Search Results (3,703)

Essential oils (EOs) are complex mixtures of volatile secondary metabolites produced by medicinal and aromatic plants (MAPs), mainly including terpenes, terpenoids and phenylpropanoid/benzenoid derivatives. Their composition depends on the plant species, chemotype, organ, developmental stage, environmental conditions and post-harvest processing, and directly affects EO yield, EO profile, biological properties, standardization and industrial value. This narrative and conceptual review connects plant biosynthesis, environmental regulation, matrix selection and extraction strategy as interdependent determinants of EO quality. Terpenoid constituents originate mainly from the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, whereas phenylpropanoid and benzenoid volatiles derive largely from the shikimate/phenylalanine pathway. Conventional extraction methods, such as hydrodistillation and steam distillation, remain widely used, while intensified and complementary approaches, including microwave-assisted methods, ultrasound pretreatment, supercritical CO₂ extraction and solvent-free methods, are increasingly investigated to improve selectivity and reduce extraction time, solvent use, water demand and energy consumption. Rather than ranking extraction methods only by yield, this review emphasizes that EO quality should be interpreted through an integrated plant-to-extraction framework, in which botanical raw material, target chemical classes, matrix properties, compound stability and intended application jointly guide the selection of an extraction strategy. This integrated perspective may support more reproducible, application-oriented and sustainable EO production. Full article

E. coli inoculation in food can be accompanied by a series of biochemical changes, during which both microbial activity and food matrix degradation may contribute to the formation of volatile organic compounds (VOCs). The composition and variation in these VOCs depend on the food, the contaminating microorganisms, and storage conditions. This study investigated VOC evolution in E. coli-inoculated chicken meat over 48 h using HS-GC-IMS and HS-SPME-GC-MS, detecting 57 and 50 VOCs, respectively. HS-GC-IMS showed advantages in detecting low-molecular-weight compounds. Through OPLS-DA and KEGG-based pathway analysis, several stage-associated VOCs were identified as candidate VOCs, including benzaldehyde (early stage of the 48 h incubation period), 3-methylbutanol and 3-(methylthio) propanal (middle stage of the 48 h incubation period), and 3-methyl-3-buten-1-ol, phenethyl alcohol, and methyl N-hydroxybenzenecarboximidate (late stage of the 48 h incubation period). Further analysis suggested that the formation of these VOCs may involve lipid oxidation, amino acid degradation, and microbial metabolism, providing a basis for the further validation of VOC-based approaches for monitoring changes in E. coli-inoculated poultry meat. Full article

Our study aimed, for the first time, to comparatively characterize edible carob powder from the Imera and Platses cultivars in terms of phenolic composition and antioxidant capacity, providing the first comprehensive characterization of the underexplored Platses cultivar using an integrated multi-analytical approach. FT-IR fingerprinting, GC-MS volatile profiling and LC-MS phenolic analysis were performed, while total phenolic content and antioxidant capacity were evaluated using Folin–Ciocalteu, FRAP, DPPH, ABTS and TSO assays. FT-IR indicated higher absorption in regions related to α- and β-glucans in Platses, while GC-MS identified 22 volatile compounds, with isobutyric acid being the dominant volatile in both cultivars. LC-MS revealed distinct phenolic profiles, with Imera exhibiting higher relative abundances of flavonoids, galloylated and flavanol derivatives, whereas Platses showed higher relative abundances of gallic acid, ferulic acid and kaempferol. Imera also exhibited significantly higher total phenolic and flavanol contents and antioxidant capacity (FRAP, DPPH, and ABTS; p < 0.05), while TSO did not differ between cultivars. Strong positive correlations were observed between phenolic content and antioxidant activity. These findings support the exploitation of Cretan carob cultivars as natural sources of bioactive compounds for functional food and nutraceutical applications. Full article

Canine cancer screening has an important limitation in that organ-specific screening strategies used in human medicine cannot be directly applied across routine veterinary clinical practice. Blood-based volatile organic compound (VOC) profiling may provide a practical approach for pan-cancer screening; however, its application in multicenter and multinational settings requires evaluation that accounts for cohort heterogeneity and analytical variability. In this study, we evaluated the canine cancer screening performance of an integrated classification framework using a headspace gas chromatography–mass spectrometry (HS-GC/MS)-based targeted blood VOC panel in a retrospective multicohort dataset comprising dogs recruited in Korea and Thailand. Whole-blood samples from 590 dogs recruited in Korea and Thailand were analyzed, including 167 dogs in the malignant tumor group and 423 dogs in the non-cancer control group. The predefined targeted VOC panel consisted of aromatic compounds and straight-chain alkanes and was analyzed using HS-GC/MS. The Korea and Thailand cohorts were incorporated into a single integrated classification framework rather than being separated into country-specific models. To evaluate performance variability associated with data partitioning, cohort-aware stratified training–validation splitting was repeated 30 times within the integrated retrospective cohort, with both national cohorts represented in the training and validation sets in each repeat. Class imbalance correction was applied only to the training data, and validation performance was assessed using both threshold-dependent and threshold-independent metrics. Across the 30 repeated validations, the integrated framework achieved an AUROC of 0.926 ± 0.019 and an AUPRC of 0.894 ± 0.023. Balanced accuracy, accuracy, sensitivity, specificity, F1-score, MCC, and Cohen’s κ were 0.858 ± 0.024, 0.895 ± 0.018, 0.772 ± 0.048, 0.943 ± 0.022, 0.805 ± 0.033, 0.736 ± 0.046, and 0.734 ± 0.045, respectively. In the sample-level prediction score analysis, the median predicted cancer probabilities for cancer and non-cancer samples were 0.954 and 0.041, respectively, indicating clear probability-based separation between the two groups. In the cohort-specific analysis, the discrimination signal was maintained in both the Korea and Thailand cohorts, although threshold-dependent performance differed between the two cohorts. These findings indicate that an HS-GC/MS-based targeted blood VOC panel provided a consistent cancer-associated classification signal under repeated internal validation within the specific integrated retrospective dataset evaluated in this study. The results demonstrate the feasibility of evaluating a common classification framework across the Korea and Thailand cohorts without constructing separate country-specific models, while not establishing independent external generalizability or platform-independent robustness. Because the Korea and Thailand cohorts were completely confounded with the Agilent and Thermo Fisher analytical platforms, respectively, the independent contributions of cohort characteristics and analytical platform cannot be determined from the present data. Further independent prospective validation in newly recruited populations and institutions, together with disease-control evaluation including clinically relevant controls, cohort-specific calibration, evaluation across analytical platforms, and assessment of clinical utility within real-world workflows, is required before the external generalizability and clinical applicability of the framework can be determined. Full article

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, renal, cardiovascular, hepatic and metabolic adverse effects. Essential oils (EO) exhibit relevant anti-inflammatory potential. However, their pharmaceutical application is limited by volatility, hydrophobicity, physicochemical instability and potentially low bioavailability. This review evaluated EO-loaded lipid nanocarriers for anti-inflammatory applications, with emphasis on physicochemical quality attributes, stability, safety and efficacy. Literature searches were carried out through PubMed/MEDLINE, PubMed Central, ScienceDirect, SciELO, Virtual Health Library, and Google Scholar websites, based on works published between 2021 and 2026. The investigated systems included liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions. Different formulations were found regarding EO nature, nanocarrier type, administration route and biological models used, predominantly involving preclinical assays. Nanoencapsulation was frequently associated with suitable physicochemical properties and release profiles, but direct comparisons with the corresponding free EO and control nanocarriers were not consistently performed. Safety findings were mainly based on cytotoxicity, local tolerability and short-term assays, with limited repeated-dose and long-term toxicological data. Several formulations showed anti-inflammatory activity in acute, subacute, or chronic experimental models. In selected works using the same experimental conditions, some formulations produced responses of similar magnitude to hydrocortisone, diclofenac, or other anti-inflammatory drugs, but these results cannot be directly correlated with therapeutic equivalence. The reported mechanisms involved modulation of the NF-κB, MAPK and Keap1/Nrf2/HO-1 signaling pathways. Overall, lipid-based nanocarriers represent platforms for investigating the stability, delivery and biological performance of EO. However, further standardization and controlled assays are required to determine their therapeutic and translational potential. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, largely due to delayed diagnosis. Current screening approaches are limited by invasiveness, cost, and low patient adherence, underscoring the urgent need for non-invasive biomarkers that could complement the existing strategies. Cancer-associated metabolic reprogramming, together with alterations in host–microbiota interactions, is reflected in the urinary volatilome, offering a potential source of candidate biomarkers. In this exploratory, case–control pilot study, urinary volatile organic metabolites (VOMs) were profiled in patients with colorectal cancer (CRC, n = 19) and healthy controls (HCs, n = 17) using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC–MS). Univariate and multivariate statistical modelling was applied to characterize disease-associated metabolic patterns. Sixty-seven urinary VOMs were identified, with terpenoids, ketones, phenolic compounds and norisoprenoids representing the predominant chemical classes. Following participant-level analysis and correction for multiple comparisons, 18 VOMs remained statistically significant between the two groups, consistent with metabolic perturbations previously associated with colorectal carcinogenesis, including gut microbial dysbiosis, oxidative stress, lipid peroxidation, chronic inflammation and altered energy metabolism. Orthogonal partial least squares-discriminant analysis (OPLS-DA), validated with participant-level cross-validation and 1000 permutations, revealed a separation between CRC and HC groups, supporting the existence of a disease-associated urinary volatilomic profile. Notably, one participant initially classified as an HC was subsequently diagnosed with metastatic CRC. This participant clustered with the CRC group in an unsupervised analysis performed using the original group label, without knowledge of the later diagnosis, raising the hypothesis, to be confirmed in a prospective cohort, that urinary volatilomic alterations may be detectable before clinical diagnosis. Our findings indicate that urinary volatilomic profiling captures metabolic changes associated with CRC and represents a promising, hypothesis-generating starting point for non-invasive biomarker discovery. Full article

The increasing use of photopolymer resins in dental three-dimensional (3D) printing has raised concerns regarding occupational exposure to volatile organic compounds (VOCs). This study aimed to characterize and compare formaldehyde (HCHO) and total volatile organic compound (TVOC) emission profiles of five commercially available dental 3D-printing resins and to explore their relationship with subjective odor perception. Subjective odor perception was assessed during routine educational laboratory activities using a numerical rating scale (0–10). Time-resolved HCHO and TVOC measurements were subsequently performed under standardized chamber conditions using a portable air-quality monitor, with three consecutive 10 min measurement cycles conducted for each resin using the same standardized 200 mL sample. Two participants reporting upper respiratory tract infection symptoms were excluded, resulting in a final sensory sample of 50 participants. Perceived odor intensity differed significantly among the tested resins (Friedman test, χ²(4) = 55.54, p < 0.001; Kendall’s W = 0.278). A positive resin-level association was observed between mean odor intensity and TVOC concentration at the 10 min endpoint of the first post-agitation measurement cycle (Spearman’s ρ = 0.70); however, this relationship was not statistically significant in the exact two-sided permutation analysis (p = 0.233) and was considered exploratory. HCHO–odor correlation analysis was not performed because HCHO concentrations for three of the five resins exceeded the upper measurement range of the instrument. Notably, a plant-based resin exhibited relatively high odor intensity despite comparatively low TVOC emissions, suggesting that total emission magnitude alone may not fully explain odor perception. The tested dental photopolymer resins exhibited distinct material-dependent emission and odor-perception characteristics. Odor perception should therefore be considered complementary to, rather than a substitute for, instrumental emission characterization. Integrating sensory assessment with instrumental emission measurements may support a more comprehensive evaluation of dental photopolymer resins and inform future occupational-safety studies. Full article

Rumen development and microecological homeostasis are critical for post-weaning health in lambs; however, effective nutritional strategies combining probiotics and antimicrobial peptides remain underexplored. This study investigated the effects of graded doses of a combined additive (Candida utilis + antimicrobial peptide (AMP)) on rumen development and microecology in weaned Hu lambs. Forty healthy pre-weaning male lambs (initial body weight: 15.77 ± 1.25 kg; age: 42.98 ± 1.80 d) were randomly assigned to four groups (n = 10): a control group (CK, fed milk/basal diet), and three treatment groups receiving the same milk/basal diet supplemented with graded doses of the combined additive, based on feed intake (LCB: AMP 0.05 g/kg + C. utilis 0.1 g/kg, MCB: AMP 0.05 g/kg + C. utilis 0.8 g/kg, HCB: AMP 0.05 g/kg + C. utilis 1.5 g/kg) over a 40-day period starting from day 6. At the end of the trial, six lambs per group were randomly selected for sampling for analyses of rumen morphology, fermentation parameters, 16S rRNA amplicon sequencing, and untargeted metabolomics. Results showed that, compared with CK, (1) MCB and HCB increased papilla height, and HCB also increased papilla width (p < 0.05); papilla width and muscular layer thickness showed significant linear increases with increasing additive dose (p < 0.05). (2) All treatments linearly reduced ruminal pH (p < 0.05), although all values remained within the normal physiological range; meanwhile, all treatment groups showed elevated levels of microbial protein (MCP), butyrate, valerate, and isovalerate; MCP also increased linearly with dose (p < 0.05); LCB decreased the acetate-to-propionate ratio(A:P), and this ratio exhibited a significant quadratic trend across treatment groups (p < 0.05). (3) HCB increased the α-diversity indices and reduced Methanobacteriota abundance; LCB elevated Bacillota; and all treatments decreased Spirochaetota, Synergistota, and Cyanobacteriota but increased Actinomycetota, Verrucomicrobiota, and Thermodesulfobacteriota (p < 0.05). (4) The number of differential metabolites and KEGG pathway enrichments gradually increased with increasing doses of the combined additive, with HCB exerting the most extensive modulatory effects on signaling and neural pathways. (5) Volatile fatty acids, Bacteroidota, and Xylanibacter were positively correlated with rumen development parameters (p < 0.05). Collectively, dietary supplementation with the combined additive improved rumen fermentation, microbial community structure, and metabolic profiles, with the high-dose (HCB) regimen showing the most effects on select parameters, whereas the low-dose (LCB) regimen exhibited advantages in specific fermentation traits. These findings provide preliminary evidence for the potential application of this combined additive in post-weaning lamb diets. Full article

Texas wines remain underrepresented in the scientific literature, and combined chemical and sensory datasets for key varieties are limited. This study characterized the physicochemical, phenolic, volatile, metabolomic, and sensory profiles of 26 Texas Cabernet Sauvignon and Tannat wines from the Texas High Plains and Texas Hill Country AVAs and compared them with benchmark wines from California, France, and Uruguay. Analyses included pH, titratable acidity, alcohol, color, antioxidant activity, targeted LC-MS/MS phenolic profiling, HS-SPME-GC-MS volatile analysis, untargeted metabolomics, and sensory profiling using Hierarchical Rate-All-That-Apply (HRATA). Multivariate analyses revealed distinct chemical and sensory patterns between Texas wines and benchmark regions, as well as notable differences between Texas subregions, as observed through PCA and PLS-DA score and loading plots. It is acknowledged that the wines in this study originated from different producers, vintages, and winemaking protocols; therefore, observed regional differences may reflect a combination of environmental conditions and winemaking practices rather than terroir alone. Texas High Plains wines were generally associated with more favorable aromatic and sensory attributes, while Texas Hill Country wines showed distinct chemical and sensory patterns. Interpretations of relationships between chemical compounds and sensory attributes are based on multivariate biplot associations and should be understood as observed co-occurrences rather than direct causal relationships. These results provide the first combined reference dataset for Texas Cabernet Sauvignon and Tannat wines and support future research on regional identity, varietal performance, and wine quality in Texas. Full article

Beer flavor depends on the composition and structural characteristics of fermentable carbohydrates generated during mashing. Although mashing strategy is known to influence wort composition, the mechanistic relationship between mashing-induced variations in carbohydrate structure and subsequent yeast metabolism and flavor formation remains poorly understood. This study aimed to compare the effects of two mashing procedures, infusion mashing (IMM) and decoction mashing (DMM), on carbohydrate structure, fermentation behavior, and flavor attributes of wheat beer. The physicochemical properties were analyzed using standard methods; organic acids, amino acids, and volatile compounds were analyzed using chromatographic techniques combined with multivariate analysis. Instrumental aroma and taste characteristics were further assessed using electronic nose and electronic tongue systems. Compared with IMM, DMM wort contained numerically higher proportions of low-degree-of-polymerization carbohydrates and higher amino acid concentrations. These compositional differences were associated with divergent fermentation kinetics and distinct volatile and nonvolatile metabolite profiles in the finished beers. DMM was associated with higher concentrations of medium-chain fatty acid ethyl esters, whereas IMM was associated with higher concentrations of acetate esters, higher alcohols, and aldehydes, consistent with faster fermentation and enhanced amino acid catabolism. Multivariate analysis confirmed differentiation in volatile profiles and instrumental aroma characteristics between the two beers. Together, these results suggest an association of mashing strategy with variations in carbohydrate structure, fermentation behavior, and volatile compound profiles in wheat beer. These findings offer a framework for the process-level control of beer flavor. Full article

Background/Objectives: The integration of artificial intelligence (AI) and digital technologies into dental practice is reshaping clinical workflows, administrative processes, and, increasingly, the patient experience and the doctor–patient relationship. While prior research has documented the attitudes of clinicians and practice managers, the perspective of the patient remains comparatively underexplored. This study examined how dental patients perceive AI integration and digital tools across the dental care pathway, together with the associated implications for data security, cost, and the human dimension of care. Methods: A cross-sectional, questionnaire-based study was conducted among 200 dental patients in Bucharest, Romania, and the surrounding region. The instrument assessed perceived difficulty and availability regarding digital technology, current use of digital tools, demographic and educational characteristics (age, gender, practice environment, educational level), and two attitudinal dimensions, namely digital prudence and concern for technological sustainability, across five subdomains of the dental care pathway: scheduling, diagnosis, treatment planning, feedback, and follow-up (dispensarization). Responses were analyzed using non-parametric tests and exploratory principal component analysis with internal-consistency validation. Results: Patients expressed moderate-to-high interest in AI support during the diagnostic (median = 3.3, IQR = 2.7–3.9) and feedback (median = 3.11, IQR = 2.78–3.67) stages and the lowest interest in scheduling (median = 2.7, IQR = 2.0–3.3). A marked level of digital prudence was observed (median = 3.24, IQR = 2.82–3.61), reflecting concerns about data security, automation, and a possible weakening of the clinician–patient bond. Younger and academically educated patients reported lower perceived difficulty, higher availability, and greater current use of digital tools (all p ≤ 0.001); counterintuitively, the same patients scored significantly higher on digital prudence (Spearman’s ρ = −0.260, p < 0.001). Greater familiarity with digital tools was therefore accompanied by a more critical awareness of their informational risks rather than by uncritical acceptance. Conclusions: Dental patients approach AI through a dual lens of openness and informed caution, welcoming efficiency gains in the clinical and continuity-of-care stages while voicing measured concerns about data security, affordability, and the preservation of human contact. To interpret this profile, we propose two conceptual contributions: a mapping of patient needs onto Maslow’s hierarchy in the context of AI-mediated care and the Informational VUCA framework, which characterizes the volatility, uncertainty, complexity, and ambiguity that patients face when navigating AI-generated information. The findings point to a clear practical agenda of transparent communication, robust data governance, and education strategies adapted to patients’ educational and demographic profiles, so that AI-enhanced workflows strengthen rather than erode the doctor–patient relationship. Full article

The sun-dried merguez sausage (DM) is deeply rooted in the Tunisian culinary culture. It is characterized by a distinctive composition and an energy-saving process. Unlike fermented or mechanically dried meats, sun-dried merguez is produced through a single, natural solar dehydration step lasting 8–12 days. Limited information is available regarding its physicochemical properties, chemical composition, and nutritional profile. To address this gap, changes in physicochemical properties during drying were monitored, and the chemical composition and microbiological flora of fresh merguez (FM) and DM were analyzed. Results showed that sun-drying contributed to a significant decrease in moisture (17.0%), water activity (0.675), and pH (5.56), ensuring microbiological stability and safety. DM was rich in lactic acid (1865 mg.kg⁻¹) and other low-molecular-weight organic acids, as well as minerals, particularly iron (13.5 mg per 100 g), with an enhanced fatty acid profile—specifically oleic acid—due to tail fat. The distinctive composition of DM, enriched with 15% spices and herbs, yielded a volatile profile dominated by terpenes (67%), which imparts its characteristic flavor and may contribute to health benefits. The current study underscored the nutritional and nutritive value of DM, offering valuable insights for stakeholders to enhance and protect this cultural heritage. Full article

The present work is a first attempt to develop, on a lab scale, herbal-infused Debina white wines containing typical or lower sulphur dioxide and to evaluate their antioxidant potential and volatile profile. Two different herbal-infused wines were prepared by adding (a) saffron plus mastic, and (b) mountain tea. During storage, all herbal-infused wines exhibited higher antioxidant capacity than the respective control ones, indicating their higher storage capability. In particular, they exhibited higher levels of free SO₂ and aminothiols, substrates of white wine oxidation. Moreover, they exhibited higher antioxidant activity as determined by the Folin, FRAP, and the scavenging of hydroxyl radicals methods. Volatile profile of herbal-infused and control wines was determined semi-quantitatively using HS-SPME coupled with GC×GC-TOF-MS methodology. Herbal-infused wines exhibited enriched volatile profiles containing volatiles originating from the herbals used. These include safranal from saffron, monoterpenes from mastic, and β-thujene, camphene, and β-ocimene from mountain tea. All herbal-infused wines exhibited satisfactory organoleptic quality, with sensory properties differentiated from the respective control ones. Full article

Methanol formation is a critical safety concern in kiwifruit wine due to the high pectin content of kiwifruit. This study aimed to establish an effective strategy to reduce methanol formation while maintaining the fermentation performance and sensory quality of kiwifruit wine. The effects of fermentation temperature, pectinase dosage, and clarification centrifugation conditions on methanol production were investigated, and the selected process-regulation strategy was further evaluated by analyzing physicochemical properties, volatile aroma compounds, and sensory characteristics. The results showed that pectinase dosage was the predominant factor affecting methanol formation. Under the selected process conditions identified within the tested parameter ranges (fermentation at 19 °C, pectinase dosage of 0.02 g/L, and centrifugation at 2500 r/min), the methanol content decreased to 167.45 ± 2.20 mg/L, representing a 37.39% reduction compared with the control group, while the ethanol content remained at 12.66 ± 0.04% (v/v). Moreover, the wine exhibited favorable physicochemical characteristics, including improved retention of phenolic compounds and balanced organic acid composition. Aroma profiling using GC–MS and multivariate statistical analysis demonstrated that the optimized wine exhibited a volatile aroma pattern comparable to that of the control wine, indicating that methanol mitigation did not substantially impair the characteristic flavor of kiwifruit wine. Sensory evaluation further confirmed the improved overall acceptability of the processed product. This study provides a practical approach to producing safer kiwifruit wine while preserving quality attributes. Full article

Ovarian cancer remains difficult to detect before dissemination, and individual circulating biomarkers are unlikely to capture its biological and clinical heterogeneity. Multimodal liquid biopsy offers a potential route forward, but most biomarker combinations are developed empirically, with limited consideration of the molecular relationships among the measured signals. In this Perspective, we propose that intracellular miRNA dysregulation may provide an organizing layer for integrating glycoprotein/glycan remodeling with blood-derived volatile organic compound (VOC) signatures, while corresponding circulating miRNA profiles constitute a distinct measurable biomarker layer that may only partially reflect the underlying intracellular regulatory state. The miRNA–glycosylation axis is supported by direct mechanistic evidence that selected miRNAs regulate glycogenes and pathways controlling fucosylation, sialylation, and other glycan features. By contrast, the proposed connection between miRNA dysregulation and VOC production is indirect and likely mediated through metabolic reprogramming, mitochondrial dysfunction, oxidative stress, ferroptosis, and lipid peroxidation. We evaluate the evidence supporting each biomarker domain, prioritize candidate bridge miRNAs, including members of the miR-200 family and miR-34a, and define the principal boundary conditions of the framework, including causal inference, disease specificity, histological heterogeneity, VOC source ambiguity, temporal variability, and cross-platform standardization. We further outline a translational strategy based on matched biospecimens, mechanism-aware computational integration, experimental perturbation, longitudinal analysis, and independent validation at clinically relevant specificity thresholds. The objective is not to assert a fixed causal chain, but to provide a testable, clinically oriented framework for moving multimodal ovarian cancer diagnostics from statistical combination to biologically informed integration. Full article