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Interpretable Machine Learning Predictions of Bruch's Membrane Opening-Minimum Rim Width Using Retinal Nerve Fiber Layer Values and Visual Field Global Indexes.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.3390/bioengineering12030321
Sat Byul Seo, Hyun-Kyung Cho

The aim of this study was to predict Bruch's membrane opening-minimum rim Width (BMO-MRW), a relatively new parameter using conventional optical coherence tomography (OCT) parameter, using retinal nerve fibre layer (RNFL) thickness and visual field (VF) global indexes (MD, PSD, and VFI). We developed an interpretable machine learning model that integrates structural and functional parameters to predict BMO-MRW. The model achieved the highest predictive accuracy in the inferotemporal sector (R2 = 0.68), followed by the global region (R2 = 0.67) and the superotemporal sector (R2 = 0.64). Through SHAP (SHapley Additive exPlanations) analysis, we demonstrated that RNFL parameters were significant contributing parameters to the prediction of various BMO-MRW parameters, with age and PSD also identified as critical factors. Our machine learning model could provide useful clinical information about the management of glaucoma when BMO-MRW is not available. Our machine learning model has the potential to be highly beneficial in clinical practice for glaucoma diagnosis and the monitoring of disease progression.

本研究的目的是利用视网膜神经纤维层(RNFL)厚度和视野(VF)全局指数(MD、PSD 和 VFI),使用传统光学相干断层扫描(OCT)参数预测布氏膜开口-最小边缘宽度(BMO-MRW)这一相对较新的参数。我们开发了一个可解释的机器学习模型,该模型整合了结构和功能参数,用于预测 BMO-MRW。该模型在颞下区的预测准确率最高(R2 = 0.68),其次是全球区域(R2 = 0.67)和颞上区(R2 = 0.64)。通过SHAP(SHapley Additive exPlanations)分析,我们证明了RNFL参数是预测BMO-MRW各种参数的重要贡献参数,年龄和PSD也是关键因素。在无法获得 BMO-MRW 的情况下,我们的机器学习模型可以为青光眼的治疗提供有用的临床信息。我们的机器学习模型有望在青光眼诊断和疾病进展监测的临床实践中大显身手。
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引用次数: 0
The Transformation Experiment of Frederick Griffith I: Its Narrowing and Potential for the Creation of Novel Microorganisms.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.3390/bioengineering12030324
Günter A Müller

The construction of artificial microorganisms often relies on the transfer of genomes from donor to acceptor cells. This synthetic biology approach has been considerably fostered by the J. Craig Venter Institute but apparently depends on the use of microorganisms, which are very closely related. One reason for this limitation of the "creative potential" of "classical" transformation is the requirement for adequate "fitting" of newly synthesized polypeptide components, directed by the donor genome, to interacting counterparts encoded by the pre-existing acceptor genome. Transformation was introduced in 1928 by Frederick Griffith in the course of the demonstration of the instability of pneumococci and their conversion from rough, non-pathogenic into smooth, virulent variants. Subsequently, this method turned out to be critical for the identification of DNA as the sole matter of inheritance. Importantly, the initial experimental design (1.0) also considered the inheritance of both structural (e.g., plasma membranes) and cybernetic information (e.g., metabolite fluxes), which, in cooperation, determine topological and cellular heredity, as well as fusion and blending of bacterial cells. In contrast, subsequent experimental designs (1.X) were focused on the use of whole-cell homogenates and, thereafter, of soluble and water-clear fractions deprived of all information and macromolecules other than those directing protein synthesis, including outer-membrane vesicles, bacterial prions, lipopolysaccharides, lipoproteins, cytoskeletal elements, and complexes thereof. Identification of the reasons for this narrowing may be helpful in understanding the potential of transformation for the creation of novel microorganisms.

人造微生物的构建通常依赖于将基因组从供体细胞转移到受体细胞。克雷格-文特尔研究所(J. Craig Venter Institute)大力推广了这种合成生物学方法,但它显然依赖于使用关系非常密切的微生物。经典 "转化的 "创造潜力 "之所以受到限制,原因之一是需要将供体基因组指导新合成的多肽成分与先前存在的受体基因组编码的对应物充分 "匹配"。1928 年,弗雷德里克-格里菲斯(Frederick Griffith)在证明肺炎球菌的不稳定性及其从粗糙的非致病性变种转化为光滑的毒性变种的过程中引入了转化法。随后,这种方法被证明是确定 DNA 为唯一遗传物质的关键。重要的是,最初的实验设计(1.0)还考虑了结构信息(如质膜)和控制论信息(如代谢通量)的遗传,它们共同决定了拓扑结构和细胞遗传,以及细菌细胞的融合和混合。与此相反,随后的实验设计(1.X)侧重于使用全细胞匀浆,此后又使用可溶性和水溶性部分,除指导蛋白质合成的信息和大分子(包括外膜囊泡、细菌朊病毒、脂多糖、脂蛋白、细胞骨架元素及其复合物)外,其余信息和大分子均被剔除。找出这一范围缩小的原因可能有助于了解转化在创造新型微生物方面的潜力。
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引用次数: 0
Multiscale Modeling in Computational Biomechanics: A New Era with Virtual Human Twins and Contemporary Artificial Intelligence.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.3390/bioengineering12030320
Tien-Tuan Dao

Over the last several decades, computational biomechanics has been intensively investigated as part of the study of human body systems (musculoskeletal, cardiovascular, digestive, etc [...].

过去几十年来,计算生物力学作为人体系统(肌肉骨骼、心血管、消化系统等[......])研究的一部分得到了深入研究。
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引用次数: 0
Robustness of the Cupriavidus necator-Catalyzed Production of α-Humulene.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.3390/bioengineering12030323
Lucas Becker, Emely Dietz, Dirk Holtmann

The increasing global demand for natural substances such as the sesquiterpene α-humulene makes optimizing microbial production essential. A production process using the versatile host Cupriavidus necator has been recently improved by adjusting the minimal media and process parameters. Understanding microbial and process robustness is key to ensuring consistent performance under different conditions. This study is the first to investigate and quantify the robustness of microbial α-humulene production and biomass formation using C. necator pKR-hum. Established process improvements and the impact of common or individual precultures were analyzed and quantified for their effect on the robustness of product and biomass formation. We report a robust α-humulene production process with even more consistent biomass formation using C. necator pKR-hum. Even with a simulated process disturbance, 79% of the maximum α-humulene level was still produced. Overall, our results show that the α-humulene production process using C. necator pKR-hum is highly robust, demonstrating its resilience to process disturbances and suitability for further industrial applications.

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引用次数: 0
Kolmogorov-Arnold Network Model Integrated with Hypoxia Risk for Predicting PD-L1 Inhibitor Responses in Hepatocellular Carcinoma.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.3390/bioengineering12030322
Mohan Huang, Xinyue Chen, Yi Jiang, Lawrence Wing Chi Chan

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, with immunotherapy being a first-line treatment at the advanced stage and beyond. Hypoxia plays a critical role in tumor progression and resistance to therapy. This study develops and validates an artificial intelligence (AI) model based on publicly available genomic datasets to predict hypoxia-related immunotherapy responses. Based on the HCC-Hypoxia Overlap (HHO) and immunotherapy response to hypoxia (IRH) genes selected by differential expression and enrichment analyses, a hypoxia model was built and validated on the TCGA-LIHC and GSE233802 datasets, respectively. The training and test sets were assembled from the EGAD00001008128 dataset of 290 HCC patients, and the response and non-response classes were balanced using the Synthetic Minority Over-sampling Technique. With the genes selected via the minimum Redundancy Maximum Relevance and stepwise forward methods, a Kolmogorov-Arnold Network (KAN) model was trained. Support Vector Machine (SVM) combined the Hypoxia and KAN models to predict immunotherapy response. The hypoxia model was constructed using 10 genes (IRH and HHO). The KAN model with 11 genes achieved a test accuracy of 0.7. The SVM integrating the hypoxia and KAN models achieved a test accuracy of 0.725. The established AI model can predict immunotherapy response based on hypoxia risk and genomic factors potentially intervenable in HCC patients.

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引用次数: 0
Exploring the Association of Hallux Limitus with Baropodometric Gait Pattern Changes.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.3390/bioengineering12030316
Natalia Tovaruela-Carrión, Ricardo Becerro-de-Bengoa-Vallejo, Marta Elena Losa-Iglesias, Daniel López-López, Juan Gómez-Salgado, Javier Bayod-López

Background: Hallux limitus (HL) is a condition marked by the restricted dorsiflexion of the first metatarsophalangeal joint, causing pain and functional limitations, especially during the propulsive phase of walking. This restriction affects the gait, particularly in the final phase, and impairs foot stability and support. HL is more common in adults and leads to biomechanical and functional adaptations. The purpose of this study was to investigate the differences in the center of pressure between subjects with hallux limitus and those with healthy feet. Methods: A total of 80 participants (40 with bilateral HL and 40 healthy controls) aged 18 to 64 were selected from a biomechanics center at the Universidade da Coruña, Spain. The gait analysis focused on three key phases: initial contact, forefoot contact, and the loading response. Data were collected using a portable baropodometric platform and analyzed using IBM SPSS Statistics 29.0.2.0; statistical significance was set at p < 0.05, with a 95% confidence interval. Results: The gait analysis indicated that the case group exhibited statistically significant differences, showing lower values in the left foot load response during the foot contact time (77.83 ± 40.17) compared to the control group (100.87 ± 29.27) (p = 0. 010) and in the foot contact percentage (p = 0. 013) during the stance phase (10.02 ± 5.68) compared to the control group (13.05 ± 3.60). Conclusions: Bilateral HL causes subtle gait changes, with individuals showing greater contact time values in the total stance phase versus the control group. Early detection may improve quality of life and prevent complications.

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引用次数: 0
Finite Element Analysis of the Effects of Different Shapes of Adult Cranial Sutures on Their Mechanical Behavior.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.3390/bioengineering12030318
Han Yang, Shiguo Yuan, Yuan Yan, Li Zhou, Chao Zheng, Yikai Li, Junhua Li

Cranial sutures play critical roles in load distribution and neuroprotection, with their biomechanical performance intimately linked to morphological complexity. The purpose of this study was to investigate the effect of different morphologies of cranial sutures on their biomechanical behavior. Based on the different morphologies of the cranial sutures, six groups of finite element models (closed, straight, sine wave, tight sinusoidal wave, layered sinusoidal wave, and layered sinusoidal wave + sutural bone) of the bone-suture-bone composite structures that ranged from simple to complex were constructed. Each model was subjected to 50 kPa impact and 98 N bilateral tensile loads to evaluate von Mises stress and total deformation variations across all groups under combined loading conditions. Key findings reveal that morphological complexity directly governs stress dynamics and mechanical adaptation; layered sinusoidal configurations delayed peak stress by 19-36% and generated elevated von Mises stresses compared to closed sutures, with stress concentrations correlating with interfacial roughness. Under impact, sutures exhibited localized energy dissipation (<0.2 μm deformation), while tensile loading induced uniform displacements (≤11 μm) across all morphologies (p > 0.05), underscoring their dual roles in localized energy absorption and global strain redistribution. Craniosacral therapy relevant forces produced sub-micron deformations far below pathological thresholds (≥1 mm), which implies the biomechanical safety of recommended therapeutic force. Staggered suture-bone in open sutures (31.93% closure rate) enhances shear resistance, whereas closed sutures prioritize rigidity. The findings provide mechanistic explanations for suture pathological vulnerability and clinical intervention limitations, offering a quantitative foundation for future research on cranial biomechanics and therapeutic innovation.

{"title":"Finite Element Analysis of the Effects of Different Shapes of Adult Cranial Sutures on Their Mechanical Behavior.","authors":"Han Yang, Shiguo Yuan, Yuan Yan, Li Zhou, Chao Zheng, Yikai Li, Junhua Li","doi":"10.3390/bioengineering12030318","DOIUrl":"10.3390/bioengineering12030318","url":null,"abstract":"<p><p>Cranial sutures play critical roles in load distribution and neuroprotection, with their biomechanical performance intimately linked to morphological complexity. The purpose of this study was to investigate the effect of different morphologies of cranial sutures on their biomechanical behavior. Based on the different morphologies of the cranial sutures, six groups of finite element models (closed, straight, sine wave, tight sinusoidal wave, layered sinusoidal wave, and layered sinusoidal wave + sutural bone) of the bone-suture-bone composite structures that ranged from simple to complex were constructed. Each model was subjected to 50 kPa impact and 98 N bilateral tensile loads to evaluate von Mises stress and total deformation variations across all groups under combined loading conditions. Key findings reveal that morphological complexity directly governs stress dynamics and mechanical adaptation; layered sinusoidal configurations delayed peak stress by 19-36% and generated elevated von Mises stresses compared to closed sutures, with stress concentrations correlating with interfacial roughness. Under impact, sutures exhibited localized energy dissipation (<0.2 μm deformation), while tensile loading induced uniform displacements (≤11 μm) across all morphologies (<i>p</i> > 0.05), underscoring their dual roles in localized energy absorption and global strain redistribution. Craniosacral therapy relevant forces produced sub-micron deformations far below pathological thresholds (≥1 mm), which implies the biomechanical safety of recommended therapeutic force. Staggered suture-bone in open sutures (31.93% closure rate) enhances shear resistance, whereas closed sutures prioritize rigidity. The findings provide mechanistic explanations for suture pathological vulnerability and clinical intervention limitations, offering a quantitative foundation for future research on cranial biomechanics and therapeutic innovation.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"12 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727829","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}
引用次数: 0
Direct Consideration of Process History During Intensified Design of Experiments Planning Eases Interpretation of Mammalian Cell Culture Dynamics.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.3390/bioengineering12030319
Samuel Kienzle, Lisa Junghans, Stefan Wieschalka, Katharina Diem, Ralf Takors, Nicole Erika Radde, Marco Kunzelmann, Beate Presser, Verena Nold

Intra-experimental factor setting shifts in intensified design of experiments (iDoE) enhance understanding of bioproduction processes by capturing their dynamics and are thus essential to fulfill quality by design (QbD) ambitions. Determining the influence of process history on the cellular responses, often referred to as memory effect, is fundamental for accurate predictions. However, the current iDoE designs do not explicitly consider nor quantify the influence of process history. Therefore, we propose the one-factor-multiple-columns (OFMC)-format for iDoE planning. This format explicitly describes stage-dependent factor effects and potential memory effects as across-stage interactions (ASIs) during a bioprocess. To illustrate its utility, an OFMC-iDoE that considers the characteristic growth phases during a fed-batch process was planned. Data were analyzed using ordinary least squares (OLS) regression as previously described via stage-wise analysis of the time series and compared to direct modeling of end-of-process outcomes enabled by the OFMC-format. This article aims to provide the reader with a framework on how to plan and model iDoE data and highlights how the OFMC-format simplifies planning, and data acquisition, eases modeling and gives a straightforward quantification of potential memory effects. With the proposed OFMC-format, optimization of bioprocesses can leverage which factor settings are most beneficial in which state of the mammalian culture and thus elevate performance and quality to the next level.

强化实验设计(iDoE)中的实验内因素设置变化通过捕捉生物生产过程的动态变化来加深对生物生产过程的理解,因此对于实现按设计保证质量(QbD)的目标至关重要。确定过程历史对细胞反应的影响(通常称为记忆效应)是准确预测的基础。然而,目前的 iDoE 设计并没有明确考虑或量化工艺历史的影响。因此,我们提出了用于 iDoE 规划的单因子多列(OFMC)格式。这种格式明确描述了生物工艺过程中与阶段相关的因素效应和潜在的记忆效应,即跨阶段相互作用(ASI)。为说明其实用性,我们规划了一个 OFMC-iDoE,其中考虑了喂料批次工艺过程中的特征生长阶段。使用普通最小二乘法(OLS)回归分析数据,如前所述,通过对时间序列进行分阶段分析,并与 OFMC 格式启用的过程结束结果直接建模进行比较。本文旨在为读者提供如何规划和模拟 iDoE 数据的框架,并重点介绍 OFMC 格式如何简化规划和数据采集、简化建模并直接量化潜在的记忆效应。利用所提出的 OFMC 格式,生物工艺的优化可以利用哪些因子设置在哺乳动物培养的哪种状态下最有利,从而将性能和质量提升到新的水平。
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引用次数: 0
Advancing Gait Analysis: Integrating Multimodal Neuroimaging and Extended Reality Technologies.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.3390/bioengineering12030313
Vera Gramigna, Arrigo Palumbo, Giovanni Perri

The analysis of human gait is a cornerstone in diagnosing and monitoring a variety of neuromuscular and orthopedic conditions. Recent technological advancements have paved the way for innovative methodologies that combine multimodal neuroimaging and eXtended Reality (XR) technologies to enhance the precision and applicability of gait analysis. This review explores the state-of-the-art solutions of an advanced gait analysis approach, a multidisciplinary concept that integrates neuroimaging, extended reality technologies, and sensor-based methods to study human locomotion. Several wearable neuroimaging modalities such as functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), commonly used to monitor and analyze brain activity during walking and to explore the neural mechanisms underlying motor control, balance, and gait adaptation, were considered. XR technologies, including virtual, augmented, and mixed reality, enable the creation of immersive environments for gait analysis, real-time simulation, and movement visualization, facilitating a comprehensive assessment of locomotion and its neural and biomechanical dynamics. This advanced gait analysis approach enhances the understanding of gait by examining both cerebral and biomechanical aspects, offering insights into brain-musculoskeletal coordination. We highlight its potential to provide real-time, high-resolution data and immersive visualization, facilitating improved clinical decision-making and rehabilitation strategies. Additionally, we address the challenges of integrating these technologies, such as data fusion, computational demands, and scalability. The review concludes by proposing future research directions that leverage artificial intelligence to further optimize multimodal imaging and XR applications in gait analysis, ultimately driving their translation from laboratory settings to clinical practice. This synthesis underscores the transformative potential of these approaches for personalized medicine and patient outcomes.

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引用次数: 0
Development and Metrological Characterization of Low-Cost Wearable Pulse Oximeter.
IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.3390/bioengineering12030314
Andrea Cataldo, Enrico Cataldo, Antonio Masciullo, Raissa Schiavoni

Pulse oximetry is essential for monitoring arterial oxygen saturation (SpO2) and heart rate (HR) in various medical scenarios. However, the traditional pulse oximeters face challenges related to high costs, motion artifacts, and susceptibility to ambient light interference. This work presents a low-cost experimental pulse oximeter prototype designed to address these limitations through design advancements. The device incorporates a 3D-printed finger support to minimize motion artifacts and excessive capillary pressure, along with an elastic element to enhance stability. Unlike conventional transmission-based oximetry, the prototype employs a reflectance-based measurement approach, improving versatility and enabling reliable readings even in cases of poor peripheral perfusion. Additionally, the integration of light-shielding materials mitigates the effects of ambient illumination, ensuring accurate operation in challenging environments such as surgical settings. Metrological characterization demonstrates that the prototype achieves accuracy comparable to that of the commercial GIMA Oxy-50 pulse oximeter while maintaining a production cost at approximately one-tenth of the commercial alternatives. This study highlights the potential of the prototype to deliver affordable and reliable pulse oximetry for different applications.

在各种医疗场景中,脉搏血氧仪对于监测动脉血氧饱和度(SpO2)和心率(HR)至关重要。然而,传统的脉搏血氧仪面临着成本高、运动伪影和易受环境光干扰等挑战。本研究提出了一种低成本的实验性脉搏血氧仪原型,旨在通过先进的设计来解决这些局限性。该设备采用三维打印手指支撑,以最大限度地减少运动伪影和过大的毛细血管压力,同时采用弹性元件来增强稳定性。与传统的透射血氧仪不同,该原型采用了基于反射的测量方法,提高了多功能性,即使在外周血流灌注不良的情况下也能获得可靠的读数。此外,光屏蔽材料的集成减轻了环境光照的影响,确保了在外科手术等挑战性环境中的精确操作。计量特性分析表明,原型机的精确度可与商用 GIMA Oxy-50 脉搏血氧仪媲美,而生产成本仅为商用替代产品的十分之一。这项研究强调了原型具有为不同应用提供经济可靠的脉搏血氧仪的潜力。
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引用次数: 0
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