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22 pages, 1531 KiB  
Article
Evaluation of the Biological Properties and Antibacterial Activities of the Natural Food Supplement “Epavin” for Liver Detoxification and Protection
by Alexia Barbarossa, Maria Pia Argentieri, Maria Valeria Diella, Anita Caforio, Antonio Carrieri, Filomena Corbo, Antonio Rosato and Alessia Carocci
Foods 2025, 14(15), 2600; https://doi.org/10.3390/foods14152600 (registering DOI) - 24 Jul 2025
Abstract
Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients [...] Read more.
Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H2O2 was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article
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19 pages, 2530 KiB  
Article
Soil Microbiome Drives Depth-Specific Priming Effects in Picea schrenkiana Forests Following Labile Carbon Input
by Kejie Yin, Lu Gong, Xinyu Ma, Xiaochen Li and Xiaonan Sun
Microorganisms 2025, 13(8), 1729; https://doi.org/10.3390/microorganisms13081729 (registering DOI) - 24 Jul 2025
Abstract
The priming effect (PE), a microbially mediated process, critically regulates the balance between carbon sequestration and mineralization. This study used soils from different soil depths (0–20 cm, 20–40 cm, and 40–60 cm) under Picea schrenkiana forest in the Tianshan Mountains as the research [...] Read more.
The priming effect (PE), a microbially mediated process, critically regulates the balance between carbon sequestration and mineralization. This study used soils from different soil depths (0–20 cm, 20–40 cm, and 40–60 cm) under Picea schrenkiana forest in the Tianshan Mountains as the research object. An indoor incubation experiment was conducted by adding three concentrations (1% SOC, 2% SOC, and 3% SOC) of 13C-labelled glucose. We applied 13C isotope probe-phospholipid fatty acid (PLFA-SIP) technology to investigate the influence of readily labile organic carbon inputs on soil priming effect (PE), microbial community shifts at various depths, and the mechanisms underlying soil PE. The results indicated that the addition of 13C-labeled glucose accelerated the mineralization of soil organic carbon (SOC); CO2 emissions were highest in the 0–20 cm soil layer and decreased trend with increasing soil depth, with significant differences observed across different soil layers (p < 0.05). Soil depth had a positive direct effect on the cumulative priming effect (CPE); however, it showed negative indirect effects through physico-chemical properties and microbial biomass. The CPE of the 0–20 cm soil layer was significantly positively correlated with 13C-Gram-positive bacteria, 13C-Gram-negative bacteria, and 13C-actinomycetes. The CPE of the 20–40 cm and 40–60 cm soil layers exhibited a significant positive correlation with cumulative mineralization (CM) and microbial biomass carbon (MBC). Glucose addition had the largest and most significant positive effect on the CPE. Glucose addition positively affected PLFAs and particularly microbial biomass. This study provides valuable insights into the dynamics of soil carbon pools at varying depths following glucose application, advancing the understanding of forest soil carbon sequestration. Full article
(This article belongs to the Section Environmental Microbiology)
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14 pages, 563 KiB  
Article
Iodized Salt Coverage and Influencing Factors in Chinese Out-of-Home Dining Venues: A Large Cross-Sectional Study from 31 Provinces of China
by Ying Zhang, Wei Ma, Jianqiang Wang, Haiyan Wang, Xiuwei Li, Jinpeng Wang and Jing Xu
Nutrients 2025, 17(15), 2415; https://doi.org/10.3390/nu17152415 (registering DOI) - 24 Jul 2025
Abstract
Background/Objectives: With the rising trend of out-of-home dining in China, the use of iodized salt (IS) in eating-out venues plays a key role in preventing iodine deficiency disorders (IDDs). However, the coverage rate of iodized salt (CRIS) and the utilization rate of adequately [...] Read more.
Background/Objectives: With the rising trend of out-of-home dining in China, the use of iodized salt (IS) in eating-out venues plays a key role in preventing iodine deficiency disorders (IDDs). However, the coverage rate of iodized salt (CRIS) and the utilization rate of adequately iodized salt (URAIS) in these venues in China remain underexplored, potentially undermining IDD prevention strategies. This study aims to assess the CRIS and URAIS in such venues across China and identify the factors influencing their prevalence. Methods: From 2021 to 2024, a nationwide cross-sectional study was conducted in China, involving 19,346 venues. A 50 g sample of cooking salt was collected from each venue, and the iodine content was measured. The CRIS and URAIS were calculated, and associations with various factors were assessed using Chi-square tests, the Cochran–Armitage trend test, and multivariate logistic regression. Results: Of the 19,346 samples, 18,519 tested positive for IS, and 17,588 contained adequately iodized salt (AIS), resulting in a CRIS of 95.7% and a URAIS of 90.9%. Significant regional differences were found, with coastal areas showing a lower CRIS and URAIS than inland areas (87.0% vs. 97.8%; 81.0% vs. 93.2%) and urbanized areas having lower rates compared to less urbanized areas (94.1% vs. 97.3%; 88.9% vs. 92.9%). Higher per capita income was associated with a lower CRIS and URAIS (Z = −19.72, p < 0.0001; Z = −13.85, p < 0.0001). Lower per capita income (OR = 3.24, OR = 1.36, p < 0.0001), inland areas (OR = 4.14, OR = 2.68, p < 0.0001), and mountainous areas (OR = 2.48, OR = 1.27, p < 0.0001) were associated with a higher likelihood of IS and AIS use. Conclusions: While the CRIS and URAIS in dining venues meet national standards, regional disparities persist, particularly in coastal, plain, and economically advanced areas. Strengthening regulatory oversight and public education on iodized salt’s health benefits is essential. Full article
(This article belongs to the Section Micronutrients and Human Health)
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14 pages, 1209 KiB  
Article
Investigation of Growth Differentiation Factor 15 as a Prognostic Biomarker for Major Adverse Limb Events in Peripheral Artery Disease
by Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
J. Clin. Med. 2025, 14(15), 5239; https://doi.org/10.3390/jcm14155239 (registering DOI) - 24 Jul 2025
Abstract
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict [...] Read more.
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article
(This article belongs to the Special Issue The Role of Biomarkers in Cardiovascular Diseases)
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35 pages, 4256 KiB  
Article
Automated Segmentation and Morphometric Analysis of Thioflavin-S-Stained Amyloid Deposits in Alzheimer’s Disease Brains and Age-Matched Controls Using Weakly Supervised Deep Learning
by Gábor Barczánfalvi, Tibor Nyári, József Tolnai, László Tiszlavicz, Balázs Gulyás and Karoly Gulya
Int. J. Mol. Sci. 2025, 26(15), 7134; https://doi.org/10.3390/ijms26157134 (registering DOI) - 24 Jul 2025
Abstract
Alzheimer’s disease (AD) involves the accumulation of amyloid-β (Aβ) plaques, whose quantification plays a central role in understanding disease progression. Automated segmentation of Aβ deposits in histopathological micrographs enables large-scale analyses but is hindered by the high cost of detailed pixel-level annotations. Weakly [...] Read more.
Alzheimer’s disease (AD) involves the accumulation of amyloid-β (Aβ) plaques, whose quantification plays a central role in understanding disease progression. Automated segmentation of Aβ deposits in histopathological micrographs enables large-scale analyses but is hindered by the high cost of detailed pixel-level annotations. Weakly supervised learning offers a promising alternative by leveraging coarse or indirect labels to reduce the annotation burden. We evaluated a weakly supervised approach to segment and analyze thioflavin-S-positive parenchymal amyloid pathology in AD and age-matched brains. Our pipeline integrates three key components, each designed to operate under weak supervision. First, robust preprocessing (including retrospective multi-image illumination correction and gradient-based background estimation) was applied to enhance image fidelity and support training, as models rely more on image features. Second, class activation maps (CAMs), generated by a compact deep classifier SqueezeNet, were used to identify, and coarsely localize amyloid-rich parenchymal regions from patch-wise image labels, serving as spatial priors for subsequent refinement without requiring dense pixel-level annotations. Third, a patch-based convolutional neural network, U-Net, was trained on synthetic data generated from micrographs based on CAM-derived pseudo-labels via an extensive object-level augmentation strategy, enabling refined whole-image semantic segmentation and generalization across diverse spatial configurations. To ensure robustness and unbiased evaluation, we assessed the segmentation performance of the entire framework using patient-wise group k-fold cross-validation, explicitly modeling generalization across unseen individuals, critical in clinical scenarios. Despite relying on weak labels, the integrated pipeline achieved strong segmentation performance with an average Dice similarity coefficient (≈0.763) and Jaccard index (≈0.639), widely accepted metrics for assessing segmentation quality in medical image analysis. The resulting segmentations were also visually coherent, demonstrating that weakly supervised segmentation is a viable alternative in histopathology, where acquiring dense annotations is prohibitively labor-intensive and time-consuming. Subsequent morphometric analyses on automatically segmented Aβ deposits revealed size-, structural complexity-, and global geometry-related differences across brain regions and cognitive status. These findings confirm that deposit architecture exhibits region-specific patterns and reflects underlying neurodegenerative processes, thereby highlighting the biological relevance and practical applicability of the proposed image-processing pipeline for morphometric analysis. Full article
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21 pages, 2576 KiB  
Systematic Review
Assessing the Effects of Moderate to High Dosage of Astaxanthin Supplementation on Lipid Profile Parameters—A Systematic Review and Meta-Analysis of Randomized Controlled Studies
by Lucas Fornari Laurindo, Victória Dogani Rodrigues, Dennis Penna Carneiro, Luiz Sérgio Marangão Filho, Eliana de Souza Bastos Mazuqueli Pereira, Ricardo José Tofano, Eduardo Federighi Baisi Chagas, Jesselina Francisco dos Santos Haber, Flávia Cristina Castilho Caracio, Letícia Zanoni Moreira, Vitor Engrácia Valenti and Sandra Maria Barbalho
Pharmaceuticals 2025, 18(8), 1097; https://doi.org/10.3390/ph18081097 (registering DOI) - 24 Jul 2025
Abstract
Background/Objectives: Astaxanthin, a xanthophyll carotenoid, has garnered significant interest due to its benefits with regard to dyslipidemia. This multifaceted functional food ingredient modulates several key enzymes associated with lipid regulation, including HMG-CoA reductase, CPT1, ACCβ, and acyl-CoA oxidase. It influences key antioxidant molecular [...] Read more.
Background/Objectives: Astaxanthin, a xanthophyll carotenoid, has garnered significant interest due to its benefits with regard to dyslipidemia. This multifaceted functional food ingredient modulates several key enzymes associated with lipid regulation, including HMG-CoA reductase, CPT1, ACCβ, and acyl-CoA oxidase. It influences key antioxidant molecular pathways like the Nrf2, limiting dyslipidemia occurrence and regulating liver cholesterol uptake through the modulation of liver lipid receptors. Due to the current lack of systematic reviews and meta-analyses assessing moderate to high dosages (6–24 mg/d) of astaxanthin supplementation on lipid dysregulation, the present manuscript aims to fill this gap in the literature. Methods: Following the PRISMA guidelines, we included eight studies comprising eleven results from the PubMed, Springer Link, Science Direct, Cochrane, and Google Scholar databases. The Jamovi (Version 2.6.26, Solid) software was utilized for statistics. Our primary objective was to assess in detail the effects of astaxanthin on LDL-C, HDL-C, triglyceride, and total cholesterol levels. Results: The meta-analysis concludes positive effects of astaxanthin (6–20 mg/d) on HDL-C (0.4200; 95% CI: 0.1081 to 0.7319) and triglyceride (−0.3058; 95% CI: −0.5138 to −0.0978) levels. Unfortunately, astaxanthin (6–20 mg/d) does not appear to significantly influence LDL-C (−0.0725; 95% CI: −0.3070 to 0.1620) and total cholesterol (−0.0448; 95% CI: −0.3369 to 0.2473) levels. Regarding HDL-C, improvements were observed from 55 ± 8 mg/dL (pre-intervention) to 63 ± 8 mg/dL (post-intervention) (p < 0.01) in the 12 mg/d of astaxanthin groups. In the assessment of triglyceride levels, results show a decrease from 151 ± 26 mg/dL (pre-intervention) to 112 ± 40 mg/dL (post-intervention) (p < 0.01) for 18 mg/d astaxanthin supplementation. Conclusions: Further research is necessary to fully harness the potential of astaxanthin, which includes assessing astaxanthin in different subsets of patients, using a GWAS, and in combination with other nutraceuticals to understand the compound’s effectiveness with regard to varying health conditions, genetic and epigenetic factors, and synergistic effects with other compounds. Full article
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18 pages, 692 KiB  
Review
Literature Review and Policy Recommendations for Single-Dose HPV Vaccination Schedule in China: Opportunities and Challenges
by Kexin Cao and Yiu-Wing Kam
Vaccines 2025, 13(8), 786; https://doi.org/10.3390/vaccines13080786 (registering DOI) - 24 Jul 2025
Abstract
Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose [...] Read more.
Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose vaccination schedule. The objective of this review is to critically examine the current HPV vaccination landscape in China, including vaccination policies, immunization schedules, supply–demand dynamics, and the feasibility of transitioning to a single-dose regimen. By synthesizing recent developments in HPV virology, epidemiology, vaccine types, and immunization strategies, we identify both opportunities and barriers unique to the Chinese context. Results indicate that China primarily adheres to a three-dose vaccination schedule, with an optional two-dose schedule for girls aged 9–14, leaving a notable gap compared to the most recent WHO recommendation. The high prevalence of HPV types 52 and 58 contributes to a distinct regional infection pattern, underscoring the specific need for nine-valent vaccines tailored to China’s epidemiological profile. Despite the growing demand, vaccine supply remains inadequate, with an estimated annual shortfall of more than 15 million doses. This issue is further complicated by strong public preference for the nine-valent vaccine and the relatively high cost of vaccination. Emerging evidence supports the comparable efficacy and durable protection of a single-dose schedule, which could substantially reduce financial and logistical burdens while expanding coverage. This review advocates for the adoption of a simplified single-dose regimen, supported by catch-up strategies for older cohorts and the integration of HPV vaccination into China’s National Immunization Program (NIP). Sustained investment in domestic vaccine development and centralized procurement of imported vaccines may also possibly alleviate supply shortage. These coordinated efforts are critical for strengthening HPV-related disease prevention and accelerating China’s progress toward the WHO’s cervical cancer elimination targets. Full article
(This article belongs to the Special Issue Vaccination Strategies for Global Public Health)
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13 pages, 2372 KiB  
Article
PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy
by Mihnea Bogdan Borz, Bogdan Fetica, Maximilian Cosma Gliga, Tamas-Csaba Sipos, Bogdan Adrian Buhas and Vlad Horia Schitcu
Diseases 2025, 13(8), 235; https://doi.org/10.3390/diseases13080235 - 24 Jul 2025
Abstract
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. [...] Read more.
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts. Full article
(This article belongs to the Section Oncology)
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14 pages, 610 KiB  
Article
Understanding the Role of Loneliness in the Relationships Between Post-Traumatic Stress Symptoms and Both Anxiety and Depressive Symptoms Among University Students: A Mediation Analysis
by Ilaria Riboldi, Cristina Crocamo, Chiara Alessandra Capogrosso, Francesco Bartoli, Jo Armes, Cath Taylor and Giuseppe Carrà
Brain Sci. 2025, 15(8), 787; https://doi.org/10.3390/brainsci15080787 - 24 Jul 2025
Abstract
Background/Objectives: Both traumatic and stressful events, including major life changes, may contribute to post-traumatic stress symptoms (PTS), often associated with anxiety and depression. Feelings of loneliness may influence these relationships, whilst social support seems to mitigate the effects of stressful events on [...] Read more.
Background/Objectives: Both traumatic and stressful events, including major life changes, may contribute to post-traumatic stress symptoms (PTS), often associated with anxiety and depression. Feelings of loneliness may influence these relationships, whilst social support seems to mitigate the effects of stressful events on mental health. Our study thus aimed to evaluate the mediating role of loneliness in the relationships between PTS and both anxiety and depressive symptoms among university students. Methods: The data were from the CAMPUS study (0058642/21; FHMS 20-21 157), a survey on university students’ mental health in Italy and the UK. Using a logit model, mediation analyses were carried out to test whether the relationships between PTS and both anxiety and depressive symptoms might be mediated by loneliness. A path analysis was then performed to jointly test the associations between the Impact of Event Scale—Revised (IES-R)’s subscales and clinical domains. Results: Positive associations were found between PTS and both anxiety (p < 0.001) and depressive symptoms (p < 0.001). However, loneliness mediated approximately 22% of the effect of the PTS on anxiety symptoms (indirect effect: 1.04, 95% CI: 0.59; 1.48, p < 0.001) and approximately 33% of the effect of the PTS on depressive symptoms (indirect effect: 1.81, 95% CI: 1.22; 2.39, p < 0.001). Furthermore, the path analysis indicated associations between the IES-R’s hyperarousal subscale and both anxiety (coeff.: 0.34, p < 0.001) and depressive symptoms (coeff.: 0.27, p < 0.001). Conclusions: Along with the associations between PTS and both anxiety and depressive symptoms, our findings highlight the key role of loneliness in both these associations. Targeted interventions to reduce loneliness, especially for students exposed to traumatic events, may ultimately improve their mental health. Full article
(This article belongs to the Special Issue Emerging Trends in Youth Mental Health)
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21 pages, 1292 KiB  
Article
Polymorphism in IFNλ Can Impact the Immune/Inflammatory Response to COVID-19 Vaccination in Older CMV-Seropositive Adults
by Ariane Nardy, Fernanda Rodrigues Monteiro, Brenda Rodrigues Silva, Jônatas Bussador do Amaral, Danielle Bruna Leal Oliveira, Érika Donizetti de Oliveira Cândido, Edison Luiz Durigon, Andressa Simões Aguiar, Guilherme Pereira Scagion, Vanessa Nascimento Chalup, Guilherme Eustáquio Furtado, Marina Tiemi Shio, Carolina Nunes França, Luiz Henrique da Silva Nali and André Luis Lacerda Bachi
Vaccines 2025, 13(8), 785; https://doi.org/10.3390/vaccines13080785 - 24 Jul 2025
Abstract
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of [...] Read more.
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article
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11 pages, 3472 KiB  
Case Report
The Use of a Digitally Generated Matrix for Consistent Shade Recording in Tooth Bleaching—A Case Report
by Cristian Abad-Coronel, Guissell Vallejo-Yupa, Paulina Aliaga, Nancy Mena-Córdova, Jorge Alonso Pérez-Barquero and José Amengual-Lorenzo
Dent. J. 2025, 13(8), 339; https://doi.org/10.3390/dj13080339 - 24 Jul 2025
Abstract
Objectives: The aim of this study was to evaluate the effectiveness of spectrophotometers for objective tooth color measurement, particularly in bleaching procedures enhanced by digital positioning templates. Methods: Tooth color registration was conducted using both subjective methods with shade guides and objective methods [...] Read more.
Objectives: The aim of this study was to evaluate the effectiveness of spectrophotometers for objective tooth color measurement, particularly in bleaching procedures enhanced by digital positioning templates. Methods: Tooth color registration was conducted using both subjective methods with shade guides and objective methods with spectrophotometers. Spectrophotometers were chosen for their ability to provide objective, quantifiable, and reproducible results, crucial for monitoring color modifications accurately. Digital workflows were implemented to enhance the registration process further. These workflows included providing a precise positioning matrix for spectrophotometer sensors and optimizing working models to ensure high-quality therapeutic splints. Results: The use of spectrophotometers demonstrated superior performance in registering tooth color objectively compared to subjective shade guides. Digital workflows significantly improved the precision and efficiency of spectrophotometer measurements through a digital matrix, enhancing the quality of therapeutic splints obtained. Conclusions: Spectrophotometers are recommended for objective and precise tooth color registration, particularly in bleaching procedures. Integrating a digital positioning matrix enhances measurement accuracy and reliability, supporting effective monitoring and treatment outcomes. Full article
(This article belongs to the Special Issue New Trends in Digital Dentistry)
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15 pages, 1585 KiB  
Article
Expression Analysis, Diagnostic Significance and Biological Functions of BAG4 in Acute Myeloid Leukemia
by Osman Akidan, Selçuk Yaman, Serap Ozer Yaman and Sema Misir
Medicina 2025, 61(8), 1333; https://doi.org/10.3390/medicina61081333 - 24 Jul 2025
Abstract
Background and Objectives: A thorough comprehension of the essential molecules and related processes underlying the carcinogenesis, proliferation, and recurrence of acute myeloid leukemia (AML) is crucial. This study aimed to investigate the expression levels, diagnostic and prognostic significance and biological roles of [...] Read more.
Background and Objectives: A thorough comprehension of the essential molecules and related processes underlying the carcinogenesis, proliferation, and recurrence of acute myeloid leukemia (AML) is crucial. This study aimed to investigate the expression levels, diagnostic and prognostic significance and biological roles of Bcl-2-associated athanogene 4 (BAG4) in AML carcinogenesis. Materials and Methods: Gene expression profiles were analyzed using publicly available datasets, particularly GSE9476 and TCGA, using tools such as GEO2R, GEPIA2, UALCAN and TIMER2.0. The immune infiltration correlation was examined using the GSCA platform, while the function of BAG4 at the single-cell level was analyzed via CancerSEA. Protein–protein and gene–gene interaction networks were constructed using STRING and GeneMANIA, and enrichment analyses were performed using GO, KEGG and DAVID. Expression validation was performed using RT-qPCR in HL-60 (AML) and HaCaT (normal) cells, and ROC curve analysis evaluated the diagnostic accuracy. Results: BAG4 was significantly overexpressed in AML tissues and cell lines compared with healthy controls. High BAG4 expression was associated with poor overall survival and strong diagnostic power (AUC = 0.944). BAG4 was positively associated with immune cell infiltration and negatively associated with CD4+/CD8+ T and NK cells. At the single-cell level, BAG4 was associated with proliferation, invasion, and DNA repair functions. Functional network analysis showed that BAG4 interacted with apoptosis and necroptosis-related genes such as BCL2, BAG3 and TNFRSF1A and was enriched in pathways such as NF-κB, TNF signaling and apoptosis. Conclusions: BAG4 is overexpressed in AML and is associated with adverse clinical outcomes and immune modulation. It may play an important role in leukemogenesis by affecting apoptotic resistance and immune evasion. BAG4 has potential as a diagnostic biomarker and treatment target in AML, but further in vivo and clinical validation is needed. Full article
(This article belongs to the Section Genetics and Molecular Medicine)
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14 pages, 1541 KiB  
Article
Effectiveness of an Essential Oil Mouthwash on Halitosis in Obese Patients with Periodontitis: A Short-Term Clinical Evaluation
by Gabriela Beresescu, Despina Luciana Bereczki-Temistocle, Liana Beresescu, Alina Ormenisan, Adriana Monea and Ion Razvan-Marius
J. Clin. Med. 2025, 14(15), 5225; https://doi.org/10.3390/jcm14155225 - 23 Jul 2025
Abstract
Background: Halitosis is a common condition often rooted in periodontal disease and exacerbated by systemic disorders such as obesity. This short-term clinical evaluation investigates the relationship between halitosis, obesity, and periodontitis, and assesses the efficacy of a natural essential oil mouthwash as an [...] Read more.
Background: Halitosis is a common condition often rooted in periodontal disease and exacerbated by systemic disorders such as obesity. This short-term clinical evaluation investigates the relationship between halitosis, obesity, and periodontitis, and assesses the efficacy of a natural essential oil mouthwash as an adjunctive oral hygiene intervention. Methods: In this randomized, placebo-controlled clinical trial, 45 obese patients with diagnosed periodontitis and self-reported halitosis were randomly assigned to either a test group (n = 30), receiving an essential oil-based mouthwash, or a control group (n = 15), receiving a placebo. Over 28 days, participants were evaluated using plaque index (PI), bleeding on probing (BOP), organoleptic scoring, and BANA test results. Both subjective and objective halitosis assessments were performed. Results: The test group showed marked improvements in all parameters compared to controls. PI decreased by 31.5% in the test group versus 9.25% in controls; BOP reduced by 34.5% versus 6.0%; BANA test positivity dropped by 38.1% in the test group. Organoleptic scores improved by 45.9% (examiner-rated) and 36.8% (self-assessed) in the test group. Conclusions: This 28-day clinical evaluation demonstrates the potential of an essential oil-based mouthwash to significantly reduce halitosis and periodontal inflammation in obese individuals with periodontitis. The necessity of future randomized trials is evident to substantiate the sustained benefits and safety of the intervention. Full article
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15 pages, 2267 KiB  
Article
Comparison Between Titanium and Thermally Activated Prostheses in Stapes Surgery
by Mila Vasiljević, Klara Dragović, Petra Povalej Bržan and Janez Rebol
Appl. Sci. 2025, 15(15), 8211; https://doi.org/10.3390/app15158211 (registering DOI) - 23 Jul 2025
Abstract
This study investigates hearing outcomes of stapedotomy using two different types of prostheses: manually crimped MatriX and thermally activated NiTiBOND. The primary objective was to determine whether the method of prosthesis fixation to the long process of incus influences postoperative results. A retrospective [...] Read more.
This study investigates hearing outcomes of stapedotomy using two different types of prostheses: manually crimped MatriX and thermally activated NiTiBOND. The primary objective was to determine whether the method of prosthesis fixation to the long process of incus influences postoperative results. A retrospective analysis was conducted on 155 patients with otosclerosis; 90 received the NiTiBOND prosthesis and 65 received the MatriX prosthesis. Choice of prosthesis was determined intraoperatively based on position of chorda tympani. If the nerve was located near the incus and the prosthesis fixation site, the surgeon opted for MatriX prosthesis to avoid potential injury from activation of the NiTiBOND. Audiometric evaluations revealed no statistically significant differences in bone conduction thresholds on the first postoperative day (p = 0.275) or at six weeks (p = 0.899), postoperative air-bone gap (p = 0.810), air-bone gap closure (p = 0.489), overclosure (p = 0.436), or bone conduction at 4 kHz (p = 0.324). Chorda tympani nerve injury occurred in 9.2% of cases with MatriX prosthesis and 6.7% with NiTiBOND prosthesis (p = 0.556). Our findings highlight the theoretical and practical significance of comparing both prostheses, demonstrating that NiTiBOND can serve as an alternative in anatomically favorable cases, thereby guiding treatment choices. Full article
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20 pages, 1816 KiB  
Article
A Self-Attention-Enhanced 3D Object Detection Algorithm Based on a Voxel Backbone Network
by Zhiyong Wang and Xiaoci Huang
World Electr. Veh. J. 2025, 16(8), 416; https://doi.org/10.3390/wevj16080416 - 23 Jul 2025
Abstract
3D object detection is a fundamental task in autonomous driving. In recent years, voxel-based methods have demonstrated significant advantages in reducing computational complexity and memory consumption when processing large-scale point cloud data. A representative method, Voxel-RCNN, introduces Region of Interest (RoI) pooling on [...] Read more.
3D object detection is a fundamental task in autonomous driving. In recent years, voxel-based methods have demonstrated significant advantages in reducing computational complexity and memory consumption when processing large-scale point cloud data. A representative method, Voxel-RCNN, introduces Region of Interest (RoI) pooling on voxel features, successfully bridging the gap between voxel and point cloud representations for enhanced 3D object detection. However, its robustness deteriorates when detecting distant objects or in the presence of noisy points (e.g., traffic signs and trees). To address this limitation, we propose an enhanced approach named Self-Attention Voxel-RCNN (SA-VoxelRCNN). Our method integrates two complementary attention mechanisms into the feature extraction phase. First, a full self-attention (FSA) module improves global context modeling across all voxel features. Second, a deformable self-attention (DSA) module enables adaptive sampling of representative feature subsets at strategically selected positions. After extracting contextual features through attention mechanisms, these features are fused with spatial features from the base algorithm to form enhanced feature representations, which are subsequently input into the region proposal network (RPN) to generate high-quality 3D bounding boxes. Experimental results on the KITTI test set demonstrate that SA-VoxelRCNN achieves consistent improvements in challenging scenarios, with gains of 2.49 and 1.87 percentage points at Moderate and Hard difficulty levels, respectively, while maintaining real-time performance at 22.3 FPS. This approach effectively balances local geometric details with global contextual information, providing a robust detection solution for autonomous driving applications. Full article
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