bluuebunny/crossref_metadata_2025 huggingface dataset:
Quercetin Protects Blood–Brain Barrier Integrity via the PI3K/Akt/Erk Signaling Pathway in a Mouse Model of Meningitis Induced by Glaesserella parasuis
Authors: Sun Peiyan , Yang Yaqiong , Yang Linrong , Qian Yuanzhuo , Liang Mingxia , Chen Hongbo , Zhang Jing , Qiu Yinsheng , Guo Ling , Fu Shulin
Published: June 2024

Glaesserella parasuis (G. parasuis) causes serious inflammation and meningitis in piglets. Quercetin has anti-inflammatory and anti-bacterial activities; however, whether quercetin can alleviate brain inflammation and provide protective effects during G. parasuis infection has not been studied. Here, we established a mouse model of G. parasuis infection in vivo and in vitro to investigate transcriptome changes in the mouse cerebrum and determine the protective effects of quercetin on brain inflammation and blood–brain barrier (BBB) integrity during G. parasuis infection. The results showed that G. parasuis induced brain inflammation, destroyed BBB integrity, and suppressed PI3K/Akt/Erk signaling-pathway activation in mice. Quercetin decreased the expression of inflammatory cytokines (Il-18, Il-6, Il-8, and Tnf-α) and BBB-permeability marker genes (Mmp9, Vegf, Ang-2, and Et-1), increased the expression of angiogenetic genes (Sema4D and PlexinB1), reduced G. parasuis-induced tight junction disruption, and reactivated G. parasuis-induced suppression of the PI3K/Akt/Erk signaling pathway in vitro. Thus, we concluded that quercetin may protect BBB integrity via the PI3K/Akt/Erk signaling pathway during G. parasuis infection. This was the first attempt to explore the protective effects of quercetin on brain inflammation and BBB integrity in a G. parasuis-infected mouse model. Our findings indicated that quercetin is a promising natural agent for the prevention and treatment of G. parasuis infection.
Strain-Modulated Flexible Bio-Organic/Graphene/PET Sensors Based on DNA-Curcumin Biopolymer
Authors: Mallem Siva Pratap Reddy , Puneetha Peddathimula , Lee Dong Yeon , An Sung Jin
Published: June 2024

In recent years, there has been growing interest in the development of metal-free, environmentally friendly, and cost-effective biopolymer-based piezoelectric strain sensors (bio-PSSs) for flexible applications. In this study, we have developed a bio-PSS based on pure deoxyribonucleic acid (DNA) and curcumin materials in a thin-film form and studied its strain-induced current-voltage characteristics based on piezoelectric phenomena. The bio-PSS exhibited flexibility under varying compressive and tensile loads. Notably, the sensor achieved a strain gauge factor of 407 at an applied compressive strain of −0.027%, which is 8.67 times greater than that of traditional metal strain gauges. Furthermore, the flexible bio-PSS demonstrated a rapid response under a compressive strain of −0.08%. Our findings suggest that the proposed flexible bio-PSS holds significant promise as a motion sensor, addressing the demand for environmentally safe, wearable, and flexible strain sensor applications.
How Social Influence Promotes the Adoption of Mobile Health among Young Adults in China: A Systematic Analysis of Trust, Health Consciousness, and User Experience
Authors: Cao Jianfei , Feng Hanlin , Lim Yeongjoo , Kodama Kota , Zhang Shuo
Published: June 2024

As mobile health (mHealth) offers several advantages in healthcare, researchers are exploring the motivational factors for its adoption. However, few studies have elucidated the complex relationship between social influence and behavioral intentions to adopt mHealth among young adults in China. This study explored the impact of social influence on young adults’ behavioral intentions to adopt mHealth, the mediating roles of trust and health consciousness, and the moderating effect of mHealth user experience on the relationship between the predictors. In total, 300 valid responses were collected from a university in China, and a research model was developed. The partial least squares structural equation modeling method was used to verify the relationship between the main research variables. mHealth adoption behavioral intentions among young adults were significantly positively impacted by social influence; it indirectly increased mHealth adoption behavioral intentions by positively affecting trust and health consciousness. mHealth use weakened the positive impact of social influence on trust and health consciousness, while user experience positively moderated the relationship between health consciousness and behavioral intentions. Trust and health consciousness play important roles in the complex multivariate relationships between social influence and behavioral intentions to adopt mHealth. Future research should consider the moderating role of the mHealth user experience. These findings enrich the mHealth technology acceptance theory framework and provide specific guidance strategies for marketing mHealth applications.
Advancing Building Assessment Tools: Achieving Sustainable Development Goals through the Fusion of Internet of Things Occupant-Centric Principles and Sustainable Practices
Authors: Metwally Esraa A. , Ismail Mostafa Refat , Farid Ayman A.
Published: June 2024

The impact of global climate change on the built environment emphasizes the need for sustainable development goals (SDGs) using technological solutions, such as the Internet of Things (IoT). The significance of innovative building assessment (BA) tools plays a pivotal role in bridging the existing gap between the theoretical and actual operational performance of buildings. The main research question is how can a new generation of BA tools leverage the IoT to optimize occupant well-being and achieve SDGs’ targets. This article delves into the pivotal role played by the IoT and occupant-centric concepts in advancing sustainability initiatives and facilitating the achievement of SDGs. The novelty of this paper lies in its exploration of the current state of IoT integration as a strategic imperative for SDGs’ achievement and climate change mitigation. Consequently, a paradigm shift is evident in this work, showcasing a comprehensive comparison between conventional and IoT occupant-centric BA tools and introducing a correlation study between IoT occupant-centric systems and future SDGs’ targets. Lastly, current gaps and valuable insights into future research possibilities are offered.
Investigating the Role of Thermal Comfort Perception on Negotiating Heritage Conservation and Energy Efficiency Decisions through System Dynamics
Authors: Karabeyeser Bakan Merve , Fouseki Kalliopi , Altamirano Hector
Published: June 2024

The building sector, which is responsible for a significant amount of total global energy consumption, provides substantial opportunities for energy efficiency studies. In the context of historic and traditional buildings, this matter becomes more crucial, as energy efficiency is more complex and challenging. The complexity partly derives from the multiple and diverse values with which the buildings are associated. These values are dynamic. In this paper, we chose historic houses in Gaziantep as our focal point. They provide an indicative example of houses with architectural features that help residents deal with the adverse effects of the hot climate. These specific features are significant for the users not only in terms of thermal comfort but also in terms of heritage values. The value that users attribute to the neighbourhood and their attitude towards buildings change over time. It is seen that thermal comfort plays a key role in energy efficiency and heritage conservation. Hence, understanding the role of thermal comfort perceptions and the ways in which they dictate certain energy efficiency and heritage conservation actions is critical. In this context, this paper addresses these dynamic, complex, and changing interrelationships over time. Drawing upon the dynamic analysis of in-depth, semi-structured interviews with three dwellings in Gaziantep’s Bey neighbourhood, we will discuss how residents of historic houses perceive thermal comfort and how they negotiate and prioritise energy efficiency and heritage conservation.
Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials
Authors: Shah Neil J. , Della Pia Alexandra , Wu Tianmin , Williams Aquino , Weber Melinda , Sinclaire Brittany , Gourna Paleoudis Elli , Alaoui Adil , Lev-Ari Shaked , Adams Shari , Kaufman Jordan , Parikh Sahil B. , Tonti Emily , Muller Eric , Serzan Michael , Cheruku Divya , Lee Albert , Sridhar Aishwarya , Hee Benjamin (Thor) Perrin , Ahn Jaeil , Pecora Andrew , Ip Andrew , Atkins Michael B.
Published: June 2024

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%—smokers, 30.4%—non-White, 22.8%—elderly, 20.8%—ECOG PS ≥ 2, 15.7%—history of AIDs, and 4.7%—history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.
Bioinformatics Analysis of Human Papillomavirus 16 Integration in Cervical Cancer: Changes in MAGI-1 Expression in Premalignant Lesions and Invasive Carcinoma
Authors: Catalán-Castorena Oscar , Garibay-Cerdenares Olga Lilia , Illades-Aguiar Berenice , Castillo-Sánchez Rocio , Zubillaga-Guerrero Ma. Isabel , Leyva-Vazquez Marco Antonio , Encarnacion-Guevara Sergio , Flores-Alfaro Eugenia , Ramirez-Ruano Mónica , del Carmen Alarcón-Romero Luz
Published: June 2024

HPV 16 integration is crucial for the onset and progression of premalignant lesions to invasive squamous cell carcinoma (ISCC) because it promotes the amplification of proto-oncogenes and the silencing of tumor suppressor genes; some of these are proteins with PDZ domains involved in homeostasis and cell polarity. Through a bioinformatics approach based on interaction networks, a group of proteins associated with HPV 16 infection, PDZ domains, and direct physical interaction with E6 and related to different hallmarks of cancer were identified. MAGI-1 was selected to evaluate the expression profile and subcellular localization changes in premalignant lesions and ISCC with HPV 16 in an integrated state in cervical cytology; the profile expression of MAGI-1 diminished according to lesion grade. Surprisingly, in cell lines CaSki and SiHa, the protein localization was cytoplasmic and nuclear. In contrast, in histological samples, a change in subcellular localization from the cytoplasm in low-grade squamous intraepithelial lesions (LSIL) to the nucleus in the high-grade squamous intraepithelial lesion (HSIL) was observed; in in situ carcinomas and ISCC, MAGI-1 expression was absent. In conclusion, MAGI-1 expression could be a potential biomarker for distinguishing those cells with normal morphology but with HPV 16 integrated from those showing morphology-related uterine cervical lesions associated with tumor progression.
Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle
Authors: Zakirova Natalia F. , Khomich Olga A. , Smirnova Olga A. , Molle Jennifer , Duponchel Sarah , Yanvarev Dmitry V. , Valuev-Elliston Vladimir T. , Monnier Lea , Grigorov Boyan , Ivanova Olga N. , Karpenko Inna L. , Golikov Mikhail V. , Bovet Cedric , Rindlisbacher Barbara , Khomutov Alex R. , Kochetkov Sergey N. , Bartosch Birke , Ivanov Alexander V.
Published: June 2024

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.
Soft Feel Material Coatings on the Surface of Plastic Products and Their Application Prospects in the Popular Fields: A Review
Authors: Jiang Bangzheng , Xu Yueyang , Zhang Lanlan , Zhou Xing , Zhang Hui , Liu Luqi , Zhao Jun
Published: June 2024

Soft-feel material (mainly polyurethane (PU), silicone rubber (SR), and polyacrylic acid (PAA), etc.) coatings can overcome the drawbacks of common plastic products such as acrylonitrile butadiene styrene copolymer (ABS), polycarbonate (PC), and polypropylene (PP), which have cold, hard, and bright surfaces, achieving warm, soft, and matte effects, thus greatly improving the quality and price level of the products. Although these coating materials can partially meet the main requirements of the soft feel effect, their comprehensive properties, such as mechanical performance, weather resistance, and foul resistance, still have shortcomings and need to be improved. Besides, there is a lack of in-depth exploration in the literature on the design philosophy and preparation strategies of soft-feel materials. Starting from the mechanism of producing this comfortable feeling and then systematically exploring their application in popular fields with high economic added value, such as mobile phone cases, electronic cigarette cases, cosmetic containers, etc., this article attempts to systematically and meticulously review the research and development progress in the related fields in recent decades and tries to provide an open outlook on their future development directions, e.g., the employment of surface engineering and hybrid materials. This review is expected to provide some rational thinking directions and convenient practical guidance for the rapid and healthy development of soft-feel materials in the research and application fields.
Twelve-Year Progression of Osteochondral Lesions of the Talus Observed Using Magnetic Resonance Imaging
Authors: Lauck Bradley J. , Shaffrey Isabel , Anastasio Albert T. , O’Neill Conor N. , Hanselman Andrew E. , Adams Samuel B.
Published: June 2024

Osteochondral lesions of the talus are common injuries that are most often the result of trauma. The natural progression of osteochondral lesions is not well understood. It is still unclear which lesions eventually lead to joint degeneration and osteoarthritic changes and if the treatment method affects the progression. The existing literature surrounding this topic is sparse, with inconsistent findings. The presented images are taken from a 72-year-old man with bilateral osteochondral lesions of the talus. To our knowledge, this is the first published series of images illustrating the natural progression of a patient with bilateral osteochondral lesions of the talus over a 12-year time period.
Impact of Gamification on Motivation and Academic Performance: A Systematic Review
Authors: Jaramillo-Mediavilla Lorena , Basantes-Andrade Andrea , Cabezas-González Marcos , Casillas-Martín Sonia
Published: June 2024

This study aims to examine the existing evidence on gamification in educational settings, highlighting its impact on motivation and academic performance. Methodologically, a Systematic Literature Review (SLR) was developed under the PRISMA statement criteria using three multidisciplinary databases: Web of Science, Scopus, and Scielo. According to the inclusion, exclusion, and quality criteria, it was determined to include 9 SLR articles on gamification that address at least one of the two key variables: student motivation or academic performance. The articles were published between 2016 and 2022, available in open access, written in English or Spanish, and with content that is directly related to the research questions. The results reveal that gamification significantly influences motivation by facilitating the assimilation of knowledge, the improvement of skills and academic competencies of students, and specifically refers to a wide range of capabilities that are essential for success in the educational environment and that can be enhanced through playful and interactive learning experiences. These skills can be cognitive, self-learning, social, or collaborative, among others. It is concluded that creativity and adaptability are key to successfully implementing gamification in the classroom.
A Compound Framework for Forecasting the Remaining Useful Life of PEMFC
Authors: Wu Chuanfeng , Fu Wenlong , Shan Yahui , Shao Mengxin
Published: June 2024

Proton exchange membrane fuel cells (PEMFC) are widely acknowledged as a prospective power source, but durability problems have constrained development. Therefore, a compound prediction framework is proposed in this paper by integrating the locally weighted scatter plot smoothing method (LOESS), uniform information coefficient (UIC), and attention-based stacked generalization model (ASGM) with improved dung beetle optimization (IDBO). Firstly, LOESS is adopted to filter original degraded sequences. Then, UIC is applied to obtain critical information by selecting relevant factors of the processed degraded sequences. Subsequently, the critical information is input into the base models of ASGM, including kernel ridge regression (KRR), extreme learning machine (ELM), and the temporal convolutional network (TCN), to acquire corresponding prediction results. Finally, the prediction results are fused using the meta-model attention-based LSTM of ASGM to obtain future degradation trends (FDT) and the remaining useful life (RUL), in which the attention mechanism is introduced to deduce weight coefficients of the base model prediction results in LSTM. Meanwhile, IDBO based on Levy flight, adaptive mutation, and polynomial mutation strategies are proposed to search for optimal parameters in LSTM. The application of two different datasets and their comparison with five related models shows that the proposed framework is suitable and effective for forecasting the FDT and RUL of PEMFC.
The Impact of the Governance Fragmentation of Forestry Communities on the Economic Performance of State-Owned Forest Enterprises in Northeast China: An Empirical Analysis Based on the Transaction Cost Perspective
Authors: Ji Yuan , Wan Shenwei , Ke Shuifa
Published: June 2024

The 2015 reform of state-owned forest regions (SOFRs) in Northeast China required state-owned forest enterprises (SOFEs) to transfer their governmental and social roles to local authorities. This transition, however, created fragmented governance within forestry communities due to the absence of cooperative mechanisms between SOFEs and local governments. This study examines the economic effects of this governance fragmentation on SOFEs and explores the underlying mechanisms. The research combines new institutional economics and transaction cost theory to develop hypotheses and employs empirical analysis using fixed-effects models on data from 39 SOFEs, belonging to two forest industry groups from 2015 to 2022, collected through surveys and field investigations. The findings indicate that governance fragmentation has a significant negative impact on the economic performance of SOFEs. The high transaction costs incurred by SOFEs in achieving community co-governance with local governments are identified as a key mediating mechanism. These costs lead to resource dispersion and diminished trust between SOFEs and local governments. The economic impact of this governance fragmentation varies based on the economic conditions of the SOFEs, their operational scales, and the clarity of geographical management boundaries with local governments. To mitigate the adverse effects of governance fragmentation, the study suggests proactive institutional designs to reduce transaction costs. These findings offer new insights into the corporate social responsibilities of Chinese SOFEs and suggest improvements in the governance structures of forestry communities in SOFRs in Northeast China. Additionally, the study expands the application of transaction cost theory in public affairs governance and enhances quantitative research on the economic impact on enterprises.
The Risk Factors Associated with the Prevalence of Multimorbidity of Anaemia, Malaria, and Malnutrition among Children Aged 6–59 Months in Nigeria
Authors: Obasohan Phillips Edomwonyi , Walters Stephen J. , Jacques Richard M. , Khatab Khaled
Published: June 2024

In the last ten years, multimorbidity in children under the age of five years has become an emerging health issue in developing countries. The study of multimorbidity of anaemia, malaria, and malnutrition (MAMM) among children in Nigeria has not received significant attention. This study aims to investigate what risk factors are associated with the prevalence of multimorbidity among children aged 6 to 59 months in Nigeria. This study used two nationally representative cross-sectional surveys, the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report. A series of multilevel mixed-effect ordered logistic regression models were used to investigate the associations between child/parent/household variables (at level 1), community-related variables (at level 2) and area-related variables (at level 3), and the multimorbidity outcome (no disease, one disease only, two or more diseases). The results show that 48.3% (4917/10,184) of the sample of children aged 6–59 months display two or more of the disease outcomes. Being a female child, the maternal parent having completed higher education, the mother being anaemic, the household wealth quintile being in the richest category, the proportion of community wealth status being high, the region being in the south, and place of residence being rural were among the significant predictors of MAMM (p < 0.05). The prevalence of MAMM found in this study is unacceptably high. If suitable actions are not urgently taken, Nigeria’s ability to actualise SDG-3 will be in grave danger. Therefore, suitable policies are necessary to pave the way for the creation/development of integrated care models to ameliorate this problem.
Exploring the Role of Rehabilitation Medicine within an Inclusion Health Context: Examining a Population at Risk from Homelessness and Brain Injury in Edinburgh
Authors: Eshun Edwin , Burke Orla , Do Florence , Maciver Angus , Mathur Anushka , Mayne Cassie , Mohamed Jemseed Aashik Ahamed , Novak Levente , Siddique Anna , Smith Eve , Tapia-Stocker David , FitzGerald Alasdair
Published: June 2024

People experiencing homelessness are at risk from a number of comorbidities, including traumatic brain injury, mental health disorders, and various infections. Little is known about the rehabilitation needs of this population. This study took advantage of unique access to a specialist access GP practice for people experiencing homelessness and a local inclusion health initiative to explore the five-year period prevalence of these conditions in a population of people experiencing homelessness through electronic case record searches and to identify barriers and facilitators to healthcare provision for this population in the context of an interdisciplinary and multispecialist inclusion health team through semi-structured interviews with staff working in primary and secondary care who interact with this population. The five-year period prevalence of TBI, infections, and mental health disorders was 9.5%, 4%, and 22.8%, respectively. Of those who had suffered a brain injury, only three had accessed rehabilitation services. Themes from thematic analysis of interviews included the impact of psychological trauma, under-recognition of the needs of people experiencing homelessness, resource scarcity, and the need for collaborative and adaptive approaches. The combination of quantitative and qualitative data suggests a potential role for rehabilitation medicine in inclusion health initiatives.
“Back Health 24/7/365”—A Novel, Comprehensive “One Size Fits All” Workplace Health Promotion Intervention for Occupational Back Health among Hospital Employees
Authors: Hasenoehrl Timothy , Steiner Margarete , Ebenberger Felix , Kull Philipp , Sternik Julia , Reissig Lukas , Jordakieva Galateja , Crevenna Richard
Published: June 2024

Background: Projects for workplace health promotion (WHP) for back pain traditionally focus exclusively on work-related but not on leisure-time stress on the spine. We developed a comprehensive WHP project on the back health of hospital workers regardless of the physical characteristics of their work and compared its effects on sedentary and physically active hospital workers. Methods: Study assessments were carried out before and six months after participation in the WHP intervention. The primary outcome parameter was back pain (Oswestry Disability Index, ODI). Anxiety (Generalized Anxiety Disorder-7), work ability (Work Ability Index), depression (Patient Health Questionnaire-9), stress (Perceived Stress Scale-10), and quality of life (Short Form-36) were assessed via questionnaires as secondary outcome parameters. Physical performance was measured via the 30 seconds Sit-to-Stand test (30secSTS). Results: Sixty-eight healthcare workers with non-specific back pain were included in the evaluation study of the WHP project “Back Health 24/7/365”. After six months, back pain, physical performance, and self-perceived physical functioning (SF-36 Physical Functioning subscale) improved significantly in both groups. Not a single parameter showed an interaction effect with the group allocation. Conclusions: A comprehensive WHP-intervention showed significant positive effects on hospital workers regardless of the physical characteristics of their work.
Dynamic Construction of Spherical Raster Voronoi Diagrams Based on Ordered Dilation
Authors: Liu Qingping , Zhao Xuesheng , Duan Yuanzheng , Qin Mengmeng , Xie Wenlan , Sun Wenbin
Published: June 2024

The Voronoi diagram on the Earth’s surface is a significant data model, characterized by natural proximity and dynamic stability, which has emerged as one of the most promising solutions for global spatial dynamic management and analysis. However, traditional algorithms for generating spherical raster Voronoi diagrams find it challenging to dynamically adjust the Voronoi diagram while maintaining precision and efficiency. The efficient and accurate construction of the spherical Voronoi diagram has become one of the bottleneck issues limiting its further large-scale application. To this end, this paper proposes a dynamic construction scheme for the spherical Voronoi diagram based on the QTM (Quaternary Triangular Mesh) system, with the aim of enabling efficient generation, local updates, and multi-scale visualization of the spherical Voronoi diagrams. In this paper, canonical ordering is introduced. Tailored for the properties of the spherical triangular grid, it constructs a unified and standardized sorting strategy for the dilation of the spherical grids. The construction and updating of the spherical Voronoi diagram are achieved through the ordered dilation of sites. Furthermore, the multi-scale visualization of the spherical Voronoi diagram is realized through the hierarchical structure of the QTM. The paper presents our algorithm intuitively through pseudocode, conducts comparative experiments on the feasibility and efficiency, and designs an experiment for the dynamic navigation and management of ocean-going vessels based on the global multi-resolution Voronoi diagram. The experimental results demonstrate that our algorithm effectively controls the error of the generation of the raster Voronoi diagram and has a significant efficiency advantage when processing dynamic environments.
The Expression of Cell Cycle Cyclins in a Human Megakaryoblast Cell Line Exposed to Simulated Microgravity
Authors: Sokolovskaya Alisa A. , Sergeeva Ekaterina A. , Metelkin Arkadiy A. , Popov Mikhail A. , Zakharova Irina A. , Morozov Sergey G.
Published: June 2024

The study of the physiological and pathophysiological processes under extreme conditions facilitates a better understanding of the state of a healthy organism and can also shed light on the pathogenesis of diseases. In recent years, it has become evident that gravitational stress affects both the whole organism and individual cells. We have previously demonstrated that simulated microgravity inhibits proliferation, induces apoptosis, changes morphology, and alters the surface marker expression of megakaryoblast cell line MEG-01. In the present work, we investigate the expression of cell cycle cyclins in MEG-01 cells. We performed several experiments for 24 h, 72 h, 96 h and 168 h. Flow cytometry and Western blot analysis demonstrated that the main change in the levels of cyclins expression occurs under conditions of simulated microgravity after 96 h. Thus, the level of cyclin A expression showed an increase in the RPM group during the first 4 days, followed by a decrease, which, together with the peak of cyclin D, may indicate inhibition of the cell cycle in the G2 phase, before mitosis. In addition, based on the data obtained by PCR analysis, we were also able to see that both cyclin A and cyclin B expression showed a peak at 72 h, followed by a gradual decrease at 96 h. STED microscopy data also confirmed that the main change in cyclin expression of MEG-01 cells occurs at 96 h, under simulated microgravity conditions, compared to static control. These results suggested that the cell cycle disruption induced by RPM-simulated microgravity in MEG-01 cells may be associated with the altered expression of the main regulators of the cell cycle. Thus, these data implicate the development of cellular stress in MEG-01 cells, which may be important for proliferating human cells exposed to microgravity in real space.
Critical Role of Mitochondrial Fatty Acid Metabolism in Normal Cell Function and Pathological Conditions
Authors: Dikalov Sergey , Panov Alexander , Dikalova Anna
Published: June 2024

There is a “popular” belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions. Fatty acids are the primary fuel source and essential cell membrane building blocks from the origin of life. The essential cell membranes phospholipids were evolutionarily preserved from the earlier bacteria in human subjects. In the past century, the discovery of fatty acid metabolism was superseded by the epidemic growth of metabolic conditions and cardiovascular diseases. The association of fatty acids and pathological conditions is not due to their “harmful” effects but rather the result of impaired fatty acid metabolism and abnormal lifestyle. Mitochondrial dysfunction is linked to impaired metabolism and drives multiple pathological conditions. Despite metabolic flexibility, the loss of mitochondrial fatty acid oxidation cannot be fully compensated for by other sources of mitochondrial substrates, such as carbohydrates and amino acids, resulting in a pathogenic accumulation of long-chain fatty acids and a deficiency of medium-chain fatty acids. Despite popular belief, mitochondrial fatty acid oxidation is essential not only for energy-demanding organs such as the heart, skeletal muscle, and kidneys but also for metabolically “inactive” organs such as endothelial and epithelial cells. Recent studies indicate that the accumulation of long-chain fatty acids in specific organs and tissues support the impaired fatty acid oxidation in cell- and tissue-specific fashion. This work, therefore, provides a basis to challenge these established dogmas and articulate the need for a paradigm shift from the “pathogenic” role of fatty acids to the critical role of fatty acid oxidation. This is important to define the causative role of impaired mitochondrial fatty acid oxidation in specific pathological conditions and develop novel therapeutic approaches targeting mitochondrial fatty acid metabolism.
The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines
Authors: Hanafi Donia , Onyenwoke Rob U. , Kimbro K. Sean
Published: June 2024

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.
The Role of the Microbiota in the Pathogenesis and Treatment of Atopic Dermatitis—A Literature Review
Authors: Wrześniewska Martyna , Wołoszczak Julia , Świrkosz Gabriela , Szyller Hubert , Gomułka Krzysztof
Published: June 2024

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence worldwide. AD pathogenesis is complex and consists of immune system dysregulation and impaired skin barrier, influenced by genetic and environmental factors. The purpose of the review is to show the complex interplay between atopic dermatitis and the microbiota. Human microbiota plays an important role in AD pathogenesis and the course of the disease. Dysbiosis is an important factor contributing to the development of atopic diseases, including atopic dermatitis. The gut microbiota can influence the composition of the skin microbiota, strengthening the skin barrier and regulating the immune response via the involvement of bacterial metabolites, particularly short-chain fatty acids, in signaling pathways of the gut–skin axis. AD can be modulated by antibiotic intake, dietary adjustments, hygiene, and living conditions. One of the promising strategies for modulating the course of AD is probiotics. This review offers a summary of how the microbiota influences the development and treatment of AD, highlighting aspects that warrant additional investigation.
Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes
Authors: Nkoy Flory L. , Stone Bryan L. , Deering-Rice Cassandra E. , Zhu Angela , Lamb John G. , Rower Joseph E. , Reilly Christopher A.
Published: June 2024

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2–18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography–tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51–11.3) years. CYP3A5*3/*3 frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with CYP3A5*3/*3, the CYP3A5*1/*x genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97–0.98; p < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56–9.07; p < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43–1.93; p < 0.001); analysis of 3/*3, *1/*1 and *1/*3 separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the CYP3A5*3/*3 genotype, as opposed to an effect on ICS PK. Detection of CYP3A5*3/3, CYPA35*1/*3, and CYP3A5*1/*1 could impact inhaled steroid treatment strategies for asthma in the future.
Cadmium Alters the Metabolism and Perception of Abscisic Acid in Pisum sativum Leaves in a Developmentally Specific Manner
Authors: Zdunek-Zastocka Edyta , Michniewska Beata , Pawlicka Angelika , Grabowska Agnieszka
Published: June 2024

Abscisic acid (ABA) plays a crucial role in plant defense mechanisms under adverse environmental conditions, but its metabolism and perception in response to heavy metals are largely unknown. In Pisum sativum exposed to CdCl2, an accumulation of free ABA was detected in leaves at different developmental stages (A, youngest, unexpanded; B1, youngest, fully expanded; B2, mature; C, old), with the highest content found in A and B1 leaves. In turn, the content of ABA conjugates, which was highest in B2 and C leaves under control conditions, increased only in A leaves and decreased in leaves of later developmental stages after Cd treatment. Based on the expression of PsNCED2, PsNCED3 (9-cis-epoxycarotenoid dioxygenase), PsAO3 (aldehyde oxidase) and PsABAUGT1 (ABA-UDP-glucosyltransferase), and the activity of PsAOγ, B2 and C leaves were found to be the main sites of Cd-induced de novo synthesis of ABA from carotenoids and ABA conjugation with glucose. In turn, β-glucosidase activity and the expression of genes encoding ABA receptors (PsPYL2, PsPYL4, PsPYL8, PsPYL9) suggest that in A and B1 leaves, Cd-induced release of ABA from inactive ABA-glucosyl esters and enhanced ABA perception comes to the forefront when dealing with Cd toxicity. The distinct role of leaves at different developmental stages in defense against the harmful effects of Cd is discussed.
Kidney Aging and Chronic Kidney Disease
Authors: Zhang Yingying , Yu Chen , Li Xiaogang
Published: June 2024

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD.
Spinal Muscular Atrophy Scoliosis in the Era of Background Therapies—A Review of the Literature
Authors: Ruythooren Fred , Moens Pierre
Published: June 2024

Spinal deformities are considered an important complication of neuromuscular disorders such as spinal muscular atrophy (SMA). SMA patients typically develop progressive early-onset scoliosis, which is associated with increased functional decline, discomfort, and respiratory dysfunction. Over the second decade of the twenty-first century, a lot has changed in terms of the therapeutic options available to people with SMA. Specifically, the use of pharmaceutical agents such as nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and risdiplam (Evrysdi) has dramatically changed the landscape for SMA patients. These medications significantly alter motor- and respiratory functioning, as well as the natural progression of spinal deformities. When evaluating these agents and their impact on the development of scoliosis and motor functioning, it is important to consider the timing of treatment initiation. In patients treated after they had already developed symptoms, a shift of phenotype to a less severe subtype has been observed. This results in a delay in the onset of scoliosis for the less severe SMA types and an increase in early-onset scoliosis for the severe types in patients who would typically not live to develop scoliosis. Patients who receive treatment before they develop symptoms achieve almost normal motor functioning and will likely have a significant decrease in scoliosis prevalence or at least delay its onset.
Contemporary Concepts of Adhesive Cementation of Glass-Fiber Posts: A Narrative Review
Authors: Tsolomitis Panayiotis , Diamantopoulou Sofia , Papazoglou Efstratios
Published: June 2024

(1) Background: Cementation of glass fiber posts to root canals has been associated with various failures, especially debonding. This narrative review aims to present the contemporary concepts concerning the adhesive cementation of glass fiber post and to discuss the optimal management of these factors. (2) Methods: Electronic search was performed in MEDLINE/Pub Med and Google Scholar using selected keywords examining the parameters post length, surface treatment of glass fiber posts, post space preparation and dentin pretreatment, resin cement selection, adhesive systems and hybrid layer formation, and clinical techniques. (3) Results: The search led to the selection of 44 articles. Epoxy resin-based endodontic sealers are recommended and the use of temporary cement in the root canal should be avoided. The minimum length of a glass fiber post adhesively cemented to a root canal is 5 mm. Irrigating the root canals with chlorhexidine, MTAD, or EDTA (alone or in combination with NaOCl) after post space preparation seems to enhance the bond strength. Silane application on the surface of the post seems to be beneficial. Concerning resin cements and adhesive systems, the results were rather inconclusive. Finally, resin cement should be applied inside the root canal with an elongation tip and photoactivation should be delayed. (4) Conclusions: Contemporary concepts of adhesive cementation of glass fiber posts can indeed improve the bond between glass fiber posts, resin cement, and root canal dentin, however, evidence coming from long-term randomized prospective clinical trials is needed in order to obtain safer conclusions.
Assessment of the Zulfiqar Frailty Scale (ZFS) in Primary Healthcare
Authors: Zulfiqar Abrar-Ahmad , Andres Emmanuel
Published: June 2024

Introduction: The primary aim of the study was to validate the Zulfiqar Frailty Scale (ZFS) and examine its concordance with the modified Short Emergency Geriatric Assessment (mSEGA) scale, Part A. Methods: A prospective observational study was conducted in Guadeloupe (France) over a two-month duration (from 20 February to 20 April 2024), involving elderly individuals aged 65 and older, deemed self-sufficient with an ADL (Activities of Daily Living) score exceeding four out of six. Results: Within this community cohort of 98 individuals, averaging 75 years in age, frailty according to the modified SEGA criteria was prevalent in 29%. Frailty according to the “ZFS” score was prevalent in 40%. Key predictors of frailty identified in our study included age, comorbidity (Charlson score), polypharmacy (total number of medications and therapeutic classes), and functional ability (ADL scores). Notably, experiences of falls and hospitalizations within the past six months significantly influenced the classification of frailty according to both ZFS and SEGA scales. Significant associations with the presence of home care aides (p < 0.0001), monopodal support test results (p < 0.0001), memory impairments (p < 0.0001), and recent hospitalizations (p = 0.0054) underscored the multidimensional impact of frailty. The Pearson correlation coefficient and its 95% confidence interval between the SEGA and Zulfiqar Frailty Scales stood at 0.73 [0.61: 0.81]. The discernment threshold for frailty was set at three out of six criteria, showcasing a sensitivity of 64% and a negative predictive value of 80%. The area under the curve (AUC) for the Zulfiqar Frailty Scale was reported as 0.8. Conclusion: The “ZFS” tool allows for the detection of frailty with a highly satisfactory sensitivity and negative predictive value.