Search Results (2,910)

The oral cavity acts as the anatomical gateway to the respiratory tract, sharing both microbiological and pathophysiological links with the lower airways. Although radiotherapy is a cornerstone treatment for lung cancer, reliable oral microbiome biomarkers for predicting patient outcomes remain lacking. We analyzed the oral microbiome of 136 lung cancer patients and 199 healthy controls across discovery and two validation cohorts via 16S rRNA sequencing. Healthy controls exhibited a significantly higher abundance of Streptococcus compared to patients (p = 0.049, p < 0.001, p < 0.001, respectively). The structure of the microbial community exhibited substantial dynamic changes during treatment. Responders showed enrichment of Rothia aeria (p = 0.027) and Prevotella salivae (p = 0.043), associated with prolonged overall survival (OS) and progression-free survival (PFS), whereas non-responders exhibited elevated Porphyromonas endodontalis (p = 0.037) correlating with shorter OS and PFS. According to Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) analysis, Akkermansia and Alistipes were nearly absent in non-responders, while Desulfovibrio and Moraxella were virtually absent in responders. A diagnostic model based on Streptococcus achieved area under the curve (AUC) values of 0.85 (95% CI: 0.78–0.91) and 0.99 (95% CI: 0.98–1) in the validation cohorts, and a response prediction model incorporating Prevotella salivae and Neisseria oralis yielded an AUC of 0.74 (95% CI: 0.58–0.90). Furthermore, in small cell lung cancer, microbiota richness and diversity were inversely correlated with Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.008, p < 0.001, respectively) and pro-gastrin-releasing peptide (ProGRP) levels (p = 0.065, p = 0.084, respectively). These results demonstrate that lung cancer-associated oral microbiota signatures dynamically reflect therapeutic response and survival outcomes, supporting their potential role as non-invasive biomarkers for diagnosis and prognosis. Full article

Background and Objectives: Thyroid nodules are common, and distinguishing benign from malignant lesions is essential for clinical decision-making. While EU-TIRADS provides ultrasound-based risk stratification, fine-needle aspiration biopsy (FNAB) and the Bethesda System remain central diagnostic tools. This study aimed to compare the diagnostic performance of EU-TIRADS and Bethesda classifications and to identify ultrasonographic features independently associated with malignancy. Materials and Methods: This retrospective single-center study included 824 patients (1132 nodules) who underwent FNAB between August 2021 and June 2024. All ultrasound examinations and FNAB procedures were performed by the same endocrinologist. Sonographic features, EU-TIRADS categories, Bethesda classes, surgical indications, and histopathology were analyzed. Diagnostic accuracy was assessed using ROC curves, and multivariable logistic regression was applied to determine independent predictors of malignancy. Results: Among all nodules, 51.0% were EU-TIRADS 3, 28.6% were EU-TIRADS 4, and 19.2% were EU-TIRADS 5. Bethesda class II constituted 62.7% of FNAB results. Of the 289 surgically treated nodules, 53.3% were malignant. Malignant nodules were smaller, more often solitary and unilateral, and more frequently located in the upper pole (p < 0.05). Irregular margins (OR = 8.15, p < 0.001) and microcalcifications (OR = 10.01, p = 0.003) were independent predictors of malignancy. Taller-than-wide shape also showed significant association. ROC analyses demonstrated that EU-TIRADS (AUC = 0.808) and Bethesda (AUC = 0.869) were both significant predictors, with Bethesda showing higher specificity. Malignancy rates were 0% in EU-TIRADS II, 4.3% in III, 14.5% in IV, and 37.8% in V. Conclusions: EU-TIRADS is a practical and sensitive non-invasive tool for malignancy risk stratification; however, Bethesda classification remains superior in overall diagnostic accuracy. Microcalcification and irregular margins were the strongest ultrasonographic predictors of malignancy, while macrocalcification, parenchymal heterogeneity, and thyroiditis showed no significant association. These findings support the complementary roles of EU-TIRADS and FNAB and highlight key sonographic markers that enhance malignancy prediction in thyroid nodule evaluation. Full article

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive neoplasm characterized by grim survival outcomes, despite significant therapeutic advances. Mortality rates (up to 70%) have remained unaltered for decades, predominantly due to profound diagnostic delays. These derive from the asymptomatic nature of the early stages of oral carcinogenesis and the emergence of dysplastic areas in previously benign lesions, acting as the bridge to malignant transformation. Hence, the establishment of reliable salivary biomarkers is crucial for non-invasive OSCC detection, even from the premalignant stage of dysplasia. Based on our previous bioinformatic research identifying stage-specific miRNAs throughout OSCC progression, which yielded miR-34a-5p as the most significant, we aimed to experimentally investigate its role in oral oncogenesis and explore its stage-reflecting biomarker potential for liquid biopsy. Methods: The expression of miR-34a was evaluated using quantitative real-time PCR in saliva samples from 9 patients with oral premalignant dysplastic lesions, 10 patients with OSCC and 10 healthy controls. The diagnostic accuracy of miR-34a expression profiles was assessed using ROC-curve analyses. Results: The expression of salivary miR-34a differed significantly across the studied groups, demonstrating a steep decrease in the presence of epithelial premalignant dysplasia, significant upregulation in OSCC and intermediate levels in normal oral mucosa (p < 0.001). The ROC results indicate strong diagnostic performance for the detection of oral dysplasia (AUC = 0.93; p < 0.001), OSCC (AUC = 0.77; p = 0.01) and excellent accuracy for the discrimination between premalignant and OSCC lesions (AUC = 0.98; p < 0.001). Conclusions: Our findings reveal a state-dependent dysregulation of miR-34a in oral carcinogenesis, suggesting its complex role as a pathogenetic agent that allows for malignant transformation through its diminished expression, and as a secondary reactive mechanism attempting to suppress tumor development. Salivary miR-34a holds great, stage-specific diagnostic potential, thereby reflecting the health state of oral mucosa in real time. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for reliable biomarkers and therapeutic targets. To address this need, we focused on UDP-glucose pyrophosphorylase 2 (UGP2). Although UGP2 has been implicated in tumorigenesis across multiple cancers, its precise role and clinical significance in CRC remain poorly understood. This study aimed to comprehensively characterize UGP2 in CRC through an integrated approach encompassing proteomic screening, bioinformatics analysis, and experimental validation. We identified UGP2 as a significantly downregulated tumor-suppressive factor in CRC. Specifically, UGP2 expression was significantly downregulated in CRC tissues compared with that in normal controls and exhibited strong correlations with aggressive clinicopathological features, including lymphatic invasion, perineural invasion, and colon polyp history, and patient age. It also demonstrated high diagnostic accuracy in CRC, with an area under the receiver operating characteristic curve (AUC) of 0.990. Reduced UGP2 levels were associated with poorer overall survival and disease-specific survival. Hypermethylation of the UGP2 promoter correlated with a favorable prognosis in patients with CRC. UGP2 expression positively correlated with immune cell infiltration within the tumor microenvironment. Functionally, UGP2 knockdown increased CRC cell proliferation and migration while suppressing apoptosis. Conversely, its overexpression yielded the opposite effects, confirming UGP2’s role in constraining malignant phenotypes. Collectively, these findings establish UGP2 as a key CRC tumor suppressor whose downregulation drives malignant progression and predicts adverse clinical outcomes, suggesting its potential as a dual-purpose diagnostic and prognostic biomarker. Full article

Background: This narrative review synthesizes evidence on AI for orthodontic malocclusion diagnosis across five imaging modalities and maps diagnostic metrics to validation tiers and regulatory readiness, with focused appraisal of Class III detection (2019–2025). Key algorithms, datasets, clinical validation, and ethical/regulatory considerations are synthesized. Methods: PubMed, Scopus, and Web of Science were searched for studies published January 2019–October 2025 using (“artificial intelligence”) AND (“malocclusion” OR “skeletal class”) AND “cephalometric.” Records were screened independently by two reviewers, with disagreements resolved by consensus. Eligible studies reported diagnostic performance (accuracy, area under the receiver operating characteristic curve (AUC), sensitivity/specificity) or landmark-localization error for AI-based malocclusion diagnosis. Data on dataset size and validation design were extracted; no formal quality appraisal or risk-of-bias assessments were undertaken, consistent with a narrative review. Results: Deep learning models show high diagnostic accuracy: cephalogram classifiers reach 90–96% for skeletal Class I/II/III; intraoral photograph models achieve 89–93% for Angle molar relationships; automated landmarkers localize ~75% of points within 2 mm. On 9870 multicenter cephalograms, landmarking achieved 0.94 ± 0.74 mm with ≈89% skeletal-class accuracy when landmarks fed a classifier. Conclusion: AI can reduce cephalometric tracing time by ~70–80% and provide consistent skeletal classification. Regulator-aligned benchmarks (multicenter external tests, subgroup reporting, explainability) and pragmatic open-data priorities are outlined, positioning AI as a dependable co-pilot once these gaps are closed. Full article

Introduction: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Left ventricular diastolic dysfunction (LVDD) represents an early sign of cardiac involvement in RA. Objectives: This study aimed to evaluate the incidence of LVDD and the association of the neutrophil-to-lymphocyte ratio (NLR) and circulating FGF21 levels with chosen LVDD echocardiographic parameters, as well as to assess their diagnostic utility for LVDD in a cohort of patients with RA. Patients and Methods: A total of 51 RA patients (46 females, 5 males; average age 48.8 ± 8.2 years; median disease duration of 12 years) were enrolled. NLR and serum FGF21 levels were analysed for association with echocardiographic parameters of LVDD using univariate regression models. The diagnostic performance of these markers was evaluated by receiver operating characteristic (ROC) analysis. Results: LVDD was diagnosed in 10 patients (19.6%). The NLR was associated negatively with E velocity (β = −4.99, p = 0.02), E/A ratio (β = −0.16, p = 0.004), lateral and medial e′ velocities (β = −1.05, p = 0.038 and β = −0.97, p = 0.013, respectively), and positively with left atrial diameter (β = 2.08, p = 0.006). Serum FGF21 levels were negatively associated with the E/A ratio (β = −0.0005, p = 0.009) and lateral e′ velocity (β = −0.003, p = 0.04). ROC analysis demonstrated a greater diagnostic value for NLR (Youden index 0.30, cut-off point 2.26, sensitivity 50%, specificity 80%, and area under curve [AUC] 0.58) compared to FGF21 (Youden index 0.30, cut-off value 852.85 pg/mL, 100% specificity, 30% sensitivity, and AUC 0.48). Conclusions: NLR and FGF21 are associated with the echocardiographic parameters of the left ventricular diastolic dysfunction prior to the fulfilment of LVDD diagnostic criteria. RA patients with elevated NLR and FGF21 serum levels should be considered for LVDD screening. Full article

Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal stem cell disorders in which disrupted post-transcriptional regulation contributes to aberrant hematopoiesis and leukemic transformation. The miRNA biogenesis machinery, which comprises Drosha, DGCR8, Dicer, TARBP2, and AGO1, ensures the precise maturation of miRNAs that control lineage commitment and proliferation. However, the extent to which alterations in this pathway reshape hematopoietic gene networks during myeloid disease evolution remains largely unexplored. Methods: Bone marrow samples from newly diagnosed, untreated MDS and AML patients and matched healthy controls were analyzed for the expression of five key miRNA biogenesis genes using quantitative real-time PCR. Statistical comparisons, correlation matrices, and ROC analyses were performed to characterize gene-expression differences. These results were integrated with multigene logistic modeling, decision-curve analysis, and exploratory random forest/SHAP approaches to evaluate molecular interactions and diagnostic relevance. Results: DROSHA, DICER1, and TARBP2 were significantly downregulated in both MDS and AML, suggesting impaired miRNA maturation and a loss of global post-transcriptional control. DGCR8 expression increased across higher-risk MDS groups, suggesting compensatory activation of the Microprocessor complex, whereas AGO1 levels remained relatively stable, consistent with partial maintenance of RISC function. Correlation analyses revealed a co-regulated DROSHA–TARBP2–AGO1 module. ROC, logistic, and machine learning models identified DGCR8 and DICER1 as the strongest diagnostic discriminators. The integrated five-gene signature achieved high discriminative performance (AUC ≈ 0.98) and showed promise but remains preliminary potential for clinical application. Conclusions: Our findings suggest that defects in miRNA biogenesis disrupt hematopoietic homeostasis, reflecting common mechanisms in MDS and AML. The dysregulation of DICER1, DGCR8, and TARBP2 offers insights into miRNA-driven leukemogenesis and may pave the way for miRNA-based diagnostic and therapeutic strategies, pending validation in larger cohorts. Although transcript-level data are provided, future studies should include functional validation to determine the impact on downstream miRNA processing and hematopoietic pathways. Full article

Background/Objectives: The cranial base, especially the posterior cranial fossa, has openings with population-specific morphometry. This study aimed to assess the morphometric characteristics of the major posterior cranial fossa openings (foramen magnum, jugular foramen, internal acoustic opening) in the Turkish population and evaluate their utility for sex estimation. It also aimed to provide population-specific reference values for forensic anthropology and cranial base surgery. Methods: This prospective study included 304 adult skulls (151 female, 153 male) obtained from forensic autopsy cases, all of which had preserved anatomical integrity. Structures in the posterior cranial fossa were exposed following a standardized dissection protocol. A total of 18 morphometric parameters were measured using a digital caliper. Inter-sex comparisons were performed, and the diagnostic performance of the parameters for sex differentiation was evaluated using receiver operating characteristic (ROC) curve analysis. Results: All morphometric parameters and inter-foraminal distances were significantly larger in male individuals compared to females (p < 0.001). Similarly, ellipticity indices were higher in males than in females (all p < 0.001). ROC analysis revealed that right internal acoustic opening transverse diameter (RIAO-T), left and right jugular foramen transverse diameters (RJF-T and LJF-T) parameters possess exceptionally high discriminatory power, yielding accuracies greater than 99%. Conclusions: Components of the posterior cranial fossa exhibit marked sexual dimorphism in the Turkish population. These morphometric data provide valuable anatomical references for forensic identification, aid in preserving neurovascular structures, and support safe surgical planning in cranial base procedures. Full article

Social media is an essential part of people’s lives worldwide. This study aimed to analyze the predictive capacity of social media addiction on academic engagement among students enrolled in the Faculty of Health Sciences at the National University of Chimborazo during the first academic period of 2023. The Social Media Addiction Questionnaire (ARS) and the Utrecht Work Engagement Scale (UWES-S-17) were applied to 1200 participants during an analytical study. According to the simple linear regression model, 11.2% of the variance in academic engagement levels was explained by social media addiction, with statistical significance (p < 0.05). The multiple linear regression model was significant, although it showed a low capacity to explain and predict the level of academic engagement, considering the dimensions of the level of addiction to social media (obsession, lack of control, and excessive use). The ROC curve parameters showed statistical significance, showing a moderate ability to discriminate insufficient academic commitment. The results serve as a basis for future studies and as a diagnostic basis for establishing policies and strategies in the institution where the research was conducted to increase academic engagement and reduce social media addiction. Full article

The rise in thermal runaway events within electric vehicle (EV) battery systems requires anticipatory models to predict critical safety failures during operation. This investigation develops a multi-physics digital twin framework that links electrochemical, thermal, and structural domains to replicate the internal dynamics of lithium-ion packs in both normal and faulted modes. Coupled simulations distributed among MATLAB 2024a, Python 3.12-powered three-dimensional visualizers, and COMSOL 6.3-style multi-domain solvers supply refined spatial resolution of temperature, stress, and ion concentration profiles. While the digital twin architecture is designed to accommodate different battery chemistries and pack configurations, the numerical results reported in this study correspond specifically to a lithium NMC-based 4S3P cylindrical cell module. Quantitative benchmarks show that the digital twin identifies incipient thermal deviation with 97.4% classification accuracy (area under the curve, AUC = 0.98), anticipates failure onset within a temporal margin of ±6 s, and depicts spatial heat propagation through three-dimensional isothermal surface sweeps surpassing 120 °C. Mechanical models predict casing strain concentrations of 142 MPa, approaching polymer yield strength under stress load perturbations. A unified operator dashboard delivers diagnostic and prognostic feedback with feedback intervals under 1 s, state-of-health (SoH) variance quantified by a root-mean-square error of 0.027, and mission-critical alerts transmitting with a mean latency of 276.4 ms. Together, these results position digital twins as both diagnostic archives and predictive safety envelopes in the evolution of next-generation EV architectures. Full article

Background/Objectives: This study investigated the influence of long-term medications and patient conditions on pulmonary arterial enhancement and image quality in computed tomography pulmonary angiography (CTPA). A cohort matched for age was divided into two main groups: a medication group (Captopril, Albuterol, and control) and a condition group (obesity, COPD, and control). Methods: Temporal enhancement (Hounsfield Units, HU), area under the curve (AUC), and washout rates were analyzed alongside image quality metrics (signal-to-noise ratio, SNR; contrast-to-noise ratio, CNR). Results: The results demonstrated significant intergroup differences. In the medication group, Albuterol was associated with significantly higher peak enhancement (368.9 ± 16.3 HU) compared to control (327.1 ± 13.8 HU; p = 0.001), while Captopril showed significantly lower baseline HU (153.5 ± 7.3 vs. 185.3 ± 9.3; p < 0.001) and reduced total AUC. In the condition group, both obesity and COPD exhibited significantly lower peak HU values, slower washout rates, and reduced total AUC compared to controls (p < 0.0001). Consequently, SNR and CNR were significantly lower in the obesity and COPD groups (p = 0.001). Linear mixed-effects models confirmed significant group × time interactions for both medication and condition groups after adjustment for confounders. Furthermore, pulmonary arterial enhancement (HU) showed a very strong positive correlation with both SNR (R² = 0.9956) and CNR (R² = 0.9848, p < 0.001). Conclusions: The findings indicate that patient-specific factors significantly impact CTPA image quality. Albuterol was associated with peak vascular opacification, whereas conditions like obesity and COPD were consistently associated with reduced enhancement and inferior image quality. The strong correlation between HU and objective image quality metrics underscores vascular enhancement as a key determinant of diagnostic CTPA quality. Full article

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders characterized by alternating episodes of flares and clinical remission, often leading to intestinal fibrosis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate, among other processes, cell proliferation, inflammation, and fibrosis, all of which are crucial in IBD pathogenesis and healing. Given their role in these mechanisms, miR-103a, miR-145, and miR-191 were selected as promising candidates for IBD diagnostic biomarkers. Serum expressions of miR-103a, miR-145, and miR-191 were analyzed in 47 IBD patients and 30 healthy controls. Expressions were quantified using qPCR and normalized to miR-375-3p. All analyzed miRNAs were significantly upregulated in both UC and CD compared to healthy controls. ROC curve analysis revealed miR-103a as the most promising biomarker, with AUC = 0.893 in UC and AUC = 0.905 in CD. Moreover, miR-103a demonstrated excellent sensitivity and specificity, 89.3% and 80% in UC, and 84.2% and 83.3% in CD, respectively. miR-191 also effectively differentiated UC patients from healthy individuals (AUC = 0.848; sensitivity 89.3%; specificity 80%). Comparable results of diagnostic indicators were obtained in the CD group, however, with lower sensitivity (73.7%). miR-145 showed good ability in differentiating both UC and CD patients with high sensitivity (85.7%; 84.2%) and satisfactory specificity (66.7%; 63.3%). The obtained results indicate the promising diagnostic potential of circulating miR-103a, miR-145, and miR-191 for both UC and CD. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) often presents at an advanced stage; therefore, the early detection of precursor lesions is crucial. However, the risk assessment of precursor lesions such as oral epithelial dysplasia (OED) remains challenging because of the subjectivity of histopathological grading. We aimed to identify molecular markers that enhance the diagnostic accuracy and prognostic stratification of OSCC and explore the differences in the molecular characterization of OED and OSCC using a few selected markers. Methods: A two-step diagnostic workflow was applied: (1) FISH evaluation of EGFR amplification and CDKN2A deletion to distinguish OED from OSCC and identify EGFR-dependent tumors, and (2) HRAS immunohistochemistry performed exclusively in EGFR-negative OSCCs to stratify EGFR-independent cases. Fluorescence in situ hybridization (FISH) was used to assess seven EGFR/cell cycle-related genes (CCND1, CDKN2A, EGFR, PIK3CA, PTEN, TP53, and 1p36 locus) in 117 formalin-fixed paraffin-embedded samples (66 OED and 51 OSCC) and 10 normal mucosa samples. HRAS expression was evaluated using immunohistochemistry (IHC) in 36 EGFR amplification-negative OSCCs samples. Results:EGFR amplification was frequent in OSCC, whereas CDKN2A deletion was common in OED. The EGFR-amplified/ CDKN2A-intact profile showed high specificity for OSCC and improved diagnostic performance (area under the curve = 0.77) when combined with the Ki-67 labeling index. It also predicted poor disease-free survival (hazard ratio [HR] = 5.08, p = 0.016) and overall survival (HR = 6.10, p = 0.047). Among EGFR-negative OSCCs, HRAS overexpression was associated with advanced-stage disease and a poor prognosis (HR = 6.15, p = 0.043). Conclusions:EGFR amplification was frequent in OSCC, and CDKN2A deletion was prevalent in OED, supporting their use as molecular markers for differential diagnoses. FISH for EGFR/CDKN2A and HRAS IHC can stratify OSCC by diagnosis and prognosis, enabling practical molecular subclassification, including EGFR-negative cases. Full article

During fetal life, the hepatic artery (HA) is responsible for a small contribution to the total hepatic blood inflow; however, it plays a key role in maintaining liver perfusion and reflects fetal hemodynamic adaptation. With advances in ultrasonography, HA Doppler assessment has emerged as a potential tool for evaluating fetal well-being. This review aims to synthesize current knowledge on the embryology, anatomy, physiology, and Doppler assessment of the fetal hepatic artery, highlighting its diagnostic and clinical significance. A prenatal hepatic arterial buffer response (HABR), analogous to that in postnatal life, allows for compensatory vasodilatation when umbilical or portal venous inflow decreases. Doppler studies demonstrate that a reduced pulsatility index (PI) and resistance index (RI) and an increased peak systolic velocity (PSV) correspond to enhanced arterial flow and decreased vascular resistance. These patterns have been observed in fetal growth restriction (FGR) and certain chromosomal abnormalities. Fetal hepatic artery Doppler assessment contributes to the understanding of fetal adaptation to hypoxia and has a promising role in fetal well-being evaluation. As of now, there are no established reference curves, and it has not yet been incorporated into routine obstetric screening; future research should focus on standardizing measurement techniques and validating its prognostic value. Full article

Background/Objectives: Cervical cancer remains a significant global health burden, underscoring the imperative for refined diagnostic and prognostic methodologies. This study aimed to evaluate the potential of extracellular vesicles (EVs) as non-invasive biomarkers for cervical cancer, focusing on diagnosis and prognosis. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines to assess the diagnostic and prognostic accuracy of EV-based biomarkers. We searched PubMed, EMBASE, and Web of Science for relevant studies. Twelve articles met the inclusion criteria: eight related to diagnostic accuracy, three to prognosis, and one to both outcomes. Six studies met the criteria for meta-analysis. We used a random-effects model to synthesise diagnostic data, while prognostic data were synthesised narratively. Results: The meta-analysis yielded a pooled area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.80–0.92) for EVs in the diagnosis of cervical cancer, indicating high accuracy. The evaluated diagnostic biomarkers were primarily non-coding RNAs. For prognosis, data heterogeneity precluded quantitative synthesis; however, individual studies identified diverse EV-associated molecules correlated with recurrence and survival. GRADE assessment indicated a high risk of bias and heterogeneity across studies. Conclusions: Extracellular vesicles demonstrate robust promise as diagnostic biomarkers for cervical cancer; however, their prognostic utility remains inconclusive due to methodological and clinical heterogeneity. Future research must prioritise the standardisation of isolation protocols and the execution of large-scale, prospective studies to validate EV biomarkers for clinical application. Systematic Review Registration: PROSPERO, identifier: CRD420251014411. Full article