Search Results (17,489)

In this study, a machine learning model for the anisotropic mechanical behavior of AA7075-T6 was successfully developed by combining classical plasticity theory with neural network algorithms. First, a yield criterion incorporating strength asymmetry and orientation dependence was constructed based on a fourth-order linear transformation of invariants, and a stress update algorithm was implemented using the return mapping and implicit integration schemes. Subsequently, a dataset comprising experimental results from tension, compression, and shear tests at multiple orientations, as well as theoretically generated data from additional strain paths, was established to train a genetic algorithm-optimized two-hidden-layer neural network. Plastic-stage assessments indicated that, for the equal-biaxial path, the RMSE values of the stress–strain curves predicted by the machine learning model relative to the constitutive implementation were 31.87 and 39.24 MPa. It should be noted that the stress–strain response under equal-biaxial loading represents an additional prediction case. The trained model exhibited satisfactory predictive performance when compared against experimental data for tension, compression, and shear and was capable of reproducing the theoretical stress paths derived from the classical constitutive model. This approach leverages the physical interpretability of conventional constitutive modeling and the high efficiency of data-driven methods, providing a viable solution for efficiently predicting the anisotropic mechanical response of metallic materials under complex stress states. Full article

Object tracking is a key component of autonomous robotic manipulation when multiple visually similar objects are present, as the system must maintain consistent object identities over time. In this work, we investigate multi-object tracking of traffic cones for an autonomous cone placement and retrieval system. A task-oriented benchmark was created using real-world recordings acquired with an eye-in-hand camera setup. The evaluation dataset consists of five sequences covering multiple object-count scenarios. Each scenario was assessed under both clean and artificially degraded detection conditions to analyze the impact of degraded detection conditions on tracking performance. Several state-of-the-art tracking-by-detection algorithms were compared using standard multi-object tracking metrics. The results reveal how increasing scene complexity and detection degradation affect identity preservation and tracking robustness. The findings highlight the limitations of current approaches in robotic manipulation environments and provide guidance for selecting and developing tracking methods for reliable cone handling tasks. Full article

Post-traumatic stress disorder (PTSD) is associated with immune and autonomic disturbances, but molecular programs linking PTSD-related blood transcriptional signals with autonomic–cardiac biology remain incompletely characterized. The public Gene Expression Omnibus (GEO) cohorts analyzed here did not directly measure palpitations or autonomic dysfunction. Peripheral-blood transcriptomes from GSE81761 and GSE63878 were integrated with a prespecified pathway-derived autonomic–cardiac gene set constructed from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Genes overlapping the curated pathway set were assessed using functional enrichment and protein–protein interaction (PPI) analyses. Multi-algorithm comparison and a separate random-forest/SHapley Additive exPlanations (SHAP) analysis were performed for internal model assessment and biological prioritization. GSE64813 and GSE97356 were analyzed using targeted single-gene analyses and cohort-specific multivariable logistic models. Model performance was examined using repeated nested cross-validation, a fully nested sensitivity analysis, and locked-transfer testing to GSE64813 and GSE97356. Interleukin 15 (IL15) and protein phosphatase 2 scaffold subunit Aalpha (PPP2R1A) were evaluated using external-cohort analyses, immune-cell deconvolution, and descriptive postmortem hippocampal single-nucleus data. Among 1679 nominally significant PTSD-associated candidate genes, 92 overlapped the curated pathway set and were enriched for cytokine signaling, chemotaxis, apoptosis, calcium transport, and PP2A-related functions. PPI analysis yielded 37 recurrent candidate hub genes. The original model comparison ranked support-vector machine (SVM) the highest across the merged and source-cohort summaries [mean area under the receiver-operating-characteristic curve (AUC) 0.853], but these estimates represent internal discovery-stage performance. IL15 was recurrently prioritized by network-based analyses, whereas PPP2R1A was a component of an enriched phosphatase-related module. IL15 and PPP2R1A showed modest single-gene effects in GSE64813 (AUC 0.566 and 0.612) and GSE97356 (AUC 0.558 and 0.593). Cohort-specific refitted models showed apparent AUC values of 0.834 and 0.749, respectively. Repeated nested cross-validation conditional on the preselected 29-gene feature set identified L2-regularized logistic regression as the best-performing algorithm (mean AUC = 0.690). Importantly, a more stringent fully nested sensitivity analysis, in which differential-expression screening and pathway intersection were repeated within each outer training fold, yielded a mean repeated outer-cross-validated AUC of 0.593 [standard deviation (SD) = 0.033; range, 0.541–0.625], indicating limited predictive performance. Locked-transfer AUCs were 0.664 in GSE64813 and 0.534 in GSE97356. Single-nucleus summaries suggested donor- and nucleus-type-dependent expression patterns for IL15 and PPP2R1A. These findings identify IL15-related cytokine signaling and PPP2R1A-related phosphatase regulation as candidate molecular programs linking PTSD-associated transcriptional variation with pathway-derived autonomic–cardiac biology. The results should therefore be interpreted as hypothesis-generating rather than direct molecular evidence for unmeasured palpitation symptoms. Prospective validation in independent, clinically well-characterized cohorts with standardized autonomic and cardiac phenotyping is warranted. Full article

Sarcopenia is an independent predictor of adverse outcomes in hospitalized patients, associated with increased mortality, prolonged length of stay, and functional decline, yet it remains underdiagnosed owing to inconsistent diagnostic criteria and the practical challenges of assessing acutely ill patients. This narrative review summarizes current evidence on sarcopenia in hospitalized patients, with emphasis on diagnostic approaches, nutritional requirements, and optimal nutritional support strategies. Sarcopenia is particularly prevalent among critically ill patients and is driven by the convergence of systemic inflammation, immobility, and anabolic resistance. Diagnosis remains challenging: no ICU-specific framework exists, and the recent Global Leadership Initiative of Sarcopenia consensus established a unified, setting-independent conceptual definition as a foundation for future operational criteria, with ICU-specific frameworks yet to be developed. Bedside tools, including handgrip strength, bioelectrical impedance analysis, and ultrasound, retain strong prognostic value despite imperfect agreement with reference imaging. Nutritional intervention is a key component of management; however, large-scale trials have demonstrated that higher energy or protein delivery does not universally improve outcomes and may be harmful in selected critically ill patients. A gradual increase in energy and protein delivery according to the phase of illness, with protein targets of ≥1.2–1.5 g/kg/day, is recommended; leucine-enriched supplementation may help counteract anabolic resistance, although direct evidence in non-ICU hospitalized patients remains limited. Early mobilization is an essential complement, as nutrient provision without a mechanical stimulus cannot reverse immobility-induced muscle loss. A practical clinical algorithm integrating screening, nutritional target-setting, route selection, and reassessment is proposed to guide decision-making in this population. Future research should focus on improving the accuracy and feasibility of muscle assessment tools in critically ill patients to enable the timely diagnosis of sarcopenia and nutritional intervention, alongside the development of validated multi-marker panels and adequately powered trials examining the combined effect of nutrition and exercise in this population. Full article

The Hydraulic Infinite Linear Actuator with Multiple Rods (HILA-MR) enables multiple outputs to share a common hydraulic piston through independently controlled clamping mechanisms. This architecture has the potential to reduce actuation-system mass, volume, sensor count, and complexity in medium-heavy unmanned aerial vehicles (UAVs). However, because multiple control surfaces compete for a shared actuation resource, actuator performance depends strongly on the scheduling strategy used to allocate piston motion. This work investigates the feasibility of using HILA-MR for primary flight-control applications and evaluates three scheduling algorithms: time-division multiplexing (TDM), round-robin (RR), and multi-grip (MG). Simulation results were validated experimentally using a three-rod HILA-MR test rig. The algorithms were assessed using representative flight control commands and subsequently evaluated in coupled flight dynamics simulations. Results show good agreement between simulation and experiments. Compared with TDM, the RR and MG algorithms significantly improve tracking performance through adaptive allocation of actuation effort. Flight-dynamics simulations further demonstrate that the HILA-MR actuator achieved acceptable tracking performance during representative climb and turning maneuvers. The results indicate that HILA-MR is a promising actuation concept for future UAV flight-control systems. Full article

Background and Objectives: Orthobiologic injectables—principally platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), cell-based therapies and, increasingly, extracellular vesicles—are widely used for chronic musculoskeletal (MSK) pain, yet their evidence base is inconsistent and guideline endorsement is heterogeneous. One frequently proposed contributor to this inconsistency is the use of biologically dissimilar products as interchangeable, one-size-fits-all injections in poorly stratified populations. This narrative review examines current evidence through a conceptual “precision” framework organized around three axes—the biology of the product, the pathology of the target tissue, and the phenotype of the patient—and around image-guided delivery as the procedural context in which these axes are operationalized. It spans osteoarthritis, tendinopathy, plantar fasciopathy, discogenic and spinal pain, and impaired bone healing, with emphasis on PRP, BMAC, and platelet- and cell-derived extracellular vesicles. Materials and Methods: PubMed/MEDLINE, Embase, Cochrane CENTRAL and Web of Science were searched from inception to 15 January 2026 and updated on 31 August 2026; 4812 de-duplicated records were screened by two authors independently, and 435 full texts were assessed, from which 76 sources are cited (36 clinical studies and evidence syntheses, 11 guidelines, consensus statements or reporting standards, and 29 narrative, mechanistic, regulatory or methodological references). Evidence was prioritized as guidelines and formal consensus, then syntheses with a certainty assessment, then individual trials, with neutral and negative trials given equal weight. This is a narrative, not a systematic, review; SANRA was used as a critical-appraisal checklist, not as a reporting guideline. Results: Across indications, pooled efficacy signals are frequently positive but of low-to-moderate certainty, with substantial risk of bias, small-study effects, and inconsistent product reporting; adequately controlled trials in knee osteoarthritis, Achilles and lateral-elbow tendinopathy, and discogenic pain have returned neutral results. Candidate response modifiers—structural phenotype, inflammatory and metabolic status, pain-processing phenotype, intraprocedural signals, and machine-learning models—are at present largely prognostic associations rather than validated treatment-effect modifiers. Guideline positions diverge, reflecting differences in methodology and evidence thresholds as well as in the underlying evidence. Conclusions: We present the three-axis framework as a testable hypothesis and a structure for stratified prospective trials, not as a validated clinical algorithm. We classify its components by clinical readiness, distinguish prognostic from predictive biomarkers, temper regenerative language where only symptomatic benefit is demonstrated, and identify platelet- and cell-derived extracellular vesicles as an early-stage, predominantly preclinical direction whose translational promise remains to be established. Full article

Serum free light chains (sFLC) reflect immunoglobulin production and renal clearance, making abnormal results biologically heterogeneous in lymphoma. We reviewed clinical, translational, and analytical evidence using a documented PubMed search. Three operational patterns should be distinguished: monoclonal-pattern elevation, polyclonal-pattern elevation, and ratio-only abnormality. The kappa-plus-lambda concentration is an overlapping measure of total circulating burden rather than a fourth exclusive phenotype. In diffuse large B-cell lymphoma, some cohorts reported International Prognostic Index-adjusted associations and improved model discrimination, whereas other studies did not confirm independent prognostic value. Evidence in classical Hodgkin lymphoma and chronic lymphocytic leukemia also depends on endpoint, adjustment, and treatment setting. Prediagnostic associations in human immunodeficiency virus infection, transplantation, and population cohorts do not establish screening utility. In Waldenström macroglobulinemia, involved-chain kinetics may supplement established assessment in selected patients, although clinical benefit from sFLC-directed management has not been demonstrated. Historical treatment regimens, overlapping cohorts, inconsistent renal adjustment, assay differences, and limited external validation restrict transferability. The proposed framework integrates phenotype, renal function, assay, sampling time, and disease context. It is an interpretive proposal, not a validated prognostic score or treatment algorithm. Full article

Few early-stage building studies combine systematic design-space exploration with concurrent assessment of embodied carbon intensity (ECI) and installed material cost intensity (MCI). Evidence therefore remains limited on how design choices jointly affect these indicators and when carbon and cost priorities converge or conflict. This study addresses this gap across an Australian commercial-office design space comprising 892 quality-screened Carbon Designer 3D scenarios. The scenarios were restricted to rectangular plans and six predominantly concrete-based structural systems, with variations in recorded gross floor area (GFA), storey count and three aspect ratios. Matched comparisons examined the effects of vertical development, plan proportion and structural system on A1–A3 product-stage ECI and MCI. Both indicators increased with storey count, although proportional increases declined with increasing recorded GFA; the size of the ECI increases may partly reflect the platform’s area-normalisation convention. Aspect-ratio effects depended on structural system. The same structural system minimised ECI and MCI in 89 of 108 matched configurations (82.4%), whereas 19 exhibited cost–carbon trade-offs. Six regression algorithms were evaluated as design-space-specific surrogates using 713 training scenarios and 179 held-out scenarios. Support vector regression produced the lowest five-fold cross-validated mean absolute error and was retained as the in-domain surrogate for both targets. The principal contribution is the joint analysis of ECI and MCI across a controlled commercial-office design space; the surrogate models provide a computational basis for rapid screening and subsequent multi-objective optimisation within that same design space. Full article

Large-scale green hydrogen production via PEM electrolysis demands control strategies that surpass the limitations of traditional distributed control systems (DCSs). Digital twin (DT) technology has been introduced as a structured design framework for predictive maintenance and operational optimization across hydrogen production pathways, from steam methane reforming and green ammonia to next-generation PEM electrolyzer. A critical constraint exists; passive DT architectures cannot autonomously close the control loop. The resulting prediction–action latency gap introduces delays of 28–120 min precisely when dynamic renewable energy loads require sub-second responses. This review makes three original contributions; it characterizes the prediction–action latency gap as a structural design constraint across SMR, green ammonia, and PEM electrolyzer DT deployments, based on a structured Scopus and Web of Science search; it proposes a three-tier DCS–digital twin–AI architecture as the solution; and it defines five purpose-designed AI algorithm modules—Stack State Estimator, Degradation Trajectory Predictor, Fleet Dispatcher, Anomaly and Fault Classifier, and Maintenance Scheduler—together with an eight-challenge research agenda with technology readiness level assessments. All projections are extrapolated from adjacent domains and require electrolyzer-specific experimental validation. Full article

Desmoid tumors (DTs) may be sporadic or associated with familial polyposis syndromes, including familial adenomatous polyposis (FAP) and its variant, Gardner syndrome (GS). DTs are pathogenetically linked to activation of the Wnt/β-catenin signaling pathway. In sporadic DT, CTNNB1 is most frequently implicated, with exon 3 somatic mutations (T41A, S45F and S45P) being the most commonly reported. APC is implicated in FAP/GS-associated DTs and occasionally in sporadic DT, most often through alterations involving the exon 15 mutation cluster region. In this study of five sporadic intra-abdominal DTs, we identified uncommon somatic missense mutations in three cases involving APC (exons 2 and 13), LRP6 (exon 3) and TCF7L2 (exons 3, 6, 8 and 10). One case harbored the canonical activating CTNNB1 exon 3 p.S45P mutation, whereas another one case showed no detectable genomic alterations. Multi-algorithm in silico assessment using AlphaMissense, REVEL, CADD, SIFT and PolyPhen-2 provided supportive computational evidence for potential functional effects of several variants, particularly TCF7L2 p.P113L, p.R243W and p.C337Y, and CTNNB1 p.S45P, while predictions were variable for other variants. All five tumors arose intra-abdominally and presented as abdominal emergencies requiring surgical intervention. During a median follow-up of 24 months (range, 18–68 months), four patients remained recurrence-free, whereas one case developed multifocal intra-abdominal recurrence approximately five years after the initial resection and underwent repeat surgery. These findings broaden the spectrum of Wnt/β-catenin pathway alterations observed in intra-abdominal DTs, although the functional consequences of the uncommon variants require experimental validation. Full article

Type 2 diabetes mellitus (T2DM) affects hundreds of millions of people worldwide, and nearly half of all cases remain undiagnosed. This technical review, conducted under conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and structured around the Population, Intervention, Comparison, Outcome and Context (PICOC) framework, identifies and synthesises the evidence on artificial intelligence (AI) algorithms for the early detection of T2DM and the risk stratification of its complications, evaluating their performance against conventional diagnostic methods and characterising their clinical implementation contexts. A systematic search in Scopus with a four-stage screening process, synthesised across five research dimensions, yielded 255 records, of which 47 studies met the inclusion criteria (2025–2026). Ensemble methods based on gradient boosting, particularly particularly extreme gradient boosting (XGBoost), emerged as the dominant primary modelling approach, while logistic regression was the most frequently reported algorithm, predominantly as a baseline comparator, with area under the receiver operating characteristic curve (AUC-ROC) values ranging from 0.63 to 0.97. AI models consistently outperformed glycated haemoglobin (HbA1c), whose reported sensitivity for prediabetes was only 49%, reaching accuracies of up to 96.7%, although that upper figure comes from a narrowly defined cohort with a high baseline prevalence and does not represent general screening performance. Multimodal approaches achieved the highest discrimination, combining wearables, continuous glucose monitoring, and genomics (AUC 0.96 internal, 0.90 external, for the separation of self-reported glycaemic states), and a real-world clinical deployment integrated into electronic health records improved glycaemic control outcomes among high-risk patients. An assessment of the eight anchor studies with thePrediction model Risk Of Bias ASsessment Tool updated for AI (PROBAST + AI) found high concern regarding quality in six of them, driven mainly by cross-sectional designs and self-reported outcomes. Overall, AI stands out as a viable and scalable complement to conventional screening, although gaps remain in multicentre prospective validation, reporting standardisation, and algorithmic equity across populations. Full article

Background: Hajj is an international mass gathering in which infection prevention and antimicrobial stewardship intersect. Methicillin-resistant Staphylococcus aureus (MRSA) was selected as the organism-specific focus because it is a clinically important antimicrobial-resistant pathogen associated with skin and soft-tissue infections, wound care, and transmission through close contact and sharing of personal items. Hajj studies have also documented MRSA-related carriage and broader antimicrobial-resistance concerns among pilgrims and other mass-gathering populations. However, the relation between general infection awareness, MRSA-specific knowledge, and self-reported antibiotic-use behaviour remains less well described. This study assessed these three domains among Hajj pilgrims arriving in Madinah, Saudi Arabia. Methods: A questionnaire-based cross-sectional study was conducted during Hajj 1446H (2025). The study dataset comprised 342 completed questionnaires. Item-level descriptive analyses were used because no validated composite scoring algorithm was documented in the available study records. The primary exploratory outcome was an undated, self-reported history of taking antibiotics without consulting a doctor. Modified Poisson regression with robust variance estimated adjusted prevalence ratios (aPRs), with sex, age group, education, healthcare employment, and MRSA awareness entered simultaneously as prespecified covariates. Results: Among 342 respondents, 213 (62.3%) were male, 155 (45.3%) were aged 46–60 years, 181 (52.9%) reported postgraduate education, and 51 (14.9%) worked in healthcare. General awareness of crowding-related bacterial-infection risk was high (256/342, 74.9%), whereas MRSA-specific knowledge was lower: 110 (32.2%) had heard of MRSA, 137 (40.1%) identified personal-item sharing as a transmission route, and 124 (36.3%) recognised that MRSA can cause serious or fatal infection. Handwashing ≥ 3 times/day was reported by 310 respondents (90.6%), and 327 (95.6%) reported not sharing personal items. However, 143 respondents (41.8%) reported taking antibiotics without consulting a doctor. In the adjusted model, the prevalence of this outcome was higher among participants aged > 60 years than among those aged < 46 years (aPR 1.86, 95% CI 1.35–2.56) and among those who had not heard of MRSA (aPR 3.60, 95% CI 2.10–6.18) or did not know whether they had heard of MRSA (aPR 3.40, 95% CI 1.84–6.30), compared with those who had heard of MRSA. Conclusions: Among pilgrims arriving in Madinah, general infection-prevention awareness and self-reported hygiene practices coexisted with limited MRSA-specific knowledge, and a substantial proportion of respondents reported taking antibiotics without consulting a doctor. The observed associations are cross-sectional and non-causal; they neither establish the timing or appropriateness of antibiotic use nor demonstrate that an education intervention would change behaviour. They identify a hypothesis for prospective evaluation of multilingual Hajj education linking MRSA transmission, wound care, and antibiotic stewardship. Full article

Background/Objectives: Oral potentially malignant diseases (OPMDs) with signs of epithelial dysplasia are characterized by a high risk of malignancy. However, there are still no algorithms for their early diagnosis and prediction, due to the many possible predisposing factors, including human papillomavirus (HPV) infection and decreased immunity. There is a need to assess the relationship between the manifestations of oral epithelial dysplasia (OED), HPV invasion in the oral cavity, and interferon status to improve the identification and characterization of patients with different degrees of dysplasia. Methods: This study was designed and reported with reference to the STROBE checklist. The study aimed to assess the association between interferon status and HPV invasion in patients with OED. As per the inclusion and exclusion criteria, this observational study included 180 patients with histologically confirmed oral epithelial dysplasia associated with leukoplakia or oral lichen planus. Interferon (IFN) status was assessed by measuring serum interferon activity, spontaneous interferon production, IFN-α/β, and IFN-γ activity in peripheral blood. HPV DNA was detected and genotyped in biopsy specimens using polymerase chain reaction. Results: HPV-positive patients demonstrated significantly lower IFN-α/β and IFN-γ activity compared with HPV-negative patients (p < 0.001). Severe OED was more frequently observed in HPV-positive individuals, whereas mild dysplasia predominated among HPV-negative patients (p < 0.05). Interferon activity progressively decreased with increasing dysplasia severity, with the lowest IFN-α/β and IFN-γ activity detected in patients with severe dysplasia (p < 0.001 and p < 0.05, respectively). A significant positive correlation between IFN-α/β and IFN-γ activity was identified in patients with moderate dysplasia (p = 0.003). Multivariate binary logistic regression analysis demonstrated that HPV positivity (adjusted OR = 4.62, 95% CI: 2.18–9.79; p < 0.001) and reduced IFN-α/β activity (adjusted OR = 1.34 per 10-unit decrease, 95% CI: 1.14–1.58; p < 0.001) were independently associated with severe dysplasia. The multivariable model demonstrated acceptable discriminatory ability for identifying patients with severe dysplasia (AUC = 0.736), with a sensitivity of 89.4% and a specificity of 56.1%. Conclusions: The findings suggest that HPV-associated OED is linked to reduced interferon status, particularly lower IFN-α/β and IFN-γ activity in more severe dysplastic lesions. Combined assessment of interferon status and HPV detection may help identify patients at higher risk of severe OED. Full article

Background/Objectives: Plantar fasciitis and Achilles tendinopathy are clinically linked conditions that share numerous biomechanical predispositions; however, the sonographic morphological correlations between the plantar fascia (PF) and Achilles tendon (AT) remain underutilized in routine diagnostic algorithms. The primary objective of this study was to investigate the concurrent relationship between the ultrasound morphometrics of the PF and AT in patients with plantar fasciitis. The secondary objective was an exploratory assessment to evaluate whether AT measurements can serve as an auxiliary diagnostic tool. Methods: A cross-sectional diagnostic study was conducted, evaluating 45 adults with clinically and ultrasonographically confirmed unilateral plantar fasciitis. The evaluation encompassed 45 affected feet and 45 contralateral unaffected control feet (internal controls). The main outcome measures included ultrasonographic PF thickness, AT thickness, and AT width. Statistical evaluations utilized the Wilcoxon signed-rank test for paired comparisons, Spearman correlations, Generalized Estimating Equations (GEE) multivariable logistic regression to account for paired-limb data clustering, and receiver operating characteristic (ROC) curves. Results: AT thickness and width correlated moderately, yet significantly, with PF thickness (r_s = 0.49 and 0.59, p < 0.001). ROC analysis demonstrated that an AT thickness >0.43 cm achieved 86.0% sensitivity, 48.1% specificity, and an area under the curve (AUC) of 0.71. Furthermore, an AT width >1.48 cm yielded 85.2% specificity and an 88.9% positive predictive value. GEE multivariable logistic regression adjusted for age and gender and accounting for within-subject clustering revealed that an AT thickness >0.43 cm was significantly associated with a 6.99-fold increase in the odds of having concurrent plantar fasciitis (Adjusted OR 6.99, 95% CI: 2.05–23.89, p = 0.002). Conclusions: Ultrasonic AT thickness and width exhibit a moderate, significant morphological association with PF thickness. An AT thickness >0.43 cm serves as a valuable supplementary diagnostic indicator associated with plantar fasciitis, underscoring the clinical importance of evaluating the entire enthesis complex concurrently. Full article

Background: Total knee arthroplasty (TKA) in patients with extra-articular deformities (EAD) presents significant technical challenges. Robot-assisted TKA (RA-TKA) has the potential to provide more precise alignment and soft tissue balance. The primary aim of this study was to compare the rate of mechanical axis outliers (>3° deviation from target hip–knee–ankle angle) between RA-TKA and manual TKA in patients with EAD. Secondary aims included comparison of functional outcomes (KSS, FJS-12) at 12 months and exploratory subgroup analyses by deformity severity. Methods: This prospective, non-randomized, single-center cohort study included 80 patients with EAD undergoing primary TKA. Group allocation was based on the operating surgeon’s clinical judgment considering deformity complexity. To minimize selection bias, propensity score matching (1:1, nearest-neighbor algorithm) was performed, yielding two comparable groups of 30 patients: RA-TKA (CUVIS system) and manual TKA. The primary outcome was the frequency of mechanical axis deviations > 3° (outliers) at 12 months. Secondary outcomes included KSS and FJS-12 scores at 12 months. All subgroup analyses were designated as exploratory. Results: After propensity score matching, the groups were comparable in baseline deformity severity (standardized mean differences < 0.1 for all covariates). The outlier rate was 6.7% in the RA-TKA group versus 23.3% in the manual group (p = 0.03). KSS Functional (84 vs. 74, p = 0.008) and FJS-12 (70 vs. 60, p = 0.02) scores were significantly higher after RA-TKA. In exploratory subgroup analyses, the advantage of the robotic technique appeared more pronounced for deformities with HKA > 10° and multiplanar deformities, though these analyses were underpowered and should be interpreted with caution. Surgery time was longer in the RA-TKA group (148 min vs. 110 min, p < 0.001), but the complication rate did not differ significantly. Conclusions: RA-TKA was associated with a significantly lower rate of mechanical axis outliers and higher functional outcome scores at 12 months compared with manual TKA in patients with EAD. Exploratory subgroup analyses suggest that the advantage may be most pronounced in severe and multiplanar deformities, but adequately powered studies are needed to confirm these findings. The longer operative time and higher cost of RA-TKA should be weighed against potential alignment benefits. Multicenter studies with longer follow-up are needed to assess implant survival and refine indications. Full article