents with different degrees of disaster exposure and measured mental health using clinically validated scales for post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and generalized anxiety disorder (GAD). Data were collected at a chronic time-point, six months post-wildfire. We used multiple regression analyses to predict the mental health outcomes based on self-reported fire exposure. Additionally, we included vulnerability and resilience factors in hierarchical regression analyses. Results. Our primary finding is that direct exposure to large scale fires significantly increased the risk for mental health disorders, particularly for PTSD and depression. Additionally, the inclusion of vulnerability and resilience factors in the hierarchical regression analyses led to the significantly improved prediction of all mental health outcomes. Childhood trauma and sleep disturbances exacerbated mental health symptoms. Notably, self-reported resilience had a positive effect on mental health, and mindfulness was associated with significantly lower depression and anxiety symptoms. Conclusion. Overall, our study demonstrated that climate-related extreme events, such as wildfires, can have severe mental illness sequelae. Moreover, we found that pre-existing stressful life events, resilient personality traits and lifestyle factors can play an important role in the prevalence of psychopathology after such disasters. Unchecked climate change projected for the latter half of this century may severely impact the mental wellbeing of the global population, and we must find ways to foster individual resiliency.
Serological Profile of Children and Young Adults with at Least One SARS-CoV-2 Positive Cohabitant: An Observational Study
Authors: Farronato Marco , Dolci Carolina , Boccalari Elisa , Izadi Sara , Salvatierra Rios Luis Hernan , Festa Maurizio , Panetta Valentina , De Vito Danila , Tartaglia Gianluca Martino
Published: February 2021

At the end of 2019, a new disease caused by the novel coronavirus SARS-CoV-2 appeared in Wuhan Province in China. Children seemed to be infected less frequently than adults, and family clusters seemed to play an important role in the spread of the pandemic. The aim of this study is to evaluate the serological profile of children and young adults between 4 and 16 years of age in order to assess the transmission patterns of COVID-19 between cohabitants. The subjects lived with at least one cohabitant who tested positive for the disease using a nasopharyngeal swab. To avoid contact with the disease, families were interviewed by telephone. Forty-nine children and adolescents with a mean age of 11 years were then subjected to a rapid lateral flow chromatographic test. Of them, seven (14.3%) were immunoglobulin G (IgG)-positive, and four (8.2%) were immunoglobulin M (IgM)-positive. In total, 16.3% of the tested sample had antibodies against SARS-CoV-2: this may confirm the lower vulnerability of children to COVID-19, despite the small sample size. The time from the negativization of the cohabitant until the test day may have influenced the results, especially when this timeframe is wide.
Selected Aspects Related to Medicinal and Aromatic Plants as Alternative Sources of Bioactive Compounds
Authors: Fierascu Radu Claudiu , Fierascu Irina , Baroi Anda Maria , Ortan Alina
Published: February 2021

Natural compounds obtained from different medicinal and aromatic plants have gained respect as alternative treatments to synthetic drugs, as well as raw materials for different applications (cosmetic, food and feed industries, environment protection, and many others). Based on a literature survey on dedicated databases, the aim of the present work is to be a critical discussion of aspects regarding classical extraction versus modern extraction techniques; possibilities to scale up (advantages and disadvantages of different extraction methods usually applied and the influence of extraction parameters); and different medicinal and aromatic plants’ different applications (medical and industrial applications, as well as the potential use in nanotechnology). As nowadays, research studies are directed toward the development of modern, innovative applications of the medicinal and aromatic plants, aspects regarding future perspectives are also discussed.
The Roles of the Ubiquitin–Proteasome System in the Endoplasmic Reticulum Stress Pathway
Authors: Qu Junyan , Zou Tingting , Lin Zhenghong
Published: February 2021

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells, which is essential for synthesis, processing, sorting of protein and lipid metabolism. However, the cells activate a defense mechanism called endoplasmic reticulum stress (ER stress) response and initiate unfolded protein response (UPR) as the unfolded proteins exceed the folding capacity of the ER due to the environmental influences or increased protein synthesis. ER stress can mediate many cellular processes, including autophagy, apoptosis and senescence. The ubiquitin-proteasome system (UPS) is involved in the degradation of more than 80% of proteins in the cells. Today, increasing numbers of studies have shown that the two important components of UPS, E3 ubiquitin ligases and deubiquitinases (DUBs), are tightly related to ER stress. In this review, we summarized the regulation of the E3 ubiquitin ligases and DUBs in ER stress.
Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis
Authors: Maliszewska Katarzyna , Kretowski Adam
Published: February 2021

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.
Targeting Redox Metabolism in Pancreatic Cancer
Authors: Abdel Hadi Nadine , Reyes-Castellanos Gabriela , Carrier Alice
Published: February 2021

Cell metabolism is reprogrammed in cancer cells to meet their high bioenergetics and biosynthetic demands. This metabolic reprogramming is accompanied by alterations in redox metabolism, characterized by accumulation of reactive oxygen species (ROS). Elevated production of ROS, mostly by mitochondrial respiration, is counteracted by higher production of antioxidant defenses (mainly glutathione and antioxidant enzymes). Cancer cells are adapted to a high concentration of ROS, which contributes to tumorigenesis, metastasis formation, resistance to therapy and relapse. Frequent genetic alterations observed in pancreatic ductal adenocarcinoma (PDAC) affect KRAS and p53 proteins, which have a role in ROS production and control, respectively. These observations led to the proposal of the use of antioxidants to prevent PDAC development and relapse. In this review, we focus on the therapeutic strategies to further increase ROS level to induce PDAC cell death. Combining the promotion of ROS production and inhibition of antioxidant capacity is a promising avenue for pancreatic cancer therapy in the clinic.
De Novo PORCN and ZIC2 Mutations in a Highly Consanguineous Family
Authors: Castilla-Vallmanya Laura , Gürsoy Semra , Giray-Bozkaya Özlem , Prat-Planas Aina , Bullich Gemma , Matalonga Leslie , Centeno-Pla Mónica , Rabionet Raquel , Grinberg Daniel , Balcells Susanna , Urreizti Roser
Published: February 2021

We present a Turkish family with two cousins (OC15 and OC15b) affected with syndromic developmental delay, microcephaly, and trigonocephaly but with some phenotypic traits distinct between them. OC15 showed asymmetrical skeletal defects and syndactyly, while OC15b presented with a more severe microcephaly and semilobal holoprosencephaly. All four progenitors were related and OC15 parents were consanguineous. Whole Exome Sequencing (WES) analysis was performed on patient OC15 as a singleton and on the OC15b trio. Selected variants were validated by Sanger sequencing. We did not identify any shared variant that could be associated with the disease. Instead, each patient presented a de novo heterozygous variant in a different gene. OC15 carried a nonsense mutation (p.Arg95*) in PORCN, which is a gene responsible for Goltz-Gorlin syndrome, while OC15b carried an indel mutation in ZIC2 leading to the substitution of three residues by a proline (p.His404_Ser406delinsPro). Autosomal dominant mutations in ZIC2 have been associated with holoprosencephaly 5. Both variants are absent in the general population and are predicted to be pathogenic. These two de novo heterozygous variants identified in the two patients seem to explain the major phenotypic alterations of each particular case, instead of a homozygous variant that would be expected by the underlying consanguinity.
The Rice Small Auxin-Up RNA Gene OsSAUR33 Regulates Seed Vigor via Sugar Pathway during Early Seed Germination
Authors: Zhao Jia , Li Wenjun , Sun Shan , Peng Liling , Huang Zhibo , He Yongqi , Wang Zhoufei
Published: February 2021

Seed vigor affects seed germination and seedling emergence, and therefore is an important agronomic trait in rice. Small auxin-up RNAs (SAURs) function in a range of developmental processes, but their role in seed vigor remains unclear. Here, we observed that disruption of OsSAUR33 resulted in reduced germination rates and low seed uniformity in early germination. Expression of OsSAUR33 was higher in mature grains and early germinating seeds. RNA-seq analysis revealed that OsSAUR33 modulated seed vigor by affecting the mobilization of stored reserves during germination. Disruption of OsSAUR33 increased the soluble sugar content in dry mature grains and seeds during early germination. OsSAUR33 interacted with the sucrose non-fermenting-1-related protein kinase OsSnRK1A, a regulator of the sugar signaling pathway, which influences the expression of sugar signaling-related genes during germination. Disruption of OsSAUR33 increased sugar-sensitive phenotypes in early germination, suggesting OsSAUR33 likely affects seed vigor through the sugar pathway. One elite haplotype of OsSAUR33 associated with higher seed vigor was identified mainly in indica accessions. This study provides insight into the effects of OsSAUR33 on seed vigor in rice.
Mild Effects of Sunscreen Agents on a Marine Flatfish: Oxidative Stress, Energetic Profiles, Neurotoxicity and Behaviour in Response to Titanium Dioxide Nanoparticles and Oxybenzone
Authors: Carvalhais Ana , Pereira Bárbara , Sabato Mariangela , Seixas Rafaela , Dolbeth Marina , Marques Ana , Guilherme Sofia , Pereira Patrícia , Pacheco Mário , Mieiro Cláudia
Published: February 2021

UV filters are potentially harmful to marine organisms. Given their worldwide dissemination and the scarcity of studies on marine fish, we evaluated the toxicity of an organic (oxybenzone) and an inorganic (titanium dioxide nanoparticles) UV filter, individually and in a binary mixture, in the turbot (Scophthalmus maximus). Fish were intraperitoneally injected and a multi-level assessment was carried out 3 and 7 days later. Oxybenzone and titanium dioxide nanoparticles induced mild effects on turbot, both isolated and in mixture. Neither oxidative stress (intestine, liver and kidney) nor neurotoxicity (brain) was found. However, liver metabolic function was altered after 7 days, suggesting the impairment of the aerobic metabolism. An increased motility rate in oxybenzone treatment was the only behavioural alteration (day 7). The intestine and liver were preferentially targeted, while kidney and brain were unaffected. Both infra- and supra-additive interactions were perceived, with a toxicodynamic nature, resulting either in favourable or unfavourable toxicological outcomes, which were markedly dependent on the organ, parameter and post-injection time. The combined exposure to the UV filters did not show a consistent increment in toxicity in comparison with the isolated exposures, which is an ecologically relevant finding providing key information towards the formulation of environmentally safe sunscreen products.
Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications
Authors: Noirrit-Esclassan Emmanuelle , Valera Marie-Cécile , Tremollieres Florence , Arnal Jean-Francois , Lenfant Françoise , Fontaine Coralie , Vinel Alexia
Published: February 2021

Bone is a multi-skilled tissue, protecting major organs, regulating calcium phosphate balance and producing hormones. Its development during childhood determines height and stature as well as resistance against fracture in advanced age. Estrogens are key regulators of bone turnover in both females and males. These hormones play a major role in longitudinal and width growth throughout puberty as well as in the regulation of bone turnover. In women, estrogen deficiency is one of the major causes of postmenopausal osteoporosis. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens not only in females but also in males, during different life stages. Effects of estrogens on bone involve either Estrogen Receptor (ER)α or ERβ depending on the type of bone (femur, vertebrae, tibia, mandible), the compartment (trabecular or cortical), cell types involved (osteoclasts, osteoblasts and osteocytes) and sex. Finally, we will discuss new ongoing strategies to increase the benefit/risk ratio of the hormonal treatment of menopause.
3D Structural Insights into β-Glucans and Their Binding Proteins
Authors: Manabe Noriyoshi , Yamaguchi Yoshiki
Published: February 2021

β(1,3)-glucans are a component of fungal and plant cell walls. The β-glucan of pathogens is recognized as a non-self-component in the host defense system. Long β-glucan chains are capable of forming a triple helix structure, and the tertiary structure may profoundly affect the interaction with β-glucan-binding proteins. Although the atomic details of β-glucan binding and signaling of cognate receptors remain mostly unclear, X-ray crystallography and NMR analyses have revealed some aspects of β-glucan structure and interaction. Here, we will review three-dimensional (3D) structural characteristics of β-glucans and the modes of interaction with β-glucan-binding proteins.
Genomic and Epigenomic Profile of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMPs) Revealed Similarities and Differences with Leiomyomas and Leiomyosarcomas
Authors: Conconi Donatella , Redaelli Serena , Lissoni Andrea , Cilibrasi Chiara , Perego Patrizia , Gautiero Eugenio , Sala Elena , Paderno Mariachiara , Dalprà Leda , Landoni Fabio , Lavitrano Marialuisa , Roversi Gaia , Bentivegna Angela
Published: February 2021

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigenomic profile of uterine smooth muscle tumors (USMTs) in order to find similarities and differences between STUMPs, leiomyosarcomas (LMSs) and leiomyomas (LMs), and possibly identify prognostic factors in this group of tumors. Array-CGH data on 23 USMTs demonstrated the presence of a more similar genomic profile between STUMPs and LMSs. Some genes, such as PRKDC and PUM2, with a potential prognostic value, were never previously associated with STUMP. The methylation data appears to be very promising, especially with regards to the divergent profile found in the sample that relapsed, characterized by an overall CGI hypomethylation. Finally, the Gene Ontology analysis highlighted some cancer genes that could play a pivotal role in the unexpected aggressive behavior that can be found in some of these tumors. These genes could prove to be prognostic markers in the future.
Comparison of Antiviral Activity of Gemcitabine with 2′-Fluoro-2′-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2
Authors: Jang Yejin , Shin Jin Soo , Lee Myoung Kyu , Jung Eunhye , An Timothy , Kim Uk-Il , Kim Kyungjin , Kim Meehyein
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human transmission. Nevertheless, there are no specific treatments clinically approved. This study aimed to compare antiviral activity of gemcitabine and its analogue 2′-fluoro-2′-deoxycytidine (2FdC) against SARS-CoV-2 as well as cytotoxicity in vitro. Fluorescent image-based antiviral assays revealed that gemcitabine was highly potent, with a 50% effective concentration (EC50) of 1.2 μM, more active than the well-known nucleoside monophosphate remdesivir (EC50 = 35.4 μM). In contrast, 2FdC was marginally active (EC50 = 175.2 μM). For all three compounds, the 50% cytotoxic concentration (CC50) values were over 300 μM toward Vero CCL-81 cells. Western blot and quantitative reverse-transcription polymerase chain reaction analyses verified that gemcitabine blocked viral protein expression in virus-infected cells, not only Vero CCL-81 cells but also Calu-3 human lung epithelial cells in a dose-dependent manner. It was found that gemcitabine has a synergistic effect when combined with remdesivir. This report suggests that the difluoro group of gemcitabine is critical for the antiviral activity and that its combination with other evaluated antiviral drugs, such as remdesivir, could be a desirable option to treat SARS-CoV-2 infection.
Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes
Authors: Song Nuri , Jeong Da Yeon , Tu Thai Hien , Park Byong Seo , Yang Hye Rim , Kim Ye Jin , Kim Jae Kwang , Park Joon Tae , Yeh Jung-Yong , Yang Sunggu , Kim Jae Geun
Published: February 2021

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.
The Impact of Seasonal Changes on Thyroxine and Thyroid-Stimulating Hormone in Newborns
Authors: McMahon Rebecca , DeMartino Lenore , Sowizral Mycroft , Powers Diana , Tracy Melissa , Caggana Michele , Tavakoli Norma P.
Published: February 2021

Newborn screening for congenital hypothyroidism (CH) is performed by measuring the concentration of thyroxine (T4) and/or thyroid-stimulating hormone (TSH) in dried blood spots. Unfortunately, the levels of T4 and TSH vary due to multiple factors, and therefore the false-positive rate for the test is a challenge. We analyzed screening data from 2008 to 2017 to determine the effect of seasonal changes and manufacturer kit lot changes on T4 and TSH values and on numbers of infants referred. Over a 10-year period, we screened 2.4 million infants using commercially available fluoroimmunoassays to measure T4 and TSH concentrations in dried blood spots. During colder months, daily mean T4 and TSH values were higher and referral rates and false-positive rates were higher. However, there was no significant difference between the number of confirmed CH cases. Furthermore, in rare instances, we observed differences in T4 daily mean values during the 10-year period when manufacturer kit lot changes were made. Seasonal temperature variations influence measured T4 and TSH values and consequently lower the positive predictive value for CH testing in colder months. Newborn screening (NBS) programs should be aware that manufacturer kit lot changes may also influence T4 values.
A Study on the Integration of Resilience and Smart City Concepts in Urban Systems
Authors: Tzioutziou Anastasia , Xenidis Yiannis
Published: February 2021

The continuous growth of cities brings out various concerns for improved development and management of the multifaceted urban systems, including those of resilience and smartness. Despite the many significant efforts in the research field, both notions remain changeable, thus retaining the lack of commonly accepted conceptual and terminological frameworks. The paper’s research goals are to designate the current direct and indirect links in the conceptualizations and research trends of the resilience and smart city frameworks and to prove the potential of the conceptual convergence between them in the context of urban systems. The application of a semi-systematic literature review, including bibliometric evidence and followed by content analysis, has led to the observation that as the resilience discourse opens up to embrace other dimensions, including technology, the smart city research turns its interest to the perspective of urban protection. Therefore, both concepts share the goal for urban sustainability realized through specific capacities and processes and operationalized with the deployment of technology. The paper’s findings suggest that the conceptual and operational foundations of these two concepts could support the emergence of an integrated framework. Such a prospect acknowledges the instrumental role of the smart city approach in the pursuit of urban resilience and unfolds a new model for sustainable city management and development.
Nutritional Deficiencies in Radiotherapy-Treated Head and Neck Cancer Patients
Authors: Powrózek Tomasz , Dziwota Joanna , Małecka-Massalska Teresa
Published: February 2021

Nutritional deficiencies (malnutrition, cachexia, sarcopenia, and unfavorable changes in the body composition) developing as a side effect of radiotherapy (RT) currently represents a significant but still inaccurately studied clinical problem in cancer patients. The incidence of malnutrition observed in head and neck cancer (HNC) patients in oncological radiology departments can reach 80%. The presence of malnutrition, sarcopenia, and cachexia is associated with an unfavorable prognosis of the disease, higher mortality, and deterioration of the quality of life. Therefore, it is necessary to identify patients with a high risk of both metabolic syndromes. However, the number of studies investigating potential predictive markers for the mentioned purposes is still significantly limited. This literature review summarizes the incidence of nutritional deficiencies in HNC patients prior to therapy and after the commencement of RT, and presents recent perspectives for the prediction of unfavorable nutritional changes developing as a result of applied RT.
Study of the Preparation and Properties of TPS/PBSA/PLA Biodegradable Composites
Authors: Wang Yuxuan , Zhong Yuke , Shi Qifeng , Guo Sen
Published: February 2021

Thermoplastic starch/butyl glycol ester copolymer/polylactic acid (TPS/PBSA/PLA) biodegradable composites were prepared by melt-mixing. The structure, microstructure, mechanical properties and heat resistance of the TPS/PBSA/PLA composites were studied by Fourier-transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), tensile test and thermogravimetry tests, respectively. The results showed that PBSA or PLA could bind to TPS by hydrogen bonding. SEM analysis showed that the composite represents an excellent dispersion and satisfied two-phase compatibility when the PLA, TPS and PBSA blended by a mass ration of 10, 30, and 60. The mechanical properties and the heat resistance of TPS/PBSA/PLA composite were improved by adding PLA with content less than 10%, according to the testing results.