bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychological Performance and Cardiac Autonomic Function in Blue- and White-Collar Workers: A Psychometric and Heart Rate Variability Evaluation
Authors: Eslami Ardalan , Nassif Najah T. , Lal Sara
Published: February 2023

The 21st century has brought a growing and significant focus on performance and health within the workforce, with the aim of improving the health and performance of the blue- and white-collar workforce. The present research investigated heart rate variability (HRV) and psychological performance between blue and white-collar workers to determine if differences were evident. A total of 101 workers (n = 48 white-collar, n = 53 blue-collar, aged 19–61 years) underwent a three lead electrocardiogram to obtain HRV data during baseline (10 min) and active (working memory and attention) phases. The Cambridge Neuropsychological Test Automated Battery, specifically the spatial working memory, attention switching task, rapid visual processing and the spatial span, were used. Differences in neurocognitive performance measures indicated that white-collar workers were better able to detect sequences and make less errors than blue-collar workers. The heart rate variability differences showed that white-collar workers exhibit lower levels of cardiac vagal control during these neuropsychological tasks. These initial findings provide some novel insights into the relationship between occupation and psychophysiological processes and further highlight the interactions between cardiac autonomic variables and neurocognitive performance in blue and white-collar workers.
Teacher Burnout in the Time of COVID-19: Antecedents and Psychological Consequences
Authors: Padmanabhanunni Anita , Pretorius Tyrone B.
Published: February 2023

The important, frontline role of teachers during the COVID-19 pandemic has often gone unrecognized, and attention to their mental health and well-being is often only the focus of scholarly research. The unprecedented challenges that teachers faced during the COVID-19 pandemic and the stresses and strains associated with it have severely impacted their psychological well-being. This study examined the predictors and the psychological consequences of burnout. Participants (N = 355) were schoolteachers in South Africa who completed the Perceived Vulnerability to Disease Questionnaire, the Fear of COVID-19 Scale, the Role Orientation Questionnaire, the Maslach Burnout Inventory, the Centre for Epidemiological Depression Scale, the Beck Hopelessness Scale, the Satisfaction with Life Scale, and the trait scale of the State-Trait Anxiety Inventory. The results of a multiple regression showed that fear of COVID-19, role ambiguity, and role conflict were significant predictors of emotional exhaustion and depersonalization, while perceived infectability and role ambiguity significantly predicted personal accomplishment. Gender and age also predicted emotional exhaustion and depersonalization, respectively, and age was also a significant predictor of personal accomplishment. Generally, the dimensions of burnout were significant predictors of indices of psychological well-being—namely, depression, hopelessness, anxiety, and life satisfaction—with the exception of the association between depersonalization and life satisfaction. Our results suggest that intervention efforts to reduce burnout need to provide teachers with adequate job resources to buffer against the demands and stressors associated with their work.
Parental Perceptions of Family-Centred Supports for Children with Developmental Disabilities
Authors: McConkey Roy , O’Hagan Pauline , Corcoran Joanne
Published: February 2023

Family-centred interventions have long been advocated in paediatric practice and in public health, but their implementation is rarer with children experiencing developmental disabilities. Moreover, the uptake is lower in families from more socially deprived backgrounds. Yet there is robust evidence that such interventions bring benefits to the family caregivers as well as to the affected children. The present study emerged from a support service that had been located in a rural county in Ireland in which nearly 100 families of children with intellectual and developmental disabilities had participated. Using a qualitative research methodology, interviews were conducted with 16 parents who had taken part in the service with the aim of gaining insights into the ways a family-centred service had been of value to them. The themes identified in their responses were validated in two ways. All parents were given the opportunity to provide their perceptions using a self-completion questionnaire, and nearly 50% responded. In addition, seven health and social care staff who had referred families to the project were asked their views through personal interviews. The core theme to emerge was the focus placed on family engagement by the service, with four subthemes emerging: parental confidence boosted; children developed; community connections were made; and supportive staff. These insights should help existing health and social care services to become more family-centred and inform the development of new support services in response to the high levels of unmet needs among marginalized families in even the most affluent countries.
Co-Use, Simultaneous Use, and Mixing of Cannabis and Tobacco: A Cross-National Comparison of Canada and the US by Cannabis Administration Type
Authors: Chu Alanna , Chaiton Michael , Kaufman Pamela , Goodwin Renee D. , Lin Jodie , Hindocha Chandni , Goodman Samantha , Hammond David
Published: February 2023

Introduction: Increasing cannabis legalization raises concerns that the use of tobacco, frequently used with cannabis, will also increase. This study investigated the association between the legal status of cannabis in places of residence and the prevalence of cannabis and tobacco co-use, simultaneous use, and mixing by comparing the prevalence among adults in Canada (prior to cannabis legalization) vs. adults in US states that had legalized recreational cannabis vs. US states that had not as of September 2018. Methods: Data were drawn from the 2018 International Cannabis Policy Study, conducted with respondents aged 16–65 in Canada and the US recruited from nonprobability consumer panels. Differences in the prevalence of co-use, simultaneous use, and mixing between tobacco and different cannabis products were examined using logistic regression models by legal status of place of residence among past-12-month cannabis consumers (N = 6744). Results: Co-use and simultaneous use in the past 12 months were most common among respondents in US legal states. Among cannabis consumers, co-use and simultaneous use were less common in US legal states, while mixing was less frequent in US states with both legal and illegal cannabis compared to Canada. Use of edibles was associated with lower odds of all three outcomes, while smoking dried herb or hash was associated with higher odds. Conclusions: The proportion of cannabis consumers who used tobacco was lower in legal jurisdictions despite higher prevalence of cannabis use. Edible use was inversely associated with co-use, suggesting that edible use does not appear to be associated with increased tobacco use.
Global Human Threat: The Potential Synergism between Mercury Intoxication and COVID-19
Authors: Arrifano Gabriela de Paula , Augusto-Oliveira Marcus , Lopes-Araújo Amanda , Santos-Sacramento Letícia , Macchi Barbarella Matos , Nascimento José Luiz Martins do , Crespo-Lopez Maria Elena
Published: February 2023

The COVID-19 pandemic affected billions of people worldwide, and exposure to toxic metals has emerged as an important risk factor for COVID-19 severity. Mercury is currently ranked as the third toxic substance of global concern for human health, and its emissions to the atmosphere have increased globally. Both COVID-19 and mercury exposure present a high prevalence in similar regions: East and Southeast Asia, South America and Sub-Saharan Africa. Since both factors represent a multiorgan threat, a possible synergism could be exacerbating health injuries. Here, we discuss key aspects in mercury intoxication and SARS-CoV-2 infection, describing the similarities shared in clinical manifestations (especially neurological and cardiovascular outcomes), molecular mechanisms (with a hypothesis in the renin-angiotensin system) and genetic susceptibility (mainly by apolipoprotein E, paraoxonase 1 and glutathione family genes). Literature gaps on epidemiological data are also highlighted, considering the coincident prevalence. Furthermore, based on the most recent evidence, we justify and propose a case study of the vulnerable populations of the Brazilian Amazon. An understanding of the possible adverse synergism between these two factors is crucial and urgent for developing future strategies for reducing disparities between developed and underdeveloped/developing countries and the proper management of their vulnerable populations, particularly considering the long-term sequelae of COVID-19.
Differentiation Governance of Rural Human Settlement Environments in China: Knowledge Mapping and Visualization
Authors: Dai Xin , Zhang Junying , Sun Xuehang , Li Junjie , Liu Bangfan
Published: February 2023

To further promote the effective governance of rural human settlements in China, it is necessary to summarize and organize the research on rural human settlements that has been undertaken in the last decade. This paper analyzes the current status of rural human settlements research from the perspectives of Chinese literature and English literature. It takes the core documents included in WOS (Web of Science) and CNKI (Chinese National Knowledge Infrastructure) as samples, and produces a visual analysis of the authors, institutions, disciplines, and research hotspots for rural human settlements research with the help of CiteSpace V and other measurement software, focus on identifying the similarities and differences between CNKI and WOS in the study of rural human settlements. The results show that the number of papers is increasing; cooperation between Chinese researchers and institutions needs to be further strengthened; the existing research has achieved interdisciplinary integration; the research hotspots are converging, but China pays more attention to the study of the hard environment, such as the macro level of rural human settlements and the natural ecological environments of residence, and lacks insight into the soft environment, such as the main body of residences, social relations, and individual needs in the urban fringe. This study is conducive to promoting the integrated development of urban and rural areas in China, promoting the revitalization and development of rural areas in China, and achieving social equity.
Accuracy of Resting Metabolic Rate Prediction Equations in Sport Climbers
Authors: Chmielewska Anna , Kujawa Krzysztof , Regulska-Ilow Bożena
Published: February 2023

Resting metabolic rate (RMR) represents the energy required to maintain vital body functions. In dietary practice, RMR is determined by predictive equations on the basis of using body weight or fat-free mass. Our study aimed to assess whether predictive equations used to estimate RMR are reliable tools for estimating the energy requirements of sport climbers. The study included 114 sport climbers whose RMR was measured with a Fitmate WM. Anthropometric measurements were performed with X-CONTACT 356. The resting metabolic rate was measured by indirect calorimetry and was compared with the RMR estimated by 14 predictive equations on the basis of using body weight/fat-free mass. All equations underestimated RMR in male and female climbers, except for De Lorenzo’s equation in the group of women. The De Lorenzo equation demonstrated the highest correlation with RMR in both groups. The results of the Bland–Altman tests revealed an increasing measurement error with increasing metabolism for most of the predictive equations in male and female climbers. All equations had low measurement reliability according to the intraclass correlation coefficient. Compared with the indirect calorimetry measurement results, none of the studied predictive equations demonstrated high reliability. There is a need to develop a highly reliable predictive equation to estimate RMR in sport climbers.
Bidirectional Comorbid Associations between Back Pain and Major Depression in US Adults
Authors: Yang Haiou , Hurwitz Eric L. , Li Jian , de Luca Katie , Tavares Patricia , Green Bart , Haldeman Scott
Published: February 2023

Low back pain and depression have been globally recognized as key public health problems and they are considered co-morbid conditions. This study explores both cross-sectional and longitudinal comorbid associations between back pain and major depression in the adult population in the United States. We used data from the Midlife in the United States survey (MIDUS), linking MIDUS II and III with a sample size of 2358. Logistic regression and Poisson regression models were used. The cross-sectional analysis showed significant associations between back pain and major depression. The longitudinal analysis indicated that back pain at baseline was prospectively associated with major depression at follow-up (PR 1.96, CI: 1.41, 2.74), controlling for health behavioral and demographic variables. Major depression at baseline was also prospectively associated with back pain at follow-up (PR 1.48, CI: 1.04, 2.13), controlling for a set of related confounders. These findings of a bidirectional comorbid association fill a gap in the current understanding of these comorbid conditions and could have clinical implications for the management and prevention of both depression and low back pain.
The Effectiveness of Electrical Vestibular Stimulation (VeNS) on Symptoms of Anxiety: Study Protocol of a Randomized, Double-Blinded, Sham-Controlled Trial
Authors: Cheung Teris , Lam Joyce Yuen Ting , Fong Kwan Hin , Ho Yuen Shan , Ho Alex , Cheng Calvin Pak-Wing , Sittlington Julie , Xiang Yu-Tao , Li Tim Man Ho
Published: February 2023

The prevalence of symptoms of anxiety is increasing, especially during the COVID-19 pandemic. A home use transdermal neurostimulation device might help to minimize the severity of anxiety disorder. To the best of our knowledge, there is no clinical trial using transdermal neurostimulation to treat individuals with symptoms of anxiety in Asia. This gives us the impetus to execute the first study which aims at evaluating the efficacy of Electrical Vestibular Stimulation (VeNS) on anxiety in Hong Kong. This study proposes a two-armed, double-blinded, randomized, sham-controlled trial including the active VeNS and sham VeNS group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 1-month (T3) and 3-month follow-up (T4). A total of 66 community-dwelling adults aged 18 to 60 with anxiety symptoms will be recruited in this study. All subjects will be computer randomised into either the active VeNS group or the sham VeNS group in a 1:1 ratio. All subjects in each group will receive twenty 30 min VeNS sessions during weekdays, which will be completed in a 4-week period. Baseline measurements and post-VeNS evaluation of the psychological outcomes (i.e., anxiety, insomnia, and quality of life) will also be conducted on all participants. The 1-month and 3-month follow-up period will be used to assess the long-term sustainability of the VeNS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyze data. Missing data were managed with multiple mutations. The level of significance will be set to p < 0.05. Results of this study will be used to determine whether this VeNS device can be considered as a self-help technological device to reduce perceived anxiety in the general population in the community setting. This clinical Trial was registered with the Clinical Trial government, identifier: NCT04999709.
The Importance of Emotional Intelligence in University Athletes: Analysis of Its Relationship with Anxiety
Authors: Mercader-Rubio Isabel , Ángel Nieves Gutiérrez
Published: February 2023

In the field of sport psychology, research on emotional intelligence and its relationship with other psychological variables to determine how it affects the athlete’s performance is becoming more frequent and prevalent. Among these psychological variables, research in this field has focused on the evaluation of the influence of aspects such as motivation, leadership, self-concept, and anxiety. The main objective of this research is to analyze the levels of each of the dimensions of emotional intelligence (attention, clarity, and emotional regulation) and their relationship with each of the SCAT items to measure pre-competitive anxiety. To do so, we analyzed the influence that one psychological construct has on the other, in order to establish the type of relationships that are established between them. The design of this research corresponds to be transversal, observational, quantitative, and descriptive. The sample consisted of 165 students belonging to university degrees (bachelor’s and master’s) related to physical activity and sport sciences. The main finding of this study allows us to affirm the relationship between emotional intelligence and anxiety. This confirms the hypothesis that anxiety is an indispensable component of any competitive situation, and that neither the total absence of anxiety nor high levels of it leads to better sports performance. Therefore, sport psychology should focus on the emotional preparation of athletes so that they can manage and control their anxiety at intermediate levels, which in addition to being typical of a competitive situation, is also synonymous with good sporting performance.
The Role of Liquidity Creation in Managing the COVID-19 Banking Crisis in Selected Mena Countries
Authors: El-Chaarani Hani , Abraham Rebecca , Azzi Georges
Published: February 2023

Banks are financial intermediaries who transform deposits into loans. Banks in the MENA (Middle East and North Africa) region use large deposits from oil companies and big businesses to finance trade, and fund government and private sector infrastructure projects. The role of banks in financing trade and development is significant as undeveloped capital markets are unable to perform this function. During the COVID-19 crisis, banks sustained liquidity shocks, as deposits were withdrawn to meet personal and business needs. Essentially, banks could not make loans, as the funds to make loans were depleted. The purpose of this study is to evaluate the effectiveness of liquidity creation as a main force, in conjunction with other performance predictors such as efficient asset management, asset quality, and bank size, on bank financial performance, either individually or in conjunction with liquidity creation during the COVID-19 financial crisis. We used bank financial data from a sample of 298 banks from 11 countries in the MENA region, including Egypt, Tunisia, Morocco, Qatar, Bahrain, Oman, Kuwait, Saudi Arabia, United Arab Emirates, Jordan, and Israel, from 2020 to2021. Liquidity creation, efficient asset management, asset quality, and bank size increased bank return on assets and return on equity. Bank size and asset quality acted jointly with liquidity creation to increase return on assets and increase return on equity. We conclude that as liquidity creation acts individually, and in conjunction with asset quality and bank size to increase bank profits, both its main effect and its moderated effect, can maintain bank profitability, during periods of extreme liquidity supply shocks, such as the COVID-19 crisis.
Learning from Accidents: Spatial Intelligence Applied to Road Accidents with Insights from a Case Study in Setúbal District, Portugal
Authors: Nogueira Pedro , Silva Marcelo , Infante Paulo , Nogueira Vitor , Manuel Paulo , Afonso Anabela , Jacinto Gonçalo , Rego Leonor , Quaresma Paulo , Saias José , Santos Daniel , Gois Patricia
Published: February 2023

Road traffic accidents are a major concern for modern society with a high toll on human life and involve hard to account economic consequences. New knowledge can be obtained from combining GIS tools with machine learning and artificial intelligence, developing what is, in this work, identified as spatial intelligence. This approach is tested in a case study of Setúbal district, Portugal, for the period of 2016 to 2019. Departing from a heatmap analysis, and applying kernel density estimation, new spatial approaches were used, namely DBSCAN and Getis-Ord. The results obtained allowed the identification of novel meaningful locations of road traffic accidents. Consequently, the knowledge built from the underlying patterns is considered the key to developing new strategies to solve this modern social curse. The methodology proposed in this study demonstrates that the combination of expertise built from the different spatial analyses can provide a better understanding of the determinants of road traffic accidents. This approach is expected to be valuable for data analysts and decision-makers, contributing to diminishing human losses related to road traffic accidents.
The Think-Aloud Method for Evaluating the Usability of a Regional Atlas
Authors: Vanicek Tomas , Popelka Stanislav
Published: February 2023

The think-aloud method is a widely used method for evaluating the usability of websites and software. However, it can also be used with cartographic products, an area which has been neglected up to now. It is a method in which test participants verbalise all their thought processes aloud. The participants are given a test scenario containing tasks to be completed. The method aims to reveal the participants’ subjective attitudes toward a product in order to evaluate its usability. The present paper describes the use of the think-aloud method to evaluate the usability of a cartographic work—the regional atlas of the Moravian-Silesian Region. The study includes (I) a complete review of the method, based on the studies conducted; (II) testing tools for working with recorded data; (III) designing an experiment for evaluating the usability of the atlas; and (IV) the resulting qualitative and quantitative evaluation of the atlas based on the obtained results. During the study, three approaches were proposed to process and analyse the audio recordings. The first option was to separate the audio recordings into individual annotations and analyse them. The second option was to convert the recordings to text and perform a linguistic analysis. The third supplementary option was to use all the material produced and to analyse it subjectively and retrospectively, from the researcher’s perspective. All three options were used in the final assessment of the atlas. Based on the participants’ statements, any shortcomings in the studied atlas were identified for each topic (e.g., non-dominant maps or exceedingly complex infographics), and recommendations for their elimination were proposed.
Detecting Urban Commercial Districts by Fusing Points of Interest and Population Heat Data with Region-Growing Algorithms
Authors: Zhao Bingbing , He Xiao , Liu Baoju , Tang Jianbo , Deng Min , Liu Huimin
Published: February 2023

Reasonable urban commercial planning must clarify the location and scope of urban commercial districts (UCDs). However, existing studies typically detect spurious UCDs owing to the bias in a single data source while ignoring the continuity and ambiguity of commercial district boundaries. Therefore, in this study, we designed a two-stage approach for detecting UCDs. First, points of interest and population heat data were fused through hotspot and overlay analyses to detect core commercial areas. The boundaries of the UCDs were then identified by considering adjacent blocks using adjusted cosine similarity and region-growing algorithms. Finally, an experiment was conducted in Xiamen, revealing concentrated businesses on Xiamen Island and sparse businesses outside Xiamen Island. An experimental comparison with other strategies confirmed the improved modeling ability of this approach for the edge ambiguity of UCDs. This framework provides tools for urban commercial planning and helps recognize urban commercial patterns in a timely manner.
MSEDDI: Multi-Scale Embedding for Predicting Drug—Drug Interaction Events
Authors: Yu Liyi , Xu Zhaochun , Cheng Meiling , Lin Weizhong , Qiu Wangren , Xiao Xuan
Published: February 2023

A norm in modern medicine is to prescribe polypharmacy to treat disease. The core concern with the co-administration of drugs is that it may produce adverse drug—drug interaction (DDI), which can cause unexpected bodily injury. Therefore, it is essential to identify potential DDI. Most existing methods in silico only judge whether two drugs interact, ignoring the importance of interaction events to study the mechanism implied in combination drugs. In this work, we propose a deep learning framework named MSEDDI that comprehensively considers multi-scale embedding representations of the drug for predicting drug—drug interaction events. In MSEDDI, we design three-channel networks to process biomedical network-based knowledge graph embedding, SMILES sequence-based notation embedding, and molecular graph-based chemical structure embedding, respectively. Finally, we fuse three heterogeneous features from channel outputs through a self-attention mechanism and feed them to the linear layer predictor. In the experimental section, we evaluate the performance of all methods on two different prediction tasks on two datasets. The results show that MSEDDI outperforms other state-of-the-art baselines. Moreover, we also reveal the stable performance of our model in a broader sample set via case studies.
Estrogen Receptor-β Gene Cytosine-Adenine (ESR2-CA) Repeat Polymorphism in Postmenopausal Colon Cancer
Authors: Honma Naoko , Arai Tomio , Matsuda Yoko , Fukunaga Yosuke , Muramatsu Masaaki , Ikeda Shinobu , Akishima-Fukasawa Yuri , Yamamoto Noriko , Kawachi Hiroshi , Ishikawa Yuichi , Takeuchi Kengo , Mikami Tetuo
Published: February 2023

The pathobiological role of estrogen is controversial in colorectal cancer. Cytosine-adenine (CA) repeat in the estrogen receptor (ER)-β gene (ESR2-CA) is a microsatellite, as well as representative of ESR2 polymorphism. Though its function is unknown, we previously showed that a shorter allele (germline) increased the risk of colon cancer in older women, whereas it decreased it in younger postmenopausal women. ESR2-CA and ER-β expressions were examined in cancerous (Ca) and non-cancerous (NonCa) tissue pairs from 114 postmenopausal women, and comparisons were made considering tissue types, age/locus, and the mismatch repair protein (MMR) status. ESR2-CA repeats <22/≥22 were designated as ‘S’/‘L’, respectively, resulting in genotypes SS/nSS (=SL&LL). In NonCa, the rate of the SS genotype and ER-β expression level were significantly higher in right-sided cases of women ≥70 (≥70Rt) than in those in the others. A decreased ER-β expression in Ca compared with NonCa was observed in proficient-MMR, but not in deficient-MMR. In NonCa, but not in Ca, ER-β expression was significantly higher in SS than in nSS. ≥70Rt cases were characterized by NonCa with a high rate of SS genotype or high ER-β expression. The germline ESR2-CA genotype and resulting ER-β expression were considered to affect the clinical characteristics (age/locus/MMR status) of colon cancer, supporting our previous findings.
Alzheimer’s Amyloid β Peptide Induces Angiogenesis in an Alzheimer’s Disease Model Mouse through Placental Growth Factor and Angiopoietin 2 Expressions
Authors: Sheikh Abdullah Md. , Yano Shozo , Tabassum Shatera , Mitaki Shingo , Michikawa Makoto , Nagai Atsushi
Published: February 2023

Increased angiogenesis, especially the pathological type, has been documented in Alzheimer’s disease (AD) brains, and it is considered to be activated due to a vascular dysfunction-mediated hypoxic condition. To understand the role of the amyloid β (Aβ) peptide in angiogenesis, we analyzed its effects on the brains of young APP transgenic AD model mice. Immunostaining results revealed that Aβ was mainly localized intracellularly, with very few immunopositive vessels, and there was no extracellular deposition at this age. Solanum tuberosum lectin staining demonstrated that compared to their wild-type littermates, the vessel number was only increased in the cortex of J20 mice. CD105 staining also showed an increased number of new vessels in the cortex, some of which were partially positive for collagen4. Real-time PCR results demonstrated that placental growth factor (PlGF) and angiopoietin 2 (AngII) mRNA were increased in both the cortex and hippocampus of J20 mice compared to their wild-type littermates. However, vascular endothelial growth factor (VEGF) mRNA did not change. Immunofluorescence staining confirmed the increased expression of PlGF and AngII in the cortex of the J20 mice. Neuronal cells were positive for PlGF and AngII. Treatment of a neural stem cell line (NMW7) with synthetic Aβ1–42 directly increased the expression of PlGF and AngII, at mRNA levels, and AngII at protein levels. Thus, these pilot data indicate that pathological angiogenesis exists in AD brains due to the direct effects of early Aβ accumulation, suggesting that the Aβ peptide regulates angiogenesis through PlGF and AngII expression.
Structural and Functional Diversity of Two ATP-Driven Plant Proton Pumps
Authors: Kabała Katarzyna , Janicka Małgorzata
Published: February 2023

Two ATP-dependent proton pumps function in plant cells. Plasma membrane H+-ATPase (PM H+-ATPase) transfers protons from the cytoplasm to the apoplast, while vacuolar H+-ATPase (V-ATPase), located in tonoplasts and other endomembranes, is responsible for proton pumping into the organelle lumen. Both enzymes belong to two different families of proteins and, therefore, differ significantly in their structure and mechanism of action. The plasma membrane H+-ATPase is a member of the P-ATPases that undergo conformational changes, associated with two distinct E1 and E2 states, and autophosphorylation during the catalytic cycle. The vacuolar H+-ATPase represents rotary enzymes functioning as a molecular motor. The plant V-ATPase consists of thirteen different subunits organized into two subcomplexes, the peripheral V1 and the membrane-embedded V0, in which the stator and rotor parts have been distinguished. In contrast, the plant plasma membrane proton pump is a functional single polypeptide chain. However, when the enzyme is active, it transforms into a large twelve-protein complex of six H+-ATPase molecules and six 14-3-3 proteins. Despite these differences, both proton pumps can be regulated by the same mechanisms (such as reversible phosphorylation) and, in some processes, such as cytosolic pH regulation, may act in a coordinated way.
Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer
Authors: Cui Xiaoli , Li Changcheng , Ding Jipeng , Yao Zhou , Zhao Tianyu , Guo Jiahui , Wang Yaru , Li Jing
Published: February 2023

Aldo-keto reductase family 1 member C3 (AKR1C3) plays an important role in prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It is necessary to establish a genetic signature associated with AKR1C3 that can be used to predict the prognosis of PCa patients and provide important information for clinical treatment decisions. AKR1C3-related genes were identified via label-free quantitative proteomics of the AKR1C3-overexpressing LNCaP cell line. A risk model was constructed through the analysis of clinical data, PPI, and Cox-selected risk genes. Cox regression analysis, Kaplan–Meier (K–M) curves, and receiver operating characteristic (ROC) curves were used to verify the accuracy of the model, and two external datasets were used to verify the reliability of the results. Subsequently, the tumor microenvironment and drug sensitivity were explored. Moreover, the roles of AKR1C3 in the progression of PCa were verified in LNCaP cells. MTT, colony formation, and EdU assays were conducted to explore cell proliferation and drug sensitivity to enzalutamide. Migration and invasion abilities were measured using wound-healing and transwell assays, and qPCR was used to assess the expression levels of AR target genes and EMT genes. CDC20, SRSF3, UQCRH, INCENP, TIMM10, TIMM13, POLR2L, and NDUFAB1 were identified as AKR1C3-associated risk genes. These risk genes, established using the prognostic model, can effectively predict the recurrence status, immune microenvironment, and drug sensitivity of PCa. Tumor-infiltrating lymphocytes and several immune checkpoints that promote cancer progression were higher in high-risk groups. Furthermore, there was a close correlation between the sensitivity of PCa patients to bicalutamide and docetaxel and the expression levels of the eight risk genes. Moreover, through in vitro experiments, Western blotting confirmed that AKR1C3 enhanced SRSF3, CDC20, and INCENP expression. We found that PCa cells with a high expression of AKR1C3 have high proliferation ability and high migration ability and were insensitive to enzalutamide. AKR1C3-associated genes had a significant role in the process of PCa, immune responses, and drug sensitivity and offer the potential for a novel model for prognostic prediction in PCa.
Application of Machine Learning Models in Systemic Lupus Erythematosus
Authors: Ceccarelli Fulvia , Natalucci Francesco , Picciariello Licia , Ciancarella Claudia , Dolcini Giulio , Gattamelata Angelica , Alessandri Cristiano , Conti Fabrizio
Published: February 2023

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and is extremely heterogeneous in terms of immunological features and clinical manifestations. This complexity could result in a delay in the diagnosis and treatment introduction, with impacts on long-term outcomes. In this view, the application of innovative tools, such as machine learning models (MLMs), could be useful. Thus, the purpose of the present review is to provide the reader with information about the possible application of artificial intelligence in SLE patients from a medical perspective. To summarize, several studies have applied MLMs in large cohorts in different disease-related fields. In particular, the majority of studies focused on diagnosis and pathogenesis, disease-related manifestations, in particular Lupus Nephritis, outcomes and treatment. Nonetheless, some studies focused on peculiar features, such as pregnancy and quality of life. The review of published data demonstrated the proposal of several models with good performance, suggesting the possible application of MLMs in the SLE scenario.
COVID-19 Biogenesis and Intracellular Transport
Authors: Mironov Alexander A. , Savin Maksim A. , Beznoussenko Galina V.
Published: February 2023

SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of SARS-CoV-2 and most of its proteins of have been deciphered. SARS-CoV-2 enters cells through the endocytic pathway and perforates the endosomes’ membranes, and its (+) RNA appears in the cytosol. Then, SARS-CoV-2 starts to use the protein machines of host cells and their membranes for its biogenesis. SARS-CoV-2 generates a replication organelle in the reticulo-vesicular network of the zippered endoplasmic reticulum and double membrane vesicles. Then, viral proteins start to oligomerize and are subjected to budding within the ER exit sites, and its virions are passed through the Golgi complex, where the proteins are subjected to glycosylation and appear in post-Golgi carriers. After their fusion with the plasma membrane, glycosylated virions are secreted into the lumen of airways or (seemingly rarely) into the space between epithelial cells. This review focuses on the biology of SARS-CoV-2’s interactions with cells and its transport within cells. Our analysis revealed a significant number of unclear points related to intracellular transport in SARS-CoV-2-infected cells.
Chitosan as a Promising Support of a CDH Activity Preservation System for Biomedical and Industrial Applications
Authors: Sulej Justyna , Osińska-Jaroszuk Monika , Jaszek Magdalena , Olszewska Anna , Belcarz Anna , Piątek-Gołda Wiktoria
Published: February 2023

Cellobiose dehydrogenase (CDH) is an extracellular hemoflavoprotein catalyzing the oxidation reaction of β-1,4-glycosidic-bonded sugars (lactose or cellobiose), which results in the formation of aldobionic acids and hydrogen peroxide as a byproduct. The biotechnological application of CDH requires the immobilization of the enzyme on a suitable support. As a carrier of natural origin used for CDH immobilization, chitosan seems to increase the catalytic potential of the enzyme, especially for applications as packaging in the food industry and as a dressing material in medical applications. The present study aimed to immobilize the enzyme on chitosan beads and determine the physicochemical and biological properties of immobilized CDHs obtained from different fungal sources. The chitosan beads with immobilized CDHs were characterized in terms of their FTIR spectra or SEM microstructure. The most effective method of immobilization in the proposed modification was the covalent bonding of enzyme molecules using glutaraldehyde, resulting in efficiencies ranging from 28 to 99%. Very promising results, compared to free CDH, were obtained in the case of antioxidant, antimicrobial, and cytotoxic properties. Summarizing the obtained data, chitosan seems to be a valuable material for the development of innovative and effective immobilization systems for biomedical applications or food packaging, preserving the unique properties of CDH.
Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers
Authors: Drozdzik Marek , Lapczuk-Romanska Joanna , Wenzel Christoph , Skalski Lukasz , Szeląg-Pieniek Sylwia , Post Mariola , Parus Arkadiusz , Syczewska Marta , Kurzawski Mateusz , Oswald Stefan
Published: February 2023

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of drug pharmacokinetics. Hepatitis C liver samples in different functional states, i.e., the Child–Pugh class A (n = 30), B (n = 21) and C (n = 7) were analyzed for protein abundances (LC-MS/MS) and mRNA levels (qRT-PCR) of 9 CYPs and 4 UGTs enzymes. The protein levels of CYP1A1, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 were not affected by the disease. In the Child–Pugh class A livers, a significant up-regulation of UGT1A1 (to 163% of the controls) was observed. The Child–Pugh class B was associated with down-regulation of the protein abundance of CYP2C19 (to 38% of the controls), CYP2E1 (to 54%), CYP3A4 (to 33%), UGT1A3 (to 69%), and UGT2B7 (to 56%). In the Child–Pugh class C livers, CYP1A2 was found to be reduced (to 52%). A significant trend in down-regulation of the protein abundance was documented for CYP1A2, CYP2C9, CYP3A4, CYP2E1, UGT2B7, and UGT2B15. The results of the study demonstrate that DMEs protein abundances in the liver are affected by hepatitis C virus infection and depend on the severity of the disease.
Vitamin D as a Shield against Aging
Authors: Fantini Cristina , Corinaldesi Clarissa , Lenzi Andrea , Migliaccio Silvia , Crescioli Clara
Published: February 2023

Aging can be seen as a physiological progression of biomolecular damage and the accumulation of defective cellular components, which trigger and amplify the process, toward whole-body function weakening. Senescence initiates at the cellular level and consists in an inability to maintain homeostasis, characterized by the overexpression/aberrant expression of inflammatory/immune/stress responses. Aging is associated with significant modifications in immune system cells, toward a decline in immunosurveillance, which, in turn, leads to chronic elevation of inflammation/oxidative stress, increasing the risk of (co)morbidities. Albeit aging is a natural and unavoidable process, it can be regulated by some factors, like lifestyle and diet. Nutrition, indeed, tackles the mechanisms underlying molecular/cellular aging. Many micronutrients, i.e., vitamins and elements, can impact cell function. This review focuses on the role exerted by vitamin D in geroprotection, based on its ability to shape cellular/intracellular processes and drive the immune response toward immune protection against infections and age-related diseases. To this aim, the main biomolecular paths underlying immunosenescence and inflammaging are identified as biotargets of vitamin D. Topics such as heart and skeletal muscle cell function/dysfunction, depending on vitamin D status, are addressed, with comments on hypovitaminosis D correction by food and supplementation. Albeit research has progressed, still limitations exist in translating knowledge into clinical practice, making it necessary to focus attention on the role of vitamin D in aging, especially considering the growing number of older individuals.
Probing the E1o-E2o and E1a-E2o Interactions in Binary Subcomplexes of the Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Complexes by Chemical Cross-Linking Mass Spectrometry and Molecular Dynamics Simulation
Authors: Ozohanics Oliver , Zhang Xu , Nemeria Natalia S. , Ambrus Attila , Jordan Frank
Published: February 2023

The human 2-oxoglutarate dehydrogenase complex (hOGDHc) is a key enzyme in the tricarboxylic acid cycle and is one of the main regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. Evidence was obtained for formation of a hybrid complex between the hOGDHc and its homologue the 2-oxoadipate dehydrogenase complex (hOADHc) in the L-lysine metabolic pathway, suggesting a crosstalk between the two distinct pathways. Findings raised fundamental questions about the assembly of hE1a (2-oxoadipate-dependent E1 component) and hE1o (2-oxoglutarate-dependent E1) to the common hE2o core component. Here we report chemical cross-linking mass spectrometry (CL-MS) and molecular dynamics (MD) simulation analyses to understand assembly in binary subcomplexes. The CL-MS studies revealed the most prominent loci for hE1o-hE2o and hE1a-hE2o interactions and suggested different binding modes. The MD simulation studies led to the following conclusions: (i) The N-terminal regions in E1s are shielded by, but do not interact directly with hE2o. (ii) The hE2o linker region exhibits the highest number of H-bonds with the N-terminus and α/β1 helix of hE1o, yet with the interdomain linker and α/β1 helix of hE1a. (iii) The C-termini are involved in dynamic interactions in complexes, suggesting the presence of at least two conformations in solution.
Molecular Mechanisms of Adaptation to Hypoxia
Authors: Rybnikova Elena , Lukyanova Ludmila
Published: February 2023

Oxygen is one of the most important elements, ensuring the vital activity of the body [...]
Hybrid Nanoparticles at Fluid–Fluid Interfaces: Insight from Theory and Simulation
Authors: Borówko Małgorzata , Staszewski Tomasz
Published: February 2023

Hybrid nanoparticles that combine special properties of their different parts have numerous applications in electronics, optics, catalysis, medicine, and many others. Of the currently produced particles, Janus particles and ligand-tethered (hairy) particles are of particular interest both from a practical and purely cognitive point of view. Understanding their behavior at fluid interfaces is important to many fields because particle-laden interfaces are ubiquitous in nature and industry. We provide a review of the literature, focusing on theoretical studies of hybrid particles at fluid–fluid interfaces. Our goal is to give a link between simple phenomenological models and advanced molecular simulations. We analyze the adsorption of individual Janus particles and hairy particles at the interfaces. Then, their interfacial assembly is also discussed. The simple equations for the attachment energy of various Janus particles are presented. We discuss how such parameters as the particle size, the particle shape, the relative sizes of different patches, and the amphiphilicity affect particle adsorption. This is essential for taking advantage of the particle capacity to stabilize interfaces. Representative examples of molecular simulations were presented. We show that the simple models surprisingly well reproduce experimental and simulation data. In the case of hairy particles, we concentrate on the effects of reconfiguration of the polymer brushes at the interface. This review is expected to provide a general perspective on the subject and may be helpful to many researchers and technologists working with particle-laden layers.
Molecular and Physiological Functions of PACAP in Sweat Secretion
Authors: Yamashita Michio , Shibato Junko , Rakwal Randeep , Nonaka Naoko , Hirabayashi Takahiro , Harvey Brian J. , Shioda Seiji , Takenoya Fumiko
Published: February 2023

Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca2+] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.
Small Extracellular Vesicles Derived from Induced Pluripotent Stem Cells in the Treatment of Myocardial Injury
Authors: Meng Wan-Ting , Guo Hai-Dong
Published: February 2023

Induced pluripotent stem cell (iPSC) therapy brings great hope to the treatment of myocardial injuries, while extracellular vesicles may be one of the main mechanisms of its action. iPSC-derived small extracellular vesicles (iPSCs-sEVs) can carry genetic and proteinaceous substances and mediate the interaction between iPSCs and target cells. In recent years, more and more studies have focused on the therapeutic effect of iPSCs-sEVs in myocardial injury. IPSCs-sEVs may be a new cell-free-based treatment for myocardial injury, including myocardial infarction, myocardial ischemia–reperfusion injury, coronary heart disease, and heart failure. In the current research on myocardial injury, the extraction of sEVs from mesenchymal stem cells induced by iPSCs was widely used. Isolation methods of iPSCs-sEVs for the treatment of myocardial injury include ultracentrifugation, isodensity gradient centrifugation, and size exclusion chromatography. Tail vein injection and intraductal administration are the most widely used routes of iPSCs-sEV administration. The characteristics of sEVs derived from iPSCs which were induced from different species and organs, including fibroblasts and bone marrow, were further compared. In addition, the beneficial genes of iPSC can be regulated through CRISPR/Cas9 to change the composition of sEVs and improve the abundance and expression diversity of them. This review focused on the strategies and mechanisms of iPSCs-sEVs in the treatment of myocardial injury, which provides a reference for future research and the application of iPSCs-sEVs.