bluuebunny/crossref_metadata_2025 huggingface dataset:
The Tapio Decoupling Principle and Key Strategies for Changing Factors of Chinese Urban Carbon Footprint Based on Cloud Computing
Authors: Shang Min , Luo Ji
Published: February 2021

The expansion of Xi’an City has caused the consumption of energy and land resources, leading to serious environmental pollution problems. For this purpose, this study was carried out to measure the carbon carrying capacity, net carbon footprint and net carbon footprint pressure index of Xi’an City, and to characterize the carbon sequestration capacity of Xi’an ecosystem, thereby laying a foundation for developing comprehensive and reasonable low-carbon development measures. This study expects to provide a reference for China to develop a low-carbon economy through Tapio decoupling principle. The decoupling relationship between CO2 and driving factors was explored through Tapio decoupling model. The time-series data was used to calculate the carbon footprint. The auto-encoder in deep learning technology was combined with the parallel algorithm in cloud computing. A general multilayer perceptron neural network realized by a parallel BP learning algorithm was proposed based on Map-Reduce on a cloud computing cluster. A partial least squares (PLS) regression model was constructed to analyze driving factors. The results show that in terms of city size, the variable importance in projection (VIP) output of the urbanization rate has a strong inhibitory effect on carbon footprint growth, and the VIP value of permanent population ranks the last; in terms of economic development, the impact of fixed asset investment and added value of the secondary industry on carbon footprint ranks third and fourth. As a result, the marginal effect of carbon footprint is greater than that of economic growth after economic growth reaches a certain stage, revealing that the driving forces and mechanisms can promote the growth of urban space.
Social Networks, Trust, and Disaster-Risk Perceptions of Rural Residents in a Multi-Disaster Environment: Evidence from Sichuan, China
Authors: Xue Kaijing , Guo Shili , Liu Yi , Liu Shaoquan , Xu Dingde
Published: February 2021

Individual perception of disaster risk is not only the product of individual factors, but also the product of social interactions. However, few studies have empirically explored the correlations between rural residents’ flat social networks, trust in pyramidal channels, and disaster-risk perceptions. Taking Sichuan Province—a typical disaster-prone province in China—as an example and using data from 327 rural households in mountainous areas threatened by multiple disasters, this paper measured the level of participants’ disaster-risk perception in the four dimensions of possibility, threat, self-efficacy, and response efficacy. Then, the ordinary least squares method was applied to probe the correlations between social networks, trust, and residents’ disaster-risk perception. The results revealed four main findings. (1) Compared with scores relating to comprehensive disaster-risk perception, participants had lower perception scores relating to possibility and threat, and higher perception scores relating to self-efficacy and response efficacy. (2) The carrier characteristics of their social networks significantly affected rural residents’ perceived levels of disaster risk, while the background characteristics did not. (3) Different dimensions of trust had distinct effects on rural residents’ disaster-risk perceptions. (4) Compared with social network variables, trust was more closely related to the perceived level of disaster risks, which was especially reflected in the impact on self-efficacy, response efficacy, and comprehensive perception. The findings of this study deepen understanding of the relationship between social networks, trust, and disaster-risk perceptions of rural residents in mountainous areas threatened by multiple disasters, providing enlightenment for building resilient disaster-prevention systems in the community.
Relationships among Affect, Hardiness and Self-Efficacy in First Aid Provision by Airline Cabin Crew
Authors: Yu Yi-Chen , Liang Jyh-Chong
Published: February 2021

Cabin crews being first responders, passengers’ health assurance is also one of their main responsibilities. This study explored the association among first aid affect, work-related hardiness and self-efficacy of first aid, as well as the mediation role of work-related hardiness in airline cabin crews. Three self-reporting instruments were applied in this study: one was the first aid affect questionnaire, the second was a work-related hardiness questionnaire, the third was self-efficacy of the first aid questionnaire. Data were collected from 525 cabin crew members across five airlines in Taiwan (480 females and 45 males). The results showed that both exploratory and confirmatory factor analyses indicated that three instruments had satisfactory validity and reliability. Positive significant relationships were found among cabin crews’ first aid affect, work-related hardiness and self-efficacy of first aid. Cabin crews’ commitment dimension of work-related hardiness turned out to be positively related to self-efficacy of first aid. In addition, the results of the study also revealed that cabin crews’ work commitment plays a mediating role between their first aid affect and self-efficacy of first aid. To enhance the self-efficacy of first aid, it is necessary for the airlines to strengthen cabin crews’ work commitment. Furthermore, fostering cabin crews’ first aid affect is also one an important training goal.
Broken Promises to the People of Newark: A Historical Review of the Newark Uprising, the Newark Agreements, and Rutgers New Jersey Medical School’s Commitments to Newark
Authors: Franklin Rosy C. , Behmer Hansen Ryan A. , Pierce Jean M. , Tsitouras Diomedes J. , Mazzola Catherine A.
Published: February 2021

Many have referred to the coronavirus disease 2019 crisis and intertwined issues of structural racism as “twin pandemics”. As healthcare workers in Newark, New Jersey, a city heavily affected by the twin pandemics, we recognize that health workforce changes must be grounded in our community’s recent history. The objective of this essay is to briefly describe the relationship between organized medicine, state and local leaders, and the people of Newark. We begin with a discussion of Newark in the 1950s and 1960s: its people experienced poor socioeconomic conditions, terrible medical care, and the many sequelae of abhorrent racism. Plans to establish a New Jersey Medical School in Newark’s Central Ward also threatened to displace many residents from their homes. We then describe the Newark Agreements of 1968, which formalized a social contract between the state, business leaders, and people of Newark. In part, the Medical School committed to indefinitely promoting public health in Newark. We share progress towards this goal. Finally, we document key healthcare administrative decisions facing our community today. Stakeholder opinions are shared. We conclude that the Newark Agreements set an important standard for communities across the country. Creative solutions to healthcare policy may be realized through extensive community collaboration.
12-Year Trends in Active School Transport across Four European Countries—Findings from the Health Behaviour in School-Aged Children (HBSC) Study
Authors: Haug Ellen , Smith Otto Robert Frans , Bucksch Jens , Brindley Catherina , Pavelka Jan , Hamrik Zdenek , Inchley Joanna , Roberts Chris , Mathisen Frida Kathrine Sofie , Sigmundová Dagmar
Published: February 2021

Active school transport (AST) is a source of daily physical activity uptake. However, AST seems to have decreased worldwide over recent decades. We aimed to examine recent trends in AST and associations with gender, age, family affluence, and time to school, using data from the Health Behaviour in School-Aged Children (HBSC) study collected in 2006, 2010, 2014, and 2018 in the Czech Republic, Norway, Scotland, and Wales. Data from 88,212 students (11, 13 and 15 years old) revealed stable patterns of AST from 2006 to 2018, apart from a decrease in the Czech Republic between 2006 and 2010. For survey waves combined, walking to and from school was most common in the Czech Republic (55%) and least common in Wales (30%). Cycling was only common in Norway (22%). AST differed by gender (Scotland and Wales), by age (Norway), and by family affluence (everywhere but Norway). In the Czech Republic, family affluence was associated with change over time in AST, and the effect of travel time on AST was stronger. The findings indicate that the decrease in AST could be levelling off in the countries considered here. Differential associations with sociodemographic factors and travel time should be considered in the development of strategies for AST.
Factors Related to Care Competence, Workplace Stress, and Intention to Stay among Novice Nurses during the Coronavirus Disease (COVID-19) Pandemic
Authors: Chen Hsiao-Mei , Liu Chien-Chi , Yang Shang-Yu , Wang Yu-Rung , Hsieh Pei-Lun
Published: February 2021

The outbreak of coronavirus (COVID-19), a public health emergency of international concern, has made healthcare staff preparation and the nurturing of high-quality and adequate nursing professionals critical issues. This study aimed to explore registered nurses’ competence in nursing care and their intention to stay in their current workplace. In this study, participants who had graduated from different nursing education systems were recruited. The results indicated that nurses’ level of commitment to the workplace and clinical stress were positively correlated with the experience of working with patients. Stepwise regression analysis revealed the following significant predictors for intention to stay: clinical stress, frequency of caring for people with infections, and taking a course on infectious nursing. The novice nurses’ competencies in the areas of pandemic disease care and care for infectious adults depended on the experience of nursing care and nursing competence in their professional careers, which may have impact on the nurses’ intention to stay. Therefore, clinical stress, frequency of caring for patients, and taking nursing courses were correlated with novice nurses’ intention to stay in their professional careers.
Community Resilience Governance on Public Health Crisis in China
Authors: Wang Chao , Dong Xuan , Zhang Yan , Luo Yiwen
Published: February 2021

The COVID-19 pandemic has immensely affected economic and social order in not only China but the entire world, seriously threatening peoples’ lives and property. In China’s fight against COVID-19, the community is at the front line of joint prevention and control of the disease, yet it faces the problem of insufficient resilience. We explored the manifestations and formation mechanism of the problem of insufficient resilience in community public health crisis governance, based on the complex adaptive system theory, which emphasizes interaction among subjects and between subjects and the environment to improve the adaptability to the environment. Questionnaires and in-depth interviews were conducted in 28 counties (districts) of 14 cities of 7 provinces in China; 2345 questionnaires and 71 interview data were collected, and we conducted descriptive statistical analysis on questionnaire data. It is found that some communities faced insufficient resilience problems such as “simply isolating households and communities”, “blindly setting limits”, “layer-by-layer law”, and “rejecting and repelling all individuals from or even related to Hubei”. These problems are due to the fact that the community have a non-interactive relationship, which is a one-dimensional linear governance model to some extent. The legal content of the building of a “comprehensive disaster-reduction demonstration community” implemented by the Chinese government is compelled to stay at the level of system design to some extent, with its existence playing an ornamental role but lacking a substantial one. In this regard, this study suggests that a resilient governance model of community pluralistic cooperation be established based on the theoretical framework of complex adaptive system. This model is designed to increase the resilience of community public health crisis governance. The authoritative role of central and local policies is expected to be truly developed and played in dealing with the grassroots community public health crisis.
Exposure to Phthalate and Organophosphate Esters via Indoor Dust and PM10 Is a Cause of Concern for the Exposed Saudi Population
Authors: Ali Nadeem , Alhakamy Nabil A. , Ismail Iqbal M. I. , Nazar Ehtisham , Summan Ahmed Saleh , Shah Eqani Syed Ali Musstjab Akbar , Malarvannan Govindan
Published: February 2021

In this study, we measured the occurrence of organophosphate esters (OPEs) and phthalates in the settled dust (floor and air conditioner filter dust) and in suspended particulate matter (PM10) from different microenvironments (households (n = 20), offices (n = 10) and hotels (n = 10)) of Jeddah, Saudi Arabia. Bis (2-Ethylhexyl) phthalate (DEHP) was the major pollutant (contributing >85% of total chemicals burden) in all types of indoor dust with a concentration up to 3,901,500 ng g−1. While dibutyl phthalate (DBP) and DEHP together contributed >70% in PM10 (1900 ng m−3), which indicate PM10 as a significant source of exposure for DBP and DEHP in different Saudi indoor settings. Tris (1-chloro-2-propyl) phosphate (TCPP) was the major OPE in PM10 with a concentration of up to 185 ng m−3 and the occurrence of OPEs in indoor dust varied in studied indoor settings. The estimated daily intake (EDI) of studied chemicals via dust ingestion and inhalation of PM10 was below the reference dose (RfD) of individual chemicals. However, estimated incremental lifetime cancer risk (ILCR) with moderate risk (1.5 × 10−5) for Saudi adults and calculated hazardous index (HI) of >1 for Saudi children from DEHP showed a cause of concern to the local public health.
The Outbreak of the COVID-19 Pandemic and its Social Impact on Education: Were Engineering Teachers Ready to Teach Online?
Authors: Revilla-Cuesta Víctor , Skaf Marta , Varona Juan Manuel , Ortega-López Vanesa
Published: February 2021

The major impacts of the COVID-19 pandemic are still affecting all social dimensions. Its specific impact on education is extensive and quite evident in the adaptation from Face-to-Face (F2F) teaching to online methodologies throughout the first wave of the pandemic and the strict rules on lockdown. As lesson formats changed radically, the relevance of evaluating student on-line learning processes in university degrees throughout this period became clear. For this purpose, the perceptions of engineering students towards five specific course units forming part of engineering degree courses at the University of Burgos, Spain, were evaluated to assess the quality of the online teaching they received. Comparisons were also drawn with their perceptions of the F2F teaching of the course units prior to the outbreak of the pandemic. According to the students’ perceptions, the teachers possessed the technical knowledge, the social skills, and the personal capabilities (empathy and understanding of the at times troubled situation of each student) for a very abrupt adaptation of their courses to an online methodology. The shortcomings of the online teaching were related to its particularities and each teacher’s personality traits. Overall, engineering teachers appeared well prepared for a situation of these characteristics and, if similar online teaching scenarios were ever repeated, the quality of engineering teaching appears to be guaranteed.
The Unmet Needs of Community-Dwelling Stroke Survivors: A Systematic Review of Qualitative Studies
Authors: Guo Yunfei , Zhang Zhenxiang , Lin Beilei , Mei Yongxia , Liu Qingxuan , Zhang Leyun , Wang Wenna , Li Yuan , Fu Zhongrong
Published: February 2021

The unmet needs perceived by community-dwelling stroke survivors may truly reflect the needs of patients, which is crucial for pleasant emotional experiences and a better quality of life for community-dwelling survivors not living in institutionalized organizations. The purpose of the study is to identify the scope of unmet needs from the perspectives of stroke patients in the community. A qualitative meta-synthesis was performed according to the Joanna Briggs Institute method. Six electronic databases were searched from inception to February 2020. A total of 24 articles were involved, providing data on 378 stroke survivors. Eight categories were derived from 63 findings, and then summarized into four synthesized findings based on the framework of ICF: (1) unmet needs regarding with the disease-related information; (2) unmet physical recovery and activity/participation needs; (3) unmet needs for social environmental resources; (4) unmet psycho-emotional support needs. We found the framework of ICF mostly complete, but unmet information needs still remain. The needs that are mainly unsatisfied include physical, psychosocial and informational, as well as the practical support from professional or environment resources. The ever-present unmet needs perceived by community-dwelling stroke survivors who do not live in institutions are discoverable and mitigable. Future studies should focus on quantifying unmet needs comprehensively derived from experiential domains, assessing the rationality of the unmet needs expressed by patients’ perspectives and developing flexible strategies for long-term and changing needs.
Metabolic Syndrome: Prevalence and Risk Factors among Adolescent Female Intermediate and Secondary Students in Saudi Arabia
Authors: Alowfi Areej , Binladen Sumayah , Irqsous Sumaya , Khashoggi Alya , Khan Muhammad Anwar , Calacattawi Ramah
Published: February 2021

Background: Metabolic syndrome (MS) has become one of the major challenges to public health worldwide due to its significant association with increased risk of developing type 2 diabetes and cardiovascular disease (CVD) among children and adolescents. Therefore, this study aims to determine the prevalence and risk factors of MS in Saudi adolescents. Methods: This cross-sectional study was conducted in two female National Guard schools (Um Kalthoom Intermediate School and Zainab Bint Jahsh Secondary School) in Jeddah, Saudi Arabia, between January 2018 and March 2018. Of the 808 female students, 172 (age range of 12–19 years) participated voluntarily, with consent from their guardian(s), fasted for at least 8 h prior to the study, and represent the final study sample. Male students were not included due to cultural constraints in conducting the study. Demographic data, physical measurement (blood pressure, weight, height, body mass index (BMI) and waist circumference (WC)), and biochemical measurement (fasting plasma glucose and triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein) were obtained. The International Diabetes Federation (IDF) criteria was utilized in the diagnosis of MS. Results: Of the 172 female adolescents, 24 (13.75%) are overweight, 20 (11.63%) are obese, and 3 (1.74%) are underweight. High-fasting plasma glucose (n = 85, 49.41%) and high waist circumference (n = 74, 43.02%) were the most common risk factors of MS among female adolescents. The overall prevalence of MS was 7% (n = 12/172). MS is more common among those who are obese or among those with a BMI that falls at the ≥95th percentile (n = 6/20, 30.0%) (p < 0.05) as compared to those who are overweight with a BMI that falls within the 85th to <95th percentiles (n = 2/24, 8.33%). Interestingly, 3.20% of the sample (n = 4/125) with normal BMI were diagnosed with MS. Conclusions: Our study indicates that MS is common among obese and overweight female adolescents but is also present among those who are not obese or with normal BMI. Moreover, the prevalence of overweight, obese, and those with MS in this reference population are lower compared to the cities of Makkah and Riyadh; however, it varies widely around the world due to different criteria and cut-off values in the diagnosis of MS.
Statistical Estimation of Effects of Implemented Government Policies on COVID-19 Situation in South Korea
Authors: Heo Gyujin , Apio Catherine , Han Kyulhee , Goo Taewan , Chung Hye Won , Kim Taehyun , Kim Hakyong , Ko Yeonghyeon , Lee Doeun , Lim Jisun , Park Taesung
Published: February 2021

Since the outbreak of novel SARS-COV-2, each country has implemented diverse policies to mitigate and suppress the spread of the virus. However, no systematic evaluation of these policies in their alleviation of the pandemic has been done. We investigate the impact of five indices derived from 12 policies in the Oxford COVID-19 Government Response Tracker dataset and the Korean government’s index, which is the social distancing level implemented by the Korean government in response to the changing pandemic situation. We employed segmented Poisson model for this analysis. In conclusion, health and the Korean government indices are most consistently effective (with negative coefficients), while the restriction and stringency indexes are mainly effective with lagging (1~10 days), as intuitively daily confirmed cases of a given day is affected by the policies implemented days before, which shows that a period of time is required before the impact of some policies can be observed. The health index demonstrates the importance of public information campaign, testing policy and contact tracing, while the government index shows the importance of social distancing guidelines in mitigating the spread of the virus. These results imply the important roles of these polices in mitigation of the spread of COVID-19 disease.
Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson’s Disease Model
Authors: Lee Seulah , Suh Yeon Ji , Yang Seonguk , Hong Dong Geun , Ishigami Akihito , Kim Hangun , Hur Jae-Seoun , Chang Seung-Cheol , Lee Jaewon
Published: February 2021

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson’s disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP+)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP+-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.
Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation
Authors: Songia Paola , Chiesa Mattia , Alfieri Valentina , Massaiu Ilaria , Moschetta Donato , Myasoedova Veronika , Valerio Vincenza , Fusini Laura , Gripari Paola , Zanobini Marco , Poggio Paolo
Published: February 2021

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.
The Endocannabinoid System and Invertebrate Neurodevelopment and Regeneration
Authors: Clarke Tristyn L. , Johnson Rachael L. , Simone Jonathan J. , Carlone Robert L.
Published: February 2021

Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.
A New Intronic Variant in ECEL1 in Two Patients with Distal Arthrogryposis Type 5D
Authors: Alesi Viola , Sessini Francesca , Genovese Silvia , Calvieri Giusy , Sallicandro Ester , Ciocca Laura , Mingoia Maura , Novelli Antonio , Moi Paolo
Published: February 2021

Distal Arthrogryposis type 5D (DA5D) is characterized by congenital contractures involving the distal joints, short stature, scoliosis, ptosis, astigmatism, and dysmorphic features. It is inherited in an autosomal recessive manner, and it is a result of homozygous or compound heterozygous variants in the ECEL1 gene. Here, we report two patients of Sardinian origin harboring a new intronic homozygous variant in ECEL1 (c.1507-9G>A), which was predicted to affect mRNA splicing by activating a cryptic acceptor site. The frequency of the variant is very low in the general human population, and its presence in our families can be attributed to a founder effect. This study provides an updated review of the known causative mutations of the ECEL1 gene, enriching the allelic spectrum to include the noncoding sequence.
The Circadian Physiology: Implications in Livestock Health
Authors: Li Hao , Li Kaiqi , Zhang Kexin , Li Yanwei , Gu Haotian , Liu Haoyu , Yang Zhangping , Cai Demin
Published: February 2021

Circadian rhythms exist in almost all types of cells in mammals. Thousands of genes exhibit approximately 24 h oscillations in their expression levels, making the circadian clock a crucial regulator of their normal functioning. In this regard, environmental factors to which internal physiological processes are synchronized (e.g., nutrition, feeding/eating patterns, timing and light exposure), become critical to optimize animal physiology, both by managing energy use and by realigning the incompatible processes. Once the circadian clock is disrupted, animals will face the increased risks of diseases, especially metabolic phenotypes. However, little is known about the molecular components of these clocks in domestic species and by which they respond to external stimuli. Here we review evidence for rhythmic control of livestock production and summarize the associated physiological functions, and the molecular mechanisms of the circadian regulation in pig, sheep and cattle. Identification of environmental and physiological inputs that affect circadian gene expressions will help development of novel targets and the corresponding approaches to optimize production efficiency in farm animals.
Molecular Regulation of Canalicular ABC Transporters
Authors: Ben Saad Amel , Bruneau Alix , Mareux Elodie , Lapalus Martine , Delaunay Jean-Louis , Gonzales Emmanuel , Jacquemin Emmanuel , Aït-Slimane Tounsia , Falguières Thomas
Published: February 2021

The ATP-binding cassette (ABC) transporters expressed at the canalicular membrane of hepatocytes mediate the secretion of several compounds into the bile canaliculi and therefore play a key role in bile secretion. Among these transporters, ABCB11 secretes bile acids, ABCB4 translocates phosphatidylcholine and ABCG5/G8 is responsible for cholesterol secretion, while ABCB1 and ABCC2 transport a variety of drugs and other compounds. The dysfunction of these transporters leads to severe, rare, evolutionary biliary diseases. The development of new therapies for patients with these diseases requires a deep understanding of the biology of these transporters. In this review, we report the current knowledge regarding the regulation of canalicular ABC transporters’ folding, trafficking, membrane stability and function, and we highlight the role of molecular partners in these regulating mechanisms.
Cellular Mechanism Underlying Highly-Active or Antiretroviral Therapy-Induced Lipodystrophy: Atazanavir, a Protease Inhibitor, Compromises Adipogenic Conversion of Adipose-Derived Stem/Progenitor Cells through Accelerating ER Stress-Mediated Cell Death in Differentiating Adipocytes
Authors: Akita Sadanori , Suzuki Keiji , Yoshimoto Hiroshi , Ohtsuru Akira , Hirano Akiyoshi , Yamashita Shunichi
Published: February 2021

Lipodystrophy is a common complication in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART). Previous studies demonstrated that endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR) is involved in lipodystrophy; however, the detailed mechanism has not been fully described in human adipogenic cell lineage. We utilized adipose tissue-derived stem cells (ADSCs) obtained from human subcutaneous adipose tissue, and atazanavir (ATV), a protease inhibitor (PI), was administered to ADSCs and ADSCs undergoing adipogenic conversion. Marked repression of adipogenic differentiation was observed when ATV was administered during 10 days of ADSC culture in adipogenic differentiation medium. Although ATV had no effect on ADSCs, it significantly induced apoptosis in differentiating adipocytes. ATV treatment also caused the punctate appearance of CCAAT-enhancer-binding (C/EBP) protein homologous protein (CHOP), and altered expression of CHOP and GRP78/Bip, which are the representation of ER stress, only in differentiating adipocytes. Administration of UPR inhibitors restored adipogenic differentiation, indicating that ER stress-mediated UPR was induced in differentiating adipocytes in the presence of ATV. We also observed autophagy, which was potentiated in differentiating adipocytes by ATV treatment. Thus, adipogenic cell atrophy leads to ATV-induced lipodystrophy, which is mediated by ER stress-mediated UPR and accelerated autophagy, both of which would cause adipogenic apoptosis. As our study demonstrated for the first time that ADSCs are unsusceptible to ATV and its deleterious effects are limited to the differentiating adipocytes, responsible target(s) for ATV-induced lipodystrophy may be protease(s) processing adipogenesis-specific protein(s).
Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome
Authors: Lombó Marta , Herráez María Paz
Published: February 2021

Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters—as well as that of kat6a—an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.
Non-Musculoskeletal Benefits of Vitamin D beyond the Musculoskeletal System
Authors: Zhang Sicheng , Miller Duane D. , Li Wei
Published: February 2021

Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most tissues and cells in the body, the mounting understanding of the role of vitamin D in humans indicates that it does not only play an important role in the musculoskeletal system, but has beneficial effects elsewhere as well. This review summarizes the metabolism of vitamin D, the research regarding the possible risk factors leading to vitamin D deficiency, and the relationships between vitamin D deficiency and numerous illnesses, including rickets, osteoporosis and osteomalacia, muscle weakness and falls, autoimmune disorders, infectious diseases, cardiovascular diseases (CVDs), cancers, and neurological disorders. The system-wide effects of vitamin D and the mechanisms of the diseases are also discussed. Although accumulating evidence supports associations of vitamin D deficiency with physical and mental disorders and beneficial effects of vitamin D with health maintenance and disease prevention, there continue to be controversies over the beneficial effects of vitamin D. Thus, more well-designed and statistically powered trials are required to enable the assessment of vitamin D’s role in optimizing health and preventing disease.
Expression and Prognostic Characteristics of m6A RNA Methylation Regulators in Colon Cancer
Authors: Huang Liting , Zhu Jie , Kong Weikaixin , Li Peifeng , Zhu Sujie
Published: February 2021

Colon cancer is a common and leading cause of death and malignancy worldwide. N6-methylation of adenosine (m6A) is the most common reversible mRNA modification in eukaryotes, and it plays a crucial role in various biological functions in vivo. Dysregulated expression and genetic changes of m6A regulators have been correlated with tumorigenesis, cancer cell proliferation, tumor microenvironment, and prognosis in cancers. This study used RNA-seq and colon cancer clinical data to explore the relationship between N6-methylation and colon cancer. Based on the seven m6A regulators related to prognosis, three molecular subgroups of colon cancer were identified. Surprisingly, we found that each subgroup had unique survival characteristics. We then identified three subtypes of tumors based on 299 m6A phenotype-related genes, and one subtype was characterized as an immunosuppressive tumor and patients in this subtype may be more suitable for immunotherapy than other subtypes. Finally, using m6A-related genes and clinical information from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model could be used to predict the prognosis of patients in clinics.
Possibility of Japanese Cedar Pollen Causing False Positives in the Deep Mycosis Test
Authors: Kanno Takashi , Kim Changmin , Yamanaka Daisuke , Ishibashi Ken-ichi , Tanaka Hiroshi , Ohno Naohito , Adachi Yoshiyuki
Published: February 2021

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.
The Relevance of Noncoding DNA Variations of Paraoxonase Gene Cluster in Atherosclerosis-Related Diseases
Authors: Wysocka Anna , Zwolak Agnieszka
Published: February 2021

The human paraoxonase (PON) gene cluster is comprised of three contiguous genes (PON1, PON2 and PON3) of presumably common origin coding three lactonases of highly similar structure and substrate specificity. The catalytic activity of PON proteins is directed toward artificial organophosphates and in physiological conditions toward thiolactones and oxidized phospholipids. Consequently, PON enzymes are regarded as an effective defense against oxidative stress and, as a result, against atherosclerosis development. Additionally, both PON’s serum activity and its concentration are influenced by several polymorphic variations in coding and noncoding DNA regions of the PON gene cluster remaining in linkage disequilibrium. Hence, the genetic polymorphism of the PON gene cluster may contribute to atherosclerotic process progression or deceleration. In this review the authors analyzed the relevance of noncoding DNA polymorphic variations of PON genes in atherosclerosis-related diseases involving coronary and peripheral artery disease, stroke, diabetes mellitus, dementia and renal disease and concluded that the effect of PON gene cluster’ polymorphism has a considerable impact on the course and outcome in these conditions. The following PON genetic variations may serve as additional predictors of the risk of atherosclerosis in selected populations and individuals.
A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder
Authors: McCarty Mark F. , DiNicolantonio James J. , Lerner Aaron
Published: February 2021

Oxidative stress and increased cytoplasmic calcium are key mediators of the detrimental effects on neuronal function and survival in Alzheimer’s disease (AD). Pathways whereby these perturbations arise, and then prevent dendritic spine formation, promote tau hyperphosphorylation, further amplify amyloid β generation, and induce neuronal apoptosis, are described. A comprehensive program of nutraceutical supplementation, comprised of the NADPH oxidase inhibitor phycocyanobilin, phase two inducers, the mitochondrial antioxidant astaxanthin, and the glutathione precursor N-acetylcysteine, may have important potential for antagonizing the toxic effects of amyloid β on neurons and thereby aiding prevention of AD. Moreover, nutraceutical antioxidant strategies may oppose the adverse impact of amyloid β oligomers on astrocyte clearance of glutamate, and on the ability of brain capillaries to export amyloid β monomers/oligomers from the brain. Antioxidants, docosahexaenoic acid (DHA), and vitamin D, have potential for suppressing microglial production of interleukin-1β, which potentiates the neurotoxicity of amyloid β. Epidemiology suggests that a health-promoting lifestyle, incorporating a prudent diet, regular vigorous exercise, and other feasible measures, can cut the high risk for AD among the elderly by up to 60%. Conceivably, complementing such lifestyle measures with long-term adherence to the sort of nutraceutical regimen outlined here may drive down risk for AD even further.
Current Perspective Regarding the Immunopathogenesis of Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms (DIHS/DRESS)
Authors: Miyagawa Fumi , Asada Hideo
Published: February 2021

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe type of adverse drug eruption associated with multiorgan involvement and the reactivation of human herpesvirus 6, which arises after prolonged exposure to certain drugs. Typically, two waves of disease activity occur during the course of DIHS/DRESS; however, some patients experience multiple waves of exacerbation and remission of the disease. Severe complications, some of which are related to cytomegalovirus reactivation, can be fatal. DIHS/DRESS is distinct from other drug reactions, as it involves herpes virus reactivation and can lead to the subsequent development of autoimmune diseases. The association between herpesviruses and DIHS/DRESS is now well established, and DIHS/DRESS is considered to arise as a result of complex interactions between several herpesviruses and comprehensive immune responses, including drug-specific immune responses and antiviral immune responses, each of which may be mediated by distinct types of immune cells. It appears that both CD4 and CD8 T cells are involved in the pathogenesis of DIHS/DRESS but play distinct roles. CD4 T cells mainly initiate drug allergies in response to drug antigens, and then herpesvirus-specific CD8 T cells that target virus-infected cells emerge, resulting in tissue damage. Regulatory T-cell dynamics are also suggested to contribute to the diverse symptoms of DIHS/DRESS. However, the pathomechanisms of this complex disease remain largely unknown. In particular, how viral infections contribute to the pathogenesis of DIHS/DRESS and why autoimmune sequelae arise in DIHS/DRESS are yet to be elucidated. This review describes the clinical features of DIHS/DRESS, including the associated complications and sequelae, and discusses recent advances in our understanding of the immunopathogenic mechanisms of DIHS/DRESS.
Editorial for Special Issue “Genetic Basis and Epidemiology of Myopathies”
Authors: Peristeri Eleni , Dardiotis Efthimios
Published: February 2021

We are pleased to announce a Special Issue on the Genetic Basis and Epidemiology of Myopathies. This Special Issue is collecting papers pertaining to various lines of research focusing on the genetic basis and the epidemiology of myopathies. The Guest Editors’ note combines the contributing authors’ reviews and findings of relevant research, and we hope that future studies on myopathies will attempt to confirm these findings and, additionally, evaluate supplementary phenotypic and histological expressions of myopathies, as well as genetic factors in their pathogenesis.
Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview
Authors: Sivandzade Farzane , Cucullo Luca
Published: February 2021

Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.
Editorial to the Special Issue “MicroRNA Dysregulation in Tumor Occurrence, Progression and Response to Therapy”
Authors: Iorio Marilena V.
Published: February 2021

In the last 20 years, the involvement of microRNAs in the biology of human tumors has been clearly demonstrated, and the scientific community has switched from an initial skepticism to an increasing interest toward what was called the “dark side” of DNA [...]
Human Placenta Exosomes: Biogenesis, Isolation, Composition, and Prospects for Use in Diagnostics
Authors: Burkova Evgeniya E. , Sedykh Sergey E. , Nevinsky Georgy A.
Published: February 2021

Exosomes are 40–100 nm nanovesicles participating in intercellular communication and transferring various bioactive proteins, mRNAs, miRNAs, and lipids. During pregnancy, the placenta releases exosomes into the maternal circulation. Placental exosomes are detected in the maternal blood even in the first trimester of pregnancy and their numbers increase significantly by the end of pregnancy. Exosomes are necessary for the normal functioning of the placenta and fetal development. Effects of exosomes on target cells depend not only on their concentration but also on their intrinsic components. The biochemical composition of the placental exosomes may cause various complications of pregnancy. Some studies relate the changes in the composition of nanovesicles to placental dysfunction. Isolation of placental exosomes from the blood of pregnant women and the study of protein, lipid, and nucleic composition can lead to the development of methods for early diagnosis of pregnancy pathologies. This review describes the biogenesis of exosomes, methods of their isolation, analyzes their biochemical composition, and considers the prospects for using exosomes to diagnose pregnancy pathologies.