Search Results (3,564)

Permanent magnet synchronous motors (PMSMs) are widely used in agricultural unmanned aerial vehicle (UAV) electromechanical systems for their high efficiency and power density. While sliding mode control (SMC) offers robustness for PMSM drives, conventional designs face challenges like slow convergence, singularity, and chattering. This paper proposes a model-free improved non-singular fast terminal SMC scheme with an improved adaptive super-twisting algorithm and a disturbance observer (MFINFTSMC-IADSTA-IFTSMO) for agricultural UAV applications. The designed sliding surface ensures fixed-time convergence without singularity, the adaptive reaching law reduces chattering, and the observer enables feedforward compensation of disturbances. Closed-loop stability is proven via Lyapunov theory. DSP-based experiments demonstrate that the proposed method outperforms existing SMC variants in dynamic response, steady-state accuracy, chattering suppression, and disturbance rejection. Specifically, the proposed method achieves a start-up convergence time of only 0.35 s, which is 56.25% shorter than that of the classic SMC-STA method, fully verifying its superior fast convergence performance. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

This paper develops an extended Cucker–Smale model that integrates nonlinear velocity alignment with state-dependent binding forces to achieve stable, collision-free flocking in multi-agent systems. Our framework introduces two dedicated control mechanisms: a velocity-dissipative term $\left(K_1\right)$ for accelerated convergence, and a distance-regulating term $\left(K_2\right)$ for formation cohesion and collision avoidance, which collectively ensure stable flocking. Rigorous Lyapunov analysis establishes provable guarantees for asymptotic velocity alignment and collision safety under verifiable initial energy conditions. Numerical simulations validate the theoretical predictions for a 20-agent swarm; scalability analysis demonstrates effective coordination in systems of up to 100 agents and reveals that velocity synchronization improves substantially—with errors decreasing by nearly two orders of magnitude—as $K_2$ increases from 0.05 to 0.50. A Pareto-optimal parameter region ($K_2\in [0.15,0.30]$) is identified, which achieves sub-centimeter-per-second alignment accuracy while maintaining energy consumption below 35% of the baseline. The proposed framework provides a theoretically rigorous yet practically viable solution for applications demanding guaranteed safety and precise coordination, such as UAV formations, robotic swarms, and autonomous vehicle platoons. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Background/Objective: In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled release of drugs at lung tumor sites through targeted and pH-responsive design. Methods: The GPDD system is formed by the self-assembly of GE11-PEG-hyd-DOX conjugates and co-loads free DOX. This system utilizes the targeting effect of the GE11 peptide with the epidermal growth factor receptor (EGFR) to accumulate at the tumor site, while the hydrazone bond serves as a pH-responsive linker that breaks in the acidic tumor microenvironment, triggering drug release. Experiments employed CCK-8 cytotoxicity assays and tumor-bearing nude mouse models (strain not specified) for in vitro and in vivo evaluations. Results: In vitro experiments showed that GE11-modified GPDD effectively inhibited tumor cell growth. In tumor-bearing nude mouse experiments, GPDD demonstrated more significant tumor suppression effects and lower systemic toxicity compared to free DOX and unmodified PDD. Conclusions: The GPDD nanocarrier integrates targeting and pH responsiveness, improving antitumor efficacy and reducing side effects, with translational potential. The novelty of the study lies in its dual-functional design and co-loading strategy, providing new insights for tumor-targeted delivery systems. Full article

Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by abnormal aggregation of β-amyloid (Aβ) peptides, tau proteins, and neuroinflammation in the central nervous system (CNS). While most AD research has focused on the brain, the molecular pathology of the spinal cord remains poorly understood. In this study, we investigated amyloid pathology, neurodegeneration, neuroinflammation, and cholesterol metabolism across distinct regions of the spinal cord and examined sex-specific differences using a model of AD, 5xFAD mice. Our data reveal that Aβ accumulation was restricted to the cervical spinal cord at 3 months but was evident in all areas of the spinal cord by 9 months, with similar patterns in both female and male animals. Despite this early and progressive Aβ deposition, no significant neuronal loss was observed in the ventral horn of the cervical spinal cord in either sex at 3 or 9 months of age. In contrast, there was a significant positive correlation between Aβ deposition and Iba1+ cell density in the spinal cord of 5xFAD mice. The number of Iba1+ cells in both the grey and white matter was significantly increased in female and male 5xFAD mice compared with age-matched wild-type (WT) littermates at 9 months of age. Astrocytic responses, however, were sex-specific: female, but not male, 5xFAD mice exhibited a significant increase in GFAP+ astrocytes in the grey matter of the thoracic and lumber spinal cord at 9 months compared with 3 months and relative to age-matched WT controls in the cervical and thoracic spinal cord. Furthermore, GFAP+ area in the thoracic spinal cord was significantly higher in female 9-month-old 5xFAD mice compared with their male counterparts, indicating a female-specific astrocytic response in AD spinal cord pathology. Our data also show an increase in free cholesterol (Filipin+ area) in 5xFAD mice at 9 months relative to WT controls, accompanied by altered expression of cholesterol metabolism genes, including downregulation of Abca1, Cyp46a1 and Cyp27a1. Collectively, these findings provide new insights into AD progression in the spinal cord, highlighting molecular pathology of AD extending beyond the brain. Full article

This study investigated the anti-inflammatory material basis and quality control of Pinellia ternata (P. ternata) to provide a modern scientific interpretation for its therapeutic properties. First, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) analysis was used to analyze different polar fractions of P. ternata, resulting in the identification of 79 compounds. Next, an in vitro evaluation using an LPS-induced RAW264.7 cell inflammation model revealed that the ethyl acetate fraction exhibited the most significant inhibition of nitric oxide (NO) production. Three cyclodipeptides, cyclo (Pro-Leu), cyclo (Phe-Pro), and cyclo (Leu-Phe), which displayed notable differences from other fractions, were subsequently screened. Molecular docking studies showed binding free energies below −5 kcal/mol with inducible nitric oxide synthase (iNOS), indicating potential anti-inflammatory targeting properties. Cellular experiments further confirmed that the reduction in NO production induced by these cyclodipeptides ranged from 11.03% to 40.38%. To enable their simultaneous quantification, a method based on ultra-high-performance liquid chromatography–triple quadrupole tandem mass spectrometry (UHPLC-QQQ-MS/MS) in the multiple reaction monitoring (MRM) mode was established, meeting all analytical validation criteria. Application of this method to P. ternata samples from different origins and growth conditions demonstrated that the contents of these cyclodipeptides were significantly influenced by both the origin and cultivation method. In conclusion, this study preliminarily identifies cyclodipeptides as an important anti-inflammatory material basis of P. ternata, and the established quantitative method provides methodological support and data for constructing its quality evaluation system. Full article

In flexible manufacturing systems, the composite mobile manipulator (CMM) is subject to nonlinear inertial disturbances arising from the dynamic coupling between the mobile platform and the robotic arm. These disturbances significantly impair positioning precision during grasping tasks. This paper addresses the dynamic decoupling of multi-body nonlinear inertial disturbances within CMM systems. Departing from the conventional “stop-then-plan” serial execution paradigm, we propose a full-cycle spatiotemporally coupled trajectory optimization method. The operation cycle is bifurcated into two synergistic stages: “dynamic calibration” and “static execution.” The dynamic calibration trajectory is pre-planned and executed synchronously during platform movement to actively compensate for inertial-induced pose deviations. Concurrently, the static execution trajectory is optimized and then triggered immediately upon platform standstill, ensuring a seamless and precise transition to the “Grasping Pose”. It is worth noting that the temporal characteristic central to this framework lies in the concurrent execution of static trajectory optimization and platform transit: by the time the platform reaches its destination, the pre-planned trajectory is already available for immediate triggering, achieving zero task-switching wait time at the planning layer. The term “zero-latency” here does not imply a fixed-cycle real-time response at the control layer, but rather the complete elimination of decision latency afforded by the parallel planning architecture. This framework eliminates computational latency, markedly enhancing operational efficiency. Key innovations include two novel constraints. First, the Adaptive Task-space Bounded Search Constraint (ATBSC) framework restricts optimization to a geometry-inspired search region, thereby enhancing search efficiency and ensuring controllable deviations. Second, the Multi-Rigid-Body Coupling Constraint (MRBCC) system explicitly models inertial transmission across motion phases to suppress pose fluctuations. The proposed framework is developed and validated within an obstacle-free workspace. In simulation-based validation on a UR10 6 degree-of-freedom manipulator model, experimental results indicate that ATBSC increases valid solution density to 84.7% and reduces average deviation by 72.8%. Furthermore, under the tested conditions, MRBCC mitigates end-effector position errors by 79.7–81.0% with a 97.5% constraint satisfaction rate. The improved Cuckoo Search algorithm (ICSA), serving as the solver component of the proposed framework, achieves an 11.9% lower fitness value and a 13.1% faster convergence rate compared to the standard Cuckoo Search algorithm in the tested scenarios, suggesting its effectiveness as a reliable solver for the constrained multi-objective trajectory optimisation problem. Full article

Background/Objectives: Central line-associated bloodstream infections (CLABSIs) remain a leading healthcare-associated infection in intensive care units (ICUs), yet independent risk factors and evidence-based catheter duration thresholds have not been defined through analytical study designs in settings with endemic multidrug-resistant organisms (MDROs). Methods: A retrospective case–control study was conducted in the ICU of a tertiary teaching university hospital in western Türkiye (January 2019–December 2024). Cases (n = 74) were patients with confirmed CLABSIs per CDC/NHSN criteria; controls (n = 148) were randomly selected central venous catheter (CVC)-bearing patients without CLABSIs. A reduced multivariate logistic regression model (seven variables; events-per-variable ratio 10.6) identified independent risk factors. Results: In multivariate analysis, catheter duration (adjusted OR: 1.19 per day; 95% CI: 1.13–1.24; p < 0.001), renal replacement therapy (aOR: 3.66; 95% CI: 1.68–7.95; p = 0.001), vasopressor support (aOR: 3.04; 95% CI: 1.50–6.17; p = 0.002), APACHE-II score (aOR: 1.07 per point; 95% CI: 1.02–1.11; p = 0.002), lower Glasgow Coma Scale (aOR: 0.86 per point; 95% CI: 0.78–0.94; p = 0.002), mechanical ventilation (aOR: 2.48; 95% CI: 1.24–4.95; p = 0.010), and total parenteral nutrition (aOR: 2.33; 95% CI: 1.12–4.86; p = 0.024) were independently associated with CLABSI. The model demonstrated good discrimination (C-statistic: 0.864) and calibration (Hosmer–Lemeshow p = 0.425). Kaplan–Meier analysis showed CLABSI-free survival declining from 98.9% at day 7 to 42.9% at day 21 (log-rank p < 0.001); these within-study estimates reflect relative risk patterns given the artificial 1:2 case-to-control ratio. Receiver operating characteristic (ROC) analysis identified day 13 as an exploratory optimal cutoff (AUC: 0.818; 95% CI: 0.762–0.874; sensitivity: 77.0%; specificity: 74.3%). CLABSI-attributable ICU mortality was 20.3% (47.3% vs. 27.0%; p = 0.004). Late-onset CLABSIs (>10 days) were dominated by Gram-negative pathogens (68.3%) versus 35.7% in early-onset infections (Fisher’s exact p = 0.012), with Acinetobacter baumannii as the predominant organism (27.0%; 83.3% carbapenem-resistant). Conclusions: Each additional catheter-day is independently associated with a 19% increment in CLABSI odds, with an exploratory critical threshold at day 13 beyond which enhanced surveillance measures should be considered, pending external validation. Full article

Articular cartilage has a limited capacity for self-repair, and effective strategies for its regeneration remain a major clinical challenge. Full-thickness cartilage defects extending to the subchondral bone induce an enhanced inflammatory response and impair spontaneous healing. This study aimed to evaluate the regenerative potential of autologous chondrocyte transplantation using an insoluble polyethersulfone (PES) scaffold in a rabbit model of grade III articular cartilage lesions. Chondrocytes were isolated and expanded in vitro and subsequently seeded onto PES membranes. Sixty-two rabbit knees with defects extending to the subchondral bone were divided into three groups: group I received chondrocyte-seeded PES scaffolds (n = 25), group II received cell-free PES scaffolds (n = 25), and group III served as an untreated control (n = 12). Cartilage regeneration was evaluated macroscopically and histologically over 52 weeks. In addition, the chondrogenic differentiation potential of cells cultured on PES scaffolds was assessed. This study extends our previous investigations of PES scaffolds in grade IV cartilage defects to a clinically relevant grade III lesion model, enabling evaluation of regenerative outcomes at an earlier stage of cartilage degeneration. The results demonstrated superior tissue regeneration in defects treated with chondrocyte-seeded PES scaffolds compared to both control groups. These findings indicate that synthetic PES scaffolds support cartilage repair and represent a promising biomaterial for the development of cell-based therapies in articular cartilage regeneration. Full article

Fungal decay fundamentally alters moisture transport in wood through complex bio-physical coupling mechanisms that remain poorly understood. Brown-rot fungi such as Coniophora puteana (Schumach.: Fr.) P. Karst. degrade wood through chelator-mediated Fenton (CMF) chemistry, producing hydroxyl radicals that depolymerise cellulose and hemicellulose before significant mass loss. This diffusion-dependent process requires elevated moisture content and leads to structural degradation. However, existing models fail to capture the interaction between boundary-driven fungal colonization, decay-induced property changes, and multi-phase multi-Fickian moisture redistribution, particularly the separate evolution of bound- and free-water phases during decay. Here, we present a transport-response bio-hygrothermal finite element model that couples boundary-driven Monod-type fungal colonization kinetics with multi-phase moisture transport (free water, bound water, vapor) in decaying wood. Although fungal biomass evolution is simulated via a reaction–diffusion equation, decay progression is not derived from biomass–substrate interaction but prescribed independently as an experimentally informed input. The model incorporates decay-modified sorption isotherms, permeability evolution, and boundary-driven biomass influx, along with associated moisture transport, into the governing equations. The model is validated against low-field nuclear magnetic resonance (LF-NMR) measurements of C. puteana decay in Scots pine over 35 days. The model successfully reproduces the experimentally observed moisture evolution: a peak free-water content of 50%–70% during weeks 1–2, followed by a progressive decline, while bound water remains remarkably constant despite advancing decay. Monte Carlo uncertainty quantification demonstrates hierarchical parameter control: bound water is governed solely by thermodynamic factors, while free water responds to interacting biological and physical processes. Time-resolved correlation analysis shows a fundamental transition from colonization-dominated (weeks 1–2) to transport-dominated (weeks 3–5) moisture control, quantitatively explaining the experimentally observed shift from accumulation to depletion. This transport-response framework for analyzing moisture behavior under externally defined decay progression establishes quantitative parameter hierarchies that may inform the development of future substrate-coupled bio-hygrothermal models. Full article

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to circulate globally across wild birds, poultry, and an expanding range of mammalian hosts, highlighting the need for antiviral strategies that address the animal–environment–human interface. The influenza A polymerase acidic (PA) endonuclease, a key enzyme in viral transcription, represents a conserved antiviral target across host species. In this study, we present a computational prioritization framework integrating homology modeling, molecular docking, molecular dynamics simulations, and physicochemical filtering to identify candidate PA endonuclease inhibitors relevant to a One Health context. Homology models of contemporary H5N1 clade 2.3.4.4b PA sequences were constructed based on the crystallographic template 6FS8 and used for cross-host docking against a targeted ligand library. Docking analysis identified baloxavir, a reference inhibitor, and entecavir, a nucleoside analog, as compounds of interest, with entecavir demonstrating favorable binding behavior, particularly in the poultry-associated model. Molecular dynamics simulations of the poultry PA–entecavir complex indicated stable interaction over 170 ns, supported by low structural deviation and favorable binding free energy (ΔG ≈ −85 kJ/mol). Physicochemical profiling suggested that entecavir possesses properties such as high polarity and predicted aqueous solubility, which were considered within the translational filtering step of this computational workflow. However, these properties do not establish antiviral efficacy or practical suitability for field use. The study provides a structured framework for integrating cross-host structural analysis with basic translational considerations, supporting the identification of candidate compounds for further biochemical and virological evaluation within the context of H5N1 control. Full article

The treatment paradigm for HER2-positive metastatic breast cancer has evolved from continuous chemotherapy-based regimens to a model of finite chemotherapy induction followed by sustained antibody-driven disease control. The CLEOPATRA trial established dual HER2 blockade with trastuzumab and pertuzumab plus a taxane as the biological and clinical anchor of this approach, demonstrating that chemotherapy is administered for a defined induction period, after which antibody maintains disease suppression. An increasing body of clinical evidence indicates that antibody-based regimens can be combined with targeted agents, including CDK4/6 inhibitors or HER2 tyrosine kinase inhibitors, to achieve durable disease control without the need for continuous chemotherapy. In the PATINA trial, the addition of palbociclib to trastuzumab, pertuzumab, and endocrine therapy was associated with a clinically meaningful improvement in progression-free survival in hormone receptor-positive, HER2-positive metastatic breast cancer. At the same time, quality of life was maintained despite higher rates of hematologic toxicity. More recently, HER2-CLIMB-05 demonstrated that the addition of tucatinib to dual HER2 antibody therapy significantly prolonged progression-free survival, supporting a model of sustained, multi-agent HER2 pathway suppression. The monarcHER trial provided biological proof of concept that antibody plus CDK4/6 inhibition can achieve disease control without chemotherapy in hormone receptor-positive, HER2-positive disease. Collectively, these advances support a translational framework in which antibody therapy serves as a central component of treatment strategies, with targeted partners selected according to tumor biology and prior therapy. This review summarizes the biological basis, clinical evidence, and future perspectives of antibody-driven maintenance in HER2-positive metastatic breast cancer. Full article

Tequila is frequently stored or aged in polymer containers and oak casks, which can enable the migration of phthalates such as di-(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemical. We quantified DEHP in tequila (55% ethanol) stored in LDPE tanks, HDPE jerry cans, PET carboys, and French oak casks with and without thermal treatment during long-term storage/aging (up to 18 and 11 months, respectively). Monthly samples were extracted and analyzed by GC–MS. Migration kinetics were evaluated using empirical exponential/sigmoidal models and an analytical solution of Fick’s second law for a semi-infinite slab. In plastics, DEHP increased nonlinearly and was best described by a modified Gompertz model, exhibiting a lag phase up to 42 days (~month 2), maximum transfer rates (Rmax) up to 0.82 µg L⁻¹ day⁻¹, and late-time concentrations near 120 µg L⁻¹. The non-toasted oak cask previously used for wine showed exponential behavior, reaching ~185 µg L⁻¹ and fitting the Minchev–Minkov model, whereas the toasted cask showed minimal transfer. Although concentrations remained below a reference safety limit (1500 µg kg⁻¹), the results indicate that food-contact plastics and commonly used oak casks are not risk-free under prolonged contact, supporting model-based forecasting for quality control. Full article

Risk stratification of impaired glycemic control remains a major challenge in biomedical data analysis due to heterogeneous metabolic, behavioral, and therapeutic factors observed in large-scale populations. This study proposes a calibrated and interpretable decision–support framework, termed Calibrated Multi-Task Stacking Ensemble (CMSE), for joint modeling of clinically related glycemic outcomes. The framework integrates demographic variables, lipid profiles, renal and inflammatory biomarkers, dietary and smoking indicators, and therapy-related features within a unified predictive architecture. Robust modeling is ensured through leakage-aware preprocessing, quantile-based Winsorization, out-of-fold stacking, and isotonic calibration of probabilistic outputs. The physiological coherence between short-term and long-term glycemic markers is investigated using an explicit intertask coupling mechanism based on the estimated average glucose (eAG) ratio. Model interpretability is supported using SHAP analysis, mutual information, distance correlation, and feature importance metrics. In the primary medication-free screening configuration, the framework is evaluated on the NHANES 2017–March 2020 dataset, achieving ROC-AUC of 0.865 for diabetes classification and R² values of 0.385 and 0.366 for plasma glucose and HbA1c prediction, respectively. These results indicate that CMSE provides a reliable and explainable approach for calibrated glycemic risk assessment and clinical decision support. Full article