bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocarditis in Athletes Recovering from COVID-19: A Systematic Review and Meta-Analysis
Authors: Modica Gloria , Bianco Massimiliano , Sollazzo Fabrizio , Di Murro Emanuela , Monti Riccardo , Cammarano Michela , Morra Lorenzo , Nifosì Francesco Maria , Gervasi Salvatore Francesco , Manes Gravina Ester , Zeppilli Paolo , Palmieri Vincenzo
Published: April 2022

Background: To assess the event rates of myocarditis detected by Cardiac Magnetic Resonance (CMR) in athletes who recovered from COVID-19. Methods: A systematic literature search was performed to identify studies reporting abnormal CMR findings in athletes who recovered from COVID-19. Secondary analyses were performed considering increased serum high sensitivity troponin (hs-Tn) levels and electrocardiographic (ECG) and echocardiographic (ECHO) abnormalities. Results: In total, 7988 athletes from 15 studies were included in the analysis. The pooled event rate of myocarditis was 1% (CI 1–2%), reaching 4% in the sub-group analysis. In addition, heterogeneity was observed (I2 43.8%). The pooled event rates of elevated serum hs-Tn levels, abnormal ECG and ECHO findings were 2% (CI 1–5%), 3% (CI 1–10%) and 2% (CI 1–6%), respectively. ECG, ECHO and serum hs-Tn level abnormalities did not show any correlation with myocarditis. Conclusions: The prevalence of COVID-19-related myocarditis in the athletic population ranges from 1 to 4%. Even if the event rate is quite low, current screening protocols are helpful tools for a safe return to play to properly address CMR studies. Trial registration: the study protocol was registered in the PROSPERO database (registration number: CRD42022300819).
How Climate Change Science Is Reflected in People’s Minds. A Cross-Country Study on People’s Perceptions of Climate Change
Authors: Petrescu-Mag Ruxandra Malina , Burny Philippe , Banatean-Dunea Ioan , Petrescu Dacinia Crina
Published: April 2022

The way people perceive climate change scientific evidence becomes relevant in motivating or demotivating their climate actions. Climate change is one of the most publicized topics globally, and media has become an important “validator” of science. Therefore, science has become more exposed to criticism. Even when most scientists, decision makers, and laypeople agree on the robust evidence of climate science, there is still room for disagreement. The main aim of this paper is to reveal how climate change knowledge generated by science is perceived by the laypeople and to observe a possible gap between them. The study answered two questions “What are the main contrasting climate change topics in the scientific literature?” and “What are Romanian and Belgian participants’ perceptions of these topics?”. A qualitative approach was chosen for data analysis, using Quirkos software. The present cross-country study showed commonalities and differences of views between the two groups of participants regarding six climate change topics. Divergent perceptions among Belgians and Romanians came out, for example, within the theme “The heroes, villains, and victims of climate change.” Thus, whereas Belgians considered all people, including themselves, responsible for climate change, Romanians blamed mostly others, such as big companies, governments, and consumers. Additionally, both groups stated that climate change existed, but contrary to Belgians, Romanians voiced that climate change was often used as an exaggerated and politicized topic. The analysis revealed that perceptions about climate change, its causes, and its impacts are social constructs with a high degree of variability between and within the two national groups. The study argued that the cleavages between scientific literature and people’s views were blind spots on which a participatory approach was needed to better cope with climate change challenges.
Removal of Sulfonamide Resistance Genes in Fishery Reclamation Mining Subsidence Area by Zeolite
Authors: Yuan Tao , Lin Zi-Bo , Cheng Sen , Wang Rui , Lu Ping
Published: April 2022

A majority of subsidence lakes were reclaimed as fish ponds, but the widespread use of antibiotics has caused the pollution of antibiotic resistance genes (ARGs). This paper uses zeolite as a filter material to construct a horizontal submersible wastewater treatment device and explores its effect on the removal of conventional pollutants and sulfonamide ARGs in wastewater. The results showed that the removal of total nitrogen and ammonia nitrogen by the zeolite filter media were 59.0% and 63.8%, respectively, which were higher than the removal of total phosphorus and COD. The absolute abundances of sul1 and sul2 in wastewater were 2.81 × 104 copies·L−1 and 2.42 × 103 copies·L−1. On average, 60.62% of sul1 and 75.84% of sul2 can be removed, and more than 90% of sul1 and sul2 can be removed. Experiments showed that the residence time of wastewater in the treatment device had a significant impact on removal. The microbial community structure of aquaculture wastewater was quite different before and after wastewater treatment. The abundance changes of Saccharimonadales and Mycobacterium affect the removal of sulfonamide ARGs.
Influence of Physical Exercise on Psychological Well-Being of Young Adults: A Quantitative Study
Authors: Granero-Jiménez Jesús , López-Rodríguez María Mar , Dobarrio-Sanz Iria , Cortés-Rodríguez Alda Elena
Published: April 2022

Physical activity is a key element in people’s health as it provides important physical benefits, as well as improves mental health and quality of life. However, recent years have seen an increase in the percentage of young adults showing high levels of inactivity. Although, it has been observed that the motivation to perform physical activity seems to be an important factor when starting and then keeping it up. Thus, the general aim of this work was to explore the association between physical activity, motivation, and psychological well-being in young adults. To do this, a descriptive cross-sectional correlational study was carried out together with a multiple linear regression analysis. An online survey was applied between December 2017 and the first quarter of 2018, in which the level of activity, motivation, and psychological well-being of the participants were measured. Starting from a final sample of 489 subjects aged between 18 and 35 years, a higher level of physical activity was found to be related to higher psychological well-being. In addition, motivation, and more specifically intrinsic motivation, was an important determinant of psychological well-being, gaining greater influence among male participants who had a higher level of physical activity. This study therefore emphasizes the clear influence of physical activity on the psychological well-being of young adults and highlights the need to work on intrinsic motivation to improve levels of physical activity.
Empowering Our People: Syndemic Moderators and Effects of a Culturally Adapted, Evidence-Based Intervention for Sexual Risk Reduction among Native Americans with Binge Substance Use
Authors: Kemp Christopher , Chambers Rachel , Larzelere Francene , Lee Angelita , Pinal Laura , Slimp Anna , Tingey Lauren
Published: April 2022

Native American (NA) communities are disproportionately affected by the intersecting, synergistic epidemics of sexually transmitted infections (STIs) and substance use. Targeted approaches to addressing these syndemics are critical given the relative scarcity of mental health and behavioral specialists in NA communities. We conducted a series of moderation analyses using data from a randomized controlled trial of the EMPWR (Educate, Motivate, Protect, Wellness, Respect) intervention for reducing sexual risk behaviors, culturally adapted for NA adults with recent binge substance use living on rural reservations. We considered several potential moderators and substance use and sexual risk outcomes at 6- and 12-months post-baseline. Three hundred and one people participated in the study. Age, marital status, educational attainment, employment, and depressive symptoms were differentially associated with intervention effects. EMPWR could be strengthened with the incorporation of additional skills-building related to condom use negotiation with casual partners. For individuals with lower educational attainment or without employment, additional supports and approaches to intervention may be needed. Importantly, this study did not identify intersecting sexual risk and substance use behaviors as moderators of EMPWR effectiveness, suggesting that NA adults with varying levels of risk behavior may be equally likely to benefit from this intervention.
Has the Volume-Based Drug Purchasing Approach Achieved Equilibrium among Various Stakeholders? Evidence from China
Authors: Xing Qian , Tang Wenxi , Li Mingyang , Li Shuailong
Published: April 2022

Volume-based drug purchasing by China’s health insurance system currently represents the largest group purchasing organization worldwide. After exchanging the market that accounted for nearly half of the volume of the healthcare system for the ultra-low-price supply of limited drugs, what are the effects on patient and funding burdens, drug accessibility, and clinical efficacy? We aimed to verify the effectiveness of the policy, explore the reasons behind the problem and identify regulatory priorities and collaborative measures. We used literature and reported data from 2019 to 2021 to conduct a stakeholder analysis and health impact assessment, presenting the benefit and risk share for various dimensions. The analysis method was a multidimensional scaling model, which visualized problematic associations. Seventy-nine papers (61 publications and 18 other resources) were included in the study, with 22 effects and 36 problems identified. The results indicated favorable affordability and poor accessibility of drugs, as well as high risk of reduced drug quality and drug-use rationality. The drug-use demand of patients was guaranteed; the prescription rights of doctors regarding clinical drug use were limited; unreasonable evaluation indicators limited the transformation of public hospitals to value- and service-oriented organizations; the sustainability of health insurance funds and policy promotion were at risk; and innovation by pharmaceutical companies was accelerated. The problems associated with high co-occurrence frequencies were divided into the following clusters: cost control, drug accessibility, system rationality, policy fairness, drug quality, and moral hazards. These findings suggested that China has achieved short-term success in reducing the burden on patients and reducing fund expenditure. However, there were still deficiencies in guaranteed supply, quality control, and efficacy tracking. The study offers critical lessons for China and other low- and middle-income countries.
Attitudes of Patients with Chronic Diseases toward Management eHealth Applications Systems in Post-COVID-19 Times
Authors: ALsharif Abdullah H.
Published: April 2022

Introduction: There has been an increase in the adoption of eHealth technologies and applications by health consumers globally because of the restrictions imposed due to the COVID-19 pandemic in the last two years. The sudden change in the users’ attitudes toward eHealth adoption needs to be critically evaluated and understood, as it can be the stepping stone toward rapid digitalization of healthcare operations in Saudi Arabia as a part of Vision 2030. Purpose: The purpose of this study was to evaluate the attitudes of the patients with chronic diseases toward eHealth applications in post-COVID times. Methods: A cross-sectional study design was adopted using the online questionnaire as a data collection instrument. All the health consumers using eHealth services aged above 18 years and living in Saudi Arabia were included in the survey. The survey was conducted for 3 weeks, resulting in a final sample of 234 participants. Results: Overall, 73.8% of the participants stated that they adopted eHealth only out of necessity, while 37.3% stated that they adopted it because no other services were available. Only 10.3% stated that they adopted eHealth out of interest. In relation to the future use of eHealth, 51.5% of the participants stated that they would definitely not use eHealth applications, and 33.6% stated that they would probably them once the pandemic ends. Only 4.4% of the participants stated that they would very much probably, and 10.5% stated they would probably not use eHealth applications once the pandemic ends. a significant difference in opinions in relation to the future adoption of eHealth applications was observed among the male and female participants, and also between the age groups of younger (age <35 years) and older (age ≥35 years) participants. Conclusions: For the change in attitudes (increased adoption of eHealth) to be sustained, policymakers need to develop relevant strategies promoting the use of eHealth in Saudi Arabia.
What Is the Burnout of Mothers with Infants and Toddlers during the COVID-19 Pandemic? In Relation to Parenting Stress, Depression, and Parenting Efficacy
Authors: Seo Jeong-Hyo , Kim Hee-Kyung
Published: April 2022

Background: The purpose of this study was to analyze the factors influencing burnout of mothers with infants or toddlers in the COVID-19 pandemic. Methods: The subjects of this study were 105 mothers who sent their children to daycare centers or kindergartens located in S and G cities. They were women who have experienced caring for children entirely at home during the COVID-19 pandemic. The collected data were analyzed using descriptive statistics, t-test, ANOVA, Man–Whitney U test, Pearson’s correlation coefficients, and a stepwise multiple regression using the SPSS Window 25.0 program. Results: The subjects’ burnout and parenting stress (r = 0.62, p < 0.001), depression (r = 0.58, p < 0.001), and parenting efficacy (r = −0.62, p < 0.001) showed a large correlation. The factors affecting the subjects’ burnout were parenting stress (β = 0.28, p < 0.001), parenting efficacy (β = −0.40, p < 0.001), depression (β = 0.27, p < 0.001), and spouse’s support (nearly none) (β = 0.18, p = 0.004). These variables explained 64.0% of the subjects’ burnout. Conclusions: Through the research results, it was confirmed that parenting stress, parenting efficacy, depression, and spouse’s support influence the mother’s burnout. Therefore, in future studies, it is necessary to expand mental health programs to lower parenting stress and depression into interventional studies on specific educational strategies such as programs to promote efficacy and improve spouse’s support.
Comprehensive Risk Assessment of Typical High-Temperature Cities in Various Provinces in China
Authors: Zhang Xueru , Long Qiuyue , Kun Dong , Yang Dazhi , Lei Liu
Published: April 2022

Global climate change results in an increased risk of high urban temperatures, making it crucial to conduct a comprehensive assessment of the high-temperature risk of urban areas. Based on the data of 194 meteorological stations in China from 1986 to 2015 and statistical yearbooks and statistical bulletins from 2015, we used GIS technology and mathematical statistics to evaluate high-temperature spatial and temporal characteristics, high-temperature risk, and high-temperature vulnerability of 31 cities across China. Over the past 30 years, most Chinese cities experienced 5–8 significant oscillation cycles of high-temperature days. A 15-year interval analysis of high-temperature characteristics found that 87% of the cities had an average of 5.44 more high-temperature days in the 15-year period from 2001 to 2015 compared to the period from 1986 to 2000. We developed five high-temperature risk levels and six vulnerability levels. Against the background of a warming climate, we discuss risk mitigation strategies and the importance of early warning systems.
Suspended Sediments Quality Assessment in a Coastal River: Identification of Potentially Toxic Elements
Authors: Zeng Jie , Han Guilin , Zhang Shitong , Zhang Qian
Published: April 2022

In coastal rivers with various human and damming activities (reservoir), the cycle and biogeochemistry of environmental pollutants in river systems has been modified. A total of 42 suspended particulate matter (SPM) samples were obtained in Jiulongjiang River, southeast China to investigate the concentration, sources, behavior, and risks of nine potentially toxic elements (PTEs) in SPM. The results of metals concentration showed relatively large variation, major for Mn and minor for Co; Mn > Zn > V > Pb > Cr > Ni > Cu > Cd > Co. Multi-index evaluation reflected that most of the PTEs are minor enrichment/moderately polluted. The Cd is defined as extremely severe enrichment/polluted level, and the Pb and Zn as minor enrichment/moderately polluted levels. Among the selected PTEs, Cd and Zn are identified as the main toxic factors of SPM with a contribution of 57 ± 18% and 14 ± 7% to the total toxic risk. The sources identification suggested that human inputs may be the primary potential source of Cd, Zn, Pb, and Co, whereas natural sources (e.g., rock weathering) are likely to be responsible for Cu, Cr, V, and Ni. In contrast, the data suggested that Mn may be attributed to both natural and anthropogenic inputs. The PTEs among dissolved, suspended, and sediment phases reflected the transportation behavior and different potential risk levels. Overall, the PTE geochemistry of river SPM can act as a good indicator of the driving mechanism of PTEs’ accumulation and provide a powerful support for controlling riverine PTEs-related pollution in coastal regions.
Heterogeneity of Capability Deprivation and Subjective Sense of Gain: Analysis of Factor Mixture Models Based on 892 Rural Households in Six Provinces
Authors: Huo Zenghui , Zhang Mei , Han Junhui
Published: April 2022

Background: The capability approach conceptualizes poverty as capability deprivation. Given that functionings and opportunities as key factors are diverse, the combination of a varied lack of functionings and opportunities will lead to different deprivation patterns. Therefore, we sought to investigate the association between the category of capacity deprivation and the subjective acquisition of rural households. Methods: Data were collected from the micro survey of 892 households in six provinces. The overall sense of acquisition was measured by self-assessment of life satisfaction and the relative sense of gain was measured by self-assessment of social status and communication confidence. Capability deprivation was assessed through evaluation functionings and opportunities for a better life, such as education, social security, medical and health services, living conditions and spiritual and cultural activities. The factor mixture models were used to investigate the group categories of capability deprivation and ordered probit regression was used to estimate the associations between the categories of capability deprivation and sense of gain. Results: There were mild, moderate and severe differences among the deprivation items reflecting functionings and opportunities. In addition, capability deprivation was grouped into four classes: double deprivation of functionings and opportunities, severe deprivation of opportunities, functionings deprivation and non-poverty. There was a significant negative relationship between deprivation classes and the subjective sense of gain. Conclusion: The deprivation from some social participation functions and services led to a reduced sense of acquisition. However, serious deprivations from educational opportunities and social participation opportunities were the main reason for the lower sense of gain. Eliminating the unequal educational opportunities and social participation opportunities for people is imperative to improving the subjective sense of gain.
Prenatal Exposure to Metals and Neurodevelopment in Infants at Six Months: Rio Birth Cohort Study of Environmental Exposure and Childhood Development (PIPA Project)
Authors: de Assis Araujo Mônica Seefelder , Froes-Asmus Carmen Ildes Rodrigues , de Figueiredo Nataly Damasceno , Camara Volney Magalhães , Luiz Ronir Raggio , Prata-Barbosa Arnaldo , Martins Marlos Melo , Jacob Silvana do Couto , Santos Lisia Maria Gobbo dos , Vicentini Neto Santos Alves , Rezende Filho Jorge Fonte de , Amim Junior Joffre
Published: April 2022

The PIPA Project is a prospective birth cohort study based in Rio de Janeiro, Brazil, whose pilot study was carried out between October 2017 and August 2018. Arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) concentrations were determined in maternal (n = 49) and umbilical cord blood (n = 46). The Denver Developmental Screening Test II (DDST-II) was applied in 50 six-month-old infants. Metals were detected in 100% of the mother and newborn samples above the limits of detection. Maternal blood lead concentrations were higher in premature newborns (GM: 5.72 µg/dL; p = 0.05). One-third of the infants (n = 17–35.4%) exhibited at least one fail in the neurodevelopment evaluation (fail group). Maternal blood arsenic concentrations were significantly (p = 0.03) higher in the “fail group” (GM: 11.85 µg/L) compared to infants who did not fail (not fail group) (GM: 8.47 µg/L). Maternal and umbilical cord blood arsenic concentrations were higher in all Denver Test’s domains in the “fail group”, albeit non-statistically significant, showing a tendency for the gross motor domain and maternal blood (p = 0.07). These findings indicate the need to further investigate the toxic effects of prenatal exposure to metals on infant neurodevelopment.
Using Mixed Methods Integration to Evaluate the Structure of Help-Seeking Barriers Scale: A Survivor-Centered Approach
Authors: Thorvaldsdottir Karen Birna , Halldorsdottir Sigridur , Saint Arnault Denise M.
Published: April 2022

Despite the high prevalence of adverse health and trauma-related outcomes associated with intimate partner violence (IPV), help-seeking and service utilization among survivors is low. This study is part of a larger mixed-methods and survivor-centered validation study on the Icelandic Barriers to Help-Seeking for Trauma (BHS-TR) scale, a new barriers measure focused on trauma recovery. A mixed-methods legitimation strategy of integration was employed to evaluate the BHS-TR structure in samples of IPV survivors. The merging of qualitative (n = 17) and quantitative (n = 137) data through a joint display analysis revealed mainly complementarity findings, strengthening the scale’s overall trustworthiness and validity evidence. Divergent findings involved items about mistrust, perceived rejection, stigmatization, fearing vulnerability, and safeguarding efforts that were significant help-seeking barriers in the survivors’ narratives, whereas factor analysis indicated their removal. These BHS-TR items were critically evaluated in an iterative spiraling process that supported the barriers’ influence, illuminated core issues, and guided potential refinements. This work contributes to the growing field of mixed methods instrument validation placing equal status on qualitative and quantitative methods and emphasizing integration to provide more complete insights. Moreover, the study’s findings highlight the added value of further exploring divergence between two sets of data and the importance of giving attention to the voices of the target population throughout the validation process.
Long-Term Care Insurance Pilot Programme in China: Policy Evaluation and Optimization Options—Taking the Pilot Programme in the Northeast of China as an Example
Authors: Han Ye , Shen Tong
Published: April 2022

China’s population is ageing rapidly and the increase in life expectancy is accompanied by a loss of capability with advancing age, especially in the Northeast. This study adopts qualitative research methods to analyze the overall status and problems of China’s LTCI policy pilots. Taking four LTCI pilot cities in three northeastern provinces as samples, we used purposive sampling to recruit 10 beneficiaries and providers of LTCI in nursing homes of different kinds, as well as 2 operators (Medical Insurance Bureau staff) for semi-structured in-depth interviews. We developed a social welfare policy analysis framework based on Gilbert’s framework, designed interview outlines and conducted a thematic analysis of the interview data along five dimensions: allocation base, type of provision, delivery strategy, finance mode, and external environment. The results of the research indicate that the coverage of the system is narrow and that disability assessment criteria are fragmented; that the substance of service provision is lacking, both in terms of precision and dynamic adjustment mechanisms; that socialized care synergy cannot be achieved, informal care lacking policy support; that there is an over-reliance on medical insurance funds and that unfair financing standards are applied; and that economic and social development is insufficient to cope with ageing needs and uncertain risks. Accordingly, this research proposes several optimization options to promote the full establishment of LTCI.
Method to Determine the Centroid of Non-Homogeneous Polygons Based on Suspension Theory
Authors: Ni Jianhua , Chen Jie , Wu Yanlan , Chen Zihao , Liang Ming
Published: April 2022

The centroid is most often used to describe the average position of an object’s mass and has very important applications in computational geometry, applied physics, and spatial information fields, amongst others. Based on the suspension theory of physics, this paper proposes a new method to determine the centroid of a non-homogeneous polygon by the intersection of the two balance lines. By considering the inside point value and distance to the balance line, the proposed method overcomes the traditional method’s limitation of only considering the geometric coordinates of the boundary points of the polygon. The results show that the consideration of grid distance and grid value is logical and consistent with the calculation of the centroid of a non-homogeneous polygon. While using this method, a suitable value for relative parameters needs to be established according to specific application instances. The proposed method can be applied to aid in solving specific problems such as location assessment, allocation of resources, spatial optimization, and other relative uses.
Swine Enteric Coronavirus: Diverse Pathogen–Host Interactions
Authors: Yan Quanhui , Liu Xiaodi , Sun Yawei , Zeng Weijun , Li Yuwan , Zhao Feifan , Wu Keke , Fan Shuangqi , Zhao Mingqiu , Chen Jinding , Yi Lin
Published: April 2022

Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV–host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways.
Chronic Kidney Disease and Gut Microbiota: What Is Their Connection in Early Life?
Authors: Hsu Chien-Ning , Tain You-Lin
Published: April 2022

The gut–kidney interaction implicating chronic kidney disease (CKD) has been the focus of increasing interest in recent years. Gut microbiota-targeted therapies could prevent CKD and its comorbidities. Considering that CKD can originate in early life, its treatment and prevention should start in childhood or even earlier in fetal life. Therefore, a better understanding of how the early-life gut microbiome impacts CKD in later life and how to develop ideal early interventions are unmet needs to reduce CKD. The purpose of the current review is to summarize (1) the current evidence on the gut microbiota dysbiosis implicated in pediatric CKD; (2) current knowledge supporting the impact of the gut–kidney axis in CKD, including inflammation, immune response, alterations of microbiota compositions, short-chain fatty acids, and uremic toxins; and (3) an overview of the studies documenting early gut microbiota-targeted interventions in animal models of CKD of developmental origins. Treatment options include prebiotics, probiotics, postbiotics, etc. To accelerate the transition of gut microbiota-based therapies for early prevention of CKD, an extended comprehension of gut microbiota dysbiosis implicated in renal programming is needed, as well as a greater focus on pediatric CKD for further clinical translation.
Bacterial Cellulose and ECM Hydrogels: An Innovative Approach for Cardiovascular Regenerative Medicine
Authors: Silva Izabela Gabriela Rodrigues da , Pantoja Bruna Tássia dos Santos , Almeida Gustavo Henrique Doná Rodrigues , Carreira Ana Claudia Oliveira , Miglino Maria Angélica
Published: April 2022

Cardiovascular diseases are considered the leading cause of death in the world, accounting for approximately 85% of sudden death cases. In dogs and cats, sudden cardiac death occurs commonly, despite the scarcity of available pathophysiological and prevalence data. Conventional treatments are not able to treat injured myocardium. Despite advances in cardiac therapy in recent decades, transplantation remains the gold standard treatment for most heart diseases in humans. In veterinary medicine, therapy seeks to control clinical signs, delay the evolution of the disease and provide a better quality of life, although transplantation is the ideal treatment. Both human and veterinary medicine face major challenges regarding the transplantation process, although each area presents different realities. In this context, it is necessary to search for alternative methods that overcome the recovery deficiency of injured myocardial tissue. Application of biomaterials is one of the most innovative treatments for heart regeneration, involving the use of hydrogels from decellularized extracellular matrix, and their association with nanomaterials, such as alginate, chitosan, hyaluronic acid and gelatin. A promising material is bacterial cellulose hydrogel, due to its nanostructure and morphology being similar to collagen. Cellulose provides support and immobilization of cells, which can result in better cell adhesion, growth and proliferation, making it a safe and innovative material for cardiovascular repair.
The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease
Authors: Giat Eitan , Ben-Zvi Ilan , Lidar Merav , Livneh Avi
Published: April 2022

Familial Mediterranean fever (FMF), the most frequent monogenic autoinflammatory disease, is manifested with recurrent and chronic inflammation and amyloid A (AA) amyloidosis, driven by overproduction of interleukin 1 (IL-1) through an activated pyrin inflammasome. Consequently, non-responsiveness to colchicine, the cornerstone of FMF treatment, is nowadays addressed by IL-1- blockers. Each of the two IL-1 blockers currently used in FMF, anakinra and canakinumab, has its own merits for FMF care. Here we focus on anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, and explore the literature by using PubMed regarding the utility of anakinra in certain conditions of FMF. Occasionally we enrich published data with our own experience. To facilitate insights to anakinra role, the paper briefs some clinical, genetic, pathogenetic, and management aspects of FMF. The clinical settings of FMF covered in this review include colchicine resistance, AA amyloidosis, renal transplantation, protracted febrile myalgia, on- demand use, leg pain, arthritis, temporary suspension of colchicine, pediatric patients, and pregnancy and lactation. In many of these instances, either because of safety concerns or a necessity for only transient and short-term use, anakinra, due to its short half-life, is the preferred IL-1 blocker.
Enhancement of the Water Affinity of Histidine by Zinc and Copper Ions
Authors: Song Yongshun , Zhan Jing , Li Minyue , Zhao Hongwei , Shi Guosheng , Wu Minghong , Fang Haiping
Published: April 2022

Histidine (His) is widely involved in the structure and function of biomolecules. Transition-metal ions, such as Zn2+ and Cu2+, widely exist in biological environments, and they are crucial to many life-sustaining physiological processes. Herein, by employing density function calculations, we theoretically show that the water affinity of His can be enhanced by the strong cation–π interaction between His and Zn2+ and Cu2+. Further, the solubility of His is experimentally demonstrated to be greatly enhanced in ZnCl2 and CuCl2 solutions. The existence of cation–π interaction is demonstrated by fluorescence, ultraviolet (UV) spectroscopy and nuclear magnetic resonance (NMR) experiments. These findings are of great importance for the bioavailability of aromatic drugs and provide new insight for understanding the physiological functions of transition metal ions.
Diet-Induced Metabolic Dysfunction of Hypothalamic Nutrient Sensing in Rodents
Authors: Arrieta-Cruz Isabel , Torres-Ávila Blanca Samara , Martínez-Coria Hilda , López-Valdés Héctor Eduardo , Gutiérrez-Juárez Roger
Published: April 2022

A sedentary lifestyle and excessive nutrient intake resulting from the consumption of high-fat and calorie-rich diets are environmental factors contributing to the rapid growth of the current pandemic of type 2 diabetes mellitus (DM2). Fasting hyperglycemia, an established hallmark of DM2, is caused by excessive production of glucose by the liver, resulting in the inability of insulin to suppress endogenous glucose production. To prevent inappropriate elevations of circulating glucose resulting from changes in nutrient availability, mammals rely on complex mechanisms for continuously detecting these changes and to respond to them with metabolic adaptations designed to modulate glucose output. The mediobasal hypothalamus (MBH) is the key center where nutritional cues are detected and appropriate modulatory responses are integrated. However, certain environmental factors may have a negative impact on these adaptive responses. For example, consumption of a diet enriched in saturated fat in rodents resulted in the development of a metabolic defect that attenuated these nutrient sensing mechanisms, rendering the animals prone to developing hyperglycemia. Thus, high-fat feeding leads to a state of “metabolic disability” in which animals’ glucoregulatory responses fail. We postulate that the chronic faltering of the hypothalamic glucoregulatory mechanisms contributes to the development of metabolic disease.
Hepatic PTEN Signaling Regulates Systemic Metabolic Homeostasis through Hepatokines-Mediated Liver-to-Peripheral Organs Crosstalk
Authors: Berthou Flavien , Sobolewski Cyril , Abegg Daniel , Fournier Margot , Maeder Christine , Dolicka Dobrochna , Correia de Sousa Marta , Adibekian Alexander , Foti Michelangelo
Published: April 2022

Liver-derived circulating factors deeply affect the metabolism of distal organs. Herein, we took advantage of the hepatocyte-specific PTEN knockout mice (LPTENKO), a model of hepatic steatosis associated with increased muscle insulin sensitivity and decreased adiposity, to identify potential secreted hepatic factors improving metabolic homeostasis. Our results indicated that protein factors, rather than specific metabolites, released by PTEN-deficient hepatocytes trigger an improved muscle insulin sensitivity and a decreased adiposity in LPTENKO. In this regard, a proteomic analysis of conditioned media from PTEN-deficient primary hepatocytes identified seven hepatokines whose expression/secretion was deregulated. Distinct expression patterns of these hepatokines were observed in hepatic tissues from human/mouse with NAFLD. The expression of specific factors was regulated by the PTEN/PI3K, PPAR or AMPK signaling pathways and/or modulated by classical antidiabetic drugs. Finally, loss-of-function studies identified FGF21 and the triad AHSG, ANGPTL4 and LECT2 as key regulators of insulin sensitivity in muscle cells and in adipocytes biogenesis, respectively. These data indicate that hepatic PTEN deficiency and steatosis alter the expression/secretion of hepatokines regulating insulin sensitivity in muscles and the lipid metabolism in adipose tissue. These hepatokines could represent potential therapeutic targets to treat obesity and insulin resistance.
Class III Peroxidases in Response to Multiple Abiotic Stresses in Arabidopsis thaliana Pyrenean Populations
Authors: Eljebbawi Ali , Savelli Bruno , Libourel Cyril , Estevez José Manuel , Dunand Christophe
Published: April 2022

Class III peroxidases constitute a plant-specific multigene family, where 73 genes have been identified in Arabidopsis thaliana. These genes are members of the reactive oxygen species (ROS) regulatory network in the whole plant, but more importantly, at the root level. In response to abiotic stresses such as cold, heat, and salinity, their expression is significantly modified. To learn more about their transcriptional regulation, an integrative phenotypic, genomic, and transcriptomic study was executed on the roots of A. thaliana Pyrenean populations. Initially, the root phenotyping highlighted 3 Pyrenean populations to be tolerant to cold (Eaux), heat (Herr), and salt (Grip) stresses. Then, the RNA-seq analyses on these three populations, in addition to Col-0, displayed variations in CIII Prxs expression under stressful treatments and between different genotypes. Consequently, several CIII Prxs were particularly upregulated in the tolerant populations, suggesting novel and specific roles of these genes in plant tolerance against abiotic stresses.
Identification and Characterization of a Double-Stranded RNA Degrading Nuclease Influencing RNAi Efficiency in the Rice Leaf Folder Cnaphalocrocis medinalis
Authors: Li Jiajing , Du Juan , Li Shangwei , Wang Xin
Published: April 2022

Rice leaf folder Cnaphalocrocis medinalis is one of the most serious pests of rice in rice-planting regions worldwide. DsRNA-degrading nucleases (dsRNases) are important factors in reducing the efficiency of RNA interference (RNAi) in different insects. In this study, a dsRNase gene from C. medinalis (CmdsRNase) was cloned and characterized. The CmdsRNase cDNA was 1395 bp in length, encoding 464 amino acids. The CmdsRNase zymoprotein contains a signal peptide and an endonuclease NS domain that comprises six active sites, three substrate-binding sites, and one Mg2+-binding site. The mature CmdsRNase forms a homodimer with a total of 16 α-helices and 20 β-pleated sheets. Homology and phylogenetic analyses revealed that CmdsRNase is closely related to dsRNase2 in Ostrinia nubilalis. Expression pattern analysis by droplet digital PCR indicated that the expression levels of CmdsRNase varied throughout the developmental stages of C. medinalis and in different adult tissues, with the highest expression levels in the fourth-instar larvae and the hemolymph. CmdsRNase can degrade dsRNA to reduce the efficiency of RNAi in C. medinalis. Co-silencing of CmCHS (chitin synthase from C. medinalis) and CmdsRNase affected significantly the growth and development of C. medinalis and thus improved RNAi efficacy, which increased by 27.17%. These findings will be helpful for green control of C. medinalis and other lepidopteran pests by RNAi.
Applying Protein–Protein Interactions and Complex Networks to Identify Novel Genes in Retinitis Pigmentosa Pathogenesis
Authors: Yoon Su-Bin , Ma Yu-Chien (Calvin) , Venkat Akaash , Liu Chun-Yu (Audi) , Zheng Jie J.
Published: April 2022

Retinitis Pigmentosa (RP) is a hereditary retinal disorder that causes the atrophy of photoreceptor rod cells. Since individual defective genes converge on the same disease, we hypothesized that all causal genes of RP belong in a complex network. To explore this hypothesis, we conducted a gene connection analysis using 161 genes attributed to RP, compiled from the Retinal Information Network, RetNet. We then examined the protein interaction network (PIN) of these genes. In line with our hypothesis, using STRING, we directly connected 149 genes out of the recognized 159 genes. To uncover the association between the PIN and the ten unrecalled genes, we developed an algorithm to pinpoint the best candidate genes to connect the uncalled genes to the PIN and identified ten such genes. We propose that mutations within these ten genes may also cause RP; this notion is supported by analyzing and categorizing the known causal genes based on cellular locations and related functions. The successful establishment of the PIN among all documented genes and the discovery of novel genes for RP strongly suggest an interconnectedness that causes the disease on the molecular level. In addition, our computational gene search protocol can help identify the genes and loci responsible for genetic diseases, not limited to RP.
Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells
Authors: Henzi Thomas , Diep Kim-Long , Oberson Anne , Salicio Valerie , Bochet Christian , Schwaller Beat
Published: April 2022

Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the ‘fourth’ form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and—as a control—immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF3) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF3 caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.
Leptosphaeria maculans-Brassica napus Battle: A Comparison of Incompatible vs. Compatible Interactions Using Dual RNASeq
Authors: Padmathilake Kaluhannadige R. E. , Fernando Wannakuwattewaduge Gerard Dilantha
Published: April 2022

Leptosphaeria maculans causes blackleg disease, which is one of the most destructive diseases of canola (Brassica napus L.). Due to the erosion of the current resistance in B. napus, it is pivotal to introduce new resistant genotypes to the growers. This study evaluated the potential of Rlm7 gene as resistance to its corresponding avirulence AvrLm7 gene is abundant. The Rlm7 line was inoculated with L. maculans isolate with AvrLm7; UMAvr7; and the CRISPR/Cas9 knockout AvrLm7 mutant, umavr7, of the same isolate to cause incompatible and compatible interactions, respectively. Dual RNA-seq showed differential gene expressions in both interactions. High expressions of virulence-related pathogen genes-CAZymes, merops, and effector proteins after 7-dpi in compatible interactions but not in incompatible interaction—confirmed that the pathogen was actively virulent only in compatible interactions. Salicyclic and jasmonic acid biosynthesis and signaling-related genes, defense-related PR1 gene (GSBRNA2T00150001001), and GSBRNA2T00068522001 in the NLR gene family were upregulated starting as early as 1- and 3-dpi in the incompatible interaction and the high upregulation of those genes after 7-dpi in compatible interactions confirmed the early recognition of the pathogen by the host and control it by early activation of host defense mechanisms in the incompatible interaction.
Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice
Authors: Opazo-Ríos Lucas , Soto-Catalán Manuel , Lázaro Iolanda , Sala-Vila Aleix , Jiménez-Castilla Luna , Orejudo Macarena , Moreno Juan Antonio , Egido Jesús , Mas-Fontao Sebastián
Published: April 2022

Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4–22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.