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Authors = Chun-Lin Tsai

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41 pages, 5624 KB  
Article
Tackling Imbalanced Data in Chronic Obstructive Pulmonary Disease Diagnosis: An Ensemble Learning Approach with Synthetic Data Generation
by Yi-Hsin Ko, Chuan-Sheng Hung, Chun-Hung Richard Lin, Da-Wei Wu, Chung-Hsuan Huang, Chang-Ting Lin and Jui-Hsiu Tsai
Bioengineering 2026, 13(1), 105; https://doi.org/10.3390/bioengineering13010105 - 15 Jan 2026
Viewed by 441
Abstract
Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide and in Taiwan, ranking as the third leading cause of death globally, and its prevalence in Taiwan continues to rise. Readmission within 14 days is a key indicator of disease instability and [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a major health burden worldwide and in Taiwan, ranking as the third leading cause of death globally, and its prevalence in Taiwan continues to rise. Readmission within 14 days is a key indicator of disease instability and care efficiency, driven jointly by patient-level physiological vulnerability (such as reduced lung function and multiple comorbidities) and healthcare system-level deficiencies in transitional care. To mitigate the growing burden and improve quality of care, it is urgently necessary to develop an AI-based prediction model for 14-day readmission. Such a model could enable early identification of high-risk patients and trigger multidisciplinary interventions, such as pulmonary rehabilitation and remote monitoring, to effectively reduce avoidable early readmissions. However, medical data are commonly characterized by severe class imbalance, which limits the ability of conventional machine learning methods to identify minority-class cases. In this study, we used real-world clinical data from multiple hospitals in Kaohsiung City to construct a prediction framework that integrates data generation and ensemble learning to forecast readmission risk among patients with chronic obstructive pulmonary disease (COPD). CTGAN and kernel density estimation (KDE) were employed to augment the minority class, and the impact of these two generation approaches on model performance was compared across different augmentation ratios. We adopted a stacking architecture composed of six base models as the core framework and conducted systematic comparisons against the baseline models XGBoost, AdaBoost, Random Forest, and LightGBM across multiple recall thresholds, different feature configurations, and alternative data generation strategies. Overall, the results show that, under high-recall targets, KDE combined with stacking achieves the most stable and superior overall performance relative to the baseline models. We further performed ablation experiments by sequentially removing each base model to evaluate and analyze its contribution. The results indicate that removing KNN yields the greatest negative impact on the stacking classifier, particularly under high-recall settings where the declines in precision and F1-score are most pronounced, suggesting that KNN is most sensitive to the distributional changes introduced by KDE-generated data. This configuration simultaneously improves precision, F1-score, and specificity, and is therefore adopted as the final recommended model setting in this study. Full article
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11 pages, 669 KB  
Article
Associations Between the Severity of Sarcopenia and Health-Related Quality of Life in Older Adults
by Wei-Syun Hung, Ying-Jen Chen, Tz-Shiu Tsai, Chern-Horng Lee, Ji-Tseng Fang, Ming-Shien Wen, Chun-Yen Lin, Kuo-Chen Liao and Chieh-Li Yen
J. Clin. Med. 2026, 15(1), 161; https://doi.org/10.3390/jcm15010161 - 25 Dec 2025
Cited by 1 | Viewed by 493
Abstract
Background: Sarcopenia is a progressive skeletal muscle disorder associated with adverse outcomes. Although the association between sarcopenia and quality of life (QoL) has been discussed, the specific relationship between different stages of sarcopenia severity—particularly distinguishing between muscle mass loss and functional impairment—and health-related [...] Read more.
Background: Sarcopenia is a progressive skeletal muscle disorder associated with adverse outcomes. Although the association between sarcopenia and quality of life (QoL) has been discussed, the specific relationship between different stages of sarcopenia severity—particularly distinguishing between muscle mass loss and functional impairment—and health-related quality of life (HRQoL) remains unclear. Method: This cross-sectional study enrolled 100 elderly participants from a geriatric outpatient clinic. Participants were categorized into four groups (normal, possible sarcopenia, sarcopenia and severe sarcopenia) based on the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. HRQoL was assessed using the Short-Form 36-Item (SF-36) questionnaire. Result: The severe sarcopenia group was significantly older and had lower calf circumference compared to the normal group. Notably, the possible sarcopenia group presented with the highest body mass index and body fat percentage, resembling a “dynapenic obesity” phenotype. In terms of QoL, participants with confirmed sarcopenia did not exhibit significant differences compared to the normal group. However, the severe sarcopenia group demonstrated significantly lower scores across almost all SF-36 domains compared to the normal group. Multivariate linear regression analysis revealed that severe sarcopenia was independently and significantly negatively associated with multiple QoL domains, including physical functioning, general health and vitality. Additionally, age, social activity and body fat were identified as independent correlates of specific QoL domains. Conclusions: Our findings suggest a non-linear relationship between sarcopenia and HRQoL. A comprehensive decline in HRQoL is strongly linked to the severity of sarcopenia (functional impairment) rather than the diagnosis of muscle mass loss alone. These results highlight the clinical importance of preserving physical performance and suggest that categorizing different severities of sarcopenia and stage-specific management strategies are necessary to improve quality of life in older adults. Full article
(This article belongs to the Section Geriatric Medicine)
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23 pages, 25807 KB  
Article
Genomic, Functional, and Evolutionary Insights into a Novel T7-like Phage B1 Infecting Multidrug-Resistant Enterobacter cloacae
by Yun-Chan Tsai, Soon-Hian Teh, Philip Huang, Ling-Chun Lin and Nien-Tsung Lin
Int. J. Mol. Sci. 2026, 27(1), 195; https://doi.org/10.3390/ijms27010195 - 24 Dec 2025
Viewed by 414
Abstract
Multidrug-resistant (MDR) Enterobacter cloacae is a growing public health issue worldwide, highlighting the urgent need for alternative antimicrobial strategies. This study reports on a lytic phage, designated B1, isolated from sewage, which exhibits specificity and lytic efficiency against MDR E. cloacae. Morphological [...] Read more.
Multidrug-resistant (MDR) Enterobacter cloacae is a growing public health issue worldwide, highlighting the urgent need for alternative antimicrobial strategies. This study reports on a lytic phage, designated B1, isolated from sewage, which exhibits specificity and lytic efficiency against MDR E. cloacae. Morphological observation revealed that B1 possesses an icosahedral head (~54 nm) and a short tail (~13 nm). Phage B1 showed a narrow host range, demonstrated stability within a temperature range of 4–37 °C, tolerance to pH values between 5 and 11, and showed an excellent bacteriolytic capacity with a short latent period of less than 10 min and a burst size of approximately 150 PFU/initially infected cell, indicating a rapid lytic cycle and efficient replication capability. Whole-genome sequencing revealed that the phage genome consists of 40,163 base pairs of double-stranded DNA containing 52 open reading frames (ORFs) with a GC content of 52%. Comparative genome-wide analysis using VIRIDIC revealed that B1 shares 75% to 92% similarity with Escherichia phage IMM-002 (accession: NC_048071), Citrobacter phage SH4, and Cronobacter phage Dev2 (accession: NC_023558), but shares less than 70% similarity with other Enterobacter phages. According to ICTV criteria, B1 represents a new species within the same genus as T7-like phages belonging to Autographiviridae, subfamily Studiervirinae, genus Kayfunavirus. In addition, B1 lacks lysogeny-associated or virulence genes and exhibits potent lytic activity against multidrug-resistant E. cloacae, making it a promising candidate for phage therapy. These findings opened up our understanding of the diversity of T7-like phages and provided insights into their evolutionary adaptability and therapeutic potential. Full article
(This article belongs to the Special Issue Research Advances in Antibiotic Resistance)
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21 pages, 2267 KB  
Article
An External Validation Study on Two Pre-Trained Large Language Models for Multimodal Prognostication in Laryngeal and Hypopharyngeal Cancer: Integrating Clinical, Treatment, and Radiomic Data to Predict Survival Outcomes with Interpretable Reasoning
by Wing-Keen Yap, Shih-Chun Cheng, Chia-Hsin Lin, Ing-Tsung Hsiao, Tsung-You Tsai, Wing-Lake Yap, Willy Po-Yuan Chen, Chien-Yu Lin and Shih-Ming Huang
Bioengineering 2025, 12(12), 1345; https://doi.org/10.3390/bioengineering12121345 - 10 Dec 2025
Viewed by 742
Abstract
Background: Laryngeal and hypopharyngeal cancers (LHCs) exhibit heterogeneous outcomes after definitive radiotherapy (RT). Large language models (LLMs) may enhance prognostic stratification by integrating complex clinical and imaging data. This study validated two pre-trained LLMs—GPT-4o-2024-08-06 and Gemma-2-27b-it—for outcome prediction in LHC. Methods: Ninety-two patients [...] Read more.
Background: Laryngeal and hypopharyngeal cancers (LHCs) exhibit heterogeneous outcomes after definitive radiotherapy (RT). Large language models (LLMs) may enhance prognostic stratification by integrating complex clinical and imaging data. This study validated two pre-trained LLMs—GPT-4o-2024-08-06 and Gemma-2-27b-it—for outcome prediction in LHC. Methods: Ninety-two patients with non-metastatic LHC treated with definitive (chemo)radiotherapy at Linkou Chang Gung Memorial Hospital (2006–2013) were retrospectively analyzed. First-order and 3D radiomic features were extracted from intra- and peritumoral regions on pre- and mid-RT CT scans. LLMs were prompted with clinical variables, radiotherapy notes, and radiomic features to classify patients as high- or low-risk for death, recurrence, and distant metastasis. Model performance was assessed using sensitivity, specificity, AUC, Kaplan–Meier survival analysis, and McNemar tests. Results: Integration of radiomic features significantly improved prognostic discrimination over clinical/RT plan data alone for both LLMs. For death prediction, pre-RT radiomics were the most predictive: GPT-4o achieved a peak AUC of 0.730 using intratumoral features, while Gemma-2-27b reached 0.736 using peritumoral features. For recurrence prediction, mid-RT peritumoral features yielded optimal performance (AUC = 0.703 for GPT-4o; AUC = 0.709 for Gemma-2-27b). Kaplan–Meier analyses confirmed statistically significant separation of risk groups: pre-RT intra- and peritumoral features for overall survival (for both GPT-4o and Gemma-2-27b, p < 0.05), and mid-RT peritumoral features for recurrence-free survival (p = 0.028 for GPT-4o; p = 0.017 for Gemma-2-27b). McNemar tests revealed no significant performance difference between the two LLMs when augmented with radiomics (all p > 0.05), indicating that the open-source model achieved comparable accuracy to its proprietary counterpart. Both models generated clinically coherent, patient-specific rationales explaining risk assignments, enhancing interpretability and clinical trust. Conclusions: This external validation demonstrates that pre-trained LLMs can serve as accurate, interpretable, and multimodal prognostic engines for LHC. Pre-RT radiomic features are critical for predicting mortality and metastasis, while mid-RT peritumoral features uniquely inform recurrence risk. The comparable performance of the open-source Gemma-2-27b-it model suggests a scalable, cost-effective, and privacy-preserving pathway for the integration of LLM-based tools into precision radiation oncology workflows to enhance risk stratification and therapeutic personalization. Full article
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20 pages, 1423 KB  
Article
Automatic Detection and Classification of Microscopic Defects in Optical Thin-Film Coatings Based on Deep Learning
by Chuen-Lin Tien, Hsiang-Hsun Tsai, Hsi-Fu Shih and Chia-Chun Yen
Coatings 2025, 15(12), 1390; https://doi.org/10.3390/coatings15121390 - 27 Nov 2025
Viewed by 935
Abstract
This study presents an effective method for detecting and classifying microscopic defects in optical thin films, aiming to enhance quality control in thin-film manufacturing. The proposed system utilizes thin-film surface defect images captured by an imaging microscope. It combines image preprocessing techniques, such [...] Read more.
This study presents an effective method for detecting and classifying microscopic defects in optical thin films, aiming to enhance quality control in thin-film manufacturing. The proposed system utilizes thin-film surface defect images captured by an imaging microscope. It combines image preprocessing techniques, such as translation, scaling, and mirroring, to expand the dataset, thereby generating a rich and representative set of defect images. All images are manually labeled by experts to ensure high-quality annotations and to optimize training efficiency. The YOLOv7 object detection framework is employed for model training and optimization. Model performance is rigorously evaluated using metrics such as the confusion matrix and mean average precision (mAP). The trained model achieved an accuracy of 87.3% on the test dataset, demonstrating both high detection accuracy and practical applicability. This method offers significant potential for automating microscopic defect detection, thus improving the efficiency of film quality inspection and contributing to better production yield in optical thin-film processes. Full article
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18 pages, 5551 KB  
Article
Isolation and Characterization of Integrin α9 Positive Extracellular Vesicles Derived from Human Corneoscleral Rings
by Hung-Yin Lai, Ming-Chieh Hsieh, Hao-Hsiang Wu, Chien-Wei Lee, Shih-Hua Liu, Hsing-Yu Lin, Yi-Wen Chen, Chun-Chi Chiang, Yi-Ching Hsieh, Ying-Hsuen Wu, You-Ling Li, Hsiao-Fan Tung, Jennifer Hui-Chun Ho and Yi-Yu Tsai
Life 2025, 15(11), 1780; https://doi.org/10.3390/life15111780 - 20 Nov 2025
Viewed by 545
Abstract
Corneoscleral-ring-derived extracellular vesicles represent a potential therapeutic strategy for promoting in vitro corneal wound healing. In this study, we successfully isolated and characterized extracellular vesicles from human corneolimbal tissue obtained from 42 donors, with a mean age of 51.62 ± 15.56 years. Donor-related [...] Read more.
Corneoscleral-ring-derived extracellular vesicles represent a potential therapeutic strategy for promoting in vitro corneal wound healing. In this study, we successfully isolated and characterized extracellular vesicles from human corneolimbal tissue obtained from 42 donors, with a mean age of 51.62 ± 15.56 years. Donor-related factors such as age, corneal endothelial cell density, and underlying systemic conditions did not confound extracellular vesicle size and concentration with mean peak size of 99.52 ± 13.00 nm by nanoparticle tracking analysis. Western blotting analysis revealed positive Alix, stable expression of CD9 and CD81, and variable expression of CD63. Limbal stem cell (LSC)-associated markers, i.e., ABCG2, p63, Notch-1, and Integrin α9 were positively detected in the isolated extracellular vesicles. Notably, Integrin α9 showed stable and relatively strong expression in all samples serving a specific marker of LSC-derived extracellular vesicles. Functional assays demonstrated that LSC-derived extracellular vesicles exhibited better wound healing potency compared to extracellular vesicles derived from mesenchymal stem cells (MSCs). These findings suggest that corneoscleral-ring-derived extracellular vesicles express distinct LSC markers, including Integrin α9, and hold significant potential for application in corneal wound healing and ocular surface regeneration. Full article
(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)
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25 pages, 7422 KB  
Article
Vitamin B1 Involved in Dendrobium Taiseed Tosnobile Extract Mediates Protection Against Cancer-Induced Muscle Wasting by Suppressing IL-6 Pathogenicity and Enhancing Myoblast Fusion
by Chen-Chu Lin, Wan-Ting Liao, Tsung-Ying Yang, Jing-Hua Tsai, Yi-Ju Lee, Chi-Luan Wen, Shih-Lan Hsu and Chun-Chi Wu
Int. J. Mol. Sci. 2025, 26(21), 10704; https://doi.org/10.3390/ijms262110704 - 3 Nov 2025
Viewed by 677
Abstract
In this report, we showed that oral administration of Dendrobium Taiseed Tosnobile (DTT, also known as Taiwan Emperor No.1) allowed Lewis Lung Carcinoma (LLC) tumor-bearing mice to maintain body weight and grip strength in a dose-dependent manner. Histological analysis showed that treatment with [...] Read more.
In this report, we showed that oral administration of Dendrobium Taiseed Tosnobile (DTT, also known as Taiwan Emperor No.1) allowed Lewis Lung Carcinoma (LLC) tumor-bearing mice to maintain body weight and grip strength in a dose-dependent manner. Histological analysis showed that treatment with DTT water extract significantly reduced muscle fiber damage by inducing muscle regeneration and improved the cross-sectional area of the rectus femoris, soleus, and gastrocnemius of LLC tumor-bearing C57BL/6 female mice. Further studies revealed that DTT water extract also reduced the expression of inflammatory cytokines such as IL-6 and TNF-α, both in vitro and in vivo. Other analyses showed that DTT water extract promoted the differentiation of C2C12 myoblasts with or without IL-6 by maintaining Myosin Heavy Chain (MyHC) levels. This suggests that DTT water extract acts against muscle wasting via multiple mechanisms. Interestingly, vitamin B1 was identified as an ingredient in DTT water extract through an HPLC analysis. Vitamin B1 was shown to ameliorate IL-6 but not TNF-α generation in active THP-1 cells and protected C2C12 myotubes against IL-6. Further studies showed that DTT and vitamin B1 promoted the multi-nucleus fusion step of C2C12 differentiation by inducing E-cadherin-β-catenin expression with or without IL-6 treatment. In summary, DTT water extract protects muscle cells under cancer conditions through direct and indirect mechanisms, with vitamin B1 being a key functional ingredient that reduces IL-6 generation and aids muscle cell fusion against IL-6 treatment. Full article
(This article belongs to the Special Issue The Role of Natural Products in Treating Human Diseases)
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15 pages, 1120 KB  
Article
Greenhouse Gas Emissions and Mitigation Strategies in Universities Under ISO 14064-1: Lessons for Global Higher Education Sustainability
by Shu-Yao Tsai, Mei-Ching Wang, Shun-Pei Yao, Gregory J. Tsay and Chun-Ping Lin
Sustainability 2025, 17(21), 9462; https://doi.org/10.3390/su17219462 - 24 Oct 2025
Viewed by 1329
Abstract
In alignment with the United Nations’ Sustainable Development Goals (SDGs) and the global pursuit of net-zero emissions, higher education institutions (HEIs) are increasingly expected to demonstrate robust climate accountability and effective decarbonization strategies. This three-year longitudinal study presents a comprehensive assessment of greenhouse [...] Read more.
In alignment with the United Nations’ Sustainable Development Goals (SDGs) and the global pursuit of net-zero emissions, higher education institutions (HEIs) are increasingly expected to demonstrate robust climate accountability and effective decarbonization strategies. This three-year longitudinal study presents a comprehensive assessment of greenhouse gas (GHG) emissions at a higher education institution, employing the ISO 14064-1:2018 framework to strengthen inventory design, boundary delineation, and data governance protocols. Findings indicate that purchased electricity constitutes the largest share; however, fugitive refrigerant leakage and Scope 3 activities—particularly commuting and business travel—represent substantial and often underestimated components of the institution’s carbon footprint. Methodological refinements, including the incorporation of updated emission factors coefficients and enhanced data verification, have revealed the sensitivity of GHG inventories to both policy reforms and behavioral changes, as well as institutional policy reforms. The study also demonstrates that targeted refrigerant management and low-carbon mobility initiatives can generate measurable mitigation effects, even under conditions of expanding campus activity. Beyond the institution-specific results, this research proposes a replicable framework that integrates ISO 14064-1 compliance with data quality assurance and digital verification tools. This framework provides HEIs globally with a structured pathway to enhance reporting credibility, develop evidence-based mitigation strategies, and accelerate progress toward carbon neutrality. These insights underline the strategic role of universities in advancing sector-wide climate leadership and contributing to sustainable development transitions. Full article
(This article belongs to the Special Issue Sustainability Management Strategies and Practices—2nd Edition)
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20 pages, 8391 KB  
Article
Short Expandable-Wing Suture Anchor for Osteoporotic and Small Bone Fixation: Validation in a 3D-Printed Coracoclavicular Reconstruction Model
by Chia-Hung Tsai, Shao-Fu Huang, Rong-Chen Lin, Pao-Wei Lee, Cheng-Ying Lee and Chun-Li Lin
J. Funct. Biomater. 2025, 16(10), 379; https://doi.org/10.3390/jfb16100379 - 10 Oct 2025
Viewed by 1188
Abstract
Suture anchors are widely used for tendon and ligament repair, but their fixation strength is compromised in osteoporotic bone and limited bone volume such as the coracoid process. Existing designs are prone to penetration and insufficient cortical engagement under such conditions. In this [...] Read more.
Suture anchors are widely used for tendon and ligament repair, but their fixation strength is compromised in osteoporotic bone and limited bone volume such as the coracoid process. Existing designs are prone to penetration and insufficient cortical engagement under such conditions. In this study, we developed a novel short expandable-wing (SEW) suture anchor (Ti6Al4V) designed to enhance pull-out resistance through a deployable wing mechanism that locks directly against the cortical bone. Finite element analysis based on CT-derived bone material properties demonstrated reduced intra-bone displacement and improved load transfer with the SEW compared to conventional anchors. Mechanical testing using matched artificial bone surrogates (N = 3 per group) demonstrated significantly higher static pull-out strength in both normal (581 N) and osteoporotic bone (377 N) relative to controls (p < 0.05). Although the sample size was limited, results were consistent and statistically significant. After cyclic loading, SEW anchor fixation strength increased by 25–56%. In a 3D-printed anatomical coracoclavicular ligament reconstruction model, the SEW anchor provided nearly double the fixation strength of the hook plate, underscoring its superior stability under high-demand clinical conditions. This straightforward implantation protocol—requiring only a 5 mm drill hole without tapping, followed by direct insertion and knob-driven wing deployment—facilitates seamless integration into existing surgical workflows. Overall, the SEW anchor addresses key limitations of existing anchor designs in small bone volume and osteoporotic environments, demonstrating strong potential for clinical translation. Full article
(This article belongs to the Special Issue Three-Dimensional Printing and Biomaterials for Medical Applications)
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14 pages, 2926 KB  
Article
A Dual-Thread Lag–Locking Screw Enhances Single Lateral Plate Fixation in Bicondylar Tibial Plateau Fractures: A Biomechanical Study
by Ya-Han Chan, Hsuan-Wen Wang, Wei-Che Tsai and Chun-Li Lin
Bioengineering 2025, 12(10), 1023; https://doi.org/10.3390/bioengineering12101023 - 25 Sep 2025
Viewed by 804
Abstract
Schatzker type V bicondylar tibial plateau fractures present a major challenge due to the difficulty of achieving stable fixation with minimally invasive strategies. This study introduces a dual-thread lag and locking plate (DLLP) design that integrates lag screw compression with unilateral locking plate [...] Read more.
Schatzker type V bicondylar tibial plateau fractures present a major challenge due to the difficulty of achieving stable fixation with minimally invasive strategies. This study introduces a dual-thread lag and locking plate (DLLP) design that integrates lag screw compression with unilateral locking plate fixation. A custom-built compression evaluation platform and standardized 3D-printed fracture models were employed to assess biomechanical performance. DLLP produced measurable interfragmentary compression during screw insertion, with a mean displacement of 1.22 ± 0.11 mm compared with 0.02 ± 0.04 mm for conventional single lateral locking plates (SLLPs) (p < 0.05). In static testing, DLLP demonstrated a significantly greater maximum failure force (7801.51 ± 358.95 N) than SLLP (6224.84 ± 411.20 N, p < 0.05) and improved resistance to lateral displacement at 2 mm (3394.85 ± 392.81 N vs. 2766.36 ± 64.51 N, p = 0.03). Under dynamic fatigue loading simulating one year of functional use, all DLLP constructs survived 1 million cycles with <2 mm displacement, while all SLLP constructs failed prematurely (mean fatigue life: 408,679 ± 128,286 cycles). These findings highlight the critical role of lag screw compression in maintaining fracture stability and demonstrate that DLLP provides superior biomechanical performance compared with SLLP, supporting its potential as a less invasive alternative to dual plating in the treatment of complex tibial plateau fractures. Full article
(This article belongs to the Special Issue Orthopedic and Trauma Biomechanics)
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27 pages, 5128 KB  
Article
Lepidium meyenii Walpers Promotes the Regeneration of Salivary Gland and Prevents Xerostomia After Irradiation Injury
by Yi-Ting Tsai, Yuan-Chuan Lin, Ming-Jen Cheng, Chun-Ming Shih, Chien-Sung Tsai, Ze-Hao Lai, Ching-Yi Wu, Chen-Wei Liu, Feng-Yen Lin and Yi-Wen Lin
Nutrients 2025, 17(19), 3033; https://doi.org/10.3390/nu17193033 - 23 Sep 2025
Viewed by 1663
Abstract
Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological [...] Read more.
Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sjögren’s syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-β1 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. Methods: In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL/6J mice and TGF-β1-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. Results: LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-β1-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. Conclusions: These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia. Full article
(This article belongs to the Special Issue Diet and Oral Health)
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11 pages, 1089 KB  
Article
CRAFITY and AFP/PIVKA-II Kinetics Predict Prognosis in Hepatocellular Carcinoma on Immunotherapy
by Shou-Wu Lee, Yi-Jie Huang, Ying-Cheng Lin, Hsin-Ju Tsai, Chia-Chang Chen, Chung-Hsin Chang, Teng-Yu Lee and Yen-Chun Peng
Cancers 2025, 17(18), 3058; https://doi.org/10.3390/cancers17183058 - 18 Sep 2025
Cited by 2 | Viewed by 1113
Abstract
Background: The CRAFITY score, integrating baseline C-reactive protein (CRP) and alpha-fetoprotein (AFP), has been validated as a prognostic biomarker in hepatocellular carcinoma (HCC) treated with immunotherapy, but many patients present with non-elevated AFP, limiting its accuracy. This study evaluated a composite model incorporating [...] Read more.
Background: The CRAFITY score, integrating baseline C-reactive protein (CRP) and alpha-fetoprotein (AFP), has been validated as a prognostic biomarker in hepatocellular carcinoma (HCC) treated with immunotherapy, but many patients present with non-elevated AFP, limiting its accuracy. This study evaluated a composite model incorporating the CRAFITY score with AFP/PIVKA-II kinetic changes. Methods: We retrospectively enrolled 69 patients with unresectable HCC (BCLC stage B/C) receiving immunotherapy between September 2021 and June 2023. Baseline CRP, AFP, and PIVKA-II, as well as 4-week changes, were recorded. The CRAFITY-100 RULE combined CRAFITY (0–2) with AFP/PIVKA-II kinetics (0–3), yielding three risk levels (I–III). Clinical outcomes included objective response (OR) and overall survival (OS). Results: Of the cohort, 10 (14.5%), 29 (42%), and 30 (43.5%) patients had CRAFITY scores 0, 1, and 2, respectively, but this score did not clearly stratify OS (median 24, 12, and 15 months; p = 0.267). In contrast, the CRAFITY-100 RULE classified 5 (7.3%), 35 (50.7%), and 29 (42%) patients into levels I–III, respectively, with significantly different survival (median OS 24, 15, and 7 months; p = 0.048). OR rates were lowest at level III (17%). Time-dependent ROC analysis confirmed superior discrimination of CRAFITY-100 RULE over CRAFITY scores at 6 months (AUROC 0.673 vs. 0.604) and 12 months (0.732 vs. 0.656). Conclusions: The CRAFITY-100 RULE provided clearer stratification and higher discrimination. This simple model integrating baseline and dynamic biomarkers may assist clinical decision-making in unresectable HCC treated with immunotherapy. Full article
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14 pages, 954 KB  
Article
A YOLO Ensemble Framework for Detection of Barrett’s Esophagus Lesions in Endoscopic Images
by Wan-Chih Lin, Chi-Chih Wang, Ming-Chang Tsai, Chao-Yen Huang, Chun-Che Lin and Ming-Hseng Tseng
Diagnostics 2025, 15(18), 2290; https://doi.org/10.3390/diagnostics15182290 - 10 Sep 2025
Viewed by 896
Abstract
Background and Objectives: Barrett’s Esophagus (BE) is a precursor to esophageal adenocarcinoma, and early detection is essential to reduce cancer risk. This study aims to develop a YOLO-based ensemble framework to improve the automated detection of BE-associated mucosal lesions on endoscopic images. [...] Read more.
Background and Objectives: Barrett’s Esophagus (BE) is a precursor to esophageal adenocarcinoma, and early detection is essential to reduce cancer risk. This study aims to develop a YOLO-based ensemble framework to improve the automated detection of BE-associated mucosal lesions on endoscopic images. Methods: A dataset of 3620 annotated endoscopic images was collected from 132 patients. Five YOLO variants, YOLOv5, YOLOv9, YOLOv10, YOLOv11, and YOLOv12, were selected based on their architectural diversity and detection capabilities. Each model was trained individually, and their outputs were integrated using a Non-Maximum Suppression (NMS)-based ensemble strategy. Multiple ensemble configurations were evaluated to assess the impact of fusion depth on detection performance. Results: The ensemble models consistently outperformed individual YOLO variants in recall, the primary evaluation metric. The entire five-model ensemble achieved the highest recall (0.974), significantly reducing missed lesion detections. Statistical analysis using McNemar’s test and bootstrap confidence intervals confirmed the superiority in most comparisons. Conclusions: The proposed YOLO ensemble framework demonstrates enhanced sensitivity and robustness in detecting BE lesions. Its integration into clinical workflows can improve early diagnosis and reduce diagnostic workload, offering a promising tool for computer-aided screening in gastroenterology. Full article
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18 pages, 4277 KB  
Article
Magnolia figo Extract Induces Enamel Shade Recovery and Inhibits Porphyromonas gingivalis Biofilm Formation: An In Vitro, Dual-Action Natural Therapeutic Approach
by Chun-Sheng Kuo, Cheng-Wen Lin, Yuan-Man Hsu, Jen-Chieh Tsai and Dan-Jae Lin
Int. J. Mol. Sci. 2025, 26(17), 8157; https://doi.org/10.3390/ijms26178157 - 22 Aug 2025
Viewed by 1014
Abstract
Dental enamel discoloration, extrinsic staining, and periodontal biofilms remain persistent challenges in oral health. This study explores the in vitro, dual-functional potential of Magnolia figo flower extract (FMO), a sesquiterpene-rich botanical active phytochemical ingredient (API), for aesthetic and antimicrobial oral applications. FTIR identified [...] Read more.
Dental enamel discoloration, extrinsic staining, and periodontal biofilms remain persistent challenges in oral health. This study explores the in vitro, dual-functional potential of Magnolia figo flower extract (FMO), a sesquiterpene-rich botanical active phytochemical ingredient (API), for aesthetic and antimicrobial oral applications. FTIR identified characteristic terpenoid and long-chain fatty acid functional groups, including β-elemene, γ-elemene, and caryophyllene oxide. Whitening efficacy on coffee-stained bovine enamel was quantified using CIELAB colorimetry. The 0.5% FMO treatment achieved ΔE* = 8.49, which was within the clinical perceptibility threshold and the optimal biocompatibility balance. SEM confirmed no demineralization on the enamel surface after immersion in 3.0% FMO for 12 h. Antimicrobial assays demonstrated inhibition of Porphyromonas gingivalis, with MIC and MBC values of 0.25% and 0.5%, respectively. Biofilm formation was reduced by over 50% at a 0.148% concentration. Cytocompatibility assays using HGF-1 cells with various concentrations of FMO showed reduced cell viability at higher concentrations. When exposed for 5 min (simulating daily oral care) or 2 h, 0.5% FMO exhibited greater biocompatibility with L929 cells compared to toothpaste and peroxide-based agents. These findings suggest that FMO may serve as a natural candidate for dual-function oral care; however, further in vivo and clinical investigations are needed to validate its potential use within oral care treatments. Full article
(This article belongs to the Special Issue Natural Compounds in Human Health and Disease)
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Article
Porphyromonas gingivalis GroEL Accelerates Abdominal Aortic Aneurysm Formation by Induction of M1 Polarization in Macrophages
by Yi-Wen Lin, Yi-Ting Tsai, Ming-Jen Cheng, Chun-Ming Shih, Chun-Yao Huang, Chien-Sung Tsai, Shih-Ying Sung, Ze-Hao Lai, Chen-Wei Liu and Feng-Yen Lin
Int. J. Mol. Sci. 2025, 26(16), 7781; https://doi.org/10.3390/ijms26167781 - 12 Aug 2025
Cited by 1 | Viewed by 1316
Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by chronic inflammation, extracellular matrix degradation, and smooth muscle cell apoptosis. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been implicated in the progression of cardiovascular diseases, including AAA, but [...] Read more.
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by chronic inflammation, extracellular matrix degradation, and smooth muscle cell apoptosis. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been implicated in the progression of cardiovascular diseases, including AAA, but the underlying mechanisms remain unclear. In this study, we investigated the role of GroEL, a bacterial heat shock protein 60 homolog derived from P. gingivalis, in AAA development. We employed a CaCl2-induced AAA mouse model to evaluate the in vivo effects of GroEL. Mice received periaortic CaCl2 application followed by intravenous injections of recombinant GroEL. Histological analyses were performed to assess aneurysmal dilation, elastin degradation, and inflammatory cell infiltration. Flow cytometry and immunohistochemistry were used to determine macrophage phenotypes, while cytokine profiles were quantified via ELISA. In vitro, THP-1 monocytes were treated with GroEL to evaluate its impact on macrophage polarization and cytokine expression. Our results showed that GroEL administration significantly enhanced aortic diameter expansion and elastin breakdown, accompanied by increased infiltration of M1-like macrophages and elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6. In vitro findings confirmed that GroEL promotes M1 polarization and inhibits M2 marker expression in THP-1-derived macrophages. These findings suggest that P. gingivalis-derived GroEL plays a pathogenic role in AAA by modulating macrophage polarization toward a pro-inflammatory phenotype. Targeting microbial components such as GroEL may offer new therapeutic strategies for AAA management. Full article
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