bluuebunny/crossref_metadata_2025 huggingface dataset:
Organizational Support Experiences of Care Home and Home Care Staff in Sweden, Italy, Germany and the United Kingdom during the COVID-19 Pandemic
Authors: Lethin Connie , Kenkmann Andrea , Chiatti Carlos , Christensen Jonas , Backhouse Tamara , Killett Anne , Fisher Oliver , Malmgren Fänge Agneta
Published: June 2021

The COVID-19 pandemic has affected care workers all over the globe, as older and more vulnerable people face a high risk of developing severe symptoms and dying from the virus infection. The aim of this study was to compare staff experiences of stress and anxiety as well as internal and external organizational support in Sweden, Italy, Germany, and the United Kingdom (UK) in order to determine how care staff were affected by the pandemic. A 29-item online questionnaire was used to collect data from care staff respondents: management (n = 136), nurses (n = 132), nursing assistants (n = 195), and other healthcare staff working in these organizations (n = 132). Stress and anxiety levels were highest in the UK and Germany, with Swedish staff showing the least stress. Internal and external support only partially explain the outcomes. Striking discrepancies between different staff groups’ assessment of organizational support as well as a lack of staff voice in the UK and Germany could be key factors in understanding staff’s stress levels during the pandemic. Structural, political, cultural, and economic factors play a significant role, not only factors within the care organization or in the immediate context.
Chromobacterium violaceum Periareolar Infection, First Non-Lethal Case in Colombia: Case Report and Literature Review
Authors: Cubides Diaz Diego Alejandro , Arsanios Martin Daniel , Bernal Ortiz Nicolas , Ovalle Monroy Ana Lucia , Hernandez Angarita Valentina , Mantilla Florez Yesid Fabian
Published: June 2021

Chromobacterium violaceum is a facultative anaerobic, Gram-negative rod found in different ecosystems, especially tropical and subtropical areas. Human infections are rare, and just a few cases have been reported in literature. In this paper, we present the first non-lethal infection due to Chromobacterium violaceum, in an adult male with polycystic kidney disease in Colombia. Periareolar soft tissue infection was documented with isolation of Chromobacterium violaceum. Clinical manifestations, treatment, and outcome are shown.
Longitudinal Association of Economic Growth with Lung Function of Chinese Children and Adolescents over 30 Years: Evidence from Seven Successive National Surveys
Authors: Gan Xiaomei , Yu Kehong , Wen Xu , Lu Yijuan
Published: June 2021

(1) Background: Recent studies reported that decrease in lung function of Chinese children and adolescents continues to decline, although the change has been insignificant and has reached a plateau. However, studies have not explored the relationship between lung function and economic development in China. This study sought to explore the longitudinal association between socio-economic indicators and lung function; (2) Method: Data were obtained from seven successive national surveys conducted by the Chinese National Survey on Students’ Constitution and Health from 1985 to 2014. Lung function of school-age children (7–22 years) was determined using forced vital capacity (FVC). GDP per capita and urbanization ratio were used as economic indicators. A fixed-effects model was employed to examine the longitudinal association after adjusting for height, weight, and time trends; (3) Results: Socio-economic indicators showed a U-curve relationship with lung function of boys and girls from urban and rural areas. Lung function initially decreased with GDP per capita or urbanization ratio and reached a minimum. Lung function then increased with increase in GDP per capita or urbanization ratio. The findings indicate that the relationship between economic growth and lung function is different in different development stages. In less-developed provinces, economic growth was negatively correlated with lung function, whereas, in developed provinces, economic growth was positively correlated with lung function; (4) Conclusion: The findings of the current study show that economic growth has significantly different effects on lung function at different economic levels. Therefore, governments should improve lung health in children and adolescents from low and middle economic regions.
Friendships in Integrative Settings: Network Analyses in Organized Sports and a Comparison with School
Authors: Steiger Alexander , Mumenthaler Fabian , Nagel Siegfried
Published: June 2021

Social networks affect health. In this empirical study, friendship networks in integrative organized sports were examined and then compared with friendship networks in integrative school. Relevant factors for friendship network formation were investigated, with a particular interest in the relevance of intellectual disability. Advanced social network analysis was performed using exponential random graph modeling (ERGM) on individual attributes and dyadic factors, while controlling for network structures. A meta-analysis of estimated ERGMs in each setting, organized sports and school, was conducted. When controlling for all other included factors, intellectual disability is not relevant for friendship networks in organized sports. Athletic ability and gender homophily are relevant factors, while language and similarity in athletic ability are not. Contrary to the results for organized sports, intellectual disability and speaking a foreign language at home are negative factors in friendship networks at school. Athletic ability is important in both settings. Regarding dyadic factors, gender homophily is important in both settings, but similarity in athletic ability is not. To foster the psychosocial health of children with intellectual disabilities, they should be encouraged to participate in integrative organized sports as, there, they are part of friendship networks in a manner equal to their peers without an intellectual disability.
Career Development of Adapted Sports Coaches: Systematic Review of Qualitative Evidence Literature
Authors: Pires Pedro , Ramalho André , Antúnez Antonio , Mesquita Helena , Ibáñez Sergio J.
Published: June 2021

This study aims to synthesize and understand the qualitative and empirical evidence previously published on adapted sports career development. This systematic literature review also aimed at developing a conceptual model of the training and career path of adapted sports coaches. The research was carried out through the following databases: PubMed, Erid, EBSCO, Web of Science and Scopus. We selected nine qualitative studies according to the specific eligibility criteria. Data extraction was carried out independently by different authors, including the assessment of the methodological quality of the articles. We developed a conceptual model composed of four descriptive subjects (adapted sport option; perception of training athletes in adapted sports; development of the adapted sports coach’s learning; adapted sports coach reality) about the adapted sports coach’s pathway and added three analytical subjects about the difficulties, opportunity and reality of adapted sports. The conceptual model suggests inclusion of practical activity programs, the specificities of related contents with the adapted modalities, and observation in a real context are fundamental.
A Threat of Customer Incivility and Job Stress to Hotel Employee Retention: Do Supervisor and Co-Worker Supports Reduce Turnover Rates?
Authors: Chung Hyunah , Quan Wei , Koo Bonhak , Ariza-Montes Antonio , Vega-Muñoz Alejandro , Giorgi Gabriele , Han Heesup
Published: June 2021

The study investigates the impact of customer incivility, job stress, perceived supervisor support, and perceived co-worker support on the turnover intention of frontline employees. A survey-questionnaire approach was used to collect the point of view of frontline employees that work in five-star hotels in a metropolitan city of Korea. Four independent variables that were extracted from valid theoretical backgrounds along with four demographic variables were used in the study. The regression analysis was conducted to test the hypotheses, which revealed that job stress directly affected the employees’ desires to leave their organization. It also showed that perceived supervisor support mitigates employee turnover, and there were significant correlations between turnover intention with the employees’ marital status and job position. Gender and years of service did not affect the employees’ thinking of quitting their job. Our findings help hotel entrepreneurs better understand how to deal with customer incivility and employee job stress, and better comprehend the factors that minimize employees’ negative behaviors for the organization.
Factors Affecting Masticatory Satisfaction in Patients with Removable Partial Dentures
Authors: Yoshimoto Tasuku , Hasegawa Yoko , Salazar Simonne , Kikuchi Satsuki , Hori Kazuhiro , Ono Takahiro
Published: June 2021

(1) Background: The degree of satisfaction with dental treatment varies among patients, and the discrepancy may exist between the patient’s subjective evaluation and the objective assessment. Further, the optimal methods for increasing patient satisfaction with mastication remain unclear. This study aimed to identify factors affecting masticatory satisfaction in patients with removable partial dentures. (2) Methods: A total of 132 participants (71.0 ± 9.0 years) were included. Masticatory satisfaction was assessed on a visual analog scale. An oral health survey was conducted to assess the number of functional teeth, missing tooth classification: Kennedy classification, occlusal support: Eichner classification, and removable partial dentures wearing jaw. Objective masticatory performance was assessed using gummy jelly, while subjective masticatory ability was assessed using food acceptance status and oral health-related quality of life. The associations of these factors with masticatory satisfaction were assessed. (3) Results: Masticatory satisfaction among removable partial denture wearers was not significantly associated with gender, age, denture wearing jaw, Kennedy classification, and occlusal support. The degree of masticatory satisfaction was significantly greater with higher levels of masticatory function: masticatory performance, food acceptance score, and OHIP-14 score. The OHIP-14 score was the only significant explanatory variable for masticatory satisfaction in the multiple regression analysis; the strongest associations were with the “psychological discomfort” and “physical disability” subscales (p = 0.02 and p = 0.005, respectively). (4) Conclusions: Masticatory satisfaction among removable partial denture wearers was strongly associated with oral health-related quality of life, in which the ability to eat meals comfortably with removable partial dentures is the most important determinant of masticatory satisfaction.
Predicting Breaststroke and Butterfly Stroke Results in Swimming Based on Olympics History
Authors: Hołub Maciej , Stanula Arkadiusz , Baron Jakub , Głyk Wojciech , Rosemann Thomas , Knechtle Beat
Published: June 2021

Here we describe historic variations in Olympic breaststroke and butterfly performance and predict swimming results for the 2021 Olympic Games in Tokyo. The results of the finalists, winners, and last participants in the women’s and men’s finals were analyzed, and a mathematical predictive model was created. The predicted times for the future Olympics were presented. Swimming performance among Olympians has been steadily improving, with record times of 18.51 s for female finalists in the 100 m butterfly (a 24.63% improvement) and 31.33 s for male finalists in the 200 m butterfly (21.44%). The results in all analyzed groups showed improvement in athletic performance, and the gap between the finalists has narrowed. Women Olympians’ performances have improved faster than men’s, reducing the gap between genders. We conclude that swimming performance among Olympians is continuing to improve.
Parental and Peer Support Matters: A Broad Umbrella of the Role of Perceived Social Support in the Association between Children’s Perceived Motor Competence and Physical Activity
Authors: Menescardi Cristina , Estevan Isaac
Published: June 2021

(1) Background: This study aimed to examine the role of social support in the relationship between perceived motor competence (MC) and physical activity (PA), according to the conceptual model of Motor Development. (2) Methods: Participants were 518 students (46.5% girls), 8–12 years old. By using a structural equation modeling approach, path analysis was used to test the actual-perceived MC relationship and the mediating influence of social support on the perceived MC–PA relationship. Analyses were done with age and sex as covariates. (3) Results: The results showed a good model fit (CFI = 0.98; RMSEA = 0.07; SRMR = 0.02), where actual MC was positively associated with perceived MC (ß = 0.26, p < 0.001), which in turn was positively related to social support (ß = 0.34, p < 0.001). The model showed the direct social support-PA path (ß = 0.42, p < 0.001) and the indirect path from perceived MC through social support to PA (ß = 0.14, p < 0.001). (4) Conclusions: This study confirms that social support mediates the perceived MC–PA relationship. As such, it is not only important to build and develop children’s actual and perceived MC, but also to promote social support for PA engagement.
Adolescent-Reported Food Insecurity: Correlates of Dietary Intake and School Lunch Behavior
Authors: Duke Naomi Nichele
Published: June 2021

Much of what is known about food insecurity (FI) experiences for young people is based on caregiver report. As such, our understanding of relationships between youth FI and dietary intake (DI) may be limited, particularly among adolescents who often eat away from home. This study examined relationships between youth-reported past-month FI, past-week DI, and school lunch behavior. Data are from middle and high school participants in the 2019 Minnesota Student Survey (N = 125,375), one of the longest-running youth surveys in the US. Logistic regression assessed relationships between FI and DI, including fruit, vegetable, milk, sugar-sweetened beverage (SSB), and fast food consumption, and school lunch behavior, adjusting for demographic, physical, and emotional health indicators. Past-month FI was associated with reduced odds of meeting minimum thresholds for daily fruit, vegetable, and milk intake, and increased odds of daily SSB and frequent fast food consumption. Among food-insecure students, no participation in the National School Lunch Program (NSLP) or NSLP participation uncertainty was associated with increased odds of skipping lunch. Findings suggest the importance of clinical and community innovations to prevent the loss of nutritional quality in favor of energy density for youth and families experiencing FI.
Association between Health-Related Physical Fitness and Respiratory Diseases in Adolescents: An Age- and Gender-Matched Study
Authors: Park Jeong-Hui , Seo Myong-Won , Jung Hyun Chul , Song Jong-Kook , Lee Jung-Min
Published: June 2021

The current study examined the differences in health-related physical fitness (HRPF), physical activity (PA), and sedentary behavior (SB) between adolescents with and without ongoing respiratory diseases (RD). This study’s participants were from 12 to 15 years old (7th–10th grade) in South Korea. Adolescents with RD were selected through RD-related questions (i.e., asthma, rhinitis, sinusitis, and bronchitis) (n = 139); in contrast, adolescents without RD, randomly selected from the general group, responded to any health problem-related questions as “No” (n = 139). HRPF was measured based on the FITNESSGRAM and EURO FIT test batteries and the measurements of HRPF included cardiovascular endurance, muscular strength, muscular endurance, flexibility, and body composition. All statistical analyses were conducted by SPSS 25.0, and the independent t-test was used to compare the HRPF and PA between the two groups. Moreover, the measured HRPF was compared with a series of analyses of three-way ANOVAs (age × gender × group). Adolescents with RD had a positive association with less participation in PA (p < 0.05; RD: 3081.81 ± 4793.37; general: 2073.64 ± 3123.47) and with more time spent on SB (above 12 h per week: RD group (38.85%) and general group (33.09%)). Furthermore, adolescents in the RD group showed significant effects on all components of HRPF (p < 0.05). Our study confirmed that HRPF is an essential predictor of adolescents’ health outcomes, especially for those with RD. We suggest that increased HRPF can be an effective treatment for respiratory diseases in adolescents, and health practitioners should pay more attention to helping adolescents with RD to gain or maintain high HRPF.
Constructing Well-Being in Organizations: First Empirical Results on Job Crafting, Personality Traits, and Insight
Authors: Gori Alessio , Arcioni Alessandro , Topino Eleonora , Palazzeschi Letizia , Di Fabio Annamaria
Published: June 2021

The construct of job crafting is gaining increasing attention in the research and practice of work psychology in light of the positive effects it has on workers and the organizational context. On this basis, the present study aimed to explore the associations between the Big Five personality traits and job crafting (and its subdimensions, individual job crafting and collaborative job crafting), as well as investigating the role of insight in mediating these relationships. A sample of 159 Italian workers took part in the study and completed the self-report measures. Results showed a positive association between extraversion, agreeableness and conscientiousness and job crafting (total), individual job crafting, and collaborative job crafting, with significant mediations of insight orientation. Openness was positively associated with job crafting (total) and individual job crafting, but not with the collaborative subdimension, with insight orientation that mediated existing relationships. Emotional stability and job crafting (total) or its subdimensions were found to have no significant relationships. These findings suggest that insight orientation could represent a promising resource for job crafting, both in terms of primary prevention, strength-based prevention, and healthy organizations.
The Effect of Work Safety on Organizational Social Sustainability Improvement in the Healthcare Sector: The Case of a Public Sector Hospital in Pakistan
Authors: Ullah Zia , Sulaiman Mohammed Ali Bait Ali , Ali Syed Babar , Ahmad Naveed , Scholz Miklas , Han Heesup
Published: June 2021

Social sustainability is the much emphasized organizational phenomenon in Western literature; however, in emerging economies, its importance has only been realized in the recent past. Social sustainability is the amiability of the relationship between employees and the organizations on a relatively permanent basis. Social sustainability is the key determinant of organizational sustainability and organizational effectiveness. As healthcare organizations are labor-intensive, the role of social sustainability in hospitals is more crucial. The purpose of the present study is to understand the role of work safety in improving social sustainability in public sector hospitals. To this effect, we collected data from 431 healthcare professionals of a large public sector tertiary and teaching hospital in the city of Lahore Pakistan and analyzed the data using structural equation modeling (SEM). The results uncovered certain important facts, which were not expected per se. Job design, coworkers’ behavior towards work safety, and supervisors’ role in ensuring work safety are the key factors that influence social sustainability. However, surprisingly, in the eyes of employees, management practices and safety programs/policies do not contribute to the work safety of the hospital under study. Keeping in view the findings, we suggest that management must participate in work safety affairs directly and formulate indigenous policies and programs according to local needs. Job analysis is needed to redesign job structures to meet workplace safety requirements. Formal and informal training will be beneficial to make workers and supervisors more aware, more sensitive, and more responsible regarding work safety.
Evaluating Cultural Landscape Remediation Design Based on VR Technology
Authors: Lin Zhengsong , Zhang Lu , Tang Su , Song Yang , Ye Xinyue
Published: June 2021

Due to the recent excessive pursuit of rapid economic development in China, the cultural heritage resources have been gradually destroyed. This paper proposes cultural recovery and ecological remediation patterns, and adopts virtual reality (VR) technology to evaluate the visual aesthetic effect of the restored landscape. The results show that: (1) the average vegetation coverage increased, providing data support for remediation design evaluation; and (2) the fixation counts and average saccade counts of the subjects increased after the remediation design, indicating that the restored cultural landscape reduced visual fatigue and provided a better visual aesthetic experience. Furthermore, the comparative analysis of the quality of the water environment shows that the remediation design project improved the ecological environment quality of the relics area. The results of this study will contribute to rural revitalization in minority areas in southwest China.
LRP5 Regulates HIF-1α Stability via Interaction with PHD2 in Ischemic Myocardium
Authors: Ju Sujin , Lim Leejin , Wi Kwanhwan , Park Changwon , Ki Young-Jae , Choi Dong-Hyun , Song Heesang
Published: June 2021

Low-density lipoprotein receptor-related protein 5 (LRP5) has been studied as a co-receptor for Wnt/β-catenin signaling. However, its role in the ischemic myocardium is largely unknown. Here, we show that LRP5 may act as a negative regulator of ischemic heart injury via its interaction with prolyl hydroxylase 2 (PHD2), resulting in hypoxia-inducible factor-1α (HIF-1α) degradation. Overexpression of LRP5 in cardiomyocytes promoted hypoxia-induced apoptotic cell death, whereas LRP5-silenced cardiomyocytes were protected from hypoxic insult. Gene expression analysis (mRNA-seq) demonstrated that overexpression of LRP5 limited the expression of HIF-1α target genes. LRP5 promoted HIF-1α degradation, as evidenced by the increased hydroxylation and shorter stability of HIF-1α under hypoxic conditions through the interaction between LRP5 and PHD2. Moreover, the specific phosphorylation of LRP5 at T1492 and S1503 is responsible for enhancing the hydroxylation activity of PHD2, resulting in HIF-1α degradation, which is independent of Wnt/β-catenin signaling. Importantly, direct myocardial delivery of adenoviral constructs, silencing LRP5 in vivo, significantly improved cardiac function in infarcted rat hearts, suggesting the potential value of LRP5 as a new target for ischemic injury treatment.
Predicting Drug–Target Interactions Based on the Ensemble Models of Multiple Feature Pairs
Authors: Wang Cheng , Zhang Jun , Chen Peng , Wang Bing
Published: June 2021

Backgroud: The prediction of drug–target interactions (DTIs) is of great significance in drug development. It is time-consuming and expensive in traditional experimental methods. Machine learning can reduce the cost of prediction and is limited by the characteristics of imbalanced datasets and problems of essential feature selection. Methods: The prediction method based on the Ensemble model of Multiple Feature Pairs (Ensemble-MFP) is introduced. Firstly, three negative sets are generated according to the Euclidean distance of three feature pairs. Then, the negative samples of the validation set/test set are randomly selected from the union set of the three negative sets in the validation set/test set. At the same time, the ensemble model with weight is optimized and applied to the test set. Results: The area under the receiver operating characteristic curve (area under ROC, AUC) in three out of four sub-datasets in gold standard datasets was more than 94.0% in the prediction of new drugs. The effectiveness of the proposed method is also shown with the comparison of state-of-the-art methods and demonstration of predicted drug–target pairs. Conclusion: The Ensemble-MFP can weigh the existing feature pairs and has a good prediction effect for general prediction on new drugs.
Neurodegeneration in Niemann–Pick Type C Disease: An Updated Review on Pharmacological and Non-Pharmacological Approaches to Counteract Brain and Cognitive Impairment
Authors: Cariati Ida , Masuelli Laura , Bei Roberto , Tancredi Virginia , Frank Claudio , D’Arcangelo Giovanna
Published: June 2021

Niemann–Pick type C (NPC) disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol in the late endo-lysosomal system of cells. Progressive neurological deterioration and the onset of symptoms, such as ataxia, seizures, cognitive decline, and severe dementia, are pathognomonic features of the disease. In addition, different pathological similarities, including degeneration of hippocampal and cortical neurons, hyperphosphorylated tau, and neurofibrillary tangle formation, have been identified between NPC disease and other neurodegenerative pathologies. However, the underlying pathophysiological mechanisms are not yet well understood, and even a real cure to counteract neurodegeneration has not been identified. Therefore, the combination of current pharmacological therapies, represented by miglustat and cyclodextrin, and non-pharmacological approaches, such as physical exercise and appropriate diet, could represent a strategy to improve the quality of life of NPC patients. Based on this evidence, in our review we focused on the neurodegenerative aspects of NPC disease, summarizing the current knowledge on the molecular and biochemical mechanisms responsible for cognitive impairment, and suggesting physical exercise and nutritional treatments as additional non-pharmacologic approaches to reduce the progression and neurodegenerative course of NPC disease.
Erythrocytes as a Model for Heavy Metal-Related Vascular Dysfunction: The Protective Effect of Dietary Components
Authors: Notariale Rosaria , Infantino Rosmara , Palazzo Enza , Manna Caterina
Published: June 2021

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.
Interleukin-1β Induces Tissue Factor Expression in A549 Cells via EGFR-Dependent and -Independent Mechanisms
Authors: Mechelke Tobias , Wittig Felix , Ramer Robert , Hinz Burkhard
Published: June 2021

Tissue factor (TF) plays an important role in the progression and angiogenesis of tumor cells. The present study investigated the mechanism of interleukin-1β (IL-1β)-induced TF expression in A549 lung cancer cells. Based on mRNA and protein analyses, including appropriate inhibitor experiments, IL-1β was shown to induce TF expression in a time-dependent manner, mediated by IL-1 receptor-dependent phosphorylation of the mitogen-activated protein kinases (MAPK) p38, p42/44 and c-jun N-terminal kinase (JNK), as well as the Src kinase and the epidermal growth factor receptor (EGFR). Thereby, inhibition of EGFR transactivation by the Src inhibitor PP1 or direct EGFR inhibition by the EGFR tyrosine kinase inhibitor (TKI) erlotinib led to a reduction of IL-1β-induced TF expression and to a suppression of p42/44 MAPK and EGFR activation, while IL-1β-induced p38 MAPK and JNK activation remained unchanged. A knockdown of EGFR by siRNA was associated with decreased IL-1β-mediated p42/44 MAPK activation, which was no longer inhibitable by erlotinib. Concentration-dependent inhibition of IL-1β-induced TF expression was also observed in the presence of gefitinib and afatinib, two other EGFR TKIs. In summary, our results suggest that IL-1β leads to increased TF formation in lung cancer cells via both Src/EGFR/p42/44 MAPK-dependent and EGFR-independent signaling pathways, with the latter mediated via p38 MAPK and JNK.
Inflammatory Mechanisms in COVID-19 and Atherosclerosis: Current Pharmaceutical Perspectives
Authors: Sagris Marios , Theofilis Panagiotis , Antonopoulos Alexios S. , Tsioufis Costas , Oikonomou Evangelos , Antoniades Charalambos , Crea Filippo , Kaski Juan Carlos , Tousoulis Dimitris
Published: June 2021

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with excess mortality worldwide. The cardiovascular system is the second most common target of SARS-CoV-2, which leads to severe complications, including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism, as well as other major thrombotic events because of direct endothelial injury and an excessive systemic inflammatory response. This review focuses on the similarities and the differences of inflammatory pathways involved in COVID-19 and atherosclerosis. Anti-inflammatory agents and immunomodulators have recently been assessed, which may constitute rational treatments for the reduction of cardiovascular events in both COVID-19 and atherosclerotic heart disease.
Understanding the Role of Protein Glycation in the Amyloid Aggregation Process
Authors: Sirangelo Ivana , Iannuzzi Clara
Published: June 2021

Protein function and flexibility is directly related to the native distribution of its structural elements and any alteration in protein architecture leads to several abnormalities and accumulation of misfolded proteins. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidosis characterized by the accumulation of amyloid aggregates both in the extracellular space of tissues and as intracellular deposits. Post-translational modifications are known to have an active role in the in vivo amyloid aggregation as able to affect protein structure and dynamics. Among them, a key role seems to be played by non-enzymatic glycation, the most unwanted irreversible modification of the protein structure, which strongly affects long-living proteins throughout the body. This study provided an overview of the molecular effects induced by glycation on the amyloid aggregation process of several protein models associated with misfolding diseases. In particular, we analyzed the role of glycation on protein folding, kinetics of amyloid formation, and amyloid cytotoxicity in order to shed light on the role of this post-translational modification in the in vivo amyloid aggregation process.
On the Use of Surface Plasmon Resonance Biosensing to Understand IgG-FcγR Interactions
Authors: Forest-Nault Catherine , Gaudreault Jimmy , Henry Olivier , Durocher Yves , De Crescenzo Gregory
Published: June 2021

Surface plasmon resonance (SPR)-based optical biosensors offer real-time and label-free analysis of protein interactions, which has extensively contributed to the discovery and development of therapeutic monoclonal antibodies (mAbs). As the biopharmaceutical market for these biologics and their biosimilars is rapidly growing, the role of SPR biosensors in drug discovery and quality assessment is becoming increasingly prominent. One of the critical quality attributes of mAbs is the N-glycosylation of their Fc region. Other than providing stability to the antibody, the Fc N-glycosylation influences immunoglobulin G (IgG) interactions with the Fcγ receptors (FcγRs), modulating the immune response. Over the past two decades, several studies have relied on SPR-based assays to characterize the influence of N-glycosylation upon the IgG-FcγR interactions. While these studies have unveiled key information, many conclusions are still debated in the literature. These discrepancies can be, in part, attributed to the design of the reported SPR-based assays as well as the methodology applied to SPR data analysis. In fact, the SPR biosensor best practices have evolved over the years, and several biases have been pointed out in the development of experimental SPR protocols. In parallel, newly developed algorithms and data analysis methods now allow taking into consideration complex biomolecular kinetics. In this review, we detail the use of different SPR biosensing approaches for characterizing the IgG-FcγR interactions, highlighting their merit and inherent experimental complexity. Furthermore, we review the latest SPR-derived conclusions on the influence of the N-glycosylation upon the IgG-FcγR interactions and underline the differences and similarities across the literature. Finally, we explore new avenues taking advantage of novel computational analysis of SPR results as well as the latest strategies to control the glycoprofile of mAbs during production, which could lead to a better understanding and modelling of the IgG-FcγRs interactions.
From Genetic Mutations to Molecular Basis of Heart Failure Treatment: An Overview of the Mechanism and Implication of the Novel Modulators for Cardiac Myosin
Authors: Chen Yu-Jen , Chien Chian-Shiu , Chiang Chern-En , Chen Chen-Huan , Cheng Hao-Min
Published: June 2021

Heart failure (HF) is a syndrome encompassing several important etiologies that lead to the imbalance between oxygen demand and supply. Despite the usage of guideline-directed medical therapy for HF has shown better outcomes, novel therapeutic strategies are desirable, especially for patients with preserved or mildly reduced left ventricular ejection fraction. In this regard, understanding the molecular basis for cardiomyopathies is expected to fill in the knowledge gap and generate new therapies to improve prognosis for HF. This review discusses an evolutionary mechanism designed to regulate cardiac contraction and relaxation through the most often genetically determined cardiomyopathies associated with HF. In addition, both the myosin inhibitor and myosin activator are promising new treatments for cardiomyopathies. A comprehensive review from genetic mutations to the molecular basis of direct sarcomere modulators will help shed light on future studies for a better characterization of HF etiologies and potential therapeutic targets.
Objective and Measurable Biomarkers in Chronic Subjective Tinnitus
Authors: Kang Dae-Woong , Kim Sung-Soo , Park Dong-Choon , Kim Sang-Hoon , Yeo Seung-Geun
Published: June 2021

Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.
Functions of Matricellular Proteins in Dental Tissues and Their Emerging Roles in Orofacial Tissue Development, Maintenance, and Disease
Authors: Nikoloudaki Georgia
Published: June 2021

Matricellular proteins (MCPs) are defined as extracellular matrix (ECM) associated proteins that are important regulators and integrators of microenvironmental signals, contributing to the dynamic nature of ECM signalling. There is a growing understanding of the role of matricellular proteins in cellular processes governing tissue development as well as in disease pathogenesis. In this review, the expression and functions of different MP family members (periostin, CCNs, TSPs, SIBLINGs and others) are presented, specifically in relation to craniofacial development and the maintenance of orofacial tissues, including bone, gingiva, oral mucosa, palate and the dental pulp. As will be discussed, each MP family member has been shown to have non-redundant roles in development, tissue homeostasis, wound healing, pathology and tumorigenesis of orofacial and dental tissues.
Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives
Authors: Sikorski Vilbert , Karjalainen Pasi , Blokhina Daria , Oksaharju Kati , Khan Jahangir , Katayama Shintaro , Rajala Helena , Suihko Satu , Tuohinen Suvi , Teittinen Kari , Nummi Annu , Nykänen Antti , Eskin Arda , Stark Christoffer , Biancari Fausto , Kiss Jan , Simpanen Jarmo , Ropponen Jussi , Lemström Karl , Savinainen Kimmo , Lalowski Maciej , Kaarne Markku , Jormalainen Mikko , Elomaa Outi , Koivisto Pertti , Raivio Peter , Bäckström Pia , Dahlbacka Sebastian , Syrjälä Simo , Vainikka Tiina , Vähäsilta Tommi , Tuncbag Nurcan , Karelson Mati , Mervaala Eero , Juvonen Tatu , Laine Mika , Laurikka Jari , Vento Antti , Kankuri Esko
Published: June 2021

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.
Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs
Authors: de-Sousa Thamires Rodrigues , Pessôa Rodrigo , Nascimento Andrezza , Fagundes Beatriz Oliveira , Sgnotto Fábio da Ressureição , Duarte Alberto José da Silva , Sanabani Sabri Saeed , Victor Jefferson Russo
Published: June 2021

The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17+ γδT cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related γ and δ variable γδTCR chains (Vγ1, Vγ2, Vγ3, Vδ4, and Vδ6.3), observing that maternal OVA-immunization inhibits Vγ2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing γδT cells possibly by an epigenetic mechanism mediated by miRNAs.
Virtual Evolution of HVEM Segment for Checkpoint Inhibitor Discovery
Authors: Yu Mingjia , Zhao Huimin , Miao Yuhui , Luo Shi-Zhong , Xue Song
Published: June 2021

Immune therapy has emerged as an effective treatment against cancers. Inspired by the PD-1/PD-L1 antibodies, which have achieved great success in clinical, other immune checkpoint proteins have drawn increasing attention in cancer research. B and T lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) are potential targets for drug development. The co-crystal structure of BTLA/HVEM have revealed that HVEM (26–38) fragment is the core sequence which directly involved on the interface. Herein, we conducted virtual evolution with this sequence by using saturation mutagenesis in silico and mutants with lower binding energy were selected. Wet-lab experiments confirmed that several of them possessed higher affinity with BTLA. Based on the best mutant of the core sequence, extended peptides with better efficacy were obtained. Furthermore, the mechanism of the effects of mutations was revealed by computational analysis. The mutated peptide discovered here can be a potent inhibitor to block BTLA/HVEM interaction and its mechanism may extend people’s view on inhibitor discovery for the checkpoint pair.
Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs
Authors: Zang Xupeng , Gu Ting , Wang Wenjing , Zhou Chen , Ding Yue , Gu Shengchen , Xu Zhiqian , Xie Yanshe , Li Zicong , Cai Gengyuan , Hu Bin , Hong Linjun , Wu Zhenfang
Published: June 2021

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.
Bioactivity of Wild Hop Extracts against the Granary Weevil, Sitophilus granarius (L.)
Authors: Paventi Gianluca , Rotundo Giuseppe , Pistillo Marco , D’Isita Ilaria , Germinara Giacinto Salvatore
Published: June 2021

The use of bioinsecticides, rather than synthetic compounds, appears a goal to be pursued in pest control, especially for species such as Sitophilus granarius (L.) which attack stored products. Since Humulus lupulus (L.) is a remarkable source of bioactive compounds, this study investigated the bioactivity of hop flower extracts against S. granarius adults by evaluating toxic (contact, inhalation, and ingestion), repellent, antifeedant, and nutritional effects as well as their anticholinesterase activity and olfactory sensitivity. Hop extracts were obtained by soaking dried and ground hop cones in solvents of decreasing polarity: methanol, acetone, and n-hexane. Dried crude extracts were resuspended in each solvent, and used in topical application, ingestion, and fumigation toxicity assays, as well as in contact and short-range repellency tests, in vitro anticholinesterase activity evaluation, and electroantennographic tests. No inhalation toxicity for the extracts was found. On the contrary, all extracts showed adult contact toxicity 24 h after treatment (LD50/LD90 16.17/33.20, 25.77/42.64, and 31.07/49.48 µg/adult for acetone, n-hexane, and methanol extracts, respectively); negligible variations for these values at 48 h were found. The anticholinesterase activity shown by all extracts suggested that the inhibition of this enzyme was one of the mechanisms of action. Interestingly, flour disk bioassays revealed a significant ingestion toxicity for the acetone extract and a lower toxicity for the other two extracts. Moreover, all extracts affected insect nutritional parameters, at the highest dose checked. Filter paper and two-choice pitfall bioassays showed repellent activity and a strong reduction of insect orientation to a highly attractive food odor source, with minor differences among extracts, respectively. Finally, the presence of volatile compounds in the different extracts that are perceived by insect antennae was confirmed by electroantennography. All these findings strongly suggest a possible use of hop cone extracts against S. granarius, thus further confirming this plant as an interesting species for pest control.