Pub Date : 2026-01-16DOI: 10.3390/bioengineering13010107
Khawla Ghannoum Al Chawaf, Salim Lahmiri
The COVID-19 outbreak has made it evident that the nature and behavior of SARS-CoV-2 requires constant research and surveillance, owing to the high mutation rates that lead to variants. This work focuses on the statistical analysis of energy measures as biomarkers of SARS-CoV-2. The main purpose of this study is to determine which energy measure can differentiate between SARS-CoV-2 variants, human cell receptors (GRP78 and ACE2), and their combinations. The dataset includes energy measures for different biological structures categorized by variants, receptors, and combinations, representing the sequence of variants and receptors. A multiple analysis of variance (ANOVA) test for equality of means and a Bartlett test for equality of variances are applied to energy measures. Results from multiple ANOVA show (a) the presence of significant differences in energy across variants, receptors, and combinations, (b) that average energy is significant only for receptors and combinations, but not for variants, and (c) the absence of significant differences observed for standard deviation across variants or combinations, but that there are significant differences across receptors. The results from the Bartlett tests show that (a) there is a presence of significant differences in the variances in energy across the variants and combinations, but no significant differences across receptors, (b) there is an absence of significant differences in variances across any group (variants, receptors, combinations), and (c) there is an absence of significant differences in variances for standard deviation of energy across variants, receptors, or combinations. In summary, it is concluded that energy and mean energy are the key biomarkers used to differentiate receptors and combinations. In addition, energy is the primary biomarker where variances differ across variants and combinations. These findings can help to implement tailored interventions, address the SARS-CoV-2 issue, and contribute considerably to the global fight against the pandemic.
{"title":"Energy Measures as Biomarkers of SARS-CoV-2 Variants and Receptors.","authors":"Khawla Ghannoum Al Chawaf, Salim Lahmiri","doi":"10.3390/bioengineering13010107","DOIUrl":"10.3390/bioengineering13010107","url":null,"abstract":"<p><p>The COVID-19 outbreak has made it evident that the nature and behavior of SARS-CoV-2 requires constant research and surveillance, owing to the high mutation rates that lead to variants. This work focuses on the statistical analysis of energy measures as biomarkers of SARS-CoV-2. The main purpose of this study is to determine which energy measure can differentiate between SARS-CoV-2 variants, human cell receptors (GRP78 and ACE2), and their combinations. The dataset includes energy measures for different biological structures categorized by variants, receptors, and combinations, representing the sequence of variants and receptors. A multiple analysis of variance (ANOVA) test for equality of means and a Bartlett test for equality of variances are applied to energy measures. Results from multiple ANOVA show (a) the presence of significant differences in energy across variants, receptors, and combinations, (b) that average energy is significant only for receptors and combinations, but not for variants, and (c) the absence of significant differences observed for standard deviation across variants or combinations, but that there are significant differences across receptors. The results from the Bartlett tests show that (a) there is a presence of significant differences in the variances in energy across the variants and combinations, but no significant differences across receptors, (b) there is an absence of significant differences in variances across any group (variants, receptors, combinations), and (c) there is an absence of significant differences in variances for standard deviation of energy across variants, receptors, or combinations. In summary, it is concluded that energy and mean energy are the key biomarkers used to differentiate receptors and combinations. In addition, energy is the primary biomarker where variances differ across variants and combinations. These findings can help to implement tailored interventions, address the SARS-CoV-2 issue, and contribute considerably to the global fight against the pandemic.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010099
Aoumria Chelef, Demet Yuksel Dal, Mahmut Ozturk, Mosab A A Yousif, Gokce Koc
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interaction and communication, along with atypical behavioral patterns. Affected individuals often seem isolated in their inner world and exhibit particular sensory reactions. The World Health Organization has indicated a persistent increase in the global prevalence of autism, with approximately 1 in 127 persons affected worldwide. This study contributes to the growing research effort by presenting a comprehensive analysis of functional connectivity patterns for ASD prediction using rs-fMRI datasets. A novel approach was used for ASD identification using the ABIDE II dataset, based on functional networks derived from BOLD signals. The sparse functional brain connectome (Lean-NET) model is employed to construct subject-specific connectomes, from which local graph metrics are extracted to quantify regional network properties. Statistically significant features are selected using Welch's t-test, then subjected to False Discovery Rate (FDR) correction and classified using a Support Vector Machine (SVM). Our experimental results demonstrate that locally derived graph metrics effectively discriminate ASD from typically developing (TD) subjects and achieve accuracy ranging from 70% up to 91%, highlighting the potential of graph learning approaches for functional connectivity analysis and ASD characterization.
{"title":"Lean-NET-Based Local Brain Connectome Analysis for Autism Spectrum Disorder Classification.","authors":"Aoumria Chelef, Demet Yuksel Dal, Mahmut Ozturk, Mosab A A Yousif, Gokce Koc","doi":"10.3390/bioengineering13010099","DOIUrl":"10.3390/bioengineering13010099","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interaction and communication, along with atypical behavioral patterns. Affected individuals often seem isolated in their inner world and exhibit particular sensory reactions. The World Health Organization has indicated a persistent increase in the global prevalence of autism, with approximately 1 in 127 persons affected worldwide. This study contributes to the growing research effort by presenting a comprehensive analysis of functional connectivity patterns for ASD prediction using rs-fMRI datasets. A novel approach was used for ASD identification using the ABIDE II dataset, based on functional networks derived from BOLD signals. The sparse functional brain connectome (Lean-NET) model is employed to construct subject-specific connectomes, from which local graph metrics are extracted to quantify regional network properties. Statistically significant features are selected using Welch's <i>t</i>-test, then subjected to False Discovery Rate (FDR) correction and classified using a Support Vector Machine (SVM). Our experimental results demonstrate that locally derived graph metrics effectively discriminate ASD from typically developing (TD) subjects and achieve accuracy ranging from 70% up to 91%, highlighting the potential of graph learning approaches for functional connectivity analysis and ASD characterization.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010104
Chamani Shiranthika, Zahra Hafezi Kafshgari, Hadi Hadizadeh, Parvaneh Saeedi
Machine Learning (ML) and Deep Learning (DL) have shown significant promise in healthcare, particularly in medical image segmentation, which is crucial for accurate disease diagnosis and treatment planning. Despite their potential, challenges such as data privacy concerns, limited annotated data, and inadequate training data persist. Decentralized learning approaches such as federated learning (FL), split learning (SL), and split federated learning (SplitFed/SFL) address these issues effectively. This paper introduces "MedSegNet10," a publicly accessible repository designed for medical image segmentation using split-federated learning. MedSegNet10 provides a collection of pre-trained neural network architectures optimized for various medical image types, including microscopic images of human blastocysts, dermatoscopic images of skin lesions, and endoscopic images of lesions, polyps, and ulcers. MedSegNet10 implements SplitFed versions of ten established segmentation architectures, enabling collaborative training without centralizing raw data and labels, reducing the computational load required at client sites. This repository supports researchers, practitioners, trainees, and data scientists, aiming to advance medical image segmentation while maintaining patient data privacy.
{"title":"MedSegNet10: A Publicly Accessible Network Repository for Split Federated Medical Image Segmentation.","authors":"Chamani Shiranthika, Zahra Hafezi Kafshgari, Hadi Hadizadeh, Parvaneh Saeedi","doi":"10.3390/bioengineering13010104","DOIUrl":"10.3390/bioengineering13010104","url":null,"abstract":"<p><p>Machine Learning (ML) and Deep Learning (DL) have shown significant promise in healthcare, particularly in medical image segmentation, which is crucial for accurate disease diagnosis and treatment planning. Despite their potential, challenges such as data privacy concerns, limited annotated data, and inadequate training data persist. Decentralized learning approaches such as federated learning (FL), split learning (SL), and split federated learning (SplitFed/SFL) address these issues effectively. This paper introduces \"MedSegNet10,\" a publicly accessible repository designed for medical image segmentation using split-federated learning. MedSegNet10 provides a collection of pre-trained neural network architectures optimized for various medical image types, including microscopic images of human blastocysts, dermatoscopic images of skin lesions, and endoscopic images of lesions, polyps, and ulcers. MedSegNet10 implements SplitFed versions of ten established segmentation architectures, enabling collaborative training without centralizing raw data and labels, reducing the computational load required at client sites. This repository supports researchers, practitioners, trainees, and data scientists, aiming to advance medical image segmentation while maintaining patient data privacy.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Tackling Imbalanced Data in Chronic Obstructive Pulmonary Disease Diagnosis: An Ensemble Learning Approach with Synthetic Data Generation.","authors":"Yi-Hsin Ko, Chuan-Sheng Hung, Chun-Hung Richard Lin, Da-Wei Wu, Chung-Hsuan Huang, Chang-Ting Lin, Jui-Hsiu Tsai","doi":"10.3390/bioengineering13010105","DOIUrl":"10.3390/bioengineering13010105","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010098
Eun-Joo Ji, Sang Sik Lee, Eun-Kyung Lee
This study aimed to develop an immersive virtual reality (VR) program and conduct preliminary evaluation of its feasibility and learner perception for enhancing nursing students' clinical practicum education. The VR program was designed using the ADDIE model (analysis, design, development, implementation, and evaluation) and implemented on the UNITY 3D platform. Expert evaluation was conducted through a VR application, and its effectiveness was further assessed among 25 fourth-year nursing students in terms of immersion, presence, and satisfaction. The expert evaluation yielded a mean score of 6.54 out of 7, indicating acceptable content validity. Among learners, evaluation demonstrated immersion at 42.28 ± 2.37 out of 50 (95% CI: 41.30-43.26), presence at 81.36 ± 7.32 out of 95 (95% CI: 78.34-84.38), and satisfaction at 13.48 ± 1.26 out of 15 (95% CI: 12.96-14.00). Overall, the developed VR program demonstrated acceptable expert validity and positive learner perceptions. These preliminary findings suggest feasibility as a supplementary practicum. However, the single-group design without control comparison and reliance on self-reported measures preclude conclusions about educational effectiveness.
{"title":"Development of an Immersive Virtual Reality-Based Nursing Program Involving Patients with Respiratory Infections.","authors":"Eun-Joo Ji, Sang Sik Lee, Eun-Kyung Lee","doi":"10.3390/bioengineering13010098","DOIUrl":"10.3390/bioengineering13010098","url":null,"abstract":"<p><p>This study aimed to develop an immersive virtual reality (VR) program and conduct preliminary evaluation of its feasibility and learner perception for enhancing nursing students' clinical practicum education. The VR program was designed using the ADDIE model (analysis, design, development, implementation, and evaluation) and implemented on the UNITY 3D platform. Expert evaluation was conducted through a VR application, and its effectiveness was further assessed among 25 fourth-year nursing students in terms of immersion, presence, and satisfaction. The expert evaluation yielded a mean score of 6.54 out of 7, indicating acceptable content validity. Among learners, evaluation demonstrated immersion at 42.28 ± 2.37 out of 50 (95% CI: 41.30-43.26), presence at 81.36 ± 7.32 out of 95 (95% CI: 78.34-84.38), and satisfaction at 13.48 ± 1.26 out of 15 (95% CI: 12.96-14.00). Overall, the developed VR program demonstrated acceptable expert validity and positive learner perceptions. These preliminary findings suggest feasibility as a supplementary practicum. However, the single-group design without control comparison and reliance on self-reported measures preclude conclusions about educational effectiveness.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010103
Yaron Ilan
This paper examines the contrasting yet complementary approaches of the Constrained Disorder Principle (CDP) and Stefan Hell's deterministic optical nanoscopy for managing noise in complex systems. The CDP suggests that controlled disorder within dynamic boundaries is crucial for optimal system function, particularly in biological contexts, where variability acts as an adaptive mechanism rather than being merely a measurement error. In contrast, Hell's recent breakthrough in nanoscopy demonstrates that engineered diffraction minima can achieve sub-nanometer resolution without relying on stochastic (random) molecular switching, thereby replacing randomness with deterministic measurement precision. Philosophically, these two approaches are distinct: the CDP views noise as functionally necessary, while Hell's method seeks to overcome noise limitations. However, both frameworks address complementary aspects of information extraction. The primary goal of microscopy is to provide information about structures, thereby facilitating a better understanding of their functionality. Noise is inherent to biological structures and functions and is part of the information in complex systems. This manuscript achieves integration through three specific contributions: (1) a mathematical framework combining CDP variability bounds with Hell's precision measurements, validated through Monte Carlo simulations showing 15-30% precision improvements; (2) computational demonstrations with N = 10,000 trials quantifying performance under varying biological noise regimes; and (3) practical protocols for experimental implementation, including calibration procedures and real-time parameter optimization. The CDP provides a theoretical understanding of variability patterns at the system level, while Hell's technique offers precision tools at the molecular level for validation. Integrating these approaches enables multi-scale analysis, allowing for deterministic measurements to accurately quantify the functional variability that the CDP theory predicts is vital for system health. This synthesis opens up new possibilities for adaptive imaging systems that maintain biologically meaningful noise while achieving unprecedented measurement precision. Specific applications include cancer diagnostics through chromosomal organization variability, neurodegenerative disease monitoring via protein aggregation disorder patterns, and drug screening by assessing cellular response heterogeneity. The framework comprises machine learning integration pathways for automated recognition of variability patterns and adaptive acquisition strategies.
本文研究了约束无序原理(CDP)和Stefan Hell的确定性光学纳米显微镜在复杂系统中管理噪声的对比但互补的方法。CDP表明,动态边界内的受控紊乱对于优化系统功能至关重要,特别是在生物环境中,变异性作为一种适应机制而不仅仅是一种测量误差。相比之下,Hell最近在纳米显微镜方面的突破表明,工程衍射最小值可以在不依赖随机(随机)分子切换的情况下实现亚纳米分辨率,从而用确定性的测量精度取代随机性。从哲学上讲,这两种方法是不同的:CDP认为噪声是功能上必要的,而Hell的方法试图克服噪声限制。然而,这两个框架解决了信息提取的互补方面。显微镜的主要目的是提供有关结构的信息,从而促进对其功能的更好理解。噪声是生物结构和功能所固有的,是复杂系统中信息的一部分。本文通过三个具体贡献实现了整合:(1)将CDP变异性边界与Hell的精度测量相结合的数学框架,通过蒙特卡罗模拟验证,显示精度提高了15-30%;(2) N = 10,000次试验的计算演示,量化了不同生物噪声制度下的性能;(3)实验实施的实际方案,包括校准程序和实时参数优化。CDP在系统层面提供了对变异模式的理论理解,而Hell的技术在分子层面提供了精确的工具进行验证。整合这些方法可以实现多尺度分析,允许确定性测量来准确量化CDP理论预测的对系统健康至关重要的功能变异性。这种合成为自适应成像系统开辟了新的可能性,该系统在保持生物学上有意义的噪声的同时实现了前所未有的测量精度。具体应用包括通过染色体组织变异性进行癌症诊断,通过蛋白质聚集紊乱模式监测神经退行性疾病,以及通过评估细胞反应异质性进行药物筛选。该框架包括用于自动识别可变性模式和自适应获取策略的机器学习集成路径。
{"title":"Integrating the Contrasting Perspectives Between the Constrained Disorder Principle and Deterministic Optical Nanoscopy: Enhancing Information Extraction from Imaging of Complex Systems.","authors":"Yaron Ilan","doi":"10.3390/bioengineering13010103","DOIUrl":"10.3390/bioengineering13010103","url":null,"abstract":"<p><p>This paper examines the contrasting yet complementary approaches of the Constrained Disorder Principle (CDP) and Stefan Hell's deterministic optical nanoscopy for managing noise in complex systems. The CDP suggests that controlled disorder within dynamic boundaries is crucial for optimal system function, particularly in biological contexts, where variability acts as an adaptive mechanism rather than being merely a measurement error. In contrast, Hell's recent breakthrough in nanoscopy demonstrates that engineered diffraction minima can achieve sub-nanometer resolution without relying on stochastic (random) molecular switching, thereby replacing randomness with deterministic measurement precision. Philosophically, these two approaches are distinct: the CDP views noise as functionally necessary, while Hell's method seeks to overcome noise limitations. However, both frameworks address complementary aspects of information extraction. The primary goal of microscopy is to provide information about structures, thereby facilitating a better understanding of their functionality. Noise is inherent to biological structures and functions and is part of the information in complex systems. This manuscript achieves integration through three specific contributions: (1) a mathematical framework combining CDP variability bounds with Hell's precision measurements, validated through Monte Carlo simulations showing 15-30% precision improvements; (2) computational demonstrations with N = 10,000 trials quantifying performance under varying biological noise regimes; and (3) practical protocols for experimental implementation, including calibration procedures and real-time parameter optimization. The CDP provides a theoretical understanding of variability patterns at the system level, while Hell's technique offers precision tools at the molecular level for validation. Integrating these approaches enables multi-scale analysis, allowing for deterministic measurements to accurately quantify the functional variability that the CDP theory predicts is vital for system health. This synthesis opens up new possibilities for adaptive imaging systems that maintain biologically meaningful noise while achieving unprecedented measurement precision. Specific applications include cancer diagnostics through chromosomal organization variability, neurodegenerative disease monitoring via protein aggregation disorder patterns, and drug screening by assessing cellular response heterogeneity. The framework comprises machine learning integration pathways for automated recognition of variability patterns and adaptive acquisition strategies.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010102
Mahmoud Mohamed, Ezaki Yuriko, Yuta Kawagoe, Kazuhiro Kawamura, Masashi Ikeuchi
Non-obstructive azoospermia (NOA) is a severe male infertility condition characterized by extremely low or absent sperm production. In microdissection testicular sperm extraction (Micro-TESE) procedures for NOA, embryologists must manually search through testicular tissue under a microscope for rare sperm, a process that can take 1.8-7.5 h and impose significant fatigue and burden. This paper presents an augmented reality (AR) microscope system with AI-based image analysis to accelerate sperm retrieval in Micro-TESE. The proposed system integrates a deep learning model (YOLOv5) for real-time sperm detection in microscope images, a multi-object tracker (DeepSORT) for continuous sperm tracking, and a velocity calculation module for sperm motility analysis. Detected sperm positions and motility metrics are overlaid in the microscope's eyepiece view via a microdisplay, providing immediate visual guidance to the embryologist. In experiments on seminiferous tubule sample images, the YOLOv5 model achieved a precision of 0.81 and recall of 0.52, outperforming previous classical methods in accuracy and speed. The AR interface allowed an operator to find sperm faster, roughly doubling the sperm detection rate (66.9% vs. 30.8%). These results demonstrate that the AR microscope system can significantly aid embryologists by highlighting sperm in real time and potentially shorten Micro-TESE procedure times. This application of AR and AI in sperm retrieval shows promise for improving outcomes in assisted reproductive technology.
{"title":"AI-Based Augmented Reality Microscope for Real-Time Sperm Detection and Tracking in Micro-TESE.","authors":"Mahmoud Mohamed, Ezaki Yuriko, Yuta Kawagoe, Kazuhiro Kawamura, Masashi Ikeuchi","doi":"10.3390/bioengineering13010102","DOIUrl":"10.3390/bioengineering13010102","url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) is a severe male infertility condition characterized by extremely low or absent sperm production. In microdissection testicular sperm extraction (Micro-TESE) procedures for NOA, embryologists must manually search through testicular tissue under a microscope for rare sperm, a process that can take 1.8-7.5 h and impose significant fatigue and burden. This paper presents an augmented reality (AR) microscope system with AI-based image analysis to accelerate sperm retrieval in Micro-TESE. The proposed system integrates a deep learning model (YOLOv5) for real-time sperm detection in microscope images, a multi-object tracker (DeepSORT) for continuous sperm tracking, and a velocity calculation module for sperm motility analysis. Detected sperm positions and motility metrics are overlaid in the microscope's eyepiece view via a microdisplay, providing immediate visual guidance to the embryologist. In experiments on seminiferous tubule sample images, the YOLOv5 model achieved a precision of 0.81 and recall of 0.52, outperforming previous classical methods in accuracy and speed. The AR interface allowed an operator to find sperm faster, roughly doubling the sperm detection rate (66.9% vs. 30.8%). These results demonstrate that the AR microscope system can significantly aid embryologists by highlighting sperm in real time and potentially shorten Micro-TESE procedure times. This application of AR and AI in sperm retrieval shows promise for improving outcomes in assisted reproductive technology.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Total anomalous pulmonary venous connection (TAPVC) is one of the most severe congenital heart defects; however, prenatal diagnosis remains suboptimal. A normal fetal heart has a junction between the pulmonary venous (PV) and left atrium (LA). In contrast, no junctions are observed in patients with TAPVC. In the present study, we attempted to visualize and detect fetal PV-LA connections using artificial intelligence (AI) trained on the fetal cardiac ultrasound videos of 100 normal cases and six TAPVC cases. The PV-LA aggregate area was segmented using the following three-dimensional (3D) segmentation models: SegResNet, Swin UNETR, MedNeXt, and SegFormer3D. The Dice coefficient and 95% Hausdorff distance were used to evaluate segmentation performance. The mean values of the shortest PV-LA distance (PLD) and major axis angle (PLA) in each video were calculated. These methods demonstrated sufficient performance in visualizing and detecting the PV-LA connection. In terms of TAPVC screening performance, MedNeXt-PLD and SegResNet-PLA achieved mean area under the receiver operating characteristic curve values of 0.844 and 0.840, respectively. Overall, this study shows that our approach can support unskilled examiners in capturing the PV-LA connection and has the potential to improve the prenatal detection rate of TAPVC.
{"title":"Three-Dimensional Visualization and Detection of the Pulmonary Venous-Left Atrium Connection Using Artificial Intelligence in Fetal Cardiac Ultrasound Screening.","authors":"Reina Komatsu, Masaaki Komatsu, Katsuji Takeda, Naoaki Harada, Naoki Teraya, Shohei Wakisaka, Takashi Natsume, Tomonori Taniguchi, Rina Aoyama, Mayumi Kaneko, Kazuki Iwamoto, Ryu Matsuoka, Akihiko Sekizawa, Ryuji Hamamoto","doi":"10.3390/bioengineering13010100","DOIUrl":"10.3390/bioengineering13010100","url":null,"abstract":"<p><p>Total anomalous pulmonary venous connection (TAPVC) is one of the most severe congenital heart defects; however, prenatal diagnosis remains suboptimal. A normal fetal heart has a junction between the pulmonary venous (PV) and left atrium (LA). In contrast, no junctions are observed in patients with TAPVC. In the present study, we attempted to visualize and detect fetal PV-LA connections using artificial intelligence (AI) trained on the fetal cardiac ultrasound videos of 100 normal cases and six TAPVC cases. The PV-LA aggregate area was segmented using the following three-dimensional (3D) segmentation models: SegResNet, Swin UNETR, MedNeXt, and SegFormer3D. The Dice coefficient and 95% Hausdorff distance were used to evaluate segmentation performance. The mean values of the shortest PV-LA distance (PLD) and major axis angle (PLA) in each video were calculated. These methods demonstrated sufficient performance in visualizing and detecting the PV-LA connection. In terms of TAPVC screening performance, MedNeXt-PLD and SegResNet-PLA achieved mean area under the receiver operating characteristic curve values of 0.844 and 0.840, respectively. Overall, this study shows that our approach can support unskilled examiners in capturing the PV-LA connection and has the potential to improve the prenatal detection rate of TAPVC.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-15DOI: 10.3390/bioengineering13010101
Tsung-Lin Lee, Scott Rodeo
Meniscal preservation is increasingly recognized as a critical determinant of long-term knee joint health, yet successful repair remains challenging due to the meniscus's limited intrinsic healing capacity. The adult meniscus is characterized by restricted vascularity, low cellularity, a dense extracellular matrix, complex biomechanical loading, and a hostile post-injury intra-articular inflammatory environment-factors that collectively impair meniscus healing, particularly in the avascular zones. Over the past several decades, a wide range of biologic augmentation strategies have been explored to overcome these barriers, including synovial abrasion, fibrin clot implantation, marrow stimulation, platelet-derived biologics, cell-based therapies, scaffold coverage, and emerging biologic and biophysical interventions. This review summarizes the biological basis of meniscal healing, critically evaluates current and emerging biologic augmentation techniques, and integrates these approaches within a unified framework of vascular, cellular, matrix, biomechanical, and immunologic targets. Understanding and modulating the cellular and molecular mechanisms governing meniscal degeneration and repair may enable the development of more effective, mechanism-driven strategies to improve healing outcomes and reduce the risk of post-traumatic osteoarthritis.
{"title":"Biologic Augmentation for Meniscus Repair: A Narrative Review.","authors":"Tsung-Lin Lee, Scott Rodeo","doi":"10.3390/bioengineering13010101","DOIUrl":"10.3390/bioengineering13010101","url":null,"abstract":"<p><p>Meniscal preservation is increasingly recognized as a critical determinant of long-term knee joint health, yet successful repair remains challenging due to the meniscus's limited intrinsic healing capacity. The adult meniscus is characterized by restricted vascularity, low cellularity, a dense extracellular matrix, complex biomechanical loading, and a hostile post-injury intra-articular inflammatory environment-factors that collectively impair meniscus healing, particularly in the avascular zones. Over the past several decades, a wide range of biologic augmentation strategies have been explored to overcome these barriers, including synovial abrasion, fibrin clot implantation, marrow stimulation, platelet-derived biologics, cell-based therapies, scaffold coverage, and emerging biologic and biophysical interventions. This review summarizes the biological basis of meniscal healing, critically evaluates current and emerging biologic augmentation techniques, and integrates these approaches within a unified framework of vascular, cellular, matrix, biomechanical, and immunologic targets. Understanding and modulating the cellular and molecular mechanisms governing meniscal degeneration and repair may enable the development of more effective, mechanism-driven strategies to improve healing outcomes and reduce the risk of post-traumatic osteoarthritis.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12837435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.3390/bioengineering13010093
Haochen Ci, Xianling Zheng, Bo Wang, Sunita P Ho
Understanding how primary structural features and secondary material properties adapt to functional loads is essential to determining their effect on changes in joint biomechanics over time. The objective of this study was to map and correlate spatiotemporal changes in primary structural features, secondary material properties, and dentoalveolar joint (DAJ) stiffness with age in rats subjected to prolonged chewing of soft foods versus hard foods. To probe how loading history shapes the balance between the primary and secondary features, four-week-old rats were fed either a hard-food (HF, N = 25) or soft-food (SF, N = 25) diet for 4, 12, 16, and 20 weeks, and functional imaging of intact mandibular DAJs was performed at 8, 12, 16, 20, and 24 weeks. Across this time course, the primary structural determinants of joint function (periodontal ligament (PDL) space, contact area, and alveolar bone socket morphology) and secondary material and microstructural determinants (tissue-level stiffness encoded by bone and cementum volume fractions, pore architecture, and bone microarchitecture) were quantified. As the joints matured, bone and cementum volume fractions increased in both the HF and SF groups but along significantly different trajectories, and these changes correlated with a pronounced decrease in PDL-space from 12 to 16 weeks in both diets. With further aging, older HF rats maintained significantly wider PDL-spaces than SF rats. These evolving physical features were accompanied by an age-dependent significant increase in the contact ratio in the SF group. The DAJ stiffness was significantly greater in SF than HF animals at younger ages, indicating that food hardness-dependent remodeling alters the relative contribution of structural versus material factors to joint function across the life course. At the tissue level, volumetric strains, representing overall volume changes, and von Mises bone strains, representing shape changes, increased with age in HF and SF joints, with volumetric strain rising rapidly from 16 to 20 weeks and von Mises strain increasing sharply from 12 to 16 weeks. Bone in SF animals exhibited higher and more variable strain values than age-matched HF bone, and changes in joint space, degrees of freedom, contact area, and bone strain correlated with joint biomechanics, demonstrating that multiscale functional biomechanics, including bone strain in intact DAJs, are colocalized with anatomy-specific physical effectors. Together, these spatiotemporal shifts in primary (structure/form), and secondary features (material properties and microarchitecture) define divergent mechanobiological pathways for the DAJ and suggest that altered loading histories can bias joints toward early maladaptation and potential degeneration.
了解主要结构特征和次要材料特性如何适应功能载荷对于确定它们对关节生物力学随时间变化的影响至关重要。本研究的目的是绘制大鼠长期咀嚼软质食物和硬质食物的主要结构特征、次级材料特性和牙槽关节(DAJ)硬度随年龄的时空变化,并将其联系起来。为了探讨负荷史如何影响主要和次要特征之间的平衡,我们在4周大的大鼠中分别饲喂硬食(HF, N = 25)或软食(SF, N = 25)饮食4、12、16和20周,并在8、12、16、20和24周对完整的下颌DAJs进行功能成像。在这个时间过程中,关节功能的主要结构决定因素(牙周韧带(PDL)空间、接触面积和牙槽骨窝形态)和次要材料和微观结构决定因素(由骨和骨质体积分数、孔隙结构和骨微结构编码的组织水平刚度)被量化。随着关节的成熟,HF组和SF组的骨和骨质体积分数均有所增加,但轨迹明显不同,这些变化与两种饮食中12至16周的pdl空间明显减少相关。随着年龄的增长,老年HF大鼠比SF大鼠保持更宽的pdl空间。这些不断变化的身体特征伴随着SF组接触比率的年龄依赖性显著增加。SF动物的DAJ刚度明显大于HF动物,这表明食物硬度依赖性重塑改变了整个生命过程中结构因素与物质因素对关节功能的相对贡献。在组织水平上,HF和SF关节的体积应变(代表整体体积变化)和von Mises骨应变(代表形状变化)随年龄的增长而增加,体积应变在16 ~ 20周迅速上升,von Mises应变在12 ~ 16周急剧上升。SF动物的骨表现出比年龄匹配的HF骨骼更高、更可变的应变值,关节间隙、自由度、接触面积和骨应变的变化与关节生物力学相关,表明包括完整daj的骨应变在内的多尺度功能生物力学与解剖学特异性物理效应物共定位。总之,这些主要(结构/形式)和次要特征(材料特性和微结构)的时空变化定义了DAJ的不同力学生物学途径,并表明改变的加载历史可能使关节偏向于早期不适应和潜在的变性。
{"title":"Chewing Affects Structural and Material Coupling, and Age-Related Dentoalveolar Joint Biomechanics and Strain.","authors":"Haochen Ci, Xianling Zheng, Bo Wang, Sunita P Ho","doi":"10.3390/bioengineering13010093","DOIUrl":"10.3390/bioengineering13010093","url":null,"abstract":"<p><p>Understanding how primary structural features and secondary material properties adapt to functional loads is essential to determining their effect on changes in joint biomechanics over time. The objective of this study was to map and correlate spatiotemporal changes in primary structural features, secondary material properties, and dentoalveolar joint (DAJ) stiffness with age in rats subjected to prolonged chewing of soft foods versus hard foods. To probe how loading history shapes the balance between the primary and secondary features, four-week-old rats were fed either a hard-food (HF, N = 25) or soft-food (SF, N = 25) diet for 4, 12, 16, and 20 weeks, and functional imaging of intact mandibular DAJs was performed at 8, 12, 16, 20, and 24 weeks. Across this time course, the primary structural determinants of joint function (periodontal ligament (PDL) space, contact area, and alveolar bone socket morphology) and secondary material and microstructural determinants (tissue-level stiffness encoded by bone and cementum volume fractions, pore architecture, and bone microarchitecture) were quantified. As the joints matured, bone and cementum volume fractions increased in both the HF and SF groups but along significantly different trajectories, and these changes correlated with a pronounced decrease in PDL-space from 12 to 16 weeks in both diets. With further aging, older HF rats maintained significantly wider PDL-spaces than SF rats. These evolving physical features were accompanied by an age-dependent significant increase in the contact ratio in the SF group. The DAJ stiffness was significantly greater in SF than HF animals at younger ages, indicating that food hardness-dependent remodeling alters the relative contribution of structural versus material factors to joint function across the life course. At the tissue level, volumetric strains, representing overall volume changes, and von Mises bone strains, representing shape changes, increased with age in HF and SF joints, with volumetric strain rising rapidly from 16 to 20 weeks and von Mises strain increasing sharply from 12 to 16 weeks. Bone in SF animals exhibited higher and more variable strain values than age-matched HF bone, and changes in joint space, degrees of freedom, contact area, and bone strain correlated with joint biomechanics, demonstrating that multiscale functional biomechanics, including bone strain in intact DAJs, are colocalized with anatomy-specific physical effectors. Together, these spatiotemporal shifts in primary (structure/form), and secondary features (material properties and microarchitecture) define divergent mechanobiological pathways for the DAJ and suggest that altered loading histories can bias joints toward early maladaptation and potential degeneration.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}