Bioengineering最新文献

{"title":"Effects of Fatigue on Six-Degree-of-Freedom Knee Kinematics in Military Personnel Marching on a Treadmill.","authors":"Longxiang Li, Longzhou Hua, Mingwei Liu, Ye Luo, Yingjie Lyu, Fei Tian, Shaobai Wang","doi":"10.3390/bioengineering13101142","DOIUrl":"https://doi.org/10.3390/bioengineering13101142","url":null,"abstract":"<p><p><b>Background</b>: Knee injuries are common during military training, and fatigue alters lower-limb movement patterns, increasing injury risk. However, little is known about fatigue effects on knee kinematics during military marching. Conventional gait analysis is limited to sagittal plane motion, leaving multi-planar knee function poorly understood. <b>Objective</b>: This study investigated six-degree-of-freedom (6DOF) knee kinematic changes in healthy male military personnel marching at 8 km/h on a treadmill before and after fatigue, focusing on initial contact (IC), stance-phase flexion peak (SPF), and stance-phase extension peak (SPE). <b>Methods</b>: Thirty-eight healthy male soldiers marched on a treadmill at 8 km/h. A motion capture system (infrared stereo cameras + reflective markers) collected 6DOF kinematic data. Fatigue was induced by loaded marching (15 kg vest), with the endpoint defined as Borg RPE ≥ 18 or heart rate ≥ 90% of age-predicted maximum. Post-fatigue data were collected at the same speed. Flexion, rotation, and anterior-posterior displacement at IC, SPF, and SPE were compared pre- vs. post-fatigue. The Holm-Bonferroni correction was applied for multiple comparisons. <b>Results</b>: After Holm-Bonferroni correction, knee flexion angles decreased significantly at SPF (3.64°, <i>p</i> = 0.009, Cohen's d = 0.52) and SPE (2.75°, <i>p</i> = 0.032, d = 0.41), with a non-significant trend at IC (2.53°, <i>p</i> = 0.086). Internal rotation shifted toward external rotation at IC (2.48°, <i>p</i> = 0.039, d = 0.46) and SPE (2.99°, <i>p</i> = 0.036, d = 0.54), with a non-significant trend at SPF (<i>p</i> = 0.076). No other kinematic changes, including anteroposterior displacement, exceeded the system's measurement error threshold or remained significant after correction. <b>Conclusions</b>: Fatigue reduces knee flexion during the stance phase at 8 km/h (with the most robust changes at SPF and SPE) and shifts internal-external rotation toward external rotation at IC and SPE. These 6DOF kinematic changes may compromise knee stability and increase ACL and patellofemoral injury risk.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RCNet: A Hybrid Network Adapted for OCTA Retinal Capillary Segmentation.","authors":"Xudong Wang, Qinghong Gao, Ran Yang, Xuelian Yang, Rui Yao, Shu'an Liu, Maosong Jiang, Caiye Fan, Zuoping Tan, Yuanyuan Wang","doi":"10.3390/bioengineering13101147","DOIUrl":"https://doi.org/10.3390/bioengineering13101147","url":null,"abstract":"<p><p>Optical Coherence Tomography Angiography (OCTA) provides clear visualization of ocular microvascular details, serving as a critical tool for assessing retinal and choroidal vascular systems. However, the complex capillary structure and low capillary-to-background contrast in high-resolution OCTA images pose significant challenges for segmentation. To address the low segmentation accuracy of traditional methods, this paper proposes RCNet, a hybrid CNN-Transformer network. RCNet adopts an encoder-decoder architecture based on Bi-Level Routing Attention (BRA), where bi-level routing attention focuses on densely vascularized regions, optimizing global capillary feature extraction. A Convolutional Bottleneck Module (CBM) splits bottleneck features into two channel groups using a fixed ratio α. A high-capacity branch enhances local details, while a lightweight branch preserves complementary information. The branches are then fused. Additionally, a Dense Skip Connection Module (DSCM) enhances feature information flow in low-contrast regions, compensating for spatial information loss. By integrating CNN's local feature extraction with Transformer's global dependency modeling, RCNet achieves accurate segmentation of OCTA capillary images. Experiments on the OCTA-500 and ROSE datasets demonstrate that RCNet achieved a higher point estimate under the current protocol, facilitating and assisting in the clinical assessment of ocular diseases.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality-Gated CycleGAN with Frequency-Split Composition for Structure-Constrained Contrast-Like Enhancement of Non-DICOM Chest CT: External Feasibility and Implications for Pulmonary Embolism AI.","authors":"Sang-Hyeon Gill, Hyun-Young Choi, Yuseop Kim","doi":"10.3390/bioengineering13101145","DOIUrl":"https://doi.org/10.3390/bioengineering13101145","url":null,"abstract":"<p><p>CT pulmonary angiography (CTPA) is the reference test for pulmonary embolism (PE), whereas AI datasets often contain display-domain (non-DICOM) non-contrast CT (NCT). We present a three-stage pipeline: a representation-consistency gate calibrated on DICOM-verified images (Stage 1), unpaired CycleGAN translation (Stage 2), and a frequency-split composition keeping the acquired finest spatial band plus support-guided residual refinement (Stage 3). Of 208 patients, 30 were held out. The final output reduced mediastinal distribution distance (14.92 to 7.19) and contrast-gap error (11.00 to 4.25; Holm-adjusted <i>p</i> < 0.001). Distribution metrics did not differ significantly from CUT, whereas three edge-based metrics favored the proposed method in all 30 patients. On 24 external NCT scans from three manufacturers (full-pipeline feasibility analysis without paired CTPA), distribution distances decreased and edge metrics again favored the method. The gate flagged all degraded external CTPA images (blur, down-sampling, heavy compression) in every calibration resample. An external 3D CTPA-trained PE model labeled unopacified arteries as embolus on NCT; enhancement reduced this volume in normal patients (12.0 to 1.7 mL), but detection stayed at chance, as on the original NCT (AUROC 0.47; original 0.42; CTPA 0.85). The pipeline harmonizes display-domain NCT with limited structural alteration for dataset preparation rather than CTPA-based detection.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical Effects of Distal Fragment Translation Guided by Target Postoperative Intermetatarsal Angle in Minimally Invasive Transverse Osteotomy for Hallux Valgus: A Patient-Specific Finite Element Study.","authors":"Jiaming Shi, Yongze Jiang, Wanqi Xiong, Tao Zhang, Yujin Dong, Xinli Dong, Jiahe Liu, Baoyi Liu","doi":"10.3390/bioengineering13101141","DOIUrl":"https://doi.org/10.3390/bioengineering13101141","url":null,"abstract":"<p><p>This study investigated the biomechanical effects of distal fragment translation guided by target postoperative first-second intermetatarsal angle (IMA) in minimally invasive transverse osteotomy (MITO) for hallux valgus using patient-specific finite element models. Three-dimensional models were reconstructed from computed tomography data of three female patients representing mild, moderate, and severe hallux valgus. The distal first-metatarsal fragment was translated laterally to achieve target postoperative IMA values of 9°, 8°, 7°, 6°, and 5°. Maximum von Mises stresses of the first through fifth metatarsals and Kirschner wires, together with mean osteotomy contact pressure and contact area, were evaluated under standardized static standing. As the target IMA decreased, the required translation increased, osteotomy contact area decreased, and mean contact pressure increased in all models. First-metatarsal stress increased most markedly in the severe model, reaching 25.74 MPa at 5°. In the mild and moderate models, further correction at the smaller IMA settings produced relatively limited additional changes in metatarsal stress while fixation stress and osteotomy-interface demands continued to increase. In contrast, the severe model showed continued increases in first-metatarsal and fixation stresses with further correction. These exploratory findings indicate that the mechanical effects of correction depend on both the target postoperative IMA and the distal fragment translation required to achieve it.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RefineSleepNet: Task-Driven Signal-Domain Transformation for EEG/EOG Sleep Staging.","authors":"Zhaoyan Zhu, Bo Yin, Pengyu Jiang, Yue-Ting Sun","doi":"10.3390/bioengineering13101146","DOIUrl":"https://doi.org/10.3390/bioengineering13101146","url":null,"abstract":"<p><p>Automatic sleep staging relies on effective representation of physiological signals. Representative raw-signal sleep-staging encoders typically transform input waveforms while progressively compressing their temporal resolution within the same encoding path. However, explicit modality-specific, sample-aligned, and task-driven signal-domain transformation before epoch-level feature extraction remains comparatively underexplored. To investigate this design, we propose RefineSleepNet, an end-to-end sequence-to-sequence framework that explicitly separates these two stages. Separately parameterized Signal Refinement U-Net (SRU-Net) branches first transform EEG and EOG waveforms while preserving the original temporal length, after which Epoch Feature Extractors (EFEs) extract epoch-level representations from the refined signals. Fused Sequence Attention (FSA) then performs multimodal integration and cross-epoch contextual modeling before epoch-wise classification. All stages are jointly optimized using the final sleep-staging objective without a separate waveform reconstruction target. RefineSleepNet was evaluated on Sleep-EDF-39, Sleep-EDF-153, and ISRUC-3 using subject-independent 10-fold cross-validation, achieving accuracy/macro-F1 (MF1) scores of 84.5%/79.8%, 83.5%/78.1%, and 80.3%/78.1%, respectively. Ablation experiments supported the coordinated design, while statistical analysis and intermediate-representation evaluations further examined the robustness and characteristics of the learned transformation. The learned transformation retained broad temporal and spectral organization while introducing local waveform changes and modality-specific spectral redistribution. These results support the staged organization as a viable modeling strategy for EEG/EOG sleep staging.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle Communication in the Central Nervous System: Mechanisms, Disease States, and Therapeutic Opportunities.","authors":"Xiaoning Bi, Hanna Gootin, Wenyue Su, Michel Baudry","doi":"10.3390/bioengineering13101140","DOIUrl":"https://doi.org/10.3390/bioengineering13101140","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are increasingly recognized as regulated mediators of intercellular communication in the central nervous system (CNS), transferring proteins, lipids, metabolites, and nucleic acids among neurons, glia, and other cells. EV communication comprises a complex integrated pathway that includes vesicle biogenesis, selective cargo sorting, secretion, extracellular transport, target-cell recognition, uptake, intracellular trafficking, functional cargo delivery, and recipient-cell responses. These processes are controlled by membrane trafficking machinery, cytoskeletal dynamics, lipid metabolism, calcium signaling, and the endosomal-lysosomal system and are further shaped by the physiological and pathophysiological states of donor and recipient cells. Genetic variation, proteotoxic stress, inflammation, metabolic and redox alterations, neuronal activity, and endolysosomal dysfunction can therefore affect multiple stages of the EV communication pathway in neurodevelopmental and neurodegenerative disorders. EV alterations reflect dynamic states rather than fixed disease signatures, with effects depending on cellular origin, EV subtype, anatomical context, developmental or disease state, and recipient-cell competence. This review examines CNS EV physiology and proposes a state-dependent framework for biomarkers and therapies, distinguishing EV detection from functional cargo delivery, cross-sectional associations from longitudinal progression, and cellular uptake from intracellular target engagement.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"End-Effector Robotic Rehabilitation After Spinal Cord Injury: A Systematic Review of Devices, Operational Characteristics Used, Outcome Measures, and Rehabilitation Effectiveness.","authors":"Michael Baldock, Silvia Caggiari, Antonio Capozio, David E Lunn, Frances Gawne, Ioannis Delis, Sarah L Astill","doi":"10.3390/bioengineering13101138","DOIUrl":"https://doi.org/10.3390/bioengineering13101138","url":null,"abstract":"<p><strong>Background: </strong>End-effector robotic devices are increasingly used in rehabilitation to retrain neural pathways through repetitive, task-specific exercise. However, the influence of movement kinematic variables remains unclear. This systematic review aimed to; (i) identify end-effector robotic systems used in upper- and lower-limb spinal cord injury rehabilitation, (ii) describe their technical specifications and operational use, and (iii) explore associations between device use characteristics and study outcomes.</p><p><strong>Methods: </strong>A systematic review of five databases was conducted from inception to June 2026.</p><p><strong>Results: </strong>Fifteen studies, ten lower-limb and five upper-limb, met the inclusion criteria. These covered five commercially available lower-limb devices and three upper-limb devices. Most lower-limb studies demonstrated moderate-to-large improvements in balance, ambulation (WISCI-II), walking endurance (6mWT), and independence (SCIM-III). End-effector training produced comparable outcomes to both conventional therapy and exoskeleton-based rehabilitation in controlled comparisons. Upper-limb studies showed substantial heterogeneity in outcome selection, reflecting diverse rehabilitation goals.</p><p><strong>Conclusions: </strong>WISCI-II and 10MWT were the most used lower-limb functional assessments, with SCIM-III used to assess independence for both upper- and lower-limb motor impairments. Reporting of kinematic settings are often limited and concentrated at study onset, limiting assessment of their contribution to outcomes. Reporting the progression of session-level metrics is needed to better understand how time-varying kinematics affect intervention effectiveness.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Bacteria to Cancer, the Dedifferentiation Hypothesis of Mitochondria to Immortal Multipotent Cancer Stem Cells.","authors":"Ciro Gargiulo Isacco, Van Hung Pham, Kieu C D Nguyen, Toai Cong Tran, Emilio Jirillo, Luigi Santacroce","doi":"10.3390/bioengineering13101139","DOIUrl":"https://doi.org/10.3390/bioengineering13101139","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Carcinogenesis has traditionally been attributed to the accumulation of somatic mutations in nuclear genes regulating cell proliferation, survival, and apoptosis. Although hereditary genetic predispositions account for less than 10% of cases, the extensive heterogeneity of the somatic mechanisms driving tumorigenesis-including subsets of neoplasms lacking canonical nuclear mutations-suggests that non-mutational mechanisms and organelle dynamics significantly influence tumor onset. Emerging evidence increasingly supports the concept that mitochondrial dysfunction and metabolic reprogramming are essential factors in tumor development, rather than merely downstream consequences of nuclear genetic alterations. While current literature establishes mitochondrial alterations as crucial co-initiators and facilitators of early transformation, defining whether metabolic failures may eventually act as primary trigger remains an ongoing area of investigation. Within this perspective, the \"Endosymbiotic/Evolutionary Theory\" provides a useful heuristic model, since it conceptualizes metabolic rewiring not as a literal genetic reversal, but as an adaptive shift toward ancestral, highly glycolytic survival programs when oxidative microenvironments are compromised. &lt;b&gt;Methods&lt;/b&gt;: We conducted a comprehensive theoretical and comparative analysis of mitochondrial biology, interrogating the structural, functional, and evolutionary parallels between mitochondria, intracellular bacteria, and viruses within the conceptual context of the endosymbiotic theory. Particular attention was given to mitochondrial proteins associated with organellogenesis, bioenergetic control, and molecular mechanisms facilitating mitochondrial-nuclear communication, including the integration of mitochondrial DNA (mtDNA) into nuclear DNA (nDNA) as nuclear mitochondrial DNA segments (NUMTs). &lt;b&gt;Results&lt;/b&gt;: Under sustained bioenergetic stress, mitochondrial retrograde signaling can achieve regulatory dominance over the nucleus, driving a functional dissociation between organellar metabolic state and nuclear control. While not autonomous in a strict sense, this shift echoes the evolutionary legacy described by the endosymbiotic theory, whereby mitochondria act as semi-independent bioenergetic systems capable of imposing profound effects on nuclear gene expression and cellular fate. The resulting state is characterized by metabolic reconfiguration, loss of differentiation fidelity, and the acquisition of cancer stem cell-like properties. This process may unfold through a sequence of interrelated events: (1) persistent endogenous or exogenous stressors that challenge cellular homeostasis; (2) establishment of a chronic inflammatory state and sustained redox imbalance; (3) progressive disruption of the cellular microenvironment and inter-organelle communication; (4) emergence of a permissive pre-neoplastic niche characterized by impaired oxidative phosphorylation (OXPHOS),","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning Approaches for Classification of Honeycombing and Ground Glass Opacity in Lung CT Imaging: A Systematic Review.","authors":"Hairul Aysa Abdul Halim Sithiq, Liyana Shuib, Muneer Ahmad, Chermaine Deepa Antony, Mohsin Iftikhar, Peer Azmat Shah","doi":"10.3390/bioengineering13101134","DOIUrl":"https://doi.org/10.3390/bioengineering13101134","url":null,"abstract":"<p><p>Lung diseases such as Honeycombing (HC) and Ground Glass Opacity (GGO) present significant challenges in medical image analysis due to their overlapping visual characteristics and complex structural patterns in Computed Tomography (CT) images. These conditions often exhibit similar appearances to normal lung tissue, making accurate differentiation difficult and highly dependent on imaging quality and expert interpretation. This paper presents a systematic literature review of studies published between 2011 and 2026 on lung disease detection and classification using medical imaging. A total of 98 selected studies is analyzed to examine recent developments in Machine Learning (ML) and Deep Learning (DL) techniques for automated lung disease analysis. The review covers key aspects including imaging modalities such as CT and chest X-ray, publicly available and private datasets, preprocessing techniques, feature extraction methods, classification models, and evaluation metrics. The findings indicate that traditional machine learning approaches were widely used in earlier studies, while recent research has increasingly shifted towards deep learning methods due to their ability to automatically learn discriminative features from medical images. Among these approaches, Convolutional Neural Networks (CNNs), ResNet-based architectures, DenseNet, and EfficientNet are the most commonly adopted models for lung disease classification. Despite significant advancements, several challenges remain, including limited availability of publicly accessible datasets, class imbalance, variability in imaging protocols, and lack of standardized evaluation frameworks. In addition, misclassification between visually similar conditions such as Honeycombing and GGO remains a persistent issue that affects diagnostic reliability. The review identifies key research gaps and highlights the need for standardized datasets, improved preprocessing techniques, and consistent evaluation protocols. Future research should focus on enhancing model generalisation and robustness across diverse datasets to support reliable automated lung disease diagnosis in clinical practice.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Parameter Genomic Evolution of SARS-CoV-2 Across Ten US States During the Vaccination Era, 2020-2025.","authors":"Som V Thomas, Jing Chen, Dong Qian, Paul Spearman, Donglu Shi","doi":"10.3390/bioengineering13101136","DOIUrl":"https://doi.org/10.3390/bioengineering13101136","url":null,"abstract":"<p><p>SARS-CoV-2 has adapted continuously since 2019, yet no multi-parameter framework has characterized this trajectory across geographically distinct United States populations. We present a systematic 13-parameter analysis of 137,059 high-quality genomes from ten diverse US states across three phases: pre-vaccination (January-December 2020), early vaccination (January-June 2021), and sustained immune pressure (July 2021-December 2025), the latter dominated by the high-volume Delta period with an early-Omicron contribution. Approximately 5000 genomes were retrieved per state per phase from GISAID EpiCoV under stringent quality filters, and each phase dataset was partitioned into three subsets, giving 90 subsamples in total, to quantify subsampling stability. Parameters spanned genome-wide mutation rate, dN/dS and Ti/Tv, site-specific selection (HyPhy FUBAR), spike and ACE2 contact-residue profiling, insertion-deletion characterization, furin cleavage site evolution, N-linked glycosylation dynamics, lineage-mutation concordance, amino acid physicochemical shifts, and protein-wise dN/dS ranking and mutation load. Genome-wide mutation rate rose monotonically in all ten states, from 0.050% to 0.149%, and dN/dS rose from 0.611 to 1.103, crossing neutrality in nine of ten states by Phase 3. Amino acid mutation load increased 3.95-fold, from 9.12 to 36.03 substitutions per sequence, while Ti/Tv fell from 3.69 to 2.11. Spike position 142 was diversifying in all ten states in Phase 3, with positions 484, 452, and 478 recurring in 70, 60, and 60 percent of states. ORF8 followed a spike-then-collapse trajectory (dN/dS 3.43, 14.23, 1.01), consistent with progressive loss of function. The reproducibility of these effects across ten geographically distinct state populations establishes a state-level baseline for SARS-CoV-2 immune escape.</p>","PeriodicalId":8874,"journal":{"name":"Bioengineering","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}