bluuebunny/crossref_metadata_2025 huggingface dataset:
iSupport for Young Carers: An Adaptation of an e-Health Intervention for Young Dementia Carers
Authors: Masterson-Algar Patricia , Egan Kieren , Flynn Greg , Hughes Gwenllian , Spector Aimee , Stott Joshua , Windle Gill
Published: December 2022

Young dementia carers need to be recognised and supported in their role. They need help to understand the illness, what changes are expected and how it can affect their family member. Many support services, partly due to the COVID pandemic, have moved online and have been shown to be acceptable as they are low cost and reduce access barriers. iSupport is an evidence-informed e-health training programme developed by the World Health Organization (WHO) to support adult dementia carers. This paper reports on the co-design of an adapted version of iSupport for young carers. A theoretically driven co-design approach, drawing on the lived experiences of young dementia carers and experts who work with this target group was followed. As a result of this study iSupport for Young Carers was created. It is the first e-health intervention of its kind and aims to support the mental health, knowledge and skills of young dementia carers. In turn, it could improve the quality of the support that service providers can offer, and this can result in increased levels of identification of these young people. The work presented also provides opportunities for other countries and demographic groups to translate and adapt iSupport for Young Carers to their specific cultural context.
Using Digital Technology to Design a Simple Interactive System for Nostalgic Gaming to Promote the Health of Slightly Disabled Elderly People
Authors: Wang Chao-Ming , Huang Chen-Siang
Published: December 2022

An interactive digital gaming system with simple tangible interfaces is proposed for use by slightly disabled elderly people to promote their health and enjoyment of playful aging. The system simulates a rice threshing machine with nostalgic and entertaining functions expected to bring better life quality to older adults. Initially, pieces of literature were reviewed to derive relevant design principles. A prototype system was constructed accordingly and refined according to the invited older users’ comments. The refined system was performed subsequently by slightly disabled elderly people, followed by a questionnaire survey conducted to collect their opinions. The opinion data were analyzed statistically by SPSS and AMOS to be reliable and valid. In addition, interviews were conducted with the users and experts were invited to collect comments on the system’s usability, which were then evaluated to reveal several findings about the system’s effectiveness: (1) digital products related to life experiences are more acceptable to slightly disabled elderly people, promoting their willingness to play games to achieve active aging; (2) simple system interfaces requiring no complicated limb functions are appropriate for the slightly disabled elderly people; and (3) digital gaming has the effects of training slightly disabled elderly peoples’ cognitive and motor abilities as well as strengthening their body and mind.
Evaluating Time Influence over Performance of Machine-Learning-Based Diagnosis: A Case Study of COVID-19 Pandemic in Brazil
Authors: Marques Julliana Gonçalves , Guedes Luiz Affonso , da Costa Abreu Márjory Cristiany
Published: December 2022

Efficiently recognising severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms enables a quick and accurate diagnosis to be made, and helps in mitigating the spread of the coronavirus disease 2019. However, the emergence of new variants has caused constant changes in the symptoms associate with COVID-19. These constant changes directly impact the performance of machine-learning-based diagnose. In this context, considering the impact of these changes in symptoms over time is necessary for accurate diagnoses. Thus, in this study, we propose a machine-learning-based approach for diagnosing COVID-19 that considers the importance of time in model predictions. Our approach analyses the performance of XGBoost using two different time-based strategies for model training: month-to-month and accumulated strategies. The model was evaluated using known metrics: accuracy, precision, and recall. Furthermore, to explain the impact of feature changes on model prediction, feature importance was measured using the SHAP technique, an XAI technique. We obtained very interesting results: considering time when creating a COVID-19 diagnostic prediction model is advantageous.
What Is the Relationship between Trunk Control Function and Arm Coordination in Adults with Severe-to-Moderate Quadriplegic Cerebral Palsy?
Authors: Cornejo María Isabel , Roldan Alba , Reina Raul
Published: December 2022

Adults with tetraparesis cerebral palsy (i.e., wheelchair users) tend to experience more accelerated ageing, resulting in physical deterioration that increases the impact of the disability, leading to a loss of mobility that interferes with people’s daily activities and participation in the community. The aim of this work is to study the relationship between trunk control and the function of the less-affected arm in this population. For this purpose, 41 para-athletes were invited to participate in this study, performing five tests to assess upper limb coordination, two tests to assess manual dexterity [i.e., Box and Block Test (BBT) and Box and Ball Test (BBLT)] and three tests to assess intra-limb coordination in different planes. Trunk control was assessed in both static and dynamic sitting conditions. The results show moderate correlations between static postural control and manual dexterity tests in the BBT (r = −0.553; p = 0.002) and BBLT (r = −0.537; p = 0.004). Large correlations were also found between static postural control and intra-limb tasks in horizontal (r = 0.769; p = 0.001) and vertical movements (r = 0.739; p = 0.009). Better static trunk control is related to a better upper limb function in the sagittal plane. Considerations and implications are explained in the manuscript.
Development of Key Principles and Best Practices for Co-Design in Health with First Nations Australians
Authors: Anderson Kate , Gall Alana , Butler Tamara , Ngampromwongse Khwanruethai , Hector Debra , Turnbull Scott , Lucas Kerri , Nehill Caroline , Boltong Anna , Keefe Dorothy , Garvey Gail
Published: December 2022

Background: While co-design offers potential for equitably engaging First Nations Australians in findings solutions to redressing prevailing disparities, appropriate applications of co-design must align with First Nations Australians’ culture, values, and worldviews. To achieve this, robust, culturally grounded, and First Nations-determined principles and practices to guide co-design approaches are required. Aims: This project aimed to develop a set of key principles and best practices for co-design in health with First Nations Australians. Methods: A First Nations Australian co-led team conducted a series of Online Yarning Circles (OYC) and individual Yarns with key stakeholders to guide development of key principles and best practice approaches for co-design with First Nations Australians. The Yarns were informed by the findings of a recently conducted comprehensive review, and a Collaborative Yarning Methodology was used to iteratively develop the principles and practices. Results: A total of 25 stakeholders participated in the Yarns, with 72% identifying as First Nations Australian. Analysis led to a set of six key principles and twenty-seven associated best practices for co-design in health with First Nations Australians. The principles were: First Nations leadership; Culturally grounded approach; Respect; Benefit to community; Inclusive partnerships; and Transparency and evaluation. Conclusions: Together, these principles and practices provide a valuable starting point for the future development of guidelines, toolkits, reporting standards, and evaluation criteria to guide applications of co-design with First Nations Australians.
Solvent-Free Synthesis of Magnetic Sewage Sludge-Derived Biochar for Heavy Metal Removal from Wastewater
Authors: Tian Jiayi , Guo Kexin , Sun Yucan , Lin Ruoxi , Chen Tan , Zhang Bing , Liu Yifei , Yang Ting
Published: December 2022

The commonly used two-step and one-pot synthesis methods for producing biochar require the use of iron salt solutions, resulting in the undesirable consequences of energy consumption for dewatering and potential pollution risks. To address this drawback, a magnetic sewage sludge-derived biochar (MSBC-2) was synthesized by a solvent-free method in this study. The pseudo-second-order kinetic model and Langmuir model provided the best fit to the experimental data, implying a monolayered chemisorption process of Pb2+, Cd2+and Cu2+ onto MSBC-2. As the reaction temperature increased from 25 °C to 45 °C, the maximum adsorption capacities increased from 113.64 mg·g−1 to 151.52 mg·g−1 for Pb2+, from 101.01 mg·g−1 to 109.89 mg·g−1 for Cd2+ and from 57.80 mg·g−1 to 74.07 mg·g−1 for Cu2+, respectively. Thermodynamic parameters (ΔG0 < 0, ΔS0 > 0, ΔH0 > 0) revealed that the adsorption processes of all three metals by MSBC-2 were favourable, spontaneous and endothermic. Surface complexation, cation-π interaction, ion exchange and electrostatic attraction mechanisms were involved in the adsorption of Pb2+, Cd2+ and Cu2+ onto MSBC-2. Overall, this study will provide a new perspective for the synthesis of magnetic biochar and MSBC-2 shows great potential as an adsorbent for heavy metal removal.
“Should I Further Engage in Staff Care?”: Employees’ Disclosure, Leaders’ Skills and Goal Conflict as Antecedents of Health-Oriented Leadership
Authors: Pischel Sarah , Felfe Jörg , Klebe Laura
Published: December 2022

Leaders play a crucial role in employees’ health and job satisfaction. When employees show early warning signs that their physical or mental health is at risk, leaders’ responsibility gains even more importance. Recent health-specific leadership approaches (health-oriented leadership; HoL) emphasize the importance of leaders ability to perceive employees’ warning signals (staff care awareness) to take appropriate action (staff care behavior). However, little is known about the factors facilitating or hindering the transfer from leaders’ awareness to concrete behaviors. In an experimental study (N = 91), we examined and manipulated antecedents of staff care behavior: (a) employees’ disclosure, (b) leaders’ HoL skills, and (c) leaders’ goal conflict in a 2 × 2 × 2 mixed factorial design. Employees’ disclosure and leaders’ skills were positively related to staff care behavior. Leaders’ goal conflict was not directly related to staff care behavior but had an indirect effect and diminished the positive relationship between disclosure and staff care behavior. The findings deepen the theoretical understanding of the HoL concept. By studying the influence of employees’ disclosure on staff care behavior, our study complements a follower-centered perspective. We provide practical recommendations for workplace health promotion and how leaders’ staff care behavior can be fostered.
Perceiving “Complex Autonomous Systems” in Symmetry Dynamics: Elementary Coordination Embedding in Circadian Cycles
Authors: Park Chulwook , Hwang Jean , Ahn Jae Woong , Park Yu Jin
Published: December 2022

This study explored the biological autonomy and control of function in circumstances that assessed the presumed relationship of an organism with an environmental cycle. An understanding of this behavior appeals to the organism–environment system rather than just the organism. Therefore, we sought to uncover the laws underlying end-directed capabilities by measuring biological characteristics (motor synchrony) in an environmental cycle (circadian temperature). We found that the typical elementary coordination (bimanual) stability measure varied significantly as a function of the day–night temperature cycle. While circadian effects under artificially manipulated temperatures were not straightforward during the day–night temperature cycle, the circadian effect divided by the ordinary circadian rhythm remained constant during the day–night cycle. Our observation of this direct, robust relationship between the biological characteristics (body temperature and motor synchrony) and environmental processes (circadian temperature cycle) could mirror the adaptation of our biological system to the environment.
Identification of Perception Differences in Personality Factors and Autonomy by Sporting Age Category in Competitive Bodybuilders
Authors: Mihăiță Elena , Badau Dana , Stoica Marius , Mitrache Georgeta , Stănescu Monica Iulia , Hidi Ioszef Laszlo , Badau Adela , Damian Cosmin , Damian Mirela
Published: December 2022

Knowing the personality and autonomy factors of bodybuilders is a necessity in order to improve sports training, which would lead to the development of mental skills specific to competitive bodybuilding. The purpose of the study was to identify perception differences in personality and autonomy factors for three age categories of competitive bodybuilders in order to optimize the sports training process. The secondary purpose of the study was to identify perception differences in the characteristics of personality and autonomy in relation to the increase in the sporting age category of the competitive bodybuilders. The research sample included 30 competitive bodybuilders aged between 18 and 53 years, of which 21 were male and 9 were female, who were divided into three groups according to the sporting age category: G1—junior (18–23 years old), 10 athletes (33.3%); G2—senior (24–35 years old for female and 24–40 years old for male), 12 athletes (40%); G3—masters (over 35 years old for female and 40 years old for male), 8 athletes (26.7%). In the precompetitive stage, three standardized questionnaires were applied to the study participants, namely, two personality questionnaires (CP5F and ZKPQ) and a personal autonomy questionnaire (PAQ), which provided us with useful information for understanding the psychological profile of bodybuilding athletes. The results of the study were statistically significant, with Cronbach’s Alpha coefficient indicating high internal consistency of the three questionnaires for all three sporting age groups, with higher values than the selected reference threshold of 0.700. According to the results of our study, the following personality and autonomy factors recorded higher and higher scores in direct relation with the increase in sporting age: extraversion, agreeableness, conscientiousness, emotional stability, autonomy, impulsive sensation seeking, value autonomy, behavioral autonomy, and cognitive autonomy. The personality and autonomy factors of which the scores did not increase directly proportionally to the sporting age category were sociability, activity, aggression–hostility, neuroticism–anxiety, and emotional autonomy. Competitive bodybuilders perceive the factors of personality and autonomy differently in relation to particularities of age and sports experience, and knowledge of these changes can contribute to the improvement of the sports training process
Student Stress and Online Shopping Addiction Tendency among College Students in Guangdong Province, China: The Mediating Effect of the Social Support
Authors: Li Huimin , Ma Xinyue , Fang Jie , Liang Getian , Lin Rongsheng , Liao Weiyan , Yang Xuesong
Published: December 2022

Online shopping addiction tendency (OSAT) among college students has become too serious to ignore. As a result, it is necessary to carefully examine the relevant factors that shape students’ online shopping addiction tendencies. This study aimed to determine whether social support mediates the relationship between college students’ stress (academic hassle, personal hassle, and negative life events) and OSAT. In this cross-sectional study using a convenient sampling method, Chinese students from eight universities in Guangdong Province, China, completed self-administered questionnaires in either printed or online format. The survey data includes daily online shopping usage, college student stress, a social support rating scale, an online shopping addiction tendency scale for college students, and demographic information. A total number of verified and valid questionnaires were returned. In a sample of 1123 (mean age = 20.28 years; 58% females). Each individual had online shopping experience. The survey revealed no gender differences in OSAT. There was a statistically significant relationship between student stress (academic hassle, personal hassle, and negative life events) and students’ OSAT scores and social support. The latter was negatively correlated with OSAT and mediated the relationship between college students’ stress and their OSAT. In conclusion, university students’ stress (academic hassle, personal hassle, and negative life events) acts as a trigger for OSAT. A combination of a high stress level and a lack of social support increases the likelihood of developing OSAT. Social support has an effect on the OSAT of college students by relieving their stress; social support is a protective factor against the OSAT for college students.
Effects of Walking as Physical Exercise on Functional Limitation through Pain in Patients with Fibromyalgia—How Does Catastrophic Thinking Contribute?
Authors: Catalá Patricia , Peñacoba Cecilia , López-Roig Sofía , Pastor-Mira María Angeles
Published: December 2022

Background: Aerobic exercise has a beneficial impact on physical and mental health. However, patients with fibromyalgia do not always report perceiving these improvements. Objective: The aim of this study was to examine whether catastrophic thinking moderated the effects of perceived pain severity once an active and regular lifestyle had been established on functional limitation in chronic pain patients, in particular in fibromyalgia patients. Methods: The sample consisted of a total of 491 women with fibromyalgia diagnosed according to the criteria of the American College of Rheumatology. Participants completed an ad-hoc item about lifestyle related to walking pattern, the Brief Pain Inventory, the Pain Catastrophization Scale, and the Fibromyalgia Impact Questionnaire-Revised. To examine the relationship between the variables, a moderate mediation analysis was performed through the macro PROCESS (model 14). Results: The relationship between the performance of the recommended walking pattern and functional limitation was mediated by the severity of pain (B = −5.19, SE = 1.59, t = −3.25, 95% CI = [−4.06, −0.28], p < 0.001). Furthermore, it was found that the mediating effect of pain severity was moderated by catastrophic thinking (Index = −0.014, SE = 0.007, 95% CI [0.002, 0.030]). Conclusions: The positive effect of walking on functionality through the reduction of pain levels is favored when patients present low catastrophizing, which affects the relevance of including interventions focused on the reduction of catastrophizing in the prescription of physical exercise in patients with fibromyalgia as the treatment of choice.
Physical Activity and Mental Health in Undergraduate Students
Authors: Rodríguez-Romo Gabriel , Acebes-Sánchez Jorge , García-Merino Sonia , Garrido-Muñoz María , Blanco-García Cecilia , Diez-Vega Ignacio
Published: December 2022

Most research support positive relationships between physical activity and mental health. However, possible moderating variables of these relationships have also been identified, such as age, gender, level of physical activity, and the scope of physical activity. This study aimed to analyze the relationships between physical activity and mental health levels in undergraduate students, assessing whether these associations can change depending on the level of physical activity (low, medium, or high) and the setting (occupational, commuting, or leisure time physical activity) in which it was performed. A descriptive and cross-sectional study was conducted. The sample comprised 847 undergraduate students. Physical activity and mental health were measured by the Global Physical Activity Questionnaire (GPAQv2) and the General Health Questionnaire (GHQ-12). We found relationships between students’ physical activity level and their mental health status. The higher the total physical activity, the better their mental health scores. High levels of commuting and leisure time physical activity is also associated with better mental health, while only moderate levels of occupational physical activity are associated with better mental health status. Regarding the possible associations between physical activity and vulnerability to mental health problems, with the fully adjusted regression model, leisure time and occupational physical activity remain protective of a poor state of mental health. Leisure time physical activity, performed at a high level, and moderate occupational physical activity seems to be the best combination of physical activity to reduce students’ vulnerability to potential mental health problems.
The Other Side of the “League of Stars”: Analysis of the Financial Situation of Spanish Football
Authors: Urdaneta-Camacho Rudemarlyn , Guevara-Pérez Juan Carlos , Martín Vallespín Emilio , Le Clech Néstor
Published: December 2022

This paper analyses the effectiveness of the financial control system implemented by the Spanish professional football League in 2015 as a tool to improve the governance of clubs in the first and second divisions as well as its probable impact on competition. Classic financial ratios are used to analyse the financial situation of the clubs both before and after the implementation of the Regulation, as well as during the first season affected by the COVID-19 pandemic. Next, the Herfindahl index is calculated to measure the concentration in the distribution of the main funding sources and is incorporated as a dependent variable in a regression model. Although a cause–effect relationship is not certain, the results suggest that the economic control measures imposed by LFP have contributed to improving the financial situation of Spanish football in the short term, but may promote imbalances between clubs that undermine the sustainability of the current management model and, therefore, of the competition system. Unlike in other sectors, the football business requires more competition to maximise profits. In this context, it would be advisable to reach agreements between clubs to weaken the bargaining position of footballers. The paper shows the effect of the intervention of a regulatory body, in this case, LFP, in the functioning of a competitive market.
Sensitivity of Zea mays and Soil Microorganisms to the Toxic Effect of Chromium (VI)
Authors: Wyszkowska Jadwiga , Borowik Agata , Zaborowska Magdalena , Kucharski Jan
Published: December 2022

Chromium is used in many settings, and hence, it can easily enter the natural environment. It exists in several oxidation states. In soil, depending on its oxidation-reduction potential, it can occur in bivalent, trivalent or hexavalent forms. Hexavalent chromium compounds are cancerogenic to humans. The aim of this study was to determine the effect of Cr(VI) on the structure of bacteria and fungi in soil, to find out how this effect is modified by humic acids and to determine the response of Zea mays to this form of chromium. A pot experiment was conducted to answer the above questions. Zea mays was sown in natural soil and soil polluted with Cr(VI) in an amount of 60 mg kg−1 d.m. Both soils were treated with humic acids in the form of HumiAgra preparation. The ecophysiological and genetic diversity of bacteria and fungi was assayed in soil under maize (not sown with Zea mays). In addition, the following were determined: yield of maize, greenness index, index of tolerance to chromium, translocation index and accumulation of chromium in the plant. It has been determined that Cr(VI) significantly distorts the growth and development of Zea mays, while humic acids completely neutralize its toxic effect on the plant. This element had an adverse effect on the development of bacteria of the genera Cellulosimicrobium, Kaistobacter, Rhodanobacter, Rhodoplanes and Nocardioides and fungi of the genera Chaetomium and Humicola. Soil contamination with Cr(VI) significantly diminished the genetic diversity and richness of bacteria and the ecophysiological diversity of fungi. The negative impact of Cr(VI) on the diversity of bacteria and fungi was mollified by Zea mays and the application of humic acids.
Distinct Effects of Beta-Amyloid, Its Isomerized and Phosphorylated Forms on the Redox Status and Mitochondrial Functioning of the Blood–Brain Barrier Endothelium
Authors: Petrovskaya Aleksandra V. , Tverskoi Artem M. , Barykin Evgeny P. , Varshavskaya Kseniya B. , Dalina Alexandra A. , Mitkevich Vladimir A. , Makarov Alexander A. , Petrushanko Irina Yu.
Published: December 2022

The Alzheimer’s disease (AD)-associated breakdown of the blood–brain barrier (BBB) promotes the accumulation of beta-amyloid peptide (Aβ) in the brain as the BBB cells provide Aβ transport from the brain parenchyma to the blood, and vice versa. The breakdown of the BBB during AD may be caused by the emergence of blood-borne Aβ pathogenic forms, such as structurally and chemically modified Aβ species; their effect on the BBB cells has not yet been studied. Here, we report that the effects of Aβ42, Aβ42, containing isomerized Asp7 residue (iso-Aβ42) or phosphorylated Ser8 residue (p-Aβ42) on the mitochondrial potential and respiration are closely related to the redox status changes in the mouse brain endothelial cells bEnd.3. Aβ42 and iso-Aβ42 cause a significant increase in nitric oxide, reactive oxygen species, glutathione, cytosolic calcium and the mitochondrial potential after 4 h of incubation. P-Aβ42 either does not affect or its effect develops after 24 h of incubation. Aβ42 and iso-Aβ42 activate mitochondrial respiration compared to p-Aβ42. The isomerized form promotes a greater cytotoxicity and mitochondrial dysfunction, causing maximum oxidative stress. Thus, Aβ42, p-Aβ42 and iso-Aβ42 isoforms differently affect the BBBs’ cell redox parameters, significantly modulating the functioning of the mitochondria. The changes in the level of modified Aβ forms can contribute to the BBBs’ breakdown during AD.
Tuning Peptide-Based Hydrogels: Co-Assembly with Composites Driving the Highway to Technological Applications
Authors: Gomes Valéria , Veloso Sérgio R. S. , Correa-Duarte Miguel A. , Ferreira Paula M. T. , Castanheira Elisabete M. S.
Published: December 2022

Self-assembled peptide-based gels provide several advantages for technological applications. Recently, the co-assembly of gelators has been a strategy to modulate and tune gel properties and even implement stimuli-responsiveness. However, it still comprises limitations regarding the required library of compounds and outcoming properties. Hence, efforts have been made to combine peptide-based gels and (in)organic composites (e.g., magnetic nanoparticles, metal nanoparticles, liposomes, graphene, silica, clay, titanium dioxide, cadmium sulfide) to endow stimuli-responsive materials and achieve suitable properties in several fields ranging from optoelectronics to biomedical. Herein, we discuss the recent developments with composite peptide-based gels including the fabrication, tunability of gels’ properties, and challenges on (bio)technological applications.
Near-Infrared Dyes: Towards Broad-Spectrum Antivirals
Authors: Mariewskaya Kseniya A. , Krasilnikov Maxim S. , Korshun Vladimir A. , Ustinov Alexey V. , Alferova Vera A.
Published: December 2022

Broad antiviral activity in vitro is known for many organic photosensitizers generating reactive oxygen species under irradiation with visible light. Low tissue penetration of visible light prevents further development of antiviral therapeutics based on these compounds. One possible solution to this problem is the development of photosensitizers with near-infrared absorption (NIR dyes). These compounds found diverse applications in the photodynamic therapy of tumors and bacterial infections, but they are scarcely mentioned as antivirals. In this account, we aimed to evaluate the therapeutic prospects of various NIR-absorbing and singlet oxygen-generating chromophores for the development of broad-spectrum photosensitizing antivirals.
Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes
Authors: den Braanker Dirk J. W. , Maas Rutger J. H. , van Mierlo Guido , Parr Naomi M. J. , Bakker-van Bebber Marinka , Deegens Jeroen K. J. , Jansen Pascal W. T. C. , Gloerich Jolein , Willemsen Brigith , Dijkman Henry B. , van Gool Alain J. , Wetzels Jack F. M. , Rinschen Markus M. , Vermeulen Michiel , Nijenhuis Tom , van der Vlag Johan
Published: December 2022

Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment.
Optogenetic Low-Frequency Stimulation of Principal Neurons, but Not Parvalbumin-Positive Interneurons, Prevents Generation of Ictal Discharges in Rodent Entorhinal Cortex in an In Vitro 4-Aminopyridine Model
Authors: Proskurina Elena Y. , Chizhov Anton V. , Zaitsev Aleksey V.
Published: December 2022

Low-frequency electrical stimulation is used to treat some drug-resistant forms of epilepsy. Despite the effectiveness of the method in suppressing seizures, there is a considerable risk of side effects. An optogenetic approach allows the targeting of specific populations of neurons, which can increase the effectiveness and safety of low-frequency stimulation. In our study, we tested the efficacy of the suppression of ictal activity in entorhinal cortex slices in a 4-aminopyridine model with three variants of low-frequency light stimulation (LFLS): (1) activation of excitatory and inhibitory neurons (on Thy1-ChR2-YFP mice), (2) activation of inhibitory interneurons only (on PV-Cre mice after virus injection with channelrhodopsin2 gene), and (3) hyperpolarization of excitatory neurons (on Wistar rats after virus injection with archaerhodopsin gene). Only in the first variant did simultaneous LFLS of excitatory and inhibitory neurons replace ictal activity with interictal activity. We suggest that LFLS caused changes in the concentration gradients of K+ and Na+ cations across the neuron membrane, which activated Na-K pumping. According to the mathematical modeling, the increase in Na-K pump activity in neurons induced by LFLS led to an antiepileptic effect. Thus, a less specific and generalized optogenetic effect on entorhinal cortex neurons was more effective in suppressing ictal activity in the 4-aminopyridine model.
The Origin of Translation: Bridging the Nucleotides and Peptides
Authors: Guo Xuyuan , Su Meng
Published: December 2022

Extant biology uses RNA to record genetic information and proteins to execute biochemical functions. Nucleotides are translated into amino acids via transfer RNA in the central dogma. tRNA is essential in translation as it connects the codon and the cognate amino acid. To reveal how the translation emerged in the prebiotic context, we start with the structure and dissection of tRNA, followed by the theory and hypothesis of tRNA and amino acid recognition. Last, we review how amino acids assemble on the tRNA and further form peptides. Understanding the origin of life will also promote our knowledge of artificial living systems.
The Multiple Functions of Insulin Put into Perspective: From Growth to Metabolism, and from Well-Being to Disease
Authors: Street Maria Elisabeth , Moghetti Paolo , Chiarelli Francesco
Published: December 2022

Insulin has pleiotropic effects, and is of importance both as a key regulator of glucose metabolism and as a growth factor [...]
Role of miRNA in Melanoma Development and Progression
Authors: Poniewierska-Baran Agata , Słuczanowska-Głąbowska Sylwia , Małkowska Paulina , Sierawska Olga , Zadroga Łukasz , Pawlik Andrzej , Niedźwiedzka-Rystwej Paulina
Published: December 2022

Melanoma is one of the most aggressive and progressive skin cancers. It develops from normal pigment-producing cells known as melanocytes, so it is important to know the mechanism behind such transformations. The study of metastasis mechanisms is crucial for a better understanding the biology of neoplastic cells. Metastasis of melanoma, or any type of cancer, is a multi-stage process in which the neoplastic cells leave the primary tumour, travel through the blood and/or lymphatic vessels, settle in distant organs and create secondary tumours. MicroRNA (miRNA) can participate in several steps of the metastatic process. This review presents the role of miRNA molecules in the development and progression as well as the immune response to melanoma.
Novel Chiral Ru(II) Complexes as Potential c-myc G-quadruplex DNA Stabilizers Inducing DNA Damage to Suppress Triple-Negative Breast Cancer Progression
Authors: Yuan Chanling , Wang Zhixiang , Wang Zongtao , Liu Wentao , Li Guohu , Meng Jinlan , Wu Ruzhen , Wu Qiong , Wang Jiacheng , Mei Wenjie
Published: December 2022

Currently, effective drugs for triple-negative breast cancer (TNBC) are lacking in clinics. c-myc is one of the core members during TNBC tumorigenesis, and G-rich sequences in the promoter region can form a G-quadruplex conformation, indicating that the c-myc inhibitor is a possible strategy to fight cancer. Herein, a series of chiral ruthenium(II) complexes ([Ru(bpy)2(DPPZ-R)](ClO4)2, Λ/Δ−1: R = -H, Λ/Δ−2: R = -Br, Λ/Δ−3: R = -C≡C(C6H4)NH2) were researched based on their interaction with c-myc G-quadruplex DNA. Λ−3 and Δ−3 show high affinity and stability to decrease their replication. Additional studies showed that Λ−3 and Δ−3 exhibit higher inhibition against different tumor cells than other molecules. Δ−3 decreases the viability of MDA-MB-231 cells with an IC50 of 25.51 μM, which is comparable with that of cisplatin, with an IC50 of 25.9 μM. Moreover, Δ−3 exhibits acceptable cytotoxic activity against MDA-MB-231 cells in a zebrafish xenograft breast cancer model. Further studies suggested that Δ−3 decreases the viability of MDA-MB-231 cells predominantly through DNA-damage-mediated apoptosis, which may be because Δ−3 can induce DNA damage. In summary, the results indicate that Ru(II) complexes containing alkinyl groups can be developed as c-myc G-quadruplex DNA binders to block TNBC progression.
Molecular Mechanisms Employed by Neurons to Receive and Transduce Signals Essential for Learning and Memory
Authors: Stamatakis Antonis , Skoulakis Efthimios M. C.
Published: December 2022

The ability to learn from the consequences of one’s actions, extracting useful information from threatening, painful or rewarding encounters and developing the skill of predicting probable events from pre-experienced stimuli, is essential for survival and reproductive success [...]
Discogenic Low Back Pain: Anatomy, Pathophysiology and Treatments of Intervertebral Disc Degeneration
Authors: Mohd Isa Isma Liza , Teoh Seong Lin , Mohd Nor Nurul Huda , Mokhtar Sabarul Afian
Published: December 2022

Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain.
Metabolomics and Lipidomics Screening Reveal Reprogrammed Signaling Pathways toward Cancer Development in Non-Alcoholic Steatohepatitis
Authors: Ahmed Eman A. , El-Derany Marwa O. , Anwar Ali Mostafa , Saied Essa M. , Magdeldin Sameh
Published: December 2022

With the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite–protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH.
Fraxetin Interacts Additively with Cisplatin and Mitoxantrone, Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis
Authors: Wróblewska-Łuczka Paula , Grabarska Aneta , Góralczyk Agnieszka , Marzęda Paweł , Łuszczki Jarogniew J.
Published: December 2022

Malignant melanoma is a skin cancer characterized by rapid development, poor prognosis and high mortality. Due to the frequent drug resistance and/or early metastases in melanoma, new therapeutic methods are urgently needed. The study aimed at assessing the cytotoxic and antiproliferative effects of scoparone and fraxetin in vitro, when used alone and in combination with three cytostatics: cisplatin, mitoxantrone, and docetaxel in four human melanoma cell lines. Our experiments showed that scoparone in the concentration range tested up to 200 µM had no significant effect on the viability of human malignant melanoma (therefore, it was not possible to evaluate it in combination with other cytostatics), while fraxetin inhibited cell proliferation with IC50 doses in the range of 32.42–73.16 µM, depending on the cell line. Isobolographic analysis allowed for the assessment of the interactions between the studied compounds. Importantly, fraxetin was not cytotoxic to normal keratinocytes (HaCaT) and melanocytes (HEMa-LP), although it slightly inhibited their viability at high concentrations. The combination of fraxetin with cisplatin and mitoxantrone showed the additive interaction, which seems to be a promising direction in melanoma therapy. Unfortunately, the combination of fraxetin with docetaxel may not be beneficial due to the antagonistic antiproliferative effect of both drugs used in the mixture.
Change in the Electronic Structure of the Cobalt(II) Ion in a One-Dimensional Polymer with Flexible Linkers Induced by a Structural Phase Transition
Authors: Yambulatov Dmitriy S. , Voronina Julia K. , Goloveshkin Alexander S. , Svetogorov Roman D. , Veber Sergey L. , Efimov Nikolay N. , Matyukhina Anna K. , Nikolaevskii Stanislav A. , Eremenko Igor L. , Kiskin Mikhail A.
Published: December 2022

A new 1D-coordination polymer [Co(Piv)2(NH2(CH2)6NH2)]n (1, Piv is Me3CCO2− anion) was obtained, the mononuclear fragments {Co(O2CR)2} within which are linked by μ-bridged molecules of hexamethylenediamine (NH2(CH2)6NH2). For this compound, two different monoclinic C2/c (α-1) and P2/n (β-1) phases were found at room temperature by single-crystal X-ray diffraction analysis, with a similar structure of chains and their packages in unit cells. The low-temperature phase (γ-1) of crystal 1 at 150 K corresponds to the triclinic space group P-1. As the temperature decreases, the structural phase transition (SPT) in the α-1 and β-1 crystals is accompanied by an increase in the crystal packing density caused by the rearrangements of both H-bonds and the nearest ligand environment of the cobalt atom (“octahedral CoN2O4 around the metal center at room temperature” → “pseudo-tetrahedral CoN2O2 at 150 K”). The SPT was confirmed by DSC in the temperature range 210–150 K; when heated above 220 K, anomalies in the behavior of the heat flow are observed, which may be associated with the reversibility of SPT; endo effects are observed up to 300 K. The SPT starts below 200 K. At 100 K, a mixture of phases was found in sample 1: 27% α-1 phase, 61% γ-1 phase. In addition, at 100 K, 12% of the new δ-1 phase was detected, which was identified from the diffraction pattern at 260 K upon subsequent heating: the a,b,c-parameters and unit cell volume are close to the structure parameters of γ-1, and the values of the α,β,γ-angles are significantly different. Further heating leads to a phase transition from δ-1 to α-1, which both coexist at room temperature. According to the DC magnetometry data, during cooling and heating, the χMT(T) curves for 1 form a hysteresis loop with ~110 K, in which the difference in the χMT values reaches 9%. Ab initio calculations of the electronic structure of cobalt(II) in α-1 and γ-1 have been performed. Based on the EPR data at 10 K and the ab initio calculations, the behavior of the χMT(T) curve for 1 was simulated in the temperature range of 2–150 K. It was found that 1 exhibits slow magnetic relaxation in a field of 1000 Oe.
A Meta-Analysis Study of SOD1-Mutant Mouse Models of ALS to Analyse the Determinants of Disease Onset and Progression
Authors: Ciuro Maria , Sangiorgio Maria , Leanza Giampiero , Gulino Rosario
Published: December 2022

A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan–Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.
Dihydromyricetin Attenuates High-Intensity Exercise-Induced Intestinal Barrier Dysfunction Associated with the Modulation of the Phenotype of Intestinal Intraepithelial Lymphocytes
Authors: Hou Pengfei , Wang Dawei , Lang Hedong , Yao Yu , Zhou Jie , Zhou Min , Zhu Jundong , Yi Long , Mi Mantian
Published: December 2022

Background: Exercise-induced gastrointestinal syndrome (GIS) has symptoms commonly induced by strenuous sports. The study aimed to determine the effect of dihydromyricetin (DHM) administration on high-intensity exercise (HIE)-induced intestinal barrier dysfunction and the underlying mechanism involved with intestinal intraepithelial lymphocytes (IELs). Methods: The HIE model was established with male C57BL/6 mice using a motorized treadmill for 2 weeks, and DHM was given once a day by oral gavage. After being sacrificed, the small intestines of the mice were removed immediately. Results: We found that DHM administration significantly suppressed HIE-induced intestinal inflammation, improved intestinal barrier integrity, and inhibited a HIE-induced increase in the number of IELs and the frequency of CD8αα+ IELs. Meanwhile, several markers associated with the activation, gut homing and immune functions of CD8αα+ IELs were regulated by DHM. Mechanistically, luciferase reporter assay and molecular docking assay showed DHM could activate the aryl hydrocarbon receptor (AhR). Conclusions: These data indicate that DHM exerts a preventive effect against HIE-induced intestinal barrier dysfunction, which is associated with the modulation of the quantity and phenotype of IELs in the small intestine. The findings provide a foundation to identify novel preventive strategies based on DHM supplementation for HIE-induced GIS.