Colorectal cancer remains a major health burden, and its early detection is crucial for effective treatment. This study investigates the use of a handheld Raman spectrometer in combination with machine learning to classify colorectal tissue samples collected during colonoscopy. A dataset of 330 spectra from 155 participants was preprocessed using a standardized pipeline, and multiple classification models were trained to distinguish between healthy and pathological tissue. Due to the strong class imbalance and limited data size, a custom grid search approach was implemented to optimize both model hyperparameters and preprocessing parameters. Unlike standard GridSearchCV, our method prioritized balanced accuracy on the test set to reduce bias toward the dominant class. Among the tested classifiers, the Decision Tree (DT) and Support Vector Classifier (SVC) achieved the highest balanced accuracy (71.77% for DT and 70.77% for SVC), outperforming models trained using traditional methods. These results demonstrate the potential of Raman spectroscopy as a rapid, non-destructive screening tool and highlight the importance of tailored model selection strategies in biomedical applications. While this study is based on a limited dataset, it serves as a promising step toward more robust classification models and supports the feasibility of this approach for future clinical validation.
- Keywords
- Balanced accuracy, Colorectal cancer, Machine learning, Preprocessing pipeline, Raman spectroscopy, Spectral classification,
- MeSH
- Colorectal Neoplasms * diagnosis diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Spectrum Analysis, Raman * methods MeSH
- Decision Trees MeSH
- Machine Learning * MeSH
- Support Vector Machine MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Cercarial dermatitis (CD; swimmer's itch) is a re-emerging skin disease caused by avian schistosomes, including Trichobilharzia franki. Here, we present morphological, genetic, and experimental evidence confirming the involvement of T. franki in recent CD outbreaks across Czechia. Ocellate furcocercariae were collected from Radix auricularia at four sites and identified as T. franki through ITS1 sequencing. Despite minor morphological differences from previously reported specimens, all isolates belonged to the genetically uniform T. franki "auricularia" clade. Experimental infection of mice with T. franki resulted in a ∼ 60 % penetration rate, accompanied by early-onset scratching and transient weight loss. Gross pathology demonstrated hemorrhages on lung surfaces and splenic atrophy at 2 days post-infection (dpi), along with a prominent enlargement of parotid lymph nodes at both 2 and 7 dpi. Histological examination of the skin revealed viable schistosomula, moderate leukocyte infiltration, epidermal hyperplasia, and the formation of hyperkeratotic crusts at 2 dpi. By 7 dpi, parasites were no longer detectable, but epidermal pathology persisted. In the lungs, eosinophil-rich foci and multifocal hemorrhages were observed at 2 dpi, transitioning to neutrophil-dominated lesions at 7 dpi, despite the absence of detectable schistosomula. Splenocytes from infected mice responded to homologous and heterologous cercarial antigens by producing IFN gamma, IL-4, and IL-10, indicating a mixed Th1/Th2/Treg profile and notable species cross-reactivity. However, parasite-specific IgG remained undetectable at 7 dpi. These findings confirm T. franki as the causative agent of CD outbreaks and underscore its capacity to induce localized and systemic pathology and immune response, cross-reacting with other schistosomes.
- Keywords
- Avian schistosomes, Cercarial dermatitis, Lungs, Skin, Trichobilharzia franki,
- Publication type
- Journal Article MeSH
Mature mammalian oocytes arrest meiosis in metaphase II (MII). If the oocyte is not fertilized, it can spontaneously break the MII arrest. Spontaneous activation and postovulatory aging hinder precisely timed and regulated embryonic development. To elucidate the role of Src family protein tyrosine kinases (SFKs) in porcine oocyte MII arrest, activation, and aging, we used a specific SFK inhibitor and immunolocalization. The 24h-prolonged oocyte culture in the presence of SFK inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) increased (P < 0.05) the proportion of spontaneously activated porcine oocytes compared to controls. Further culture with PP2 inhibitor led to an increase (P < 0.05) in the parthenogenetic embryos and a decrease (P < 0.05) in lytic oocytes. SFK inhibition did not affect (P > 0.05) the proportion of ionophore A23187-activated oocytes. SFKs were localized in the perichromosomal region, in the pronuclei, in the cytoplasm, and on the plasma membrane of oocytes and parthenogenetic embryos after 24, 48, and 72 h of prolonged in vitro culture. The greatest SFKs fluorescence was detected after a 24h-prolonged culture on the plasma membrane of MII oocytes. In embryos and fragmented oocytes, intense fluorescence was detected in the cleavage furrow region and on the membrane of apoptotic vesicles, respectively. Our results reveal the involvement of SFKs in MII arrest maintenance, though they don't appear to modulate the early processes of ionophore-stimulated parthenogenetic activation. Changes in the distribution of SFKs during prolonged culture suggest their role in signaling cascades associated with actin filament cytoskeleton organization.
- Keywords
- Meiotic arrest, Pig, Postovulatory aging, Tyrosine kinases,
- MeSH
- Meiosis * physiology MeSH
- Metaphase * physiology MeSH
- Oocytes * physiology enzymology drug effects MeSH
- Parthenogenesis MeSH
- Swine physiology MeSH
- Pyrimidines pharmacology MeSH
- src-Family Kinases * metabolism antagonists & inhibitors physiology MeSH
- Cellular Senescence physiology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Pyrimidines MeSH
- src-Family Kinases * MeSH
Inflammatory changes in perivascular adipose tissue are associated with atherosclerotic lesions in the adjacent artery and can also be used as a marker in patient workup. While adipocyte size is known to be closely related to adipose tissue dysfunction and inflammation, it has not been widely studied in perivascular adipose tissue obtained from healthy human subjects without clinical atherosclerosis. In this cross-sectional study, we addressed this issue by measuring adipocyte size and defining its relationship to cardiovascular risk factors in a healthy cohort of living kidney donors. The presence of cardiovascular risk factors was established by a standardized questionnaire, clinical measurements and body composition analyses. Adipocyte size was measured in the perivascular depot. The proportions of various macrophage subtypes were determined by flow cytometry. To confirm the results, the proportion of CD68 + macrophages was additionally assessed by immunohistochemistry. A correlation and principal component analyses were performed to explore associations. Adipocyte size in perivascular adipose tissue correlated with markers of lipid metabolism, inflammation, and glucose metabolism. Further, the positive correlation with the pro-inflammatory subpopulation of macrophages suggests a strong local effect of perivascular adipose tissue. Perivascular adipocyte size was associated with cardiovascular risk factors and markers of inflammation in a healthy cohort of living kidney donors. This further supports the local role of adipose tissue dysfunction and inflammation in early atherosclerosis development and detection.
- Keywords
- Perivascular adipose tissue, adipocyte size, cardiovascular risk factors, inflammation, macrophages,
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipids * MeSH
- Macrophages metabolism MeSH
- Lipid Metabolism MeSH
- Cross-Sectional Studies MeSH
- Adipose Tissue metabolism MeSH
- Adipocytes * metabolism cytology MeSH
- Cell Size MeSH
- Inflammation * metabolism pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lipids * MeSH
Epithelial-mesenchymal transition (EMT) generates heterogeneity in circulating tumor cells (CTCs), affecting their biological properties and hampering their detection. This limits our understanding of the mechanisms underlying hematogenous dissemination, especially in early breast cancer (BC), where CTCs are rare. Here, we aimed to detect CTCs with different EMT statuses from BC patients. CTCs in blood samples from 107 BC patients were evaluated using immunomagnetic depletion and multi-marker immunofluorescence (EpCAM, E-cadherin, MCAM, cell surface vimentin, CD31, CD45), followed by single-cell transcriptomics. CTCs were detected in 51.9% of therapy-naïve early BC cases, with 3.8% showing only epithelial CTCs (eCTCs), 5.8% epithelial-mesenchymal (emCTCs), 26.0% mesenchymal (mCTCs), and 16.3% mixed phenotypes. CTC heterogeneity was more frequent in triple-negative (86%) than in luminal BC (17%, P = 0.008). Lymph node involvement strongly predicted dissemination of all CTC phenotypes, while tumor size correlated with mCTC abundance. Single-cell RNA sequencing revealed downregulation of ribosomal genes and translation inhibition in CTCs with mesenchymal features, linked to mTORC1 signaling. Findings were also validated in an independent dataset, highlighting vulnerabilities in CTCs during dissemination.
- Keywords
- RNA‐Seq, breast cancer, circulating tumor cells, epithelial–mesenchymal transition, metastasis, single cell transcriptomics,
- Publication type
- Journal Article MeSH
OBJECTIVES: The incidence of oral and oropharyngeal cancer is continually rising and affects increasingly younger patients. Consequently, many studies focus on early diagnosis using appropriate biomarkers. Neopterin and interleukin-6 (IL-6) are promising predictive and prognostic markers of immune response activation, both systemic and local, due to the anatomical proximity of malignancies to the salivary glands. MATERIAL AND METHODS: We collected oral fluid samples from 50 patients before and after the surgical resection of squamous cell carcinoma of the oral cavity and oropharynx. Additionally, blood samples were withdrawn from 20 of these patients and levels of neopterin and IL-6 were estimated using ELISA commercial kits. All gathered data were subsequently statistically analyzed for evaluation and compared to values from a control group of healthy individuals. RESULTS: In patients with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), there was a significant decrease in neopterin and IL-6 levels in saliva following the surgical removal of the malignancy. These postoperative levels approached those of the control group. There was no significant decrease in neopterin and IL-6 levels in plasma. CONCLUSION: Detection of neopterin and IL-6 in saliva is a reliable diagnostic method for early detection of OSCC and its recurrence, as well as for monitoring therapeutic success, compared to plasma. Neopterin and IL-6 appear to be promising prognostic and predictive markers of the disease.
- Keywords
- interleukin‐6, neopterin, squamous cell carcinoma of head and neck,
- MeSH
- Adult MeSH
- Interleukin-6 * blood analysis metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * blood analysis metabolism MeSH
- Oropharyngeal Neoplasms * blood metabolism surgery diagnosis MeSH
- Mouth Neoplasms * blood metabolism surgery diagnosis MeSH
- Neopterin * blood analysis metabolism MeSH
- Prospective Studies MeSH
- Aged MeSH
- Saliva * chemistry metabolism MeSH
- Carcinoma, Squamous Cell * blood surgery metabolism diagnosis MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- IL6 protein, human MeSH Browser
- Interleukin-6 * MeSH
- Biomarkers, Tumor * MeSH
- Neopterin * MeSH
OBJECTIVE: We previously proposed two cell-free (cf) DNA-based scores (genome-wide Z-score and nucleosome score) as candidate non-invasive biomarkers to further improve the presurgical diagnosis of ovarian malignancy. We aimed to investigate the added value of these cfDNA-based scores in combination with the clinical and ultrasound predictors of the Assessment of Different NEoplasias in the adneXa (ADNEX) model to estimate the risk of ovarian malignancy. METHODS: In this prospective cohort study, 526 patients with an adnexal mass scheduled for surgery were recruited consecutively in three oncology referral centers. All patients underwent a transvaginal ultrasound examination, and adnexal masses were described according to the International Ovarian Tumor Analysis terms and definitions. cfDNA was extracted from preoperative plasma samples and genome-wide Z-scores and nucleosome scores were calculated. Logistic regression models were fitted for ADNEX predictors alone and after inclusion of the cfDNA-based scores. We report likelihood ratios, area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity and net benefit for thresholds between 5% and 40%, to assess the diagnostic performance of the models in discriminating between benign and malignant ovarian masses. RESULTS: The study included 272 benign, 86 borderline, 36 Stage-I invasive, 113 Stage-II-IV invasive, and 19 secondary metastatic tumors. The likelihood ratios for adding the cfDNA-based scores to the ADNEX model were statistically significant (P < 0.001 for ADNEX without CA 125; P = 0.001 for ADNEX including CA 125). The accompanying increases in AUC were 0.013 when the cfDNA biomarkers were added to the ADNEX model without CA 125, and 0.003 when added to the ADNEX model including CA 125. Net benefit, sensitivity and specificity were similar for all models. The increase in net benefit at the recommended 10% threshold estimated risk of malignancy when adding the cfDNA-based scores was 0.0017 and 0.0020, respectively, for the ADNEX model without CA 125 and the ADNEX model with CA 125. According to these results, adding cfDNA markers would require at least 453 patients per additional true-positive test result at the 10% risk threshold. CONCLUSION: Although statistically significant, cfDNA-based biomarker scores have limited clinical utility in addition to established clinical and ultrasound-based ADNEX predictors for discriminating between benign and malignant ovarian masses. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.
- Keywords
- ADNEX, circulating tumor DNA, diagnosis, early detection, fragmentomics, liquid biopsies, nucleosome, ovarian cancer,
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor blood MeSH
- Ovarian Neoplasms * diagnosis diagnostic imaging blood genetics pathology MeSH
- Prospective Studies MeSH
- ROC Curve MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Ultrasonography methods MeSH
- Cell-Free Nucleic Acids * blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Names of Substances
- Biomarkers, Tumor MeSH
- Cell-Free Nucleic Acids * MeSH
OBJECTIVES: The detection and classification of oral mucosal lesions is a challenging task due to high heterogeneity and overlap in clinical appearance. Nevertheless, differentiating benign from potentially malignant lesions is essential for appropriate management. This study evaluated whether a deep learning model trained to discriminate 11 classes of oral mucosal lesions could exceed the performance of general dentists. METHODS: 4079 intraoral photographs of benign, potentially malignant and malignant oral lesions were labeled using bounding boxes and classified into 11 classes. The data were split 80:20 for training (n = 3031) and validation (n = 766), keeping an independent test set (n = 282). The YOLOv8 computer vision model was implemented for image classification and object detection. Model performance was evaluated on the test set which was also assessed by six general dentists and three specialists in oral surgery. Evaluation metrics included sensitivity, specificity, F1-score, precision, area under the receiver operating characteristic curve (AUROC), and average precision (AP) at multiple thresholds of intersection over union. RESULTS: In terms of classification, the highest F1-score (0.80) and AUROC (0.96) were observed for human papillomavirus (HPV)-related lesions, whereas the lowest F1-score (0.43) and AUROC (0.78) were obtained for keratosis. In terms of object detection, the best results were achieved for HPV-related lesions (AP25 = 0.82) and proliferative verrucous leukoplakia (AP25 = 0.80; AP50 = 0.76), while the lowest values were noted for leukoplakia (AP25 = 0.36; AP50 = 0.20). Overall, the model performed comparable to specialists (p = 0.93) and significantly better than general dentists (p < 0.01). CONCLUSION: The developed model performed as well as specialists in oral surgery, highlighting its potential as a valuable tool for oral lesion assessment. CLINICAL SIGNIFICANCE: By providing performance comparable to oral surgeons and superior to general dentists, the developed multi-class model could support the clinical evaluation of oral lesions, potentially enabling earlier diagnosis of potentially malignant disorders, enhancing patient management and improving patient prognosis.
- Keywords
- Artificial intelligence, Computer-assisted diagnosis, Deep learning, Early detection of cancer, Mouth neoplasms, Oral potentially malignant disorders (OPMDs), Squamous cell carcinoma,
- MeSH
- Deep Learning MeSH
- Humans MeSH
- Mouth Neoplasms * classification diagnosis pathology diagnostic imaging MeSH
- Mouth Diseases * classification diagnosis MeSH
- Leukoplakia, Oral MeSH
- ROC Curve MeSH
- Sensitivity and Specificity MeSH
- Machine Learning * MeSH
- Mouth Mucosa * pathology diagnostic imaging MeSH
- Dentists * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
PURPOSE: Patients with PTEN Hamartoma Tumor Syndrome (PHTS) have high hereditary cancer risks for breast, endometrial, and thyroid cancer. Patients develop multiple primary cancers, but these risks remain uncertain. We aimed to provide the second primary cancer risk. METHODS: This European cohort study assessed second primary cancer risks with Kaplan-Meier analyses using data from medical files, registries and/or patient questionnaires. RESULTS: Overall, 279 adult PHTS patients with (a history of) cancer were included (80% female). Among females, 106 (54%) developed a PHTS-related second primary cancer after a PHTS-related first primary cancer, whereas 10 (29%) males developed a PHTS-related second primary cancer after a PHTS-related first primary cancer. The 5- and 10-year PHTS-related second primary cancer risks were 24.5% (95% CI = 18.1-32.5) and 45.7% (95% CI = 36.9-55.4) in females and 14.5% (95% CI = 5.7-34.1) and 19.8% (95% CI = 8.6-41.9) in males, respectively. Furthermore, 5- and 10-year risks for a second primary breast cancer after a first primary breast cancer were 23.3% (95% CI = 14.9-35.2) and 45.6% (95% CI = 33.0-60.2) in females, respectively. CONCLUSION: This study demonstrated that PHTS patients have high second primary cancer risks, which is driven by breast cancer in females. Hence, identifying patients with PHTS before or at first primary cancer diagnosis is essential to enable potential early detection or prevention of a second primary cancer through surveillance or risk-reducing surgery.
- Keywords
- PTEN, PTEN Hamartoma Tumor Syndrome, hereditary cancer, second primary cancer risk,
- MeSH
- Adult MeSH
- PTEN Phosphohydrolase * genetics MeSH
- Genetic Predisposition to Disease MeSH
- Kaplan-Meier Estimate MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Risk Factors MeSH
- Neoplasms, Second Primary * genetics epidemiology pathology etiology MeSH
- Aged MeSH
- Hamartoma Syndrome, Multiple * genetics complications epidemiology pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- PTEN Phosphohydrolase * MeSH
- PTEN protein, human MeSH Browser
BACKGROUND: Axial involvement in psoriatic arthritis (axPsA) is associated with more severe disease and increased pain, yet no consensus definition of axPsA exists. This study aims to describe the occurrence and characteristics of MRI and radiographic sacroiliac joint (SIJ) involvement in a European PsA cohort. METHODS: Patients with a clinical diagnosis of PsA or of axial spondyloarthritis with psoriasis and available routine care SIJ MRIs were included from five European registries in the EuroSpA collaboration. SIJ MRIs and radiographs were centrally assessed for inflammatory and structural lesions, differential diagnoses, and globally evaluated for SpA-indicative findings. RESULTS: Among 581 PsA patients (mean age 45 years, 47% male), 31% exhibited SpA-indicative SIJ-MRI findings (MRI-axPsA). In MRI-axPsA patients, the most common lesions were bone marrow edema (BME) (69%), erosions (68%), and fat lesions (58%), generally present bilaterally. BME ≥ 1 cm, inflammation in an erosion cavity, capsulitis, fat lesions ≥ 1 cm, backfill, and ankylosis were observed almost exclusively in MRI-AxPsA patients. Differential diagnoses included osteitis condensans ilii (8%), probable strain-related BME (11%) and degenerative disease (16%). Among 259 patients with radiographs, 29% met the radiographic mNY criteria for ankylosing spondylitis and 38% had SpA-indicative MRI findings. Male sex, HLA-B27 positivity, elevated CRP and history of inflammatory back pain (but not current back pain) were independently associated with MRI-detected axial involvement. CONCLUSION: In this large European cohort, one-third of routine care PsA patients had axial involvement, based on global SIJ MRI assessment. The study supports incorporating MRI into the future definition of axPsA to enable early identification.
- Keywords
- Axial psoriatic arthritis, Axial spondyloarthritis, Imaging, Magnetic resonance imaging,
- MeSH
- Axial Spondyloarthritis diagnostic imaging MeSH
- Adult MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Arthritis, Psoriatic * diagnostic imaging epidemiology pathology MeSH
- Radiography MeSH
- Registries MeSH
- Sacroiliac Joint * diagnostic imaging pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe epidemiology MeSH