Search Results (4,165)

This review examines the clinical and practical implications of embedding molecular profiles directly into the 2023 FIGO staging system for endometrial carcinoma, in the context of the 2025 ESGO/ESTRO/ESP guidelines. The primary purpose is to navigate a central conflict in modern oncology: how to deliver increasingly personalized care while maintaining a globally accessible, equitable, and standardized cancer classification system. The 2023 FIGO update represents a paradigm shift from the traditional dualistic model (Type I versus Type II) by allowing molecular findings to redefine stage itself. While this integration offers clear benefits, it introduces significant challenges. First, the system depends on advanced molecular testing, creating a “rich-poor” divide where patients in resource-limited settings are systematically overtreated because testing is unavailable. Second, stage becomes unstable, changing with sequential histologic and molecular re-review, which causes confusion for patients and clinicians. Third, the system lumps prognostically distinct histotypes (Serous, Clear Cell, Carcinosarcoma, and Grade 3 Endometrioid) into a single aggressive stage, obscuring meaningful differences in survival. Fourth, it relies on subjective parameters such as “substantial” lymphovascular space invasion, for which no standardized definition exists, leading to high inter-observer variability. After analyzing these controversies, the review proposes a pragmatic solution: decouple anatomical staging from molecular risk stratification. Staging should remain a purely anatomical, universally applicable descriptor of tumor extent, while molecular and histologic data are used separately within a dynamic risk assessment model, as suggested by the European guidelines. This dual-track approach preserves global comparability, reduces inequity, and maintains diagnostic stability, while still enabling personalized treatment where advanced diagnostics are available. Full article

The universal operator-growth hypothesis (OGH) states that, in a closed chaotic system, the Lanczos coefficients grow linearly, $b_n\simeq \alpha n$. We ask how this structure is modified when the system is coupled to a Markovian environment, so that the generator becomes non-Hermitian. Applying the Arnoldi recursion to the vectorized Lindbladian in the infinite-temperature Wightman inner product, we organize the resulting pair of growth rates ${\alpha }_{\mathbb{C}}\equiv {\alpha }_R+i{\alpha }_I$—defined as effective slopes of the sub-diagonal and diagonal Arnoldi coefficients over a pre-registered fit window—around two statements whose logical status we delimit precisely. First, whenever the dissipator acts as $\mathcal{D}=-2\gamma \widehat{G}$ with $\widehat{G}$, a Hermitian grading (all dephasing-type baths), the diagonal obeys the identity $\mathrm{Re}{a}_n=-2\gamma {⟨\widehat{G}⟩}_n$: the imaginary rate measures how fast the growing operator accumulates weight in the dissipation channels. Second, we prove a conditional parity theorem: if the Hamiltonian, jump operators, and seeds can be made simultaneously real in some basis (an antiunitary condition), then $b_n$ is even, and $\mathrm{Re}{a}_n$ is odd in $\gamma$ exactly, so ${\alpha }_R$ is renormalized only at $O\left({\gamma }^2\right)$, and ${\alpha }_I=2{\kappa }_0\gamma$ follows from closed-system data alone. We exhibit a one-qubit Lindbladian that satisfies the often-assumed generator symmetry ${\mathcal{G}}^{†}\left(\gamma \right)=-\mathcal{G}(-\gamma )$ yet violates parity ($b_1=|1-\gamma |$), showing that the extra condition is essential; all models studied here satisfy it bit-exactly. For large-q SYK, these ingredients predict ${\alpha }_{\mathbb{C}}=\mathcal{J}-2i(q-2)\gamma$, whose imaginary part is fixed solely by the interaction range; the first ladder step is exact, and the multi-step increments approach $q-2$ with system size ($1.92\pm 0.04$ at $N=12$, $q=4$). Under a common fit protocol, the closed-system rates saturate by $N=10$ (${\alpha }_R\left(0\right)\to 0.437$, $2{\kappa }_0\to 0.224$). The imaginary rate is not an independent observable at leading order—its content is its sign, which resolves how the growing operator meets its environment (opposite for spin chains and SYK). Full article

Background: Handgrip strength has been proposed as an objective marker of post-COVID functional impairment, but its contribution relative to fatigue and sleep quality has not been formally evaluated in Latin American populations. Methods: We conducted an exploratory cross-sectional analysis of 130 adults with post-COVID condition in Palmira, Colombia. The outcome was any functional limitation on the Post-COVID Functional Status (PCFS) scale (grades 1–4 versus grade 0). Eight predictors were pre-specified on clinical grounds before examining outcome associations, and ridge-penalized logistic regression was pre-specified as the primary model. Sample size adequacy followed the criteria of Riley et al. Internal validation used bootstrap optimism correction (B = 1000), re-running the complete pipeline within each replicate. We assessed calibration, decision curves, prediction stability, SHapley Additive exPlanations (SHAP) with bootstrap rank intervals, and subgroup performance. Reporting followed TRIPOD + AI; risk of bias was self-assessed with PROBAST + AI. Results: Functional limitation affected 91/130 participants (70.0%). The minimum sample required for eight parameters was 566; the cohort met 23.0% of this requirement, so the analysis is exploratory. The optimism-corrected area under the curve was 0.748 (95% confidence interval (CI) 0.669–0.830), with calibration slope 1.15 (0.71–1.69). Fatigue ranked first in SHAP importance (54.0% of resamples), whereas grip strength ranked fifth (median rank 6). Net benefit exceeded both default strategies between thresholds 0.38 and 0.88. Thirty percent of participants changed classification in over 20% of resamples. Conclusions: Fatigue, sleep quality and acute-phase severity, rather than grip strength, emerged as the most influential correlates. These hypothesis-generating findings require confirmation in adequately powered cohorts. Full article

Background/Objectives: Oxidative stress and low-grade chronic inflammation are implicated in the early pathogenesis of non-communicable diseases (NCDs). Malondialdehyde (MDA), a biomarker of lipid peroxidation, may reflect subclinical oxidative stress in apparently healthy young adults. This study aimed to establish a population-specific reference interval for plasma MDA in healthy Thai undergraduate students and evaluate associations with lifestyle risk factors. Methods: This cross-sectional study enrolled 141 Thai college students aged 18–27 years. Plasma MDA was measured using the thiobarbituric acid reactive substances (TBARS) assay. A reference interval was determined non-parametrically (P2.5–P97.5) following IFCC recommendations in a reference subgroup (n = 94). The 75th percentile (P75) was used as an exploratory cutoff for elevated MDA. Associations between MDA and lifestyle risk factors were assessed using logistic regression and multiple linear regression. Results: The plasma MDA reference interval was 1.16–9.23 µmol/L, with P75 = 6.07 µmol/L. Using this cutoff, 25.5% of participants had elevated MDA. High sugar intake was associated with elevated MDA in the P75-based model (adjusted OR = 3.42; 95% CI: 1.08–10.87; p = 0.036). In the linear regression model, BMI emerged as independently associated with MDA (p = 0.004). Conclusions: This study established the first population-specific plasma MDA reference interval for Thai young adults. High sugar intake and BMI emerged as complementary exploratory associations with elevated lipid peroxidation across different models. These findings support plasma MDA as a practical, cost-effective candidate biomarker, providing a basis for further early oxidative stress surveillance and NCD prevention in young populations. Full article

Background: The integration of immune checkpoint inhibitors (ICIs) has transformed metastatic non-small cell lung cancer (NSCLC) therapy. However, the immunomodulatory influence of concurrent medications, including angiotensin-converting enzyme inhibitors (ACEIs), remains poorly defined in real-world practice. Methods: This retrospective observational study included 452 patients with metastatic NSCLC treated with first-line ICI-based therapy (ICI monotherapy or chemo-immunotherapy) between 2017 and 2025. Patients were stratified according to chronic ACEI exposure, defined as administration for >2 years. Primary endpoints were overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs). Results: Among 452 patients, 71 (15.7%) were chronic ACEI users. ACEI use was associated with significantly longer median OS in univariable analysis (17.0 vs. 14.0 months; HR = 0.78, 95% CI: 0.61–0.99; p = 0.047) and a favorable trend toward improved PFS (14.0 vs. 11.0 months; HR = 0.81, 95% CI: 0.64–1.02; p = 0.066). ACEI users had higher rates of cutaneous rash (25.4% vs. 13.1%; p = 0.011) and transaminase elevation (29.6% vs. 8.9%; p < 0.001). Severe grade 3–5 irAEs remained uncommon and did not differ significantly between groups (p > 0.05). Conclusions: Chronic ACEI use was associated with longer OS in univariable analysis, but this association was not statistically significant after multivariable adjustment. ACEI use was also associated with increased low-grade cutaneous and hepatic toxicities without a significant increase in severe irAEs. Prospective studies are warranted to clarify the clinical significance of these associations. Full article

The fine-structure constant is an empirical boundary datum of quantum electrodynamics (QED), not a value derived by the Standard Model. We give a conditional structural derivation in which its inverse is matched to the response capacity of a neutral codimension-two holonomy defect. The Indefinite Reconstruction Stability Principle and the topology of a punctured transverse space select codimension two and an integer winding group $\mathbb{Z}$. Phase and spin read-outs are represented by native norm-one groups $\mathrm{U}\left(1\right)$ and $\mathrm{SU}\left(2\right)$. Preserving their algebraic identities and multiplicative norms fixes the measures $2\pi$ and $2{\pi }^2$. Their three nonempty exposures have total capacity $\Omega =4{\pi }^3+{\pi }^2+\pi$. Four first-interface roles and one protected identity select $\mathbb{Z}/5\mathbb{Z}$; its 24 nonzero outgoing–returning state pairs form one symmetry orbit, fixing the first correction. At later resolutions, a separately declared asymmetric complete-source/exposed-target transfer rule—not the Chinese remainder theorem used only for common refinement—fixes the coefficients by unit counting without assuming composite-level transitivity. With a declared paired-interface grading rule, they yield an absolutely convergent odd-power tower with an exact logarithmic sum. A separate low-energy QED matching postulate identifies the structural response with the renormalized zero-momentum Maxwell coefficient, giving $\alpha {\left(0\right)}^{-1}=137.035999176142$, $0.041$ standard deviations below the 2022 CODATA value. No numerical coefficient is adjusted once the declared read-out, counting, transfer, grading, and matching assumptions are fixed. The construction does not derive QED dynamics or the running coupling. Full article

Background/Objectives: Sunitinib and pazopanib are administered at fixed doses in patients with metastatic renal cell carcinoma (mRCC), without adjustment for body composition. This study aimed to investigate the association between body mass index (BMI) and treatment-related toxicity and treatment discontinuation in patients with mRCC receiving first-line sunitinib or pazopanib. Methods: A total of 136 patients with mRCC treated with sunitinib (n = 90) or pazopanib (n = 46) were retrospectively evaluated. BMI was compared according to toxicity grade (1–2 and 3–4) and treatment discontinuation using Student’s t-tests and chi-square/Fisher’s exact tests. Given the limited number of grade 3–4 toxicity events, Firth’s penalized logistic regression was used for multivariable analysis, with adjustment for age, sex, and treatment type. BMI was evaluated as a continuous variable in the primary model and categorically in a supportive analysis. p < 0.05 was considered statistically significant. Results: Higher BMI was significantly associated with grade 1–2 (p < 0.001) and grade 3–4 toxicity (p < 0.001). In the Firth penalized multivariable analysis, higher BMI remained independently associated with grade 3–4 toxicity (OR per 1 kg/m² increase, 1.160; 95% CI, 1.057–1.283; p = 0.0015). Increasing age (OR per 1-year increase, 1.061; 95% CI, 1.021–1.106; p = 0.0022) and sunitinib treatment (OR, 2.629; 95% CI, 1.104–6.785; p = 0.028) were also independently associated with grade 3–4 toxicity. In the supportive categorical analysis, obesity (BMI ≥ 30 kg/m²) was associated with higher odds of grade 3–4 toxicity compared with BMI < 25 kg/m² (OR, 4.173; 95% CI, 1.533–11.982; p = 0.005). Conclusions: A higher BMI was associated with a greater likelihood of grade 3–4 TKI-related toxicity in patients with mRCC receiving fixed-dose sunitinib or pazopanib. BMI may represent a practical clinical marker for identifying patients who warrant closer toxicity monitoring. Full article

Green tea quality is largely determined by the metabolite profile of fresh leaves. However, the time-of-day-dependent dynamics of these metabolites remain largely unknown in Xinyang Maojian (XYMJ), a premium Chinese green tea. In this study, we performed the first integrative transcriptomic and metabolomic analysis of Camellia sinensis cv. Xinyang 10 shoots (one bud and one leaf) sampled at 7:00, 13:00, and 18:00 under field conditions with light intensities of 19.2, 113, and 5.4 klx, respectively. We identified 525 differentially accumulated metabolites and 19,767 differentially expressed genes exhibiting distinct time-of-day-dependent patterns. Physiological measurements confirmed significant fluctuations in starch, soluble sugars, chlorophyll, relative water content, and polyphenols throughout the daytime. A key finding was a daytime carbon allocation trade-off: primary metabolism (starch biosynthesis, glycolysis, TCA cycle) peaked at 13:00, whereas secondary metabolism (flavonoids, theaflavins, phenolic acids, anthocyanins) dominated at 18:00, supported by strong negative correlations between primary and secondary metabolic modules. Chlorophyll and oligomeric catechins peaked at 7:00; theaflavins at 13:00; and starch, soluble sugars, theanine, and organic acids at 18:00. Light-responsive transcription factors (bZIP, NF-Y, HD-Zip, SPL, ARF, MADS) and other regulators (MYB, AP2/ERF, WRKY, NAC, GRAS, bHLH) exhibited time-specific expression, sequentially modulating flavonoid, caffeine, and theanine biosynthesis, along with specific gene modules including SS3/SS4 (starch synthesis), BAM3 (starch degradation), FBA1 (carbon fixation), CYP72A219 (terpenoid metabolism), and L7A (theaflavin biosynthesis). Evening-harvested leaves accumulated higher levels of theanine (umami) and soluble sugars (sweetness), whereas morning leaves were enriched in astringent catechins and flavonols. This multi-omics dissection of time-of-day-dependent metabolism in XYMJ tea provides a scientific basis for time-of-day harvesting strategies and graded processing of tea products. Full article

Background and Objectives: Facial nerve palsy (FNP) remains a clinically relevant complication after vestibular schwannoma (VS) resection. Recovery trajectories vary according to the severity of neural injury and early postoperative facial function. This study aimed to characterize the temporal pattern of facial nerve recovery during the first postoperative year and to explore factors associated with favorable long-term function. Materials and Methods: We retrospectively analyzed 51 adult patients who developed FNP after VS surgery between 2020 and 2023. Facial nerve function was assessed using the House–Brackmann (HB) grading system and the Sunnybrook Facial Grading System (SBFGS) at discharge and at 1, 3, 6, and 12 months postoperatively. Longitudinal changes were analyzed using non-parametric repeated-measures methods with effect-size estimation. Favorable 12-month facial nerve function was defined as HB grade I–II. Given the limited number of unfavorable outcomes, associations with 12-month recovery were explored using parsimonious Firth-penalized logistic regression models. Results: At discharge, 45.1% of patients had HB II, 29.4% HB III–IV, and 25.5% HB V–VI. Facial function improved significantly during follow-up. Median SBFGS total score increased from 58.0 at discharge to 99.0 at 12 months (Friedman χ² = 118.78, df = 4, p < 0.001; Kendall’s W = 0.58), while HB grade also improved significantly (χ² = 107.48, df = 4, p < 0.001; W = 0.53). At 12 months, 37/51 patients (72.5%) achieved HB I–II and none remained in the HB V–VI category. Synkinesis, defined as an SBFGS synkinesis subscore > 0, was observed in 10/51 patients (19.6%) at 6 months and 19/51 (37.3%) at 12 months. HB grade and SBFGS score at discharge were strongly inversely correlated (Spearman ρ = −0.943, p < 0.001) and were therefore evaluated in separate models. After adjustment for age and tumor size, each one-grade increase in discharge HB was associated with lower odds of favorable 12-month function (OR 0.30, 95% CI 0.11–0.58; p < 0.001), whereas each 10-point increase in discharge SBFGS was associated with higher odds of favorable function (OR 1.90, 95% CI 1.32–3.53; p < 0.001). Conclusions: Facial nerve function showed substantial longitudinal improvement during the first year after VS surgery. Early postoperative facial function was independently associated with 12-month outcome in exploratory penalized regression analyses. Recovery may continue over several months, supporting prolonged functional surveillance, while the independent contribution of rehabilitation and the effect of nerve grafting require evaluation in larger prospective cohorts. Full article

Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD and PED who developed RPE tears between 2020 and 2025 after treatment with intravitreal aflibercept (2 mg or 8 mg) or faricimab. Multimodal imaging, including spectral-domain OCT and infrared imaging, was reviewed. PED morphology, fluid characteristics, RPE denudation, timing of RPE tear, and visual outcomes were analyzed using manual grading and AI-assisted software. Results: Among 375 PED-bearing eyes, 11 eyes of 11 patients developed an RPE tear (2.9%), of which 10 (90.9%) were temporally associated with anti-VEGF treatment. Rates were similar across agents—2.7% (aflibercept 2 mg), 3.0% (aflibercept 8 mg) and 2.4% (faricimab)—with no significant difference. Eight eyes (72.7%) were treatment-naïve and one tear (9.1%) occurred spontaneously after hemorrhage without recent injection. Among treatment-associated tears, 30% followed the first and 50% the second injection (mean 2.1 injections), detected a mean of 44 ± 30 days after the last injection. Mean baseline PED height was 594.8 ± 239.2 μm and median AI-derived PED volume was 2922 nL. Mean RPE-denudation area at detection was 5.25 ± 3.87 mm², remaining stable in 7 of 9 evaluable eyes. Visual acuity was stable or improved in seven eyes; four lost ≥15 ETDRS letters. Conclusions: RPE tears were an uncommon, predominantly early complication occurring in eyes with large PEDs, with no excess risk from second-generation agents. AI-assisted OCT may aid anatomical characterisation, and most eyes retained vision with continued therapy. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder caused by recurrent upper-airway collapse during sleep, leading to intermittent hypoxia, sleep fragmentation, and excessive daytime sleepiness. Although continuous positive airway pressure (CPAP) remains the first-line therapy, long-term adherence is often suboptimal, underscoring the need for more tolerable and flexible treatment options. This review aims to summarize the pathophysiological rationale for pharmacotherapy in OSA and to discuss recent developments in drug-based interventions. Methods: We conducted a narrative review of the literature on pharmacological interventions for OSA, with a systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 4 August 2026. We included randomised controlled trials, observational studies, meta-analyses, and mechanistic human or animal studies that reported relevant sleep and respiratory outcomes, and graded evidence according to the principles of GRADE framework. Results: Several drug classes have shown promise: agents that increase upper-airway dilator muscle activity, respiratory stabilizers that reduce loop gain, medications that raise the arousal threshold, topical anti-inflammatory drugs for mucosal edema, and systemic metabolic modulators such as glucagon-like peptide-1 receptor agonists and dual incretin receptor agonists. Emerging strategies, including gene therapy directed at the hypoglossal motor system, are also under investigation at the preclinical stage. Moreover, combining pharmacotherapy with CPAP or other devices can produce synergistic benefits, enabling lower device pressures and enhanced patient comfort. Conclusions: Pharmacotherapy for OSA is progressively moving from exploratory research towards targeted, phenotype-driven personalized treatment. Future studies should focus on robust patient phenotyping, multi-mechanistic combination regimens, and long-term clinical outcome evaluations to facilitate the integration of drug-based therapies into routine OSA management, particularly in specific subgroups such as those with COMISA. Full article

Background/Objectives: To investigate early treatment outcomes, including tumor response, predictors of response, and safety of nivolumab plus ipilimumab (Nivo/Ipi) therapy for unresectable hepatocellular carcinoma (uHCC) in a multicenter setting. Methods: We conducted a retrospective analysis of 64 Japanese patients with uHCC who received Nivo/Ipi therapy at participating centers between July 2025 and April 2026. Treatment efficacy was assessed according to RECIST version 1.1, and adverse events (AEs) were evaluated using CTCAE version 5.0. Results: Among the 64 patients, 28 received first-line therapy, and 36 received later-line therapy. The median observation period was 5.4 months. The overall response rate (ORR) was significantly higher in the first-line group (60.7%) than in the later-line group (30.6%) (p = 0.016). ORRs according to CRAFITY score were 25.0% for score 0, 55.6% for score 1, and 53.8% for score 2. The ORR in patients with CRAFITY scores ≥ 1 was significantly higher than in patients with a CRAFITY score of 0 (55.0% vs. 25.0%; p = 0.022). Multivariable analysis of pretreatment variables predicting response revealed first-line treatment (OR 3.83, 95% CI 1.270–11.558; p = 0.017) and a CRAFITY score ≥ 1 (OR 4.02, 95% CI 1.232–13.106; p = 0.021) as significant independent factors. Immune-mediated AEs occurred in 70.3% of patients overall and were grade ≥ 3 in 35.9%. Conclusions: Nivo/Ipi yielded a favorable response when used as first-line therapy. The baseline CRAFITY score may be a useful predictor of response to Nivo/Ipi therapy. Full article

The transition toward urban-scale digital twin and smart city management requires survey-grade 3D basemaps, yet conventional documentation remains time-consuming and prone to inaccuracies. While Terrestrial Laser Scanning (TLS) offers rapid 3D acquisition, capturing complex, GNSS-denied multi-story interiors frequently causes cumulative registration errors and isolated indoor–outdoor data silos. To address this, this study proposes a comprehensive typology-agnostic framework for developing high-fidelity digital twin basemaps. Treating the building as a unified spatial network, the methodology systematically mitigates error propagation through strategic linkage planning, rigid shell-first registration, continuous vertical core anchoring (via stairwells), and adaptive multi-source data fusion. Implemented on an adaptively reused heritage building, the developed basemap achieved an absolute georeferencing accuracy of 30.0 mm (RMSE) against an independent total station control network, alongside a mean relative error of 3.11 mm. Comparative analysis against legacy 2D CAD floor plans revealed simplified geometric representations and categorical dimensional deviations of up to 29.8 cm. Demonstrating its practical utility, the point cloud-centric geometric hub avoids forced geometric idealization, successfully supporting direct immersive visualization, architectural slicing (floor plans, sections, elevations), and multi-LOD algorithmic planar segmentation. This spatially constrained acquisition strategy bypasses legacy limitations, delivering a mathematically verified 3D reality capture essential for smart facility management, heritage conservation, and downstream semantic intelligence. Full article

Biodiesel production from waste cooking oils, non-edible oils and other low-grade lipid feedstocks is constrained by free fatty acids, water, salts, oxidation products, and the poor miscibility of triglycerides with short-chain alcohols. Carbon–inorganic hybrid catalysts are attractive because the inorganic phase can provide strong acid or base sites, while the carbon phase can alter dispersion, wettability, pore accessibility, microenvironment polarity, leaching, and recovery. Yet the term hybrid is often applied to materials for which the carbon component has not been shown to affect catalysis. This critical review therefore focuses on one defined reaction scenario: esterification and transesterification for biodiesel production from low-grade lipid feedstocks. The discussion is organized by the catalytic problem rather than by an unrestricted catalogue of materials. Carbon-supported CaO and MgO, carbon-coupled layered-double-hydroxide-derived mixed oxides, sulfonated carbon–inorganic acids, bifunctional acid–base systems, magnetically recoverable ferrite/carbon catalysts, and graphenic supports are compared through structure–activity relationships, reaction conditions, feedstock quality, FAME yield, heterogeneity, reusability, and post-reaction evidence. Particular attention is given to the distinction between a true interfacial effect and activity caused by leached Ca, K, Na or sulfonic species. A minimum evidence hierarchy is proposed, requiring carbon-only, inorganic-only, and physical-mixture controls, hot-filtration tests, elemental analysis of the liquid phase, recovered-mass accounting, and post-reaction structural characterization. The literature shows that high first-cycle yield is common, whereas water tolerance, low leaching, retained active-site density, and continuous operation remain uncommon. The most defensible future direction is therefore not greater compositional complexity, but simpler hybrid architectures designed around a specific failure mode and validated under realistic feedstock and reactor conditions. Full article

Online incremental orthophoto generation with multiple unmanned aerial vehicles (UAVs) remains challenging, as it requires accurate, efficient, and scalable mapping from distributed aerial observations. In this paper, we present a centralized GNSS-assisted multi-UAV 3D Gaussian Splatting SLAM framework for online incremental orthophoto mapping. Each UAV independently performs visual odometry to build local submaps, which are first aligned into a unified global coordinate system using GNSS constraints and further refined via inter-agent visual loop closures for improved cross-agent consistency. To enable scalable and high-quality mapping, we introduce two complementary Gaussian map maintenance modules: plane-guided grid-based collaborative densification, which improves mapping quality and accelerates convergence under multi-UAV conditions, and visibility-aware adaptive pruning, which effectively controls redundancy and memory usage. These components allow efficient joint optimization within a unified Gaussian representation. Experiments on multiple aerial datasets using video-derived image frames captured by consumer-grade UAV cameras demonstrate that the proposed system provides a favorable trade-off between geo-consistency, visual fidelity, and efficiency compared with existing methods. Quantitatively, the proposed method achieves a GCP RMSE of 2.32 m, completes multi-UAV orthophoto generation within 3.3–5.5 min, and reduces the total mapping time by approximately 35–55% compared with the corresponding single-UAV setting, while supporting online tracking and incremental orthophoto updates with bounded latency and memory consumption. Full article