Multidisciplinary Digital Publishing Institute (Switzerland)
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Anti-Fibrotic and Anti-Inflammatory Effects of Hesperidin in an Ex Vivo Mouse Model of Early-Onset Liver Fibrosis
Liver fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins as a wound-healing response to chronic liver injury, leading to tissue scarring and organ dysfunction. Natural compounds, including phytonutrients and polyphenols, have been shown to exert protective effects by reducing profibrotic biomarkers in vitro and in vivo models. Here, we provide the first evidence that the polyphenol hesperidin (HE) can counteract the onset of fibrotic responses in an ex vivo mouse liver fibrosis model induced by Transforming Growth Factor-β1 (TGF-β1) (5 ng/mL). Notably, HE drives early ECM remodeling in the fibrotic mouse liver tissue. Fibrosis-related parameters were assessed at both the transcriptional and translational levels after treatment with HE at increasing concentrations of 50, 75, and 100 µg/mL. Interestingly, HE at 75 µg/mL exerted the strongest beneficial effect, significantly decreasing the gene expression of α-SMA, SERPINH-1, FN-1, VIM and COL1A1 and counteracting the TGF-β1-induced upregulation of key fibrotic markers, including α-SMA, COL1A2, and VIM, reflecting its capacity to attenuate myofibroblast activation and ECM production and modulating membrane lipid peroxidation. Furthermore, HE inhibited SMAD2 phosphorylation, suggesting that its antifibrotic activity may involve the modulation of the TGF-β/SMAD signaling pathway. Moreover, it promoted an anti-inflammatory response, due to a decrease in IL-1β and IL-6 expression. Our study highlights the potential of the ex vivo model as a platform for evaluating the antifibrotic efficacy of natural molecules, and it suggests significant translational implications and new opportunities for developing innovative therapeutic strategies
Application of Transthoracic and Endobronchial Elastography—A Systematic Review
Introduction: Ultrasound elastography is increasingly used across medical imaging, yet its role in thoracic disease remains poorly defined. While both transthoracic ultrasonography (TUS) and endobronchial ultrasound (EBUS) offer real-time assessment of pleural and pulmonary structures, the diagnostic and clinical value of elastography in this context remains uncertain. Materials and Method: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted according to PRISMA guidelines (April 2023; updated January 2025). Original studies evaluating transthoracic or endobronchial elastography for pleural or pulmonary conditions were included. Data extraction and quality assessment were performed independently by three reviewers, with QUADAS-2 used to evaluate risk of bias. Results: Thirty studies met inclusion criteria. Twenty-eight evaluated TUS elastography and two examined EBUS. Shear wave elastography was most frequently applied, particularly for differentiating malignant from benign pleural effusion or subpleural lesions. Surface wave elastography demonstrated consistently higher stiffness values in patients with interstitial lung disease compared with healthy controls, correlating with radiological and functional disease severity. Elastography-guided pleural biopsy improved diagnostic yield compared with conventional ultrasound-guided biopsy. Overall, substantial methodological variation existed among scanning techniques, elastography modalities, reporting methods, and diagnostic thresholds, limiting cross-study comparison. Conclusions: Ultrasound elastography shows promise for evaluating pleural effusion and pulmonary lesions, procedural guidance, and interstitial lung disease possibly improving diagnostic possibilities with bedside evaluation and reducing patient exposure to radiation. However, methodological variation and limited high-quality evidence preclude clinical implementation. Standardized acquisition protocols and multicentre validation studies are necessary to define its diagnostic utility in thoracic imaging
The Effect of an Educational Intervention Program on Allied Health Students’ Knowledge and Attitudes Regarding Organ Donation and Transplantation
Background: A significant shortage of available organs for transplantation persists globally, with insufficient education on organ donation recognized as a key contributing factor. Allied health students, when equipped with accurate knowledge, have the potential to serve as advocates for organ donation, influencing public attitudes through their social networks. Enhancing their understanding may contribute to increased organ donation awareness and acceptance within the broader community. Methods: This study employed a quasi-experimental design to examine the effect of an educational intervention program on allied health students’ knowledge and attitudes toward organ donation and transplantation. A total of 150 allied health students were recruited through simple random sampling. Data were collected using a valid and reliable translated self-administered online questionnaire. Participants were divided into intervention and control groups. Descriptive statistics, independent sample t-tests, and one-way ANOVA were used for data analysis. Results: Following the intervention, the mean score of knowledge and attitudes in the intervention group (M = 41.09, SD = 2.57) was significantly higher than that in the control group (M = 40.29, SD = 2.40), with a t-value of −3.49 and a p-value of <0.001. These results indicate that the educational program had a statistically significant positive effect on participants’ knowledge and attitudes regarding organ donation and transplantation. Conclusions: The implementation of the educational intervention significantly improved allied health students’ knowledge and attitudes toward organ donation and transplantation. This suggests that targeted educational programs for future health professionals may be an effective strategy to promote organ donation awareness and address the shortage of organ donors
The Impact of Perceptual Load and Distractors’ Perceptual Grouping on Visual Search in ASD
This study examined potential visual search advantages in individuals with autism spectrum disorder (ASD) and explored the roles of distractor grouping and perceptual load by comparing their performance with that of typically developing (TD) controls. Participants were required to search for large or small targets under two levels of perceptual load, with distractors being either large or small. The results showed the following: (1) Search speed in the ASD group was slower than that of the TD group. (2) The effect of distractor grouping was stronger in the Target–Nontarget (T-N) size-inconsistent condition than in the consistent condition. Both groups showed a T-N size-consistency effect—response speeds in the T-N size-inconsistent condition were faster, indicating that distractor grouping improves search efficiency. (3) Under high load, the TD group exhibited a stronger T-N size-consistency effect than the ASD group, whereas no significant difference was observed under low load. This suggests that distractor grouping in the ASD group is less effective than in TD participants under high load. (4) Under the T-N size-inconsistent condition, participants with ASD detected small targets faster under low load, whereas TD participants detected large targets faster under high load. This indicates that distractor grouping facilitates visual search in ASD under low load. Both groups focus more on targets under high load. In conclusion, although ASD shows no search advantage, improving distractor grouping can speed up target search. Nevertheless, under high load, distractor grouping in individuals with ASD is weaker than in TD individuals, consistent with the weak central coherence theory. Additionally, ASD displays size asymmetry that is influenced by load, with distractor grouping aiding target detection in low load and reducing distractor processing under high load
Comprehensive Genomic Characterization of 102 Cervical Adenocarcinoma Tumors
Background and Objectives: Cervical adenocarcinoma (CAC) is a histologically distinct subtype of cervical cancer with a rising incidence in many regions. While the roles of key driver mutations are known, a comprehensive understanding of its genomic landscape, particularly variations across different populations and tumor stages, remains incomplete. This study aims to characterize the somatic genomic landscape of CAC by identifying recurrent mutations, copy number alterations (CNAs), and patterns of co-occurrence, with a focus on variations across racial groups and between primary and metastatic tumors. Materials and Methods: We conducted a comprehensive genomic analysis of 102 tumor samples from 99 patients diagnosed with cervical adenocarcinoma using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Results: The most frequently mutated genes were PIK3CA (25.5%), TP53 (21.6%), ARID1A (20.6%), and KRAS (16.7%). Significant amplification of ERBB2 was also observed (n = 3; 4.83%). Our analysis revealed notable genomic disparities across racial groups, with TP53 mutations being significantly more frequent in White patients compared to Asian and Black patients (p = 0.0236). Furthermore, we identified significant co-occurrence between mutations in KRAS and MSH2 (p = 0.011) as well as ATM and STK11 (p = 0.037). In comparing tumor types, mutations in BCL6 were found to be significantly enriched in metastatic samples. Conclusions: This study validates the primary drivers of cervical adenocarcinoma and reveals novel findings, including notable racial disparities in TP53 mutation frequency and unique patterns of co-occurring mutations. These findings highlight the genomic heterogeneity of the disease and suggest that ancestry and tumor evolution may influence its molecular pathogenesis, offering potential avenues for the development of targeted therapies and personalized biomarkers
Sociodemographic and Health-Seeking Factors Associated with First-Trimester Prenatal Care: A Cross-Sectional Study of PRAMS Data
Objective: This study assessed sociodemographic, health-seeking and social services related factors associated with first-trimester prenatal care. Study Design: This cross-sectional study used Phase 8 pooled data from the Kentucky Pregnancy Risk Assessment Monitoring System (PRAMS) for 2017 to 2020 and 2022. A logistic regression model was used to estimate unadjusted and adjusted odds ratios and 95% confidence intervals. Results: Among the 3502 women in the analytic sample, 89.3% had first-trimester prenatal care. Most respondents were White (weighted percentage, 83.3%), between the ages of 25 and 29 (31.2%), had more than a high school education (59.5%), were married (59.8%), lived in an urban area (59.4%), and had public insurance (53.9%). Maternal education was associated with the highest odds of first-trimester prenatal care, relative to other covariates, and was highest among those who completed more than high school (aOR 4.23, 95% CI 2.72–6.59) and high school (aOR 3.09, 95% CI 2.06–4.64) relative to less than high school. Private insurance, having a healthcare visit one year prior to pregnancy, and WIC receipt during pregnancy were associated with higher odds of first-trimester prenatal care. Conclusions: The findings of this study suggest that sociodemographic factors and access to healthcare and social services are important factors in first-trimester prenatal care
Twig and Leaf Morphological Traits and Photosynthetic Physiological Characteristics of Periploca sepium in Response to Different Light Environments in Taohe Riparian Forests
Understanding the variations in twig and leaf morphologies and photosynthetic physiological characteristics of riparian forest plants in heterogeneous habitats is of great significance for revealing their phenotypic plasticity mechanisms and ecological adaptation strategies. In this study, the riparian forest plant Periploca sepium Bunge was selected as the research object. According to the canopy light environment experienced by the P. sepium population, three habitats were established: under-canopy, gap, and full-sun areas. We studied the twig and leaf morphological and photosynthetic characteristics of P. sepium under heterogeneous light environments, as well as the relationships between these two aspects. Plants in the under-canopy area developed long and thick twigs with few large leaves, coupled with high actual photosynthetic efficiency of photosystem II (Y(II)) and low non-photochemical quenching (NPQ), whereas those in the full-sun area exhibited the opposite covariation strategy. Significant correlations between twig and leaf morphologies and photosynthetic physiological characteristics were found across all habitats. The coordinated variations in twig and leaf morphologies and photosynthetic physiology of P. sepium embody a resource investment trade-off strategy that plants have evolved through long-term adaptation to heterogeneous light environments
Capital City Relocation and Spatial Governance in Archipelagic Indonesia: Institutional Inertia and Urban Vitality in North Maluku
This study explores global experiences of capital relocation to extract lessons relevant to North Maluku, Indonesia, where Sofifi has yet to develop into a functional provincial capital. Drawing on six theoretical perspectives, including growth pole theory, polycentric development, institutional inertia, urban metabolism, spatial justice, and urban vitality, the paper analyzes how political vision, institutional integration, and social participation influence relocation outcomes. Comparative cases from Abuja, Brasília, Putrajaya, Naypyidaw, Randstad, and Nusantara show that successful relocations occur when governance reform aligns with spatial planning and participatory urban design. For Sofifi, enhancing urban vitality through connectivity, inclusiveness, and institutional coordination is essential to transform relocation from a symbolic decision into a functional urban system. The study contributes a conceptual framework linking spatial design, institutional reform, and social vibrancy in the pursuit of sustainable and equitable capital development
Comparison of Body Position Perception, Tongue Pressure and Neck Muscle Endurance in Patients with Bruxism and Temporomandibular Joint Dysfunction: Occlusal Splint Users and Non-Users
Background: This study aimed to investigate the association between occlusal splint use and several key parameters, including body position perception, tongue pressure, temporomandibular joint dysfunction (TMD) severity, jaw functional limitation, and neck muscle endurance. Methods: A total of 157 individuals diagnosed with bruxism were screened, and 52 eligible participants were enrolled and divided into two groups: occlusal splint users (n = 26) and non-users (n = 26). Body position perception was assessed with a digital inclinometer, tongue pressure was measured using the Iowa Oral Performance Instrument (IOPI), and neck muscle endurance was evaluated by the Cranio-Cervical Flexion Test (CCFT). TMD severity and jaw functional limitation were assessed via the Fonseca Anamnestic Questionnaire and Jaw Functional Limitation Scale-20, respectively. Gender-based analyses showed higher TMD severity and mandibular limitation scores in females using occlusal splints than in males. Results: No statistically significant differences were found between the splint and non-splint groups in body position perception, tongue pressure and neck muscle endurance (p > 0.05). However, significant differences were observed in the Jaw Functional Limitation Scale (CFKS) subscales. Splint users reported higher functional limitations in chewing, mobility, and expression compared to non-splint users (all p = 0.000), with small effect sizes (d = 0.23–0.29). Conclusions: Occlusal splint use was not associated with better proprioception, orofacial muscle function, or TMD-related symptoms compared with non-splint users. However, splint users were associated with higher mandibular functional limitation based on CFKS subscale scores
A Fractional Calculus Approach to Energy Balance Modeling: Incorporating Memory for Responsible Forecasting
Global climate change demands modeling approaches that are both computationally efficient and physically faithful to the system’s long-term dynamics. Classical Energy Balance Models (EBMs), while valuable, are fundamentally limited by their memoryless exponential response, which fails to represent the prolonged thermal inertia of the climate system—particularly that associated with deep-ocean heat uptake. In this study, we introduce a fractional Energy Balance Model (fEBM) by replacing the classical integer-order time derivative with a Caputo fractional derivative of order α(0<α≤1), thereby embedding long-range memory directly into the model structure. We establish a rigorous mathematical foundation for the fEBM, including proofs of existence, uniqueness, and asymptotic stability, ensuring theoretical well-posedness and numerical reliability. The model is calibrated and validated against historical global mean surface temperature data from NASA GISTEMP and radiative forcing estimates from IPCC AR6. Relative to the classical EBM, the fEBM achieves a substantially improved representation of observed temperatures, reducing the root mean square error by approximately 29% during calibration (1880–2010) and by 47% in out-of-sample forecasting (2011–2023). The optimized fractional order α=0.75±0.03 emerges as a physically interpretable measure of aggregate climate memory, consistent with multi-decadal ocean heat uptake and observed persistence in temperature anomalies. Residual diagnostics and robustness analyses further demonstrate that the fractional formulation captures dominant temporal dependencies without overfitting. By integrating mathematical rigor, uncertainty quantification, and physical interpretability, this work positions fractional calculus as a powerful and responsible framework for reduced-order climate modeling and long-term projection analysis