Search Results (9,561)

Nearly half of dementia cases are attributed to fourteen modifiable risk factors listed by the 2024 Lancet Commission; meal timing is not among them. Disrupted daily (circadian) rhythms are linked to faster neurodegeneration, yet it is unknown whether meal timing affects cognitive ageing. We review the evidence for the hypothesis that early time-restricted eating (eTRE) helps preserve cognition in older adults. We define eTRE as eating within a window of no more than 10 h, with at least 80% of daily energy eaten before 16:00. We evaluate three candidate pathways: daily rhythms in the removal of amyloid-beta and tau from the brain (glymphatic clearance), daily rhythms that keep brain inflammation low, and clock genes that support memory-related plasticity in the hippocampus. Nutrient-sensing and gut microbiota pathways are considered as alternatives. An AI co-scientist analysis, checked by the authors, suggested a “Dual-Gating” model: finishing meals early may lower nervous-system arousal and insulin levels at night, and both changes may favour brain clearance during sleep. We outline a three-arm trial (eTRE, late time-restricted eating, habitual eating) that tests whether any cognitive benefit is explained by changes in markers of clearance and inflammation. Meal timing remains a candidate exposure that needs prospective testing. Full article

Undoped PbWO₄ single crystals were irradiated with 231 MeV ¹³¹Xe ions at fluences of 1 × 10¹¹ and 1 × 10¹³ ions cm⁻² and investigated by optical absorption, Raman spectroscopy, low-temperature excitation–emission spectroscopy, photoluminescence, and room-temperature X-ray luminescence. SRIM/TRIM calculations show a strongly electronic-stopping-dominated regime (S_e/S_n ≈ 258) with a projected ion range of approximately 14.36 μm. Using an effective displacement energy of 50 eV for Pb, W, and O, the calculated peak nominal ballistic damage is approximately 1.5 × 10⁻⁴ and 1.5 × 10⁻² dpa at the two fluences, respectively; these values exclude electronic excitation damage. Xe irradiation produces pronounced fluence-dependent optical attenuation and shifts the operational absorption onset to lower energies. The 785 nm non-confocal, surface-focused Raman response shows no dominant PbWO₄-III signature; it does not establish structural integrity throughout the Xe-modified layer. At 8 K, the excitation-action spectra broaden, and their apparent near-edge maxima shift from 4.10–4.11 eV to approximately 4.19–4.22 eV; this behavior is attributed to a combination of optical filtering, reabsorption, and excitation-dependent non-radiative competition rather than to an intrinsic shift of the electronic excitation edge. The blue host emission remains observable after irradiation, whereas long-wavelength green/yellow and red defect-related components gain relative weight. The relative integrated X-ray-luminescence output decreases strongly with increasing fluence; the stated screen-factor correction for induced absorption gives estimates of approximately 38.9% and 31.8% of the pristine value, consistent with losses beyond single-pass optical attenuation. The optical and luminescence changes are consistent with enhanced carrier trapping and non-radiative relaxation, without providing a depth-resolved structural characterization of the irradiated layer. Full article

Background/Objectives: Texture-modified (TM) food knowledge, attitudes and behaviours (KAB) among older adults remain poorly characterized in multi-ethnic populations. The study aims: (i) to characterize food liking, consumption frequency, and TM-related KAB among community-dwelling older adults in multi-ethnic Singapore; (ii) to examine whether TM-related KAB differs by ethnicity and other demographic factors, and (iii) to evaluate associations between TM-related KAB and food liking and eating frequency. Methods: A cross-sectional survey was conducted from February to April 2025 among 200 older adults (≥60 years) recruited at nine active ageing centres across Singapore. Participants rated liking and consumption frequency of Chinese, Malay, Indian and Western dishes and completed KAB items related to balanced diets, nutrient importance, TM foods, and sensory attributes of soft foods. Linear mixed-effects models adjusted for age, sex, ethnicity, and body mass index were used to derive liking, frequency, and composite (liking–frequency) scores and to examine associations between KAB and food preferences. Results: Participants (mean age 72.7 ± 6.1 years) were 71.0% Chinese, 19.0% Malay and 10.0% Indian, with a proportion reporting dysphagia-related symptoms (5.0%) and chewing difficulties (10.0%). Compared with Chinese participants, Malay participants placed less emphasis on ease of chewing/swallowing (β = −0.860, Padj = 0.023) and soft-food aroma (β = −0.711, Padj = 0.030) but greater emphasis on maintaining a balanced diet when chewing becomes difficult (β = 0.602, Padj = 0.001). Conclusions: TM-related KAB varied markedly by ethnicity and cuisine but not by self-reported chewing or swallowing difficulty. These exploratory findings suggest that TM nutrition strategies tailored by ethnicity and cuisine may warrant further investigation to support healthy ageing. Full article

Determining the construction age of vernacular buildings is essential for the conservation and documentation of historical and cultural heritage. Traditional approaches, however, rely heavily on questionnaire surveys and expert judgment, which can be time-consuming and may be affected by incomplete historical information and variability in expert interpretation. To reduce reliance on direct expert assessment of construction age and improve the reproducibility of the dating process, this paper presents a machine-learning-assisted method for predicting construction age from manually coded facade features derived from building images. First, we visited 29 villages in the Dezhou region of China and compiled 630 vernacular building cases, creating a facade image dataset that spans multiple periods and architectural styles, with construction ages labeled as time intervals; human observers then coded 14 facade attributes for each building before model training. Random forest and decision tree models were then introduced to identify the core factors influencing age determination from a wide range of facade features and to establish their quantitative criteria. The results reveal that wall finishing materials, the presence of sunrooms, window materials, and wall body materials are the core factors affecting the judgment of construction age. Based on these factors, a decision tree model was constructed for age determination. This model achieved an accuracy of 97.62% on the test set, with both precision and recall exceeding 97% and an F1 score of 0.975, demonstrating the effectiveness and robustness of the proposed quantitative classification system. Within the Dezhou study setting and the coded time intervals, the method offers an interpretable and accurate technical pathway for supporting the dating of vernacular architectural heritage. Full article

Background: 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. Methods: 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). Results: 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), altered mitochondrial dynamics, and sustained retrograde signaling; (5) activation of adaptive survival pathways and escape from canonical cell death and checkpoint controls; and (6) progression toward a dedifferentiated, stem-like cellular phenotype associated with metabolic plasticity and increased resilience. Conclusions: We recommend that cancer be reframed as a dedifferentiated cellular state primarily driven by mitochondria-derived signaling, reflecting the organelle’s ancestral autonomy and the reactivation of evolutionarily conserved mechanisms involving transposons, retrotransposons, Long Interspersed Nuclear Element-1 (L1), transposable elements (TEs), reactive oxygen species (ROS), and mtDNA–nDNA crosstalk, including the generation of nuclear mitochondrial DNA segments (NUMTs). This perspective extends the canonical view of predominantly nuclear-driven oncogenesis by reframing carcinogenesis as a bioenergetic and bio-evolutionary process, thereby highlighting mtDNA–nDNA interactions and mitochondrial signaling as central targets for cancer prevention, diagnosis, and therapy. Full article

Electric robotaxis have no tailpipe emissions, but the carbon associated with operating the service depends on empty travel, passenger load, vehicle electricity use, and the electricity supply. This study uses 29 months of California commercial robotaxi reporting from August 2023 to December 2025 to examine those factors on a passenger-mile basis. Vehicle-Miles Traveled per Passenger-Mile Traveled (VMT/PMT) is decomposed exactly into deadheading and passenger-stage occupancy and then linked to electricity use and location-based operational carbon dioxide equivalent (CO₂e) emissions. Between 2024 and 2025, deadheading fell from 50.73% to 45.06%, while distance-weighted passenger-stage occupancy fell from 1.455 to 1.316. The two changes nearly offset each other, and VMT/PMT declined by only 0.83%. Under a constant-grid scenario using the 2023 California regional grid factor and 0.42 kWh/mile, modeled 2025 carbon intensity was 118.3 g CO₂e/PMT. Passenger-miles rose by 269.9% over the same period, and modeled emissions associated with reported passenger-service mileage rose by 266.8%. These are service-attributed accounting estimates rather than a net transportation-emissions effect. The case shows why empty mileage alone is not enough to judge operating efficiency and why emissions intensity should be reported alongside service scale when electric robotaxi services are expanding. The same accounting can help operators and regulators track whether utilization gains keep pace with service growth. Full article

Gallbladder cancer (GBC) is an uncommon but highly lethal malignancy, characterized by striking geographic clustering, late diagnosis, and a prevention profile that differs from other gastrointestinal malignancies. This narrative review synthesizes epidemiologic, mechanistic, clinical, and public-health evidence on GBC determinants with a prevention-oriented lens. Rather than merely cataloguing risk factors, we propose a pragmatic framework that combines epidemiologic credibility, population-attributable burden, baseline risk, biologic plausibility, feasibility, and the benefit-risk balance of possible interventions. The strongest opportunities for prevention arise from risk-stratified management of gallbladder disease and congenital biliary abnormalities, reduction of excess and dysfunctional adiposity, promotion of physical activity, control of chronic Salmonella carriage in endemic settings, and mitigation of selected food- and water-borne toxic exposures. Several other determinants, including diet, alcohol consumption, smoking, reproductive factors, and socioeconomic disadvantage, may inform risk stratification or broader cancer-prevention policy, but currently offer less specific actionability. Effective prevention will require matching interventions to context: population-wide metabolic and lifestyle prevention, targeted clinical management of high-risk gallbladder conditions, and endemic-area strategies addressing infection, environmental exposure, and access to surgery. GBC prevention is therefore possible through carefully evaluated risk-adapted strategies. Full article

Background/Objectives: The incidence of thyroid cancer (TC) has increased worldwide over recent decades, particularly for well-differentiated histological subtypes, a trend largely attributed to overdiagnosis. Given potential geographical differences, this study analyzed TC incidence and temporal trends in the province of Girona, Spain, between 2002 and 2021. Methods: We conducted a cross-sectional study using data from the Girona Cancer Registry. Crude incidence rates (CRs), age-standardized incidence rates using the 2013 European (ASRe) and the 1960 World (ASRw) standard populations were calculated per 100,000 person-years. Temporal trends were assessed via the annual percentage change (APC) using generalized linear models. Results: A total of 998 incident TC cases were identified. Most patients were women (78.0%), with a median age at diagnosis of 48 years. Papillary TC was the predominant histological subtype (81.7%), and 70.6% of cases were diagnosed at Stage I. The overall ASRe was 6.8 and ASRw was 5.5, with incidence rates 3–4 times higher in women than in men. Overall, TC incidence increased significantly (APC: 2.7%), driven by increases in the 35–44 and ≥55 age groups, papillary histology, and early-stage disease (Stages I–II). Conclusions: The rise in TC incidence in Girona over the last two decades has been largely driven by Stage I papillary tumors, in both sexes, supporting a potentially substantial contribution of overdiagnosis. However, the concurrent increase in Stage II disease warrants continued surveillance, as it may reflect additional risk factors. Full article

Owing to various uncertainty factors during the construction process, foundation pit engineering is prone to crisis situations and various risks, and thus quick and rational decisions on construction risk control options must be made. In response to the phenomenon that the evaluation values of certain indicators in the decision making of deep foundation pit support schemes may be missing, this paper proposes a decision making method for construction risk control schemes that combines prospect theory with evidence theory. The method establishes a prospect decision matrix based on a decision indicator system for deep foundation pit construction risk control schemes, taking the decision maker’s desired goal for the project as the reference point; the indicator prospect values of each scheme are then used as evidence, and the belief intervals of all schemes are obtained through evidence synthesis to serve as the basis for scheme decision making. This method enriches the existing theoretical framework for the decision making of engineering construction risk control schemes. Compared with existing decision models, the decision method proposed in this paper exhibits the following distinctive features: First, the method accommodates decision situations in which some attribute evaluation values are missing, without requiring the missing values to be interpolated with precise values, fuzzy numbers, interval numbers, or probability distributions, and without necessarily discarding the decision attributes containing missing values, reflecting its better decision adaptability. Second, the degree of information incompleteness, i.e., the number of missing values, is intuitively reflected in the decision results, demonstrating the method’s better information fidelity and model interpretability. Third, the method incorporates behavioral factors such as the target expectation and risk attitude of the decision maker into the decision making process, and can objectively reveal the influence of these factors on the decision results through sensitivity analysis, thereby providing a basis for the decision maker to select the decision results more rationally. Combined with the analysis of a large-scale underground pit project, the results show that this method is not constrained by the completeness or incompleteness of the evaluation information of the indicators, and by taking the decision maker’s reasonable expectation as the reference point, it proves more reasonable than methods that take the absolute optimum or the worst value as the ideal reference point for scheme decision making. The method developed in this study can be applied to the decision making of risk control schemes in similar underground engineering or other civil engineering projects. Full article

Objective: This study aims to evaluate the potential role of metformin as an adjunct to fertility-sparing treatment strategies for women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AEH/EIN) and early-stage endometrioid endometrial cancer (EEC), with particular emphasis on oncologic and reproductive outcomes. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library was conducted from database inception through May 2026. Eligible studies included randomized controlled trials, prospective studies, and retrospective cohort studies evaluating metformin-containing fertility-sparing treatment regimens in women with AEH/EIN or early-stage EEC. Owing to substantial clinical and methodological heterogeneity in study design, treatment protocols, metformin dosage, follow-up duration, and outcome reporting, a quantitative meta-analysis was considered inappropriate, and the findings were synthesized narratively. Results: Eight publications represented approximately 795 unique patients after accounting for overlapping cohorts. Complete response was reported in 63/92 patients overall (69%) in Acosta-Torres et al., including 23/34 (68%) receiving progestin plus metformin, and in 61/63 (97%) receiving medroxyprogesterone acetate plus metformin in Mitsuhashi et al. Reported recurrence rates ranged from 13.1% to 34.2%. Live births occurred in 2/34 (6%) metformin-treated patients in Acosta-Torres et al., 14/31 (45%) women wished to conceive in Mitsuhashi et al., and 29/79 (36.7%) patients overall in Jing et al. Differences in populations, assessment times, and reproductive denominators limited direct comparisons and attribution of benefit to metformin. Conclusions: Current evidence suggests that metformin may have a promising adjunctive role in fertility-sparing treatment for women with AEH/EIN and early-stage EEC, particularly among patients with obesity, insulin resistance, polycystic ovary syndrome, or other metabolic risk factors. Nevertheless, the overall body of evidence should be interpreted with caution because of substantial heterogeneity across studies, the predominance of retrospective designs, and the limited number of prospective randomized trials. Well-designed multicenter randomized controlled trials are required to define the optimal role of metformin, identify the patients most likely to benefit, and establish standardized treatment strategies before routine incorporation into clinical practice can be recommended. Full article

Genetic selection for rapid growth, improved feed efficiency, and increased breast-muscle yield has substantially enhanced broiler production; however, it has also increased the functional demands placed on the locomotor system. This review critically examines locomotor health in modern broiler chickens in relation to welfare and production efficiency. Particular attention is given to the multifactorial interactions among genotype, growth rate, body weight and conformation, skeletal development, nutrition, physical activity, housing conditions, age, and infectious factors. Major locomotor disorders, including valgus–varus deformities, tibial dyschondroplasia, infectious arthritis and tenosynovitis, bacterial chondronecrosis with osteomyelitis, osteochondrosis, rickets, and fractures, are discussed in terms of their biological basis and welfare consequences. The review also evaluates current approaches to locomotor assessment, including gait scoring, standing ability, latency-to-lie testing, radiography, post-mortem examination, biomarkers, infrared thermography, force-plate analysis, and camera- and sensor-based monitoring. Evidence indicates that locomotor disorders should not be attributed solely to rapid growth but rather to insufficient coordination between increasing body mass and the adaptive capacity of skeletal and muscular tissues. Future strategies should integrate balanced genetic selection, precision nutrition, activity-promoting environments, and precision livestock farming technologies for early detection of impaired mobility. Such an integrated approach may help maintain high production efficiency while improving broiler welfare, supporting locomotor health, and reducing production losses. Full article

Magnesium stearate (MgSt), although well established as a pharmaceutical lubricant in solid oral dosage forms, plays a more complex role in carrier-based dry powder inhalers (DPIs), where it functions as a surface modifier and force control agent (FCA). In DPI formulations, MgSt can influence powder rheology, moisture resistance, interparticulate interactions, and aerosolization efficiency; however, these effects depend not simply on its presence or concentration, but on whether effective surface modification is achieved. This review critically evaluates experimental evidence on MgSt-mediated particle coating in carrier-based DPIs, with particular emphasis on how material attributes, particle cohesion and surface area, process energy, coating strategy, and MgSt concentration interact to determine coating efficiency and formulation performance. By integrating these factors, the review aims to provide a mechanistic framework for selecting and optimizing MgSt coating strategies and to identify methodological priorities for future research. The available evidence indicates that process energy is a major determinant of coating efficiency. High-energy techniques, particularly mechanofusion, can effectively modify highly cohesive micronized particles that are difficult to coat using conventional blending, whereas high-shear blending may provide sufficient energy for surface modification of larger, coarse lactose carriers. Mechanical milling represents a distinct strategy in which particle-size reduction and surface modification occur simultaneously. Direct comparison between coating approaches remains difficult because studies differ in MgSt grade, carrier and API properties, particle size distribution, processing conditions, and methods used to assess coating efficiency. MgSt generally improves aerosolization by modifying cohesive and adhesive interactions, but the magnitude of this effect is formulation-specific. Improvements in fine-particle delivery depend on MgSt particle size and specific surface area, the properties and surface area of the particles being coated, process energy, and the resulting coating efficiency. Consequently, increasing MgSt concentration does not necessarily improve performance, and excessive amounts may lead to overlubrication or MgSt agglomeration. Despite considerable progress, important knowledge gaps remain regarding how MgSt coating translates into improved DPI performance. Further studies integrating material properties, processing conditions, surface modification, and formulation performance are needed to establish more robust relationships between coating strategy and functional outcomes. Such knowledge may support more rational and formulation-specific use of MgSt in carrier-based DPIs. Full article

Low efficiency of environmental regulation (ERE) has become a major obstacle to effective environmental governance in developing countries. There is an urgent need to identify the key weak links of low ERE and explore external driving factors to improve ERE. Based on the operational mechanism of government environmental regulation, the regulatory process is divided into a supervision stage and a governance stage, and the intrinsic mechanism through which digital infrastructure affects ERE is theoretically explored. Subsequently, this paper uses a two-stage Data Envelopment Analysis (DEA) to measure the ERE in China from 2007 to 2022. On this basis, this study uses econometric models to test the theoretical mechanism. The findings are as follows: Firstly, although ERE has shown an upward trend over time, there is significant heterogeneity across regions. The increasing trend in ERE is largely attributed to improvements in governance efficiency (GE). Secondly, digital infrastructure is significantly and positively related to ERE. The relationship is mainly reflected in the governance efficiency stage. Thirdly, heterogeneity analysis shows that the positive correlation between digital infrastructure and ERE and GE is more prominent in the central–western regions and resource-based regions. The positive correlation between digital infrastructure and supervision efficiency (SE) is stronger in regions with stronger promotion incentives. In regions with close external environmental attention, the positive correlation between digital infrastructure and GE is more pronounced. However, we found no evidence that environmental assessment pressure significantly affected this relationship. Full article

Moringa oleifera (Moringaceae) is a tropical tree whose leaves and stems have long been used in South Asian and African traditional medicine for infectious and inflammatory disorders. These tissues contain a diverse array of secondary metabolites, chiefly flavonoids, phenolic acids, isothiocyanates, sterols, and peptides, and exhibit broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Their anti-inflammatory effects have been attributed to the suppression of nuclear factor-κB (NF-κB)/Toll-like receptor 4 (TLR4) signaling and activation of the NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) antioxidant axis. This review synthesizes the phytochemistry of Moringa leaves and stems and critically evaluates current evidence for their antibacterial and anti-inflammatory activities, molecular targets, and potential crosstalk between the two. We further discuss extraction methods, structure–activity relationships, pharmacokinetics, safety, and applications spanning medicine, animal production, food preservation, and cosmetics. The evidence base is heterogeneous owing to variation in plant origin, extraction protocols, bacterial strains, and assay design; mechanistic and dosing data specific to leaves and stems remain preliminary. Across reports, leaf and stem extracts inhibit common Gram-positive and Gram-negative pathogens at MICs mostly in the approximate 0.2–4 mg/mL range, and isolated flavonoids and glucosinolate isothiocyanates act on bacterial membranes and quorum sensing and on host NF-κB/Nrf2 signaling; however, no study has formally quantified antibacterial–anti-inflammatory synergy within one assay system. Key gaps include standardized preparations, direct tests of antibacterial–anti-inflammatory synergy, systematic pharmacokinetic/pharmacodynamic and long-term safety studies, and high-quality clinical trials. Full article

Mismodeling of solar radiation pressure (SRP) is a leading error source in BeiDou precise orbit determination (POD), yet the temporal predictability of the empirical SRP parameters remains poor. Using the five-year (2020–2025) daily ECOMC parameter series of 42 BeiDou-2/BeiDou-3 (BDS-2/BDS-3) satellites (67,824 records) and driving attribution, we build orbit-group- and manufacturer-specific prior-constraint and parameter-reduction strategies. The BDS-2 GEO YSIN is almost linear in the solar elevation angle β; the BDS-3 IGSO YRAD follows a second-order harmonic in β; and the BDS-3 MEO-CAST (China Academy of Space Technology) DCOS is well described by a joint cosβ and eclipse-season-offset prior (\({R}\)² = 0.814). These priors are purely empirical statistical models, and the IGSO group contains only three satellites, so transferring these priors to newly launched satellites of the same type carries risk. Full-year 2023 five-scheme POD validation shows the priors are neutral relative to free estimation, whereas indiscriminate parameter reduction degrades the within-day fit by a factor of 7.35; the recommended partial reduction for the BDS-3 IGSO and BDS-3 MEO-SECM (Shanghai Engineering Center for Microsatellites) satellites avoids this degradation. For the CAST group, reduction is not recommended: a control experiment shows the DCOS prior cannot recover the accuracy lost to reduction. Parameter-domain statistics alone cannot guide reduction; orbit-domain POD validation is mandatory. Full article