Search Results (7,148)

Phishing detection models often report strong benchmark performance, yet their reliability under realistic deployment conditions remains uncertain. This study examines this problem by investigating three failure modes of cross-dataset phishing email detection: corpus generalization failure, asymmetric prevalence-shift failure, and artifact-driven spurious learning. Using six public email corpora, CEAS_08, Enron, Ling, Nazario, Nigerian Fraud, and SpamAssassin, the study evaluates Term Frequency (TF) and Inverse Document Frequency (IDF)-based Logistic Regression and Linear Support Vector Classifier (SVC) models across pooled baseline testing, single-corpus cross-dataset transfer, leave-one-corpus-out pooled training, prevalence-shift simulation, training prevalence manipulation, dataset-identification analysis, top-feature inspection, artifact-removal ablation, and targeted feature-sensitivity masking. The findings show that single-corpus models are unstable under cross-dataset transfer, with F1-scores varying substantially across source–target combinations. In contrast, leave-one-corpus-out pooled training improves robustness, with Logistic Regression achieving sustained F1-scores between 0.8201 and 0.8994, and Linear SVC achieving F1-scores between 0.7607 and 0.8910 across unseen corpora. Prevalence-shift experiments reveal that failure is asymmetric and threshold-dependent. High-prevalence-trained models maintain high recall under fixed thresholds but suffer sharp recall degradation when operational alert-budget constraints are imposed. Conversely, low-prevalence-trained models become overly conservative in high-threat environments, producing high precision but substantially lower recall and poorer calibration. Artifact analyses further show that source corpus identity is highly learnable, with dataset-identification accuracy reaching 0.9722 for Logistic Regression and 0.9806 for Linear SVC. Top-feature and masking analyses indicate that models rely partly on corpus markers, date tokens, URL/domain terms, headers, and other artifact-like features rather than only general phishing indicators. The study contributes a deployment-aware and adversary-aware evaluation framework for phishing detection. It shows that benchmark accuracy alone is insufficient for assessing real-world robustness and that reliable phishing detection requires cross-corpus validation, prevalence-aware thresholding, and systematic testing for artifact-driven spurious learning. Full article

Background: Professional triathlon training is widely recognized as one of the most physiologically demanding forms of training, combining the multicomponent development of physical, biomechanical, and neuromuscular capacities across the three disciplines of swimming, cycling, and running. In this research, the authors measured the impact of two different training periods in elite male athletes on the serum concentrations of GLP-1, GIP, testosterone, and NF-κB and assessed their potential correlations. Methods: We compared a group of 37 triathletes, aged between 25 and 50, during preparatory and competitive periods, with a group of 20 healthy untrained males. The aim of the study was to assess the concentrations of testosterone, GLP-1, GIP, and NF-κB in both groups and in different exercise periods. We determined the markers using the ELISA method. Results: The results demonstrated an increase in GLP-1 concentration between two training groups (preparatory 44.73 ± 5.34 (pmol/L) vs. competitive 45.92 ± 6.13 (pmol/L); p < 0.001). Moreover, higher values of GIP serum concentration were observed in the training groups compared to the control group (33.21 ± 3.54 (ng/mL) vs. 38.83 ± 4.5 (ng/mL); p = 0.038). There were no statistically significant differences (p > 0.05) between the groups in terms of testosterone and NF-κB concentrations. There was also a statistically significant, strong positive correlation between NF-κB and GLP-1, GIP during each training period. In spite of the absence of definite changes in mean values of testosterone concentration between the groups, a minor increase in the median value in the group during the competitive period and a significantly lower median value in the control group were detected, suggesting a trend toward statistical significance. Conclusions: These findings may have clinical significance in athletes, as incretins and NF-κB could serve as biomarkers of metabolic adaptation to exercise and support individual training optimization. Further research is needed to investigate these relationships. Full article

Background: Intermittent Hypoxic–Hyperoxic Training (IHHT) induces physiological adaptations. While its efficacy in athletic performance remains debated, IHHT improves health markers in pathological and geriatric populations. This Exploratory Pilot Study aimed to explore the safety and feasibility of two IHHT protocols through preliminary responses. Methods: Twelve healthy volunteers completed a 4-week intervention (two sessions/week, 45 min/session) combining IHHT simultaneously during low-intensity exercise. The study compared a Training Group (TG: 30 min hypoxia, 7.5 min normoxia, 7.5 min hyperoxia) with a Conditioning Group (CG: 15 min hypoxia, 22.5 min normoxia, 7.5 min hyperoxia). Outcomes assessed included cardiorespiratory parameters, Acute Mountain Sickness symptoms, Perceived Exertion, a comprehensive biochemical panel, systemic inflammation, oxidative stress, and renal status. Results: Both protocols were well-tolerated. The TG exhibited significantly greater oxygen desaturation than the CG (p = 0.048). Moreover, the CG demonstrated a significantly attenuated increase in Interleukin-6 (p = 0.021) compared to the TG. Additionally, preliminary variations highlighted an interesting reduction in lipid parameters (TC, LDL, and Apo A1/B ratios) in both groups, although these did not reach statistical significance after FDR correction. Conclusions: While both protocols proved feasible and safe, a more balanced hyperoxic-to-hypoxic exposure (CG) showed better acute physiological tolerability, attenuating cardiovascular strain and mitigating systemic pro-inflammatory responses compared to the unbalanced exposure (TG). Finally, the preliminary variations observed in lipid parameters provide a rationale that warrants further controlled investigations. Full article

ANCA-associated vasculitis (AAV) with kidney involvement represents small-vessel vasculitis, characterized by rapidly progressive glomerulonephritis and a high risk of end-stage kidney disease (ESKD) and increased mortality. AAV typically presents with multisystem involvement, with renal manifestations occurring more frequently in microscopic polyangiitis (MPA) (90–100%) and granulomatosis with polyangiitis (GPA) (50–80%). The classic clinical presentation includes acute kidney injury with hematuria and proteinuria, accompanied by ANCA positivity (MPO-ANCA or PR3-ANCA). Histologically, the predominant pattern is segmental necrotizing glomerulonephritis with crescent formation. Treatment consists of two phases: (a) induction of remission with a lower cumulative dose of glucocorticoids (according to the reduced-dose PEXIVAS regimen) in combination with rituximab or cyclophosphamide and (b) maintenance of remission with rituximab for 2–4 years. The C5a receptor inhibitor avacopan can be used as a steroid-sparing agent in patients with severe kidney involvement or at high risk of corticosteroid-related complications. Beyond the traditional markers of disease activity (hematuria, proteinuria, eGFR), novel biomarkers such as urinary soluble CD163, MCP-1, complement activation products (C5a, sC5b-9), and urinary Treg/Th17 profiles have demonstrated prognostic value. Early diagnosis and prompt initiation of immunosuppressive therapy significantly improve both kidney and overall survival, while prevention of relapses and long-term complications plays a key role in improving the long-term prognosis of patients with AAV. Full article

Background: Obesity is a multifactorial metabolic disorder characterized by excessive adiposity, chronic low-grade inflammation, and dysregulated incretin and energy-sensing pathways, including glucagon-like peptide-1 (GLP-1) and AMP-activated protein kinase (AMPK). Methods: This in vitro and in vivo study evaluated the potential of select phytochemical candidates and botanical formulations to stimulate GLP-1 secretion and activate AMPK signaling. Results: Fourteen phytochemicals and six combinations were screened in human NCI-H716 enteroendocrine cells at 10–20 µg/mL to assess cytotoxicity and GLP-1 secretion. In human adipocytes, selected combinations reduced lipid accumulation and monocyte chemoattractant protein-1 (MCP-1) secretion. Among the tested formulations, combination #4, consisting of ginseng root extract, curcumin, white kidney bean extract, fenugreek extract, capsaicin, and bitter melon extract, significantly increased phosphorylated AMPK levels in vitro. In high-fat diet-induced obese mice, oral administration of combination 4 reduced body weight gain and white adipose tissue mass, improved metabolic biochemical parameters, restored leptin and MCP-1 levels toward normal values, increased GLP-1 level, and normalized GLP-1 receptor expression in subcutaneous adipose tissue. Conclusions: These preclinical findings demonstrate that this multi-component botanical formulation modulates GLP-1 secretion, AMPK phosphorylation, lipid accumulation, and inflammatory markers in cellular and murine models. These data provide a foundational rationale for its further evaluation as a non-toxic candidate for metabolic management. Full article

Background/Objectives: Hypertension is a multifactorial condition in which inflammation plays a pivotal role. Current preclinical models fail to fully capture the complexity of the underlying mechanisms, limiting therapeutic discovery, while compounds targeting endothelial inflammatory pathways may offer promising alternatives. Methods: An advanced in vitro model of hypertension, consisting of a bioreactor for endothelial cell culture coupled with a peristaltic pump to mimic blood circulation, and a pressure modulator as mechanical stimulus (Live-Pa System) to reproduce hemodynamic stimuli, was employed to investigate the effects of the imidazo-pyrazolyl urea (IPU) 3l, known for its chemotaxis inhibition properties. The effects of 3l were investigated on hypertension-related inflammatory/vasoconstrictor markers, alone or in combination with hypertensive stimuli (ANGII and/or Live-Pa). Results: IPU 3l effectively counteracted ANGII-induced inflammation by significantly reducing NF-κB activation across all experimental conditions (static, dynamic, and Live-Pa) and IL-8 secretion under static and dynamic conditions. Conclusions: IPU 3l exhibits a consistent anti-inflammatory profile, primarily through inhibition of ANGII-induced NF-κB activation across all experimental conditions, with additional context-dependent effects on IL-8 secretion. This study introduces a new strategy for drug discovery by distinguishing biochemical from mechanical stress, providing a clearer framework to interpret condition-specific pharmacological responses. Such insights, difficult to obtain with conventional in vitro or in vivo models, are essential for developing more effective cardiovascular therapies. Full article

Osteoporotic vertebral fractures (OVFs) are the most common osteoporotic fracture type and remain substantially underdiagnosed despite their diagnostic, prognostic, and therapeutic importance. This review examines OVFs as sentinel events in osteoporosis, emphasizing their role in diagnosis, fracture-risk stratification, treatment selection, and secondary fracture prevention. This narrative review synthesizes evidence from contemporary clinical practice guidelines, epidemiological studies, randomized controlled trials, systematic reviews, meta-analyses, and selected observational studies addressing imaging and artificial-intelligence-assisted detection. References were selected based on clinical relevance, methodological rigor, and recency, in keeping with the conventions of a focused narrative review rather than a systematic review. OVFs frequently occur without classic osteoporosis-range bone mineral density and often remain clinically silent or incidentally detected. Nevertheless, they independently predict future vertebral, hip, and non-OVFs, particularly during the early post-fracture period. Vertebral fracture assessment on dual-energy X-ray absorptiometry (DXA), opportunistic CT screening, standardized radiology reporting, and AI-assisted detection may improve case finding. Management should combine acute pain control, rehabilitation, appropriate use of vertebral augmentation in selected patients, pharmacological osteoporosis therapy, and structured secondary prevention. Patients with recent or multiple OVFs often meet criteria for high or very-high fracture risk and may benefit from anabolic-first or sequential therapy strategies. Fracture Liaison Services provide a system-level model to close the diagnosis and treatment gap. Recognizing OVFs as actionable markers of skeletal fragility is essential for reducing subsequent fracture burden. Full article

Objectives: The histologic grade is an important prognostic factor in hepatocellular carcinoma (HCC). A Gd-EOB-DTPA-enhanced MRI may provide noninvasive imaging markers related to tumour differentiation. This study aimed to evaluate the association of Gd-EOB-DTPA-enhanced MRI features, together with the albumin–bilirubin (ALBI) score and alpha-fetoprotein (AFP), with the HCC histologic grade and to assess the performance of combined predictive models. Methods: In this prospective cross-sectional study, 75 patients (mean age, 56.4 years; 66 men) with 88 histopathologically confirmed HCC lesions were enrolled. Patients were classified into well-differentiated (grades I–II, n = 24) and poorly differentiated (grades III–IV, n = 51) groups according to the Edmondson–Steiner system. The MRIs were performed on a 1.5-T scanner and included T1-weighted in-phase/opposed-phase imaging; T2-weighted imaging; diffusion-weighted imaging; and dynamic Gd-EOB-DTPA-enhanced sequences, including arterial, portal venous, transitional, and 20 min hepatobiliary phases. Two radiologists, blinded to the pathology, assessed predefined imaging features, and the lesion-to-liver ratio (LLR) was measured. Group comparisons were performed using Student’s t-test, a Mann–Whitney U test, and a chi-square or Fisher’s exact test, followed by a multivariable logistic regression and ROC analysis with bootstrap resampling. Results: Compared with well-differentiated HCC, poorly differentiated HCC showed a higher frequency of peritumoral hepatobiliary phase (HBP) hypointensity (62.7% vs. 4.2%, p < 0.001) and peritumoral arterial hyperintensity (39.2% vs. 0%, p < 0.001). In the multivariable analysis, peritumoral HBP hypointensity remained independently associated with poorly differentiated HCC (OR = 30.89, p = 0.002). The two-parameter MRI model, including peritumoral HBP hypointensity and HBP tumour signal, yielded an AUC of 0.84. The combined MRI + ALBI + AFP model yielded an AUC of 0.87 and an accuracy of 78.7%, representing only a small exploratory improvement over the two-parameter MRI model (AUC = 0.84) in this cohort. Conclusions: Gd-EOB-DTPA-enhanced MRI features, particularly peritumoral HBP hypointensity, were associated with a high histologic grade in HCC. In this surgically treated, predominantly HBV-related cohort with mostly preserved liver function, these findings provide a preliminary basis for preoperative histologic risk stratification; however, they remain exploratory and require external validation in larger, more diverse cohorts before broader clinical application. Full article

Laural (Laurus nobilis) is a Mediterranean plant with reported antibacterial properties, yet the genetic basis of its antibacterial efficacy remains largely unexplored. This study evaluated the antibacterial activity of Laurus nobilis methanolic extracts against Escherichia coli, Staphylococcus aureus, and Bacillus cereus, combined with genome-wide association studies (GWAS) and machine learning (ML) approaches to identify genetic markers and predict antibacterial efficacy in 92 plant samples. Antibacterial tests revealed significant variability in inhibition zones, with E. coli showing the highest inhibition (Canakkale2: 24.5 mm), followed by S. aureus (Aydin2: 26.0 mm). Minimum inhibitory concentration (MIC) analysis demonstrated notable regional differences; extracts from Mersin3 showed the highest efficacy (MIC = 6.25 mg/mL), while Aydin1 exhibited the lowest activity (MIC = 100 mg/mL). Population structure and neighbor joining tree analysis split the germplasm into two groups. GWAS identified significant genetic markers associated with antibacterial traits, including marker 26557159 for EC-MEAN (Escherichia coli-Mean) (p = 1.10 × 10⁻⁴, MarkerR² = 0.1799, genetic variance = 9.41792) and marker 26584774 for BC-MEAN (Bacillus cereus-Mean) (p = 8.89 × 10⁻⁵, MarkerR² = 0.18512, genetic variance = 12.48948). Protein–protein interaction network of loci associated with marker trait association (MTA) marker (26557159) indicated involvement in high-affinity secondary active ammonium transmembrane transporter activity, providing insights into genetic regions influencing antibacterial properties. ML models predicted antibacterial activity with high accuracy. XGBoost achieved the best performance for MIC predictions (R² = 0.999, RMSE = 0.434), while random forest (R² = 0.984) demonstrated robust performance for both MIC and disc diffusion assays. LightGBM performed well for MIC prediction (R² = 0.988) but showed limited accuracy for disc diffusion outcomes (R² = 0.695). This study is the first to combine GWAS and ML for predicting antibacterial efficacy in L. nobilis, identifying specific genetic markers (e.g., 26557159, 26584774) and demonstrating that XGBoost achieves near-perfect MIC prediction (R² = 0.999). These findings provide a genomic and computational foundation for marker-assisted breeding of laurel with enhanced antibacterial properties and support the sustainable use of plant-derived anti-microbials. Full article

Glycemic variability is a stand-alone risk factor for diabetic complications. Background/Objectives: We investigated whether combining quercetin-rich Allium cepa L. (white onion) juice with the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin could reduce glycemic variability beyond that achieved with monotherapy in experimental diabetes. Methods: Wistar rats were made diabetic with streptozotocin (35 mg/kg) and maintained for 60 days in the following groups: vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), and dapagliflozin + fresh onion juice (5 mL twice daily). Diabetic Wistar rats (n = 10/group) were gavaged with vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), or both. The juice was expected to contain phytochemicals (quercetin derivatives and organosulfur compounds) based on published reports on similar A. cepa cultivars. A validated immunoassay was used to measure glycated hemoglobin (HbA1c) every 10 days. All treatments reduced HbA1c to the same level (~7.1–7.2%) as compared to diabetic controls (9.0 ± 0.3%) (p < 0.001), though only the combination treatment reduced glycemic variability (HbA1C coefficient of variation 3.9 ± 0.6% vs. 7.8 ± 1.2% with dapagliflozin and 11.2 ± 1.8% with onion) (p < 0.001). Results: Across the 10-day sampling schedule, the combination kept HbA1c within a narrow 6.8–7.2% band, whereas the monotherapies fluctuated more widely; because intraday and postprandial glucose were not captured, effects on short-term excursions could not be directly assessed. There were no cases of severe hypoglycemia and only infrequent and non-repeated cases of mild hypoglycemia. Conclusions: In this exploratory, hypothesis-generating study, the additive interaction between onion phytochemicals and dapagliflozin was associated with lower glycemic variability via mechanisms proposed in the literature; quercetin-rich A. cepa juice may therefore warrant further investigation as an adjunct in diabetes management, pending batch-specific phytochemical characterization and confirmatory studies. Full article

This study presents an archaeometric characterization of fifteen blue-and-white Chinese porcelain sherds (17^th–19^th centuries) from the Jingdezhen, Anxi, and Dehua kiln systems, compared with fragments recovered from the Santana Convent (Lisbon), particularly eighteenth-century materials. A combination of non-invasive, minimally invasive and micro-destructive techniques, including Ground-State Diffuse Reflectance Spectroscopy (GSDR), X-ray Photoelectron Spectroscopy (XPS), micro-Raman spectroscopy, X-ray Fluorescence (XRF), X-ray diffraction (XRD), and stereomicroscopy, was employed to investigate cobalt pigments, glaze composition, firing conditions, and provenance indicators. The results reveal systematic differences between dark- and light-blue glazes, reflecting distinct pigment-processing technologies or simple concentration effects inducing different cobalt coordination environments and/or oxidation states. Raman spectroscopy confirms that cobalt occurs mainly as Co²⁺ ions dissolved in the amorphous silicate glaze matrix. No Raman-detectable crystalline cobalt silicate or cobalt aluminate phases were identified. XRF and XPS analyses show elevated Mn/Co and Fe/Co ratios combined with extremely low arsenic contents, suggesting the predominant use of domestic Chinese cobalt sources. XRD analyses identified quartz, mullite, and minor anorthite, consistent with traditional high-fired hard-paste porcelain technology. Dark-blue radiating star-shaped colored radiating features, particularlyfrequent in Dehua porcelains, were also identified in selected Santana Convent samples, suggesting their attribution to Dehua kiln production and demonstrating the value of glaze defects as complementary provenance markers. Full article

Perfluorohexanesulfonic acid (PFHxS) is a per- and polyfluoroalkyl substance (PFAS) frequently detected in aquatic environments, while chlorpyrifos (CPF) is a widely used organophosphate insecticide. Although their individual toxicity is well described, their combined effects remain poorly understood. Here, we evaluated the effects of CPF (0.7 to 700 µg/L), alone or in combination with PFHxS (10 µg/L), in zebrafish embryos. Survival, hatching, malformations, locomotor activity, oxidative stress, apoptosis, and gene expression were assessed after five days of exposure. CPF reduced survival in a concentration-dependent manner, with moderate enhancement under co-exposure, while hatching success was unaffected. Deformities increased with CPF concentration, which remained consistent with PFHxS co-exposure, suggesting toxicity was mediated by CPF. Locomotor activity was largely decreased in a concentration- and phase-dependent manner. No significant changes were observed in ROS levels or apoptosis. Gene expression analysis revealed upregulation of neurotoxicity-related markers (ache, gfap, shha, syn2a), particularly at intermediate CPF concentrations and under co-exposure. Oxidative stress-related genes showed differential responses, with sod1 upregulated and cat downregulated only in the combined treatment. Overall, combined exposure did not substantially enhance toxicity compared with CPF alone, suggesting that CPF was the main contributor to the observed effects, whereas PFHxS had limited influence. Full article

Gliomas account for over half of all primary malignant tumors of the central nervous system and remain associated with poor prognosis. Although irinotecan is an effective chemotherapeutic agent, its clinical utility is limited by systemic toxicity, prompting interest in phytochemicals such as ellagic acid (EA) as potential sensitizers. This study aimed to investigate whether EA enhances the antiproliferative and pro-apoptotic effects of irinotecan in C6 glioma cells. C6 glioma cells were treated with EA (100 µM), irinotecan (100 µM), or their combination for 24, 48, and 72 h. Cell proliferation was assessed by BrdU assay, p53 and caspase-3 protein expression by immunocytochemistry (H-SCORE), and multidrug resistance gene 1 (MDR1), MGMT, p53, and caspase-3 mRNA levels by RT-qPCR. EA significantly enhanced irinotecan-mediated suppression of proliferation at 24 h (p < 0.001), 48 h (p < 0.001), and 72 h (p < 0.001), with the combination producing the strongest inhibition across all time points. Immunocytochemical p53 expression increased significantly in all treatment groups at 24 h and 48 h (EA: p < 0.01; irinotecan: p < 0.01; EA + irinotecan: p < 0.01) and remained elevated at 72 h (p < 0.05). Caspase-3 immunoreactivity showed robust early activation at 24 h (Ir: p < 0.05; EA: p < 0.01), persisted at 48 h (p < 0.01), and remained significantly elevated in the EA group at 72 h (p < 0.001). At the mRNA level, irinotecan induced the highest p53 expression at 24 h (p < 0.001), with sustained elevation at 48 h and 72 h (p < 0.001 and p < 0.05, respectively). Caspase-3 mRNA peaked at 24 h only in the irinotecan group (p < 0.001). EA significantly increased MDR1 and MGMT transcription at 24 h and 48 h (p < 0.001), whereas the EA + irinotecan combination attenuated this increase and remained close to control levels at early time points. MGMT remained significantly elevated in EA and EA + irinotecan groups through 72 h (p < 0.001). EA cooperatively enhanced the antitumor activity of irinotecan primarily by enhancing proliferation inhibition and modulating drug-resistance gene expression, while maintaining, rather than further augmenting, apoptotic protein markers comparable to those induced by single-agent treatments. These findings support EA as a promising adjunct to irinotecan-based glioma therapy. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. Alpha-fetoprotein (AFP), a widely used and accessible tumoral marker, has limited performance in the early detection of HCC among high-risk populations. This study aims to evaluate the potential added value of ccfDNA (circulating cell-free DNA) fragment size, alone or in a multiparameter panel, using accessible, feasible ccfDNA analysis. Methods: A prospective cohort of 125 patients with chronic liver disease was analyzed. Patients with incomplete clinical or laboratory data and patients without cirrhosis were excluded from the final analysis. Nonparametric tests, logistic regression and ROC curve analysis were performed. ccfDNA fragment size was measured using on-chip electrophoresis. Results: ccfDNA fragment size was significantly lower in the cirrhosis-HCC subgroup compared to the cirrhosis-only subgroup (p < 0.001). While AFP remains an independent predictor of HCC among cirrhosis patients, ccfDNA fragment size did not prove to be an independent predictor in this cohort. AUROC (area under the receiver operating characteristic curve) analysis revealed that a combined model of AFP, age, liver reserve, and ccfDNA fragment size did not perform better than the corresponding panel without ccfDNA. Moreover, after DeLong comparison, the difference between the two AUROCs proved statistically insignificant. Age and platelet count remain the strongest independent predictors in our exploratory cohort. Conclusions: Although ccfDNA fragment size proved to be lower in the HCC subgroup, its statistical significance fades when included into a multimarker panel. However, all panels should undergo further validation in a larger cohort, in order to better assess the individual contribution of each parameter and to discriminate between added diagnostic value and confounding effect of age and liver reserve parameters. Full article

Multiple endocrine neoplasia (MEN) syndromes are rare hereditary disorders characterized by the development of multiple endocrine and non-endocrine tumours with variable penetrance and age-dependent expression. Although uncommon, these syndromes are highly relevant from both biological and clinical perspectives, as they exemplify the direct link between germline genetic alterations and tumorigenesis. Early tumour detection is critical in MEN syndromes because many associated neoplasms—such as medullary thyroid carcinoma (MTC), pancreatic neuroendocrine tumours (NETs), pheochromocytomas, and parathyroid disease—may remain clinically silent for prolonged periods while retaining malignant potential. Delayed diagnosis is associated with advanced disease and worse outcomes, whereas early identification enables curative or organ-preserving interventions. This clinical challenge has driven the development of integrated diagnostic strategies combining genetic testing, biochemical markers, and imaging. Among these, genetic testing plays a pivotal role, providing definitive diagnosis, enabling family screening, and guiding risk-adapted surveillance. The aim of this review is to provide a comprehensive synthesis of genetically driven diagnostics in MEN syndromes, outlining the current state of the art and future directions in precision medicine. Full article