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28 pages, 1420 KB  
Review
Ethnoveterinary Potential of Acacia (Vachellia and Senegalia) Species for Managing Livestock Health in Africa: From Traditional Uses to Therapeutic Applications
by Nokwethemba N. P. Msimango, Adeyemi O. Aremu, Stephen O. Amoo and Nqobile A. Masondo
Plants 2025, 14(19), 3107; https://doi.org/10.3390/plants14193107 (registering DOI) - 9 Oct 2025
Abstract
In Africa, the folkloric practices involving plant-based remedies play a crucial role in livestock farming, often attributed to the limited access to modern veterinary services. The use of Acacia species (including those reclassified as Vachellia species) in ethnoveterinary medicine has garnered increasing interest [...] Read more.
In Africa, the folkloric practices involving plant-based remedies play a crucial role in livestock farming, often attributed to the limited access to modern veterinary services. The use of Acacia species (including those reclassified as Vachellia species) in ethnoveterinary medicine has garnered increasing interest due to their high protein content and medicinal (including anti-parasitic) properties, offering a sustainable source of fodder particularly in arid and semi-arid regions. However, scientific assessment of their efficacy and safety remains limited. This systematic review examines the ethnoveterinary uses, biological efficacy and safety of Acacia species across Africa. A literature search was conducted using PubMed, Google Scholar and Scopus, yielding 519 relevant studies published between 2001 and 2024. After applying the inclusion and exclusion criteria, 43 eligible studies were analyzed based on their relevance, geographical location and livestock disease applications. Plants of the World online database was used to validate the names of the species and authority. Ethiopia had the highest usage of Acacia species (25%), then Nigeria (20%) followed by both South Africa (15%) and Namibia (15%). Vachellia nilotica (Acacia nilotica) was the most frequently cited species (26.3%), followed by Vachellia karroo (Acacia karroo) (15.8%). Ethnobotanical records indicate that the different Acacia species have been traditionally used to treat conditions such as diarrhea, wound infections and complications such as retained placenta. Pharmacological studies corroborate the therapeutic benefits of Acacia species with evidence of their antimicrobial, anti-inflammatory, antioxidant and anthelmintic effects, though some toxicity concerns exist at high dosages. The systematic review revealed the efficacy and safety (to some extent) of Acacia species in livestock disease management, emphasizing their potential integration into veterinary medicine. However, the dearth of in vivo studies underscores the need for pre-clinical and clinical trials to establish safe and effective dosages for use in livestock. Full article
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21 pages, 2038 KB  
Review
Densifying the Future: A Critical Review of Osseodensification and Implant Dentistry
by Rafael Ortiz, Paulo Maurício and Paulo Sobral Mascarenhas
Dent. J. 2025, 13(10), 461; https://doi.org/10.3390/dj13100461 (registering DOI) - 9 Oct 2025
Abstract
Osseodensification (OD) compacts trabecular bone during implant site preparation rather than removing it, potentially enhancing primary stability versus conventional drilling. This review critically appraised clinical and preclinical evidence for OD’s biological and biomechanical efficacy in implant dentistry. We conducted electronic searches in seven [...] Read more.
Osseodensification (OD) compacts trabecular bone during implant site preparation rather than removing it, potentially enhancing primary stability versus conventional drilling. This review critically appraised clinical and preclinical evidence for OD’s biological and biomechanical efficacy in implant dentistry. We conducted electronic searches in seven databases (PubMed, Scopus, Web of Science, ScienceDirect, SciELO, LILACS, DOAJ) for the period January 2014 to March 2024. Studies comparing osseodensification with conventional drilling in clinical and large-animal models were included. Primary outcomes were insertion torque, implant stability quotient (ISQ), bone-to-implant contact (BIC), bone area fraction occupancy (BAFO), and complications. Of 75 retrieved records, 38 studies (27 clinical, 11 preclinical) provided analysable data. Based on descriptive averages from the narrative synthesis, osseodensification increased mean insertion torque by around 45% (range 32–59%) and initial ISQ by 3–10 units compared with conventional drilling. These gains permitted immediate loading in 78% of cases and shortened operating time (mean reduction 15–20 min). Animal studies demonstrated 12–28% higher BIC and increased peri-implant bone density at 4–12 weeks. No serious adverse events were recorded. Postoperative morbidity was similar between techniques. The collated evidence indicates that osseodensification significantly improves primary stability and may accelerate healing protocols, particularly in low-density (Misch D3–D4) bone. However, the predominance of short-term data and heterogeneity in surgical parameters limit definitive conclusions. Long-term randomised controlled trials with standardised protocols are needed before universal clinical recommendations can be established. Full article
(This article belongs to the Section Dental Implantology)
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15 pages, 349 KB  
Review
Optimizing Aesthetic Results in Implant-Based Breast Reconstruction: Patient Factors, Surgical Techniques, and Adjunctive Strategies
by Elisa Bertulla and Edoardo Raposio
J. Clin. Med. 2025, 14(19), 7106; https://doi.org/10.3390/jcm14197106 (registering DOI) - 9 Oct 2025
Abstract
Background: Breast reconstruction following mastectomy plays a crucial role in breast cancer management, restoring physical form and significantly impacting psychological well-being and quality of life. Implant-based breast reconstruction (IBBR) is the most performed technique worldwide due to its relative simplicity, shorter operative [...] Read more.
Background: Breast reconstruction following mastectomy plays a crucial role in breast cancer management, restoring physical form and significantly impacting psychological well-being and quality of life. Implant-based breast reconstruction (IBBR) is the most performed technique worldwide due to its relative simplicity, shorter operative times, and avoidance of donor site morbidity. Achieving satisfactory aesthetic outcomes, however, remains challenging, as multiple factors—including patient characteristics, surgical technique, implant selection, timing of reconstruction, and adjuvant therapies—can influence the final appearance. Methods: Literature research was performed via PubMed, Scopus and Cochrane Library Database, focusing on studies examining aesthetic outcomes in implant-based breast reconstruction published between 2015 and 2025. Data on type of study, sample size, aesthetic evaluation methods, and duration of follow-up were collected and summarized. Results: Among 747 articles identified, only 25 articles fulfilled inclusion criteria, including mostly retrospective studies, but also prospective studies, randomized clinical trials, and reviews. Factors such as BMI, inframammary fold management, and implant selection were consistently reported to influence aesthetic outcomes. Surgical techniques including ADM use, axillary advancement sutures, hybrid reconstruction with fat grafting, and prepectoral implant placement were associated with improved patient satisfaction. Patient satisfaction often differs from surgeon-assessed outcomes, emphasizing the importance of subjective evaluation. Conclusions: Despite the heterogeneity and retrospective nature of many studies, evidence indicates that optimizing aesthetic outcomes in IBBR relies on careful patient selection, tailored surgical planning, and meticulous use of evidence-based techniques, including implant selection, flap-based support, and adjunctive strategies. Patient-reported outcomes are essential for evaluating success, and future research should focus on standardized outcome measures and prospective studies to further refine reconstructive approaches and maximize both cosmetic satisfaction and quality of life. Full article
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27 pages, 407 KB  
Systematic Review
Beyond Racial Categorization in Sports Cardiology: A Systematic Review of Cardiac Adaptations in Athletes
by Douglas Corsi, Rafael Hernandez, Jasmine Yimeng Bao, Stephen Garrova and David Shipon
J. Clin. Med. 2025, 14(19), 7107; https://doi.org/10.3390/jcm14197107 (registering DOI) - 9 Oct 2025
Abstract
Background/Objectives: Race-based cardiac screening criteria in sports cardiology, including the “Black athlete’s heart” concept, assume biological distinctions that may not reflect physiological reality. This systematic review evaluates whether geographic ancestry provides more clinically relevant predictors of cardiac adaptation than racial categorization. Methods: PubMed [...] Read more.
Background/Objectives: Race-based cardiac screening criteria in sports cardiology, including the “Black athlete’s heart” concept, assume biological distinctions that may not reflect physiological reality. This systematic review evaluates whether geographic ancestry provides more clinically relevant predictors of cardiac adaptation than racial categorization. Methods: PubMed was searched (January 2005–July 2025) for studies examining cardiac adaptations in athletes by ethnicity. Data extraction captured demographics, geographic origin, cardiac assessments, and outcomes. Narrative synthesis was employed due to methodological heterogeneity. Results: Forty-seven studies (n = 66,130) revealed substantial within-race heterogeneity. The “Black athlete repolarization variant” prevalence ranged from 1.8% (Brazilian) to 30% (Ghanaian) Black athletes. Left ventricular wall thickness >12 mm (normal <11 mm) occurred in 7.1% of Black versus 0.4% of White athletes, yet varied significantly within Black populations—10.8 ± 1.2 mm in Sub-Saharan versus 9.4 ± 1.1 mm in African-American athletes (p < 0.001). Relative wall thickness ≥0.44 (normal ≤0.42) was presented in 43% of West/Middle African, 23% of East African, and 7% of White athletes. T-wave inversion showed four-fold variation within Black populations (3.6–8.5% West African versus 0.5–2.0% African-American/Caribbean). Current International Criteria demonstrated inequitable specificity: 3.3% false-positive rate in Black versus 1.4% in White athletes. Conclusions: Geographic ancestry explains more cardiac variation than racial categories, supporting contemporary understanding of race as a sociopolitical construct. The persistent diagnostic disparities in ECG screening specificity highlight the need for reform. Transitioning toward protocols incorporating continental origin, anthropometric factors, and social determinants of health—while eliminating terminology like “Black athlete’s heart”—represents an important step toward achieving equity in cardiovascular care for diverse athletic populations. Full article
(This article belongs to the Section Sports Medicine)
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36 pages, 1058 KB  
Systematic Review
Functionalization Strategies of Chitosan-Based Scaffolds with Growth Factors for Bone Regeneration: A Systematic Review
by Jan Kiryk, Mateusz Michalak, Zuzanna Majchrzak, Marzena Laszczyńska, Sylwia Kiryk, Sylwia Szotek, Hanna Gerber, Izabela Nawrot-Hadzik, Jacek Matys and Maciej Dobrzyński
Mar. Drugs 2025, 23(10), 396; https://doi.org/10.3390/md23100396 (registering DOI) - 9 Oct 2025
Abstract
Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search [...] Read more.
Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search was conducted in July 2025 across the PubMed, Scopus, and Web of Science databases. Search terms included combinations of (chitosan scaffold) AND (growth factor OR BMP-2 OR VEGF OR FGF OR TGF-beta OR periostin OR PDGF OR IGF-1 OR EGF OR ANG-1 OR ANG-2 OR GDF-5 OR SDF-1 OR osteopontin). The study selection process followed PRISMA 2020 guidelines and the PICO framework. Out of 367 records, 226 were screened, and 17 studies met the eligibility criteria for qualitative analysis. BMP-2 was the most frequently investigated growth factor, studied in both in vitro and in vivo models, with rats and rabbits as the most common animal models. Scaffold compositions varied, incorporating hydroxyapatite, heparin, polyethylene glycol diacrylate, octacalcium phosphate-mineralized graphene, silk fibroin, and aloe vera. Growth factors were introduced using diverse methods, including microspheres, chemical grafting, covalent coupling, protein carriers, and nanohydroxyapatite mesopores. Most studies reported enhanced bone regeneration, although differences in models, scaffold composition, and delivery methods preclude definitive conclusions. The addition of growth factors generally improved osteoblast proliferation, angiogenesis, bone density, and expression of osteogenic markers (RunX2, COL1, OPN, OCN). Combining two bioactive agents further amplified osteoinduction and vascularization. Sustained-release systems, particularly those using heparin or hydroxyapatite, prolonged biological activity and improved regenerative outcomes. In conclusion, functionalization of chitosan-based scaffolds with growth factors shows promising potential for bone regeneration. Controlled-release systems and combinations of different bioactive molecules may offer synergistic effects on osteogenesis and angiogenesis. Further research should focus on optimizing scaffold compositions and delivery methods to tailor bioactive agent release for specific clinical applications. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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17 pages, 768 KB  
Article
Exploratory Pre–Post Study of School-Based Stress Interventions in Primary School Children
by Isabelle May
Behav. Sci. 2025, 15(10), 1374; https://doi.org/10.3390/bs15101374 (registering DOI) - 9 Oct 2025
Abstract
Background: This exploratory, non-randomized pre–post study compares three school-based stress interventions—Yoga, Climbing, and Social–Emotional Learning—in primary school children. Methods: We compared three low-threshold interventions delivered during regular lessons: (1) a six-week video-guided Yoga sequence (n = 64; grade 3), (2) a 2.5-week [...] Read more.
Background: This exploratory, non-randomized pre–post study compares three school-based stress interventions—Yoga, Climbing, and Social–Emotional Learning—in primary school children. Methods: We compared three low-threshold interventions delivered during regular lessons: (1) a six-week video-guided Yoga sequence (n = 64; grade 3), (2) a 2.5-week social–emotional learning (SEL) module focused on emotion recognition and regulation (n = 60; grade 3), and (3) a two-week Climbing program implemented with a small special-education sample (n = 12). Parallel class-matched controls were included for Yoga and SEL (n = 64 and n = 60, respectively). A quasi-experimental pre–post design was used. Primary outcomes were overall stress and the emotion subdomains of anger, anxiety, and sadness (SSKJ 3–8); the secondary outcome for the Climbing pilot was general self-efficacy (SWE). Non-parametric statistics (Wilcoxon signed-rank, Mann–Whitney U) and rank-biserial effect sizes (r) were reported with Holm-adjusted α = 0.05. Results: Yoga and SEL produced significant within-group reductions in overall stress and all emotional subdomains (all p < 0.001; r = 0.59–0.75) and outperformed their respective controls at post-test (p ≤ 0.038; r = 0.22–0.48). Change-score comparisons between Yoga and SEL were not statistically different (p ≥ 0.44). In the exploratory Climbing group, self-efficacy increased significantly (V = 64.5, p = 0.006, r = 0.80); stress outcomes mirrored Yoga/SEL trends but were under-powered. Conclusions: A brief classroom Yoga routine and a condensed SEL module each yielded clinically meaningful reductions in stress among primary-school pupils, offering flexible options for post-pandemic recovery. Preliminary evidence suggests that Climbing may enhance self-efficacy in older students with psychological challenges; however, larger samples are required. Integrating cost-effective physical and emotional strategies can help schools promote resilience and well-being amid ongoing educational disruptions. Full article
(This article belongs to the Special Issue School-Based Intervention for Stress in Children and Adolescents)
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29 pages, 356 KB  
Review
Telemedicine in Obstetrics: Building Bridges in Reproductive Healthcare—A Literature Review
by Zahi Hamdan, Rhianon Bou Deleh, Joenne Al Khoury, Somar Soufan, Rafi Haddad, Emile Dabaj, Sami Azar, Hilda E. Ghadieh and Marouan Zoghbi
Reprod. Med. 2025, 6(4), 30; https://doi.org/10.3390/reprodmed6040030 (registering DOI) - 9 Oct 2025
Abstract
Telemedicine has emerged as a promising tool in obstetric and reproductive healthcare, offering new possibilities for patient-centered care delivery. This literature review explores its impact across key areas, including abortion, assisted reproduction, childbirth, contraception, gestational diabetes, mental health, opioid and smoking cessation, and [...] Read more.
Telemedicine has emerged as a promising tool in obstetric and reproductive healthcare, offering new possibilities for patient-centered care delivery. This literature review explores its impact across key areas, including abortion, assisted reproduction, childbirth, contraception, gestational diabetes, mental health, opioid and smoking cessation, and perinatal care during the COVID-19 pandemic. A structured narrative approach was applied, with studies identified through PubMed and Scopus databases for screening, with selection based on predefined inclusion and exclusion criteria, and synthesized narratively with attention to clinical outcomes, access, satisfaction, and barriers to implementation. Perspectives on the acceptance of telemedicine among healthcare providers, technological advancements enhancing reproductive outcomes, and telemedicine’s pivotal role in maintaining continuity of care during crises, such as the COVID-19 pandemic, are examined. The review also addresses challenges and barriers, including technological proficiency and patient acceptance, while emphasizing telemedicine’s potential to improve accessibility, patient satisfaction, and healthcare outcomes across diverse reproductive health services. Full article
10 pages, 342 KB  
Article
A VR-Based Trauma Nursing Education Program for Clinical Nurses: Integrating Jeffries’ Model and the 5E Learning Cycle
by Heeyeon Kim, Gyuli Baek and Eunju Lee
Healthcare 2025, 13(19), 2542; https://doi.org/10.3390/healthcare13192542 (registering DOI) - 9 Oct 2025
Abstract
Background/Objectives: Nurses’ professional competencies are critical in trauma patient care, and educational programs that strengthen these competencies contribute to improved patient safety and higher-quality care. This study aimed to develop and evaluate the effectiveness of a virtual reality (VR)-based trauma nursing education program [...] Read more.
Background/Objectives: Nurses’ professional competencies are critical in trauma patient care, and educational programs that strengthen these competencies contribute to improved patient safety and higher-quality care. This study aimed to develop and evaluate the effectiveness of a virtual reality (VR)-based trauma nursing education program by applying Jeffries’ simulation model and the 5E Learning Cycle. Methods: A quasi-experimental, non-equivalent control group pretest–post-test design was employed. Participants were 34 nurses with more than one year of clinical experience, recruited from three university hospitals in Daegu, Korea, each with over 800 beds. Participants were allocated to either the experimental group (n = 17) or the control group (n = 17). The experimental group received the VR-based program, while the control group received standard training. Effectiveness was assessed using validated questionnaires measuring trauma-related knowledge, confidence in trauma care, and emergency nursing competency. Data were analyzed with repeated-measures ANOVA. Results: The experimental group demonstrated significant improvements in trauma-related knowledge and confidence in trauma care compared with the control group. Emergency nursing competency also increased significantly in both groups over time, but the degree of improvement did not differ between groups. Conclusions: The VR-based trauma nursing education program, designed using Jeffries’ simulation model and the 5E Learning Cycle, enhanced trauma-related knowledge and confidence among clinical nurses. Although no between-group difference was found for emergency nursing competency, the findings provide foundational evidence supporting the use of VR-based interventions to advance emergency and critical care nursing education. Full article
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27 pages, 1751 KB  
Systematic Review
Therapeutic Efficacy of Soy-Derived Bioactives: A Systematic Review of Nutritional Potency, Bioactive Therapeutics, and Clinical Biomarker Modulation
by Zara Fatima, Nizwa Itrat, Beenish Israr and Abdul Momin Rizwan Ahmad
Foods 2025, 14(19), 3447; https://doi.org/10.3390/foods14193447 (registering DOI) - 9 Oct 2025
Abstract
Soybeans (Glycine max) are nutrient-dense legumes and a high-quality plant-based protein source containing all essential amino acids. With a protein content of 36–40%, soy surpasses many other plant-derived proteins in nutritional value. Its bioactive components, particularly peptides and isoflavones, contribute to [...] Read more.
Soybeans (Glycine max) are nutrient-dense legumes and a high-quality plant-based protein source containing all essential amino acids. With a protein content of 36–40%, soy surpasses many other plant-derived proteins in nutritional value. Its bioactive components, particularly peptides and isoflavones, contribute to reducing inflammation, oxidative stress, and the risk of chronic diseases. In undernourished regions such as Pakistan, where protein-energy malnutrition is prevalent among women and children, soy offers a sustainable and cost-effective nutritional intervention. This review synthesizes findings from biochemical analyses, nutritional profiling, and clinical trials evaluating the impact of soybean protein and its bioactive compounds on growth, metabolic health, immune function, and disease prevention. Emphasis was placed on studies relevant to food-insecure populations and technological innovations enhancing soy product bioavailability. Soy protein has been shown to have positive effects on hormonal regulation, cardiovascular health, cognitive function, and immune support. Technological approaches such as fortification and fermentation improve nutritional bioavailability and sensory acceptance. The integration of soy into local diets enhanced nutritional adequacy, promoted environmental sustainability, and aligned with Sustainable Development Goals. Soybeans represent a sustainable, nutrient-rich solution to combat protein-energy malnutrition in vulnerable communities. Their high-quality protein profile, therapeutic properties, and adaptability to local food systems make them an effective strategy for improving public health and supporting environmental resilience. Full article
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18 pages, 931 KB  
Article
Rare BLK, CEL, KLF11, PDX1, and PAX4 Gene Variants in Russian Patients with Monogenic Diabetes: Clinical and Molecular Characterization
by Rita I. Khusainova, Ildar R. Minniakhmetov, Dmitry N. Laptev, Mariya P. Koltakova, Roman V. Deev, Bulat I. Yalaev, Yaroslav V. Dvoryanchikov, Elena A. Sechko and Natalia G. Mokrysheva
Biomedicines 2025, 13(10), 2452; https://doi.org/10.3390/biomedicines13102452 (registering DOI) - 9 Oct 2025
Abstract
Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics [...] Read more.
Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics become increasingly accessible, an expanding number of novel genetic variants are being identified. Objectives: The aim of this study was to characterize the clinical and genetic features of patients carrying rare variants in the BLK, KLF11, PAX4, PDX1, and CEL genes, with attention to population-specific aspects, family history, and treatment outcomes. Methods: Targeted next-generation sequencing (NGS) using a custom-designed panel covering 27 genes implicated in MODY, neonatal diabetes, and related hereditary syndromes was performed on the Illumina NovaSeq 6000 platform (Illumina). Results: We identified 21 variants in five genes associated with rare MODY subtypes among 24 unrelated patients. MODY9 was diagnosed in two unrelated patients of Russian ethnicity harboring an identical heterozygous missense mutation in exon 5 of the PAX4 gene (HG38, chr7:127615049G>A, c.191C>T, p.Thr64Ile), which has not been previously described in patients with diabetes. MODY11 was diagnosed in a patient carrying the c.773-1G>A variant in the BLK gene. A patient with a de novo c.40_41dupGC (p.Val15Glnfs*41) variant in the KLF11 gene was clinically diagnosed with type 1 diabetes. Conclusion: Our findings expand the current understanding of rare MODY subtypes and contribute to the growing body of evidence on the spectrum and frequency of potentially pathogenic variants in BLK, CEL, KLF11, PDX1, and PAX4 genes across ethnically diverse populations worldwide. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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16 pages, 1613 KB  
Review
Application of Machine Learning in Predicting Osteogenic Differentiation of Mesenchymal Stem Cells
by Hanyue Mao, Zheng Zhou, Ying Yang, Kunlu Lin, Chuyao Zhou and Xiaoyan Wang
Bioengineering 2025, 12(10), 1089; https://doi.org/10.3390/bioengineering12101089 - 9 Oct 2025
Abstract
This article reviews the progress made in applying machine learning to predict the osteogenic differentiation of mesenchymal stem cells. Bone defects pose a significant clinical challenge due to limitations of traditional therapies such as autologous bone graft donor shortages, allograft immune risks and [...] Read more.
This article reviews the progress made in applying machine learning to predict the osteogenic differentiation of mesenchymal stem cells. Bone defects pose a significant clinical challenge due to limitations of traditional therapies such as autologous bone graft donor shortages, allograft immune risks and so on. Mesenchymal stem cells offer a promising solution for bone regeneration due to their osteogenic differentiation potential, but their clinical utility is hindered by unpredictable differentiation efficiency and heterogeneity. Machine learning has emerged as a powerful tool to address these issues by enabling early, non-invasive prediction of osteogenic differentiation and high-throughput analysis of complex data like morphology and omics. This review systematically summarizes the application of ML in three key areas: early prediction using cellular morphology, omics data analysis for biomarker discovery, and drug/biomaterial screening for enhancing osteogenesis. We compare the performance of multiple ML models like ResNet-50, LASSO, and random forests and highlight their advantages and limitations. Additionally, we discuss challenges in data standardization and model interpretability, and propose future directions for translating ML into clinical practice. This review provides a comprehensive overview of how ML can revolutionize MSC-based bone regeneration by improving prediction accuracy and optimizing therapeutic strategies. Full article
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26 pages, 1116 KB  
Review
Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring
by Joaquim Faria Monteiro, Alexandrina Fernandes, Diogo Gavina Tato, Elias Moreira, Ricardo Ribeiro, Henrique Reguengo, Jorge Gonçalves and Paula Fresco
Cancers 2025, 17(19), 3262; https://doi.org/10.3390/cancers17193262 - 8 Oct 2025
Abstract
Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 [...] Read more.
Anti-PD-1 therapies have transformed cancer treatment by restoring antitumor T cell activity. Despite their broad clinical use, variability in treatment response and immune-related adverse events underscore the need for therapeutic optimization. This article provides an integrative overview of the pharmacokinetics (PKs) of anti-PD-1 antibodies—such as nivolumab, pembrolizumab, and cemiplimab—and examines pharmacokinetic–pharmacodynamic (PK-PD) relationships, highlighting the impact of clearance variability on drug exposure, efficacy, and safety. Baseline clearance and its reduction during therapy, together with interindividual variability, emerge as important dynamic biomarkers with potential applicability across different cancer types for guiding individualized dosing strategies. The review also discusses established biomarkers for anti-PD-1 therapies, including tumor PD-L1 expression and immune cell signatures, and their relevance for patient stratification. The evidence supports a shift from traditional weight-based dosing toward adaptive dosing and therapeutic drug monitoring (TDM), especially in long-term responders and cost-containment contexts. Notably, the inclusion of clearance-based biomarkers—such as baseline clearance and its reduction—into therapeutic models represents a key step toward individualized, dynamic immunotherapy. In conclusion, optimizing anti-PD-1 therapy through PK-PD insights and biomarker integration holds promise for improving outcomes and reducing toxicity. Future research should focus on validating PK-based approaches and developing robust algorithms (machine learning models incorporating clearance, tumor burden, and other validated biomarkers) for tailored cancer treatment. Full article
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15 pages, 1715 KB  
Article
Fracture Resistance of 3D-Printed Hybrid Abutment Crowns Made from a Tooth-Colored Ceramic Filled Hybrid Composite: A Pilot Study
by Josef Schweiger, Kurt-Jürgen Erdelt, Isabel Lente, Daniel Edelhoff, Tobias Graf and Oliver Schubert
J. Funct. Biomater. 2025, 16(10), 375; https://doi.org/10.3390/jfb16100375 (registering DOI) - 8 Oct 2025
Abstract
The aim of this pilot in vitro study is to investigate the fracture strength of hybrid abutment crowns (HACs) made of a 3D-printable, tooth-colored, ceramic-reinforced composite (CRC). Based on an upper first premolar, a crown was designed, and specimens were additively fabricated from [...] Read more.
The aim of this pilot in vitro study is to investigate the fracture strength of hybrid abutment crowns (HACs) made of a 3D-printable, tooth-colored, ceramic-reinforced composite (CRC). Based on an upper first premolar, a crown was designed, and specimens were additively fabricated from a composite material (VarseoSmile Crown plus) (N = 32). The crowns were bonded to standard abutments using a universal resin cement. Half (n = 16) of the samples were subjected to artificial aging, during which three samples suffered minor damage. All specimens were mechanically loaded at an angle of 30° to the implant axis. In addition, an FEM simulation was computed. Statistical analysis was performed at a significance level of p < 0.05. The mean fracture load without aging was 389.04 N (SD: 101.60 N). Two HACs suffered screw fracture, while the crowns itself failed in all other specimens. In the aged specimens, the mean fracture load was 391.19 N (SD: 143.30 N). The failure mode was predominantly catastrophic crown fracture. FEM analysis showed a maximum compressive stress of 39.79 MPa, a maximum tensile stress of 173.37 MPa and a shear stress of 60.29 MPa when loaded with 389 N. Within the limitations of this pilot study, the tested 3D-printed hybrid abutment crowns demonstrated fracture resistance above a clinically acceptable threshold, suggesting promising potential for clinical application. However, further investigations with larger sample sizes, control groups, and clinical follow-up are required. Full article
25 pages, 588 KB  
Review
Influence of Ultrasonic Activation of Endodontic Irrigants on Microbial Reduction and Postoperative Pain: A Scoping Review of In Vivo Studies
by Jacob Marx, Corban Ward, Bayler Gunnell, Zachary Marx, Alicia Parry, Samuel Dyal, Amir Mohajeri and Man Hung
Dent. J. 2025, 13(10), 459; https://doi.org/10.3390/dj13100459 - 8 Oct 2025
Abstract
Objective: Root canal irrigation plays a critical role in achieving effective chemomechanical disinfection during endodontic therapy. Conventional syringe irrigation, typically using sodium hypochlorite, ethylenediaminetetraacetic acid, and chlorhexidine, is limited by its delivery method and often fails to adequately penetrate complex canal anatomies, compromising [...] Read more.
Objective: Root canal irrigation plays a critical role in achieving effective chemomechanical disinfection during endodontic therapy. Conventional syringe irrigation, typically using sodium hypochlorite, ethylenediaminetetraacetic acid, and chlorhexidine, is limited by its delivery method and often fails to adequately penetrate complex canal anatomies, compromising disinfection. Advancements such as ultrasonic and multisonic irrigation systems aim to address these limitations. This scoping review compares the clinical effectiveness of ultrasonic irrigation techniques with conventional syringe irrigation, focusing exclusively on in vivo studies conducted within the oral environment. Methods: A comprehensive scoping review was conducted using PubMed, Scopus, Dentistry & Oral Sciences Source, and Google Scholar. Peer-reviewed, full-text articles published in English between 2015 and 2025 were screened by four independent reviewers based on predefined inclusion and exclusion criteria. Eligible studies were thematically analyzed. Results: Of 312 records screened, eleven studies met the inclusion criteria. Ultrasonic irrigation was associated with improved clinical outcomes, particularly greater reductions in bacterial load and endotoxins; however, findings regarding its effect on postoperative pain were inconsistent, with some studies reporting a benefit while others observed no significant difference. These outcomes were attributed to mechanisms such as acoustic streaming and cavitation, which enhance irrigant penetration, promote fluid dynamics, and facilitate debridement in anatomically complex regions. Conclusions: Ultrasonic irrigation appears to hold promise for enhancing the efficacy and efficiency of root canal treatment. Existing in vivo studies suggest potential clinical advantages over conventional syringe irrigation, underscoring the need for further high-quality clinical research to more definitively establish its benefits. Full article
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Article
A Comprehensive Analysis of Adverse Events Associated with HER2 Inhibitors Approved for Breast Cancer Using the FDA Adverse Event Report System (FAERS)
by Airi Yajima and Yoshihiro Uesawa
Pharmaceuticals 2025, 18(10), 1510; https://doi.org/10.3390/ph18101510 - 8 Oct 2025
Abstract
Background/Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have markedly improved outcomes in patients with HER2-positive breast cancer. Clinical treatment often involves the sequential or combined use of multiple HER2 inhibitors, making it essential to clarify their distinct adverse event (AE) profiles. [...] Read more.
Background/Objectives: Human epidermal growth factor receptor 2 (HER2) inhibitors have markedly improved outcomes in patients with HER2-positive breast cancer. Clinical treatment often involves the sequential or combined use of multiple HER2 inhibitors, making it essential to clarify their distinct adverse event (AE) profiles. However, AE trends remain insufficiently understood. This study aimed to comprehensively analyze characteristic AEs associated with HER2 inhibitors. Methods: Using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS, January 2004–September 2024), we conducted disproportionality analyses of AEs associated with HER2 inhibitors approved for breast cancer. Based on the natural logarithm of the reporting odds ratio (lnROR), hierarchical cluster analysis and principal component analysis (PCA) were performed. Results: Disproportionality analysis treating HER2 inhibitors as a single group identified several signals, with hair disorder (ROR 39.93 [95% CI: 37.68–42.32]) as a representative example. Hierarchical clustering showed that monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) diverged early in the dendrogram, and clusters broadly corresponded to pharmacological classes. The cluster of hair-related AEs closely corresponded to mAbs. PCA indicated that the first component reflected AE occurrence risk (R2 = 0.655, p < 0.0001), the second component distinguished mAbs from TKIs (tucatinib: r = 0.667; trastuzumab: r = −0.567), and the third component separated molecular targeted agents from antibody–drug conjugates (neratinib: r = 0.521; T-DXd: r = −0.440). Conclusions: FAERS-based analyses enabled visualization of the distinct AE profiles of HER2 inhibitors. These findings may support safe drug selection, risk stratification, and improved AE management strategies. Full article
(This article belongs to the Section Pharmacology)
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