bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Function and Visual Perception among Senior Citizens with Mild Cognitive Impairment in Taiwan
Authors: Chang Chi-Wu , Su Kuo-Chen , Lu Fang-Chun , Cheng Hong-Ming , Cheng Ching-Ying
Published: December 2021

Purpose: With the benefits of advanced medical technology, Taiwan has gradually changed from an aged society to a super-aged society. According to previous studies, the prevalence rate of mild cognitive impairment (MCI) over the age of 60 is 15% to 20%. Therefore, the main purpose of our study was to analyze the correlation of cognitive function with visual function (specifically, binocular vision and visual perception) in Taiwanese volunteers aged 60 years or older. Methods: Thirty-six healthy participants who were not taking psychiatric medications and who had not been diagnosed with any retinal or optic nerve diseases were enrolled. Addenbrooke’s cognitive examination III (ACE-III), binocular visual function, and visual perception evaluation were performed, and the data analyzed statistically by t-test, χ2, linear regression, and MANOVA. Results: Cognitive function was closely correlated with visual function and visual perception; the horizontal adjustment time of binocular eye movement, stereopsis, the motor-free visual perception test-4 (MVPT-4), and peripheral awareness actually displayed higher explanatory power in predicting cognitive function. In addition, various interactive parameters between visual function and visual perception were found to affect specific aspects of ACE-III. Discussion: Our study revealed that there was a close correlation of cognitive function with visual function; as such, it may be possible to predict visual function deficits in patients with mild cognitive impairment.
The Experiences of Home Care Nurses in Regard to the Care of Vulnerable Populations: A Qualitative Study
Authors: Fernández-Medina Isabel María , Ruíz-Fernández María Dolores , Gálvez-Ramírez Felisa , Martínez-Mengíbar Evangelina , Ruíz-García Manuel Eduardo , Jiménez-Lasserrotte María del Mar , Ortega-Galán Ángela María , Hernández-Padilla José Manuel
Published: December 2021

Home care nurses have become the main references in home care for vulnerable patients. In patients’ homes they offer comprehensive and continuous care to both the vulnerable population and their families. The aim of this qualitative study was to explore experiences and perspectives of home care nurses regarding the care of vulnerable patients in Spain. We conducted in-depth semi-structured interviews with 15 home care nurses working with a vulnerable population. From a data analysis, two themes and four subthemes emerged: (1) “barriers to providing home care to vulnerable populations”, with the following subthemes: “the particularities of the patient and their home caregivers” and “perceived barriers for the involvement of home care nurses in the care”; and (2) “the emotional cost of home care” with the subthemes “home care is draining for caregivers” and “the impact of home care on the home care nurses”. These findings show us that nurses face a number of difficulties in home care for vulnerable patients. The training of nurses in certain competencies and skills by the social health services would enhance the quality of care offered to these patients.
The Art of Everyday Objects: A Non-Invasive In Situ Investigation of Materials and Techniques of Italian Pop Art Paintings on Aluminium
Authors: Longoni Margherita , Cicala Norma , Guglielmi Vittoria , Poldi Gianluca , Bruni Silvia
Published: December 2021

Two paintings, made on aluminium support by Silvio Pasotti (among the major exponents of 1960s Italian pop art) were investigated in a totally non-invasive manner to identify the materials used by the artist. Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), visible reflectance spectroscopy, and spectrofluorimetry with visible excitation were exploited as molecular analysis techniques, which are particularly suitable to recognise also synthetic organic materials, such as pigments and binders. The effectiveness of this multi-analytical approach was demonstrated, leading to the identification of several synthetic organic pigments, both conventional and “special effect” ones, introduced during the first half of the 20th century, as well as some well-established inorganic ones. Combining FTIR results both in the medium and near IR ranges, considerations regarding the binders employed by the artist could also be made, suggesting the use of both nitrocellulose and acrylic paints. Imaging techniques, such as IR reflectography, false colour IR, UV induced fluorescence, and portable microscopy, were also used to achieve a better knowledge of the painting practice.
Mechanism of Dyspnea during Exercise in Children with Corrected Congenital Heart Disease
Authors: Chlif Mehdi , Ammar Mohamed Mustapha , Said Noureddine Ben , Sergey Levushkin , Ahmaidi Said , Alassery Fawaz , Hamam Habib
Published: December 2021

This study will evaluate cardiorespiratory and peripheral muscle function and their relationship with subjective dyspnea threshold after the surgical correction of congenital heart disease in children. Thirteen children with surgically repaired congenital heart disease were recruited. Each participant performed an incremental exercise test on a cycle ergometer until exhaustion. Gas exchanges were continuously sampled to measure the maximal aerobic parameters and ventilatory thresholds. The functional capacity of the subjects was assessed with a 6 min walk test. At the end of the exercise test, isokinetic Cybex Norm was used to evaluate the strength and endurance of the knee extensor muscle in the leg. Dyspnea was subjectively scored with a visual analog scale during the last 15 s of each exercise step. Oxygen consumption measured at the dyspnea score/VO2 relationship located at the dyspnea threshold, at which dyspnea suddenly increased. Results: The maximal and submaximal values of the parameters describing the exercise and the peripheral muscular performances were: VO2 Peak: 33.8 ± 8.9 mL·min−1·kg−1; HR: 174 ± 9 b·min−1; VEmax: 65.68 ± 15.9 L·min−1; P max: 117 ± 27 W; maximal voluntary isometric force MVIF: 120.8 ± 41.9 N/m; and time to exhaustion Tlim: 53 ± 21 s. Oxygen consumption measured at the dyspnea threshold was related to VO2 Peak (R2 = 0.74; p < 0.01), Tlim (R2 = 0.78; p < 0.01), and the distance achieved during the 6MWT (R2 = 0.57; p < 0.05). Compared to the theoretical maximal values for the power output, VO2, and HR, the surgical correction did not repair the exercise performance. After the surgical correction of congenital heart disease, exercise performance was impeded by alterations of the cardiorespiratory function and peripheral local factors. A subjective evaluation of the dyspnea threshold is a reliable criterion that allows the prediction of exercise capacity in subjects suffering from congenital heart disease.
Spatial-Temporal Pattern and Evolution Trend of the Cultivated Land Use Eco-Efficiency in the National Pilot Zone for Ecological Conservation in China
Authors: Fan Zhenggen , Deng Chao , Fan Yuqi , Zhang Puwei , Lu Hua
Published: December 2021

The cultivated land use eco-efficiency (CLUE) is an important indicator to evaluate ecological civilization construction in China. Research on the spatial-temporal pattern and evolution trend of the CLUE can help to assess the level of ecological civilization construction and reveal associated demonstration and driving effects on surrounding areas. Based on the perspective of the CLUE, this paper obtains cultivated land use data pertaining to National Pilot Zones for Ecological Conservation in China and neighboring provinces from 2008 to 2018. In this study, the SBM-undesirable, Moran’s I, and Markov chain models are adopted to quantitatively measure and analyze the CLUE and its temporal and spatial patterns and evolution trend. The research results indicate that the CLUE in the whole study area exhibited the characteristics of one growth, two stable, and two decline stages, with a positive spatial autocorrelation that increased year by year, and a spatial spillover effect was observed. Geographical spatial patterns and spatial spillover effects played a major role in the evolution of the CLUE, and there occurred a higher probability of improvement in the vicinity of cities with high CLUE values. In the future, practical construction experience should be disseminated at the provincial level, and policies and measures should be formulated according to local conditions. In addition, a linkage model between prefecture-level cities should be developed at the municipal level to fully manifest the positive spatial spillover effect. Moreover, we should thoroughly evaluate the risk associated with CLUE transition from high to low levels and establish a low-level early warning mechanism.
Market Segmentation by Motivations of Urban Forest Users and Differences in Perceived Effects
Authors: Byun Hyo-Jeong , Lee Byeong-Cheol , Kim Donghan , Park Kwang-Hi
Published: December 2021

The purpose of this study aims at segmenting the urban forest users’ market by motivation and analyzing the difference in perceived effects of urban forests. Based on a literature review, the study selected seven motivating factors of urban forest users: experiential activity, relaxatin/healing, health management, escape from everday life, daily leisure, affinity toward nature. Data were collected online from 21 to 29 Sepember 2020 with urban forest visitors. We analyzed 878 questionnaires received from those with experience of visiting an urban forest within the previous 24 months. We performed a cluster analysis to classify the subjects according to the characteristics of urban forest utilization, and assigned them to four clusters (rest in nature, family leisure, passive participation, and multiple pursuit). An additional analysis was performed to determine intergroup differences, which revealed differences in perceived benefits and healing effects of urban forests as well as satisfaction. The results of this study provide implications for urban forest operation and strategy setup.
Numbers and Mortality Risk of Hypertensive Patients with or without Elevated Body Mass Index in China
Authors: Luo Xiaoqin , Yang Hexiang , He Zhangya , Wang Shanshan , Li Chao , Chen Tao
Published: December 2021

Objective: Our study aimed to estimate the number of hypertension patients with or without elevated body mass index (BMI), and assess their mortality risk. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS) to estimate the population of hypertensive patients with or without elevated BMI. The mortality risk of hypertension with elevated BMI was estimated by using the China Health and Nutrition Survey (CHNS) data. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI). Results: In total, 23.02% of adults, representing 117.74 (95% CI: 108.79, 126.69) million, had both high BMI and hypertension. Among them, 38.53 (95% CI: 35.50, 41.56) million were recommended to initiate antihypertensive medication but did not take it. Moreover, there were 38.40 (95% CI: 35.50, 41.56) million hypertensive patients with elevated BMI who did not achieve the goal of blood pressure control. All-cause mortality and premature death mortality, especially for the elderly, were significantly and positively associated with the severity of the hypertensive condition (p for trend = 0.001). Conclusion: In China, there were a huge number of patients with hypertension and elevated BMI, and the treatment and control rates for them were low. The more severe the degree of hypertension, the higher risk of all-cause death and premature death in these patients.
Multilevel Analysis of Urban–Rural Variations of Body Weights and Individual-Level Factors among Women of Childbearing Age in Nigeria and South Africa: A Cross-Sectional Survey
Authors: Akokuwebe Monica Ewomazino , Idemudia Erhabor Sunday
Published: December 2021

Background: An unhealthy body weight is an adverse effect of malnutrition associated with morbidity among women of childbearing age. While there is increasing attention being paid to the body weights of children and adolescents in Nigeria and South Africa, a major surge of unhealthy body weight in women has received less attention in both countries despite its predominance. The purpose of this study was to explore the prevalence of body weights (underweight, normal, overweight, and obese) and individual-level factors among women of childbearing age by urban–rural variations in Nigeria and South Africa. Methods: This study used the 2018 Nigeria Demographic Health Survey data (n = 41,821) and 2016 South Africa Demographic Health Survey (n = 8514). Bivariate, multilevel, and intracluster correlation coefficient analyses were used to determine individual-level factors associated with body weights across urban–rural variations. Results: The prevalence of being overweight or obese among women was 28.2% and 44.9%, respectively, in South Africa and 20.2% and 11.4% in Nigeria. A majority, 6.8%, of underweight women were rural residents in Nigeria compared to 0.8% in South Africa. The odds of being underweight were higher among women in Nigeria who were unemployed, with regional differences and according to breastfeeding status, while higher odds of being underweight were found among women from poorer households, with differences between provinces and according to cigarette smoking status in South Africa. On the other hand, significant odds of being overweight or obese among women in both Nigeria and South Africa were associated with increasing age, higher education, higher wealth index, weight above average, and traditional/modern contraceptive use. Unhealthy body weights were higher among women in clustering areas in Nigeria who were underweight (intracluster correlation coefficient (ICC = 0.0127), overweight (ICC = 0.0289), and obese (ICC = 0.1040). Similarly, women of childbearing age in clustering areas in South Africa had a lower risk of experiencing underweight (ICC = 0.0102), overweight (ICC = 0.0127), and obesity (ICC = 0.0819). Conclusions: These findings offer a deeper understanding of the close connection between body weights variations and individual factors. Addressing unhealthy body weights among women of childbearing age in Nigeria and South Africa is important in preventing disease burdens associated with body weights in promoting Sustainable Development Goal 3. Strategies for developing preventive sensitization interventions are imperative to extend the perspectives of the clustering effect of body weights on a country level when establishing social and behavioral modifications for body weight concerns in both countries.
Changes in Physical Activity Compared to the Situation before the Outbreak of COVID-19 in Korea
Authors: Lee Yoonmi , Baek Seunghui , Shin Jieun
Published: December 2021

The purpose of this study is to examine changes in physical activity in Korean society, after the outbreak of COVID-19. Method This study was conducted using the Korean Community Health Survey conducted in 2019 and 2020. Subjects that have been diagnosed with hypertension and diabetes were excluded; a total of 355,914 cases were involved for analysis. In terms of the analysis method, General Linear Model (GLM) was conducted to examine the changes in physical activities in 2019 and 2020 depending on the presence of a spouse, educational status, and economic activities. In addition, the GLM was adopted to divide the subjects by gender and age, and analyze their physical activity changes in 2019 and 2020 with spouse presence, educational status, and economic activities as adjusted variables. Result In terms of Koreans, those without a spouse, high educational attainment, and economically inactive were less engaged in physical activities. Differences were found in subjects regarding moderate-intensity physical activities after social distancing following the spread of COVID-19. Senior females without a spouse, both males and females with low educational attainment, economically inactive adult females, and economically active senior males showed a greater drop in physical activities. For walking hours, both adult males and females without a spouse, adult females with all educational attainment level excluding elementary and middle school graduates, and economically inactive adult males and females also showed a downward trend. Conclusion The study recommends that people develop a strategy to increase their post-outbreak physical activity, taking into account the sociodemographic.
The Dynamic Impact of Natural Resource Rents, Financial Development, and Technological Innovations on Environmental Quality: Empirical Evidence from BRI Economies
Authors: Zuo Siming , Zhu Mingxia , Xu Zhexiao , Oláh Judit , Lakner Zoltan
Published: December 2021

Until recently, many countries’ policies were motivated by economic growth; however, few strategies were developed to prevent environmental deterioration including reducing the ecological footprint. In this context, the purpose of this study was to analyze the role of natural resource rents, technological innovation, and financial development on the ecological footprint in 90 Belt and Road Initiative (BRI) economies. This research divided the BRI economies into high income, middle-income, and low-income levels to capture income differences. This research used the second-generation panel unit root, cointegration, and augmented mean group estimators to calculate the robust and reliable outcomes. Based on the annual data from 1991 to 2018, the findings show that natural resource rents drastically damage the quality of the environment, whereas technological innovations are helpful in reducing ecological footprint. Moreover, the outcome of the interaction term (natural resource rents and technological innovations) negatively impacts the ecological footprint. Interestingly, these findings were similar in the three income groups. In addition, financial development improved environmental quality in the middle-income BRI economies, but reduced it in high-income, low-income, and full sample countries. Furthermore, the Environmental Kuznets Curve (EKC) concept has been validated across all BRI economies. Policymakers in BRI countries should move resources away from resource-rich sectors of industries/manufacturing sectors to enhance/promote economic growth and use these NRRs efficiently for a progressive, sustainable environment. Based on these findings, several efficient policy suggestions are proposed.
Examining the Effects of Mindfulness–Acceptance–Commitment Training on Self-Compassion and Grit among Elite Female Athletes
Authors: Mohebi Mahmoud , Sadeghi-Bahmani Dena , Zarei Sahar , Gharayagh Zandi Hassan , Brand Serge
Published: December 2021

Background: Mindfulness-based interventions are well-established in the field of psychotherapy, and such interventions have also gained increased attention in the field of sport psychology, either to cope with psychological pressure or to improve an athlete’s performance. The goal of the present study was to examine whether a Mindfulness–Acceptance–Commitment (MAC) program could increase self-compassion and grit among elite female athletes compared to an active control condition. To this end, we performed a randomized trial among female adult athletes. Methods: Forty female adult athletes (Mage = 22.22, SD = 2.40) were randomly assigned either to the Mindfulness–Acceptance–Commitment group (n = 20; 7 group sessions, 60 min each) or the active control group (n = 20; 7 group sessions, 60 min each). At baseline, seven weeks later at the end of the study and again four weeks later at follow-up, participants completed a series of self-rating questionnaires on mindfulness, self-compassion and grit. Results: Dimensions of mindfulness, self-compassion and grit improved over time, but more so in the Mindfulness–Acceptance–Commitment condition compared to the active control condition. Improvements remained stable from the study end to follow-up. Conclusions: While the active control condition improved dimensions of mindfulness, self-compassion and grit among female adult athletes, improvements were much stronger in the Mindfulness–Acceptance–Commitment condition. Importantly, improvements in the Mindfulness–Acceptance–Commitment condition remained stable over a time lapse of four weeks at follow-up after study completion, suggesting that the Mindfulness–Acceptance–Commitment intervention appeared to improve cognitive–emotional learning processes.
Association between Anxious and Depressive Symptomatology and Sexual Activity in Spain: A Cross-Sectional Study during the COVID-19 Quarantine
Authors: Gil-Salmerón Alejandro , López-Sánchez Guillermo F. , López-Bueno Rubén , Pardhan Shahina , Grabovac Igor , Smith Lee
Published: December 2021

Introduction: Evidence on sexual behaviour and COVID-19 shows a change in sexual habits; however, there is no research on the association between mental health and sexual activity. Aim: To examine the relationship between mental health and sexual activity during the quarantine in Spanish adults. Methods: A sample of 305 adults filled out an online questionnaire. Sexual activity was assessed with one question. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively. To check associations between levels of both anxiety and depressive symptoms (exposure) and weekly prevalence of sexual activity (outcome), we conducted multiple logistic regression adjusted for control variables (marital status, employment, average household annual income, place of living, pre-COVID-19 sexual activity, current smoking, current alcohol consumption, chronic physical conditions, chronic psychiatric conditions, physical symptoms, and days of confinement). Results: Higher depression level was associated with lower weekly sexual activity in a dose-response fashion in the three implemented models. Participants with higher levels of depression were associated with significantly lower sexual activity in the fully adjusted model (OR: 0.09, 95% CI 0.01–0.61). Mild anxiety-level participants consistently presented significantly lower ORs for lower sexual activity than their minimal-anxiety category counterparts. Particularly, the fully adjusted model showed the lower values (OR: 0.40, 95% CI 0.19–0.84). Conclusion: The results of this study support existing evidence stressing the association between mental health and sexual activity in quarantined adults.
Physical Intimate Partner Violence, Childhood Physical Abuse and Mental Health of U.S. Caribbean Women: The Interrelationship of Social, Contextual, and Migratory Influences
Authors: Lacey Krim K. , Parnell Regina , Drummond-Lewis Sasha R. , Wood Maxine , Powell Sears Karen
Published: December 2021

The literature has shown an increased risk for mental health conditions among victims of domestic violence. Few studies have examined the relationship between mental health disorders and domestic violence among Caribbean women, and how the association might be influenced by migratory and contextual factors. This study addresses the mental well-being of U.S. Caribbean Black women victims of domestic violence, and the relationships between acculturation, discrimination, and demographic influences. An analysis of data from the 2001–2003 National Survey of American Life (NSAL) re-interview, the first and most complete study on U.S. Caribbean Blacks, was conducted. Bivariate analysis revealed an association between acts of physical domestic violence and mental health conditions, with generally higher risk among women who reported both severe physical intimate partner violence and childhood physical abuse. Multivariate logistic regression indicates an association between specific mental disorders and acts of domestic violence. Acculturation, length of residence in the United States, age, education, poverty, and country of origin were also associated with mental health. The study highlights future directions for exploration including additional investigation of the influence of acculturation on the physical health of victims of domestic violence.
Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine
Authors: Tretter Verena , Hochreiter Beatrix , Zach Marie Louise , Krenn Katharina , Klein Klaus Ulrich
Published: December 2021

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term “oxidative stress” is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.
The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses
Authors: Jacques Camille , Chatelais Mathias , Fekir Karim , Fauconnier Louis , Mellier Manon , Togbe Dieudonnée , Floris Ilaria
Published: December 2021

This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by influenza A virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs (p = 0.1051) and slightly increased the circulating levels of IgM (p = 0.1655). Furthermore, MIM stimulated the proliferation of CD3-primed T lymphocytes and decreased the secretion of the immunosuppressive cytokine IL-10 in CD14+-derived macrophages. Human umbilical vein endothelial cells were finally used to explore the effect of MIM on endothelial cells, in which it slightly increased the expression of immune-related markers such as HLA-I, CD137L, GITRL, PD-L1 and ICAM-1. In conclusion, the present study suggests that MIM might be a promising nonspecific (without antigen specificity) immunostimulant drug in preventing and early treating respiratory infections, but not only exclusively, as it would gently support several facets of the immune system and host defenses.
Resveratrol-Encapsulated Mitochondria-Targeting Liposome Enhances Mitochondrial Respiratory Capacity in Myocardial Cells
Authors: Tsujioka Takao , Sasaki Daisuke , Takeda Atsuhito , Harashima Hideyoshi , Yamada Yuma
Published: December 2021

The development of drug delivery systems for use in the treatment of cardiovascular diseases is an area of great interest. We report herein on an evaluation of the therapeutic potential of a myocardial mitochondria-targeting liposome, a multifunctional envelope-type nano device for targeting pancreatic β cells (β-MEND) that was previously developed in our laboratory. Resveratrol (RES), a natural polyphenol compound that has a cardioprotective effect, was encapsulated in the β-MEND (β-MEND (RES)), and its efficacy was evaluated using rat myocardioblasts (H9c2 cells). The β-MEND (RES) was readily taken up by H9c2 cells, as verified by fluorescence-activated cell sorter data, and was observed to be colocalized with intracellular mitochondria by confocal laser scanning microscopy. Myocardial mitochondrial function was evaluated by a Seahorse XF Analyzer and the results showed that the β-MEND (RES) significantly activated cellular maximal respiratory capacity. In addition, the β-MEND (RES) showed no cellular toxicity for H9c2 cells as evidenced by Premix WST-1 assays. This is the first report of the use of a myocardial mitochondria-targeting liposome encapsulating RES for activating mitochondrial function, which was clearly confirmed based on analyses using a Seahorse XF Analyzer.
chi-miR-487b-3p Inhibits Goat Myoblast Proliferation and Differentiation by Targeting IRS1 through the IRS1/PI3K/Akt Signaling Pathway
Authors: Lyu Ming , Wang Xu , Meng Xiangyu , Qian Hongrun , Li Qian , Ma Baoxia , Zhang Zhiying , Xu Kun
Published: December 2021

MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs and play critical roles in the regulation of post-transcriptional gene expression. Our previous study uncovered that chi-miR-487b-3p is widespread in different goat tissues, which is significantly higher in muscle, especially in lamb. Here, we demonstrate the role of chi-miR-487b-3p as a myogenic miRNA that regulates skeletal muscle development. chi-miR-487b-3p overexpression was demonstrated to significantly inhibit goat myoblast proliferation and differentiation, whereas chi-miR-487b-3p inhibition resulted in the opposite effects. Next, chi-miR-487b-3p was predicted to target the 3′UTR of insulin receptor substrate 1 (IRS1) gene by Target-Scan and miRDB. The results of dual-luciferase assay, RT-qPCR, and western blot all confirmed that IRS1 might be a direct target of chi-miR-487b-3p as its expression was negatively regulated by chi-miR-487b-3p. siRNA silencing of IRS1 further demonstrated significant inhibition on goat myoblast proliferation and differentiation, confirming the effect of IRS1 downregulation by chi-miR-487b-3p in myogenesis. In addition, chi-miR-487b-3p knockout goat myoblast clones were generated using CRISPR/Cas9 technology, and we further illustrated that chi-miR-487b-3p regulates goat myoblast growth through the PI3K/Akt signaling pathway by targeting IRS1. Collectively, our work demonstrated that chi-miR-487b-3p is a potent inhibitor of skeletal myogenesis and provided new insights into the mechanisms of miRNA on the regulation of goat growth.
Structural Features of Cytochrome b5–Cytochrome b5 Reductase Complex Formation and Implications for the Intramolecular Dynamics of Cytochrome b5 Reductase
Authors: Gutiérrez-Merino Carlos , Martínez-Costa Oscar H. , Monsalve Maria , Samhan-Arias Alejandro K.
Published: December 2021

Membrane cytochrome b5 reductase is a pleiotropic oxidoreductase that uses primarily soluble reduced nicotinamide adenine dinucleotide (NADH) as an electron donor to reduce multiple biological acceptors localized in cellular membranes. Some of the biological acceptors of the reductase and coupled redox proteins might eventually transfer electrons to oxygen to form reactive oxygen species. Additionally, an inefficient electron transfer to redox acceptors can lead to electron uncoupling and superoxide anion formation by the reductase. Many efforts have been made to characterize the involved catalytic domains in the electron transfer from the reduced flavoprotein to its electron acceptors, such as cytochrome b5, through a detailed description of the flavin and NADH-binding sites. This information might help to understand better the processes and modifications involved in reactive oxygen formation by the cytochrome b5 reductase. Nevertheless, more than half a century since this enzyme was first purified, the one-electron transfer process toward potential electron acceptors of the reductase is still only partially understood. New advances in computational analysis of protein structures allow predicting the intramolecular protein dynamics, identifying potential functional sites, or evaluating the effects of microenvironment changes in protein structure and dynamics. We applied this approach to characterize further the roles of amino acid domains within cytochrome b5 reductase structure, part of the catalytic domain, and several sensors and structural domains involved in the interactions with cytochrome b5 and other electron acceptors. The computational analysis results allowed us to rationalize some of the available spectroscopic data regarding ligand-induced conformational changes leading to an increase in the flavin adenine dinucleotide (FAD) solvent-exposed surface, which has been previously correlated with the formation of complexes with electron acceptors.
Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer
Authors: Czajka-Francuz Paulina , Cisoń-Jurek Sylwia , Czajka Aleksander , Kozaczka Maciej , Wojnar Jerzy , Chudek Jerzy , Francuz Tomasz
Published: December 2021

Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.
Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis
Authors: Kay Alasdair G. , Treadwell Kane , Roach Paul , Morgan Rebecca , Lodge Rhys , Hyland Mairead , Piccinini Anna M. , Forsyth Nicholas R. , Kehoe Oksana
Published: December 2021

Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.
Methyl 2-Halo-4-Substituted-5-Sulfamoyl-Benzoates as High Affinity and Selective Inhibitors of Carbonic Anhydrase IX
Authors: Zakšauskas Audrius , Čapkauskaitė Edita , Paketurytė-Latvė Vaida , Smirnov Alexey , Leitans Janis , Kazaks Andris , Dvinskis Elviss , Stančaitis Laimonas , Mickevičiūtė Aurelija , Jachno Jelena , Jezepčikas Linas , Linkuvienė Vaida , Sakalauskas Andrius , Manakova Elena , Gražulis Saulius , Matulienė Jurgita , Tars Kaspars , Matulis Daumantas
Published: December 2021

Among the twelve catalytically active carbonic anhydrase isozymes present in the human body, the CAIX is highly overexpressed in various solid tumors. The enzyme acidifies the tumor microenvironment enabling invasion and metastatic processes. Therefore, many attempts have been made to design chemical compounds that would exhibit high affinity and selective binding to CAIX over the remaining eleven catalytically active CA isozymes to limit undesired side effects. It has been postulated that such drugs may have anticancer properties and could be used in tumor treatment. Here we have designed a series of compounds, methyl 5-sulfamoyl-benzoates, which bear a primary sulfonamide group, a well-known marker of CA inhibitors, and determined their affinities for all twelve CA isozymes. Variations of substituents on the benzenesulfonamide ring led to compound 4b, which exhibited an extremely high observed binding affinity to CAIX; the Kd was 0.12 nM. The intrinsic dissociation constant, where the binding-linked protonation reactions have been subtracted, reached 0.08 pM. The compound also exhibited more than 100-fold selectivity over the remaining CA isozymes. The X-ray crystallographic structure of compound 3b bound to CAIX showed the structural position, while several structures of compounds bound to other CA isozymes showed structural reasons for compound selectivity towards CAIX. Since this series of compounds possess physicochemical properties suitable for drugs, they may be developed for anticancer therapeutic purposes.
Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS
Authors: Li Chun , Li Jiyu , Loreno Ethyn G. , Miriyala Sumitra , Panchatcharam Manikandan , Sun Hong
Published: December 2021

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIαCreERT2/+/L-PGDS+/+, and CaMKIIαCreERT2/+/L-PGDSflox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIαCreERT2/+/L-PGDS+/+ and CaMKIIαCreERT2/+/L-PGDSflox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIαCreERT2/+/L-PGDS+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIαCreERT2/+/L-PGDSflox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.
Molecular Profiling and Novel Therapeutic Strategies for Mucosal Melanoma: A Comprehensive Review
Authors: Indini Alice , Roila Fausto , Grossi Francesco , Massi Daniela , Mandalà Mario
Published: December 2021

Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of KIT mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also SF3B1 mutation, CDK4 amplifications, and CDKN2A gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.
Synthesis and Characterization of Novel Copper(II)-Sunitinib Complex: Molecular Docking, DFT Studies, Hirshfeld Analysis and Cytotoxicity Studies
Authors: Tarasi Facundo , Lanza Priscila Ailín , Ferretti Valeria , Echeverría Gustavo Alberto , Piro Oscar Enrique , Cacicedo Maximiliano , Gehring Stephan , León Ignacio Esteban , Islas María Soledad
Published: December 2021

The main goal of this work was to report the synthesis, characterization, and cytotoxicity study of a novel copper(II)-sunitinib complex, CuSun. It has been synthesized and characterized in solid state and in solution by different methods (such as DFT, FTIR, Raman, UV-vis, EPR, NMR, etc.). The solid-state molecular structure of trichlorosunitinibcopper(II), where sunitinib: N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, for short Cu(Sun)Cl3, was determined by X-ray diffraction. It crystallizes in the triclinic space group P-1 with a = 7.9061(5) Å, b = 12.412(1) Å, c = 13.7005(8) Å, α = 105.021(6)°, β = 106.744(5)°, γ = 91.749(5)°, and Z = 2 molecules per unit cell. Also, we have found π-π interactions and classic and non-classic H-bonds in the crystal structure by using Hirshfeld surface analysis. In the speciation studies, the complex has dissociated in protonated sunitinib and chlorocomplex of copper(II), according to 1HNMR, EPR, UV-vis and conductimetric analysis. Molecular docking of the complex in both, ATP binding site and allosteric site of VEGFR2 have shown no improvement in comparison to the free ligand. Besides, cytotoxicity assay on HepG2 cell line shows similar activity for complex and ligand in the range between 1–25 μM supporting the data obtained from studies in solution.
Big Data and Energy Security: Impacts on Private Companies, National Economies and Societies
Authors: Hassani Hossein , Komendantova Nadejda , Kroos Daniel , Unger Stephan , Yeganegi Mohammad Reza
Published: December 2021

The importance of energy security for the successful functioning of private companies, national economies, and the overall society cannot be underestimated. Energy is a critical infrastructure for any modern society, and its reliable functioning is essential for all economic sectors and for the well-being of everybody. Uncertainty in terms of the availability of information, namely reliable data to make predictions and to plan for investment as well as for other actions of stakeholders in the energy markets is one of the factors with the highest influence on energy security. This uncertainty can be connected with many factors, such as the availability of reliable data or actions of stakeholders themselves. For example, the recent outbreak of the COVID-19 pandemic revealed negative impacts of uncertainty on decision-making processes and markets. At the time point when the market participants started to receive real-time information about the situation, the energy markets began to ease. This is one scenario where Big Data can be used to amplify information to various stakeholders to prevent panic and to ensure market stability and security of supply. Considering the novelty of this topic, our methodology is based on the meta-analysis of existing studies in the area of impacts of energy security on private companies, the national economy, and society. The results show that, in a fast-paced digital world characterized by technological advances, the use of Big Data technology provides a unique niche point to close this gap in information disparity by levering the use of unconventional data sources to integrate technologies, stakeholders, and markets to promote energy security and market stability. The potential of Big Data technology is yet to be fully utilized. Big Data can handle large data sets characterized by volume, variety, velocity, value, and complexity. Our conclusion is that the challenge for energy markets is to leverage this technology to mine available socioeconomic, political, geographic, and environmental data responsibly and to provide indicators that predict future global supply and demand. This information is crucial for energy security and ensuring global economic prosperity.
Treatment outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues
Authors: Lemaître Daniel , Barjol Amandine , Abdelmassih Youssef , Farnoux Caroline , Martin Gilles C. , Metge Florence , Chapron Thibaut , Caputo Georges
Published: December 2021

This study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2%), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines.