Search Results (411)

Background/Objective: The incidence and clinical utility of pleural tissue debris, occasionally encountered in drainage systems, have not been systematically evaluated. We aimed to determine the frequency of tissue debris detection in patients undergoing drainage for pleural effusion, and its utility for the differential diagnosis of exudative effusion and pathological diagnosis of malignant pleural effusion (MPE). Methods: This retrospective proof-of-concept analysis included 325 consecutive patients who underwent percutaneous effusion drainage. The incidence, histopathological findings, and potential predictors of tissue debris were evaluated. For patients with MPE, the adequacy of tissue for immunohistochemistry and molecular testing was evaluated, and the diagnostic sensitivity of tissue debris for MPE was calculated and compared with that of cytology with cell blocks. Results: Tissue debris was detected in 151 patients (46.5%), more frequently in exudates than in transudates (51.7% vs. 23.3%, p < 0.001), and most frequently in patients with MPE (64.6%, p < 0.001). MPE was the only independent predictor of tissue debris detection (adjusted odds ratio 5.74, 95% CI 2.25–9.31). The pathological findings of the debris were classified into metastatic carcinoma/lymphoma (49.0%), acute/chronic inflammation (30.4%), fibrinoid material with inflammation (17.2%), mesothelial reaction (2.6%), and acute suppurative pleuritis/abscess (0.7%). Among the 74 cases with MPE diagnosed using tissue debris, immunohistochemistry and molecular testing were feasible in 85.1% and 69.0% cases, respectively. Diagnostic sensitivity of tissue debris for MPE was significantly higher than that of cytology (77.9% vs. 66.3%; p = 0.035) with a combined sensitivity of 84.2%. Conclusions: Systematic collection of tissue debris, a previously underrecognized clinical specimen obtained during effusion drainage, may be highly valuable for the diagnosis of MPE and adequate for immunohistochemistry and molecular testing, reducing the reliance on invasive biopsy and supporting precise oncological decisions. Full article

Background/Objectives: Preoperative differentiation between benign thyroid nodules and papillary thyroid carcinoma (PTC) remains clinically challenging, particularly after indeterminate cytology. This study evaluated routinely available complete blood count (CBC)-derived indices, erythrocyte parameters, thyroid function tests, and arithmetic thyroid hormone ratios. Methods: This retrospective, single-center case–control study reviewed thyroidectomy records from July 2020 to November 2024. Histopathology was re-adjudicated from the source reports; 158 adults with clearly benign nodules (n = 93) or PTC (n = 65) formed the final analytic cohort. Missing laboratory values were handled by variable-specific complete-case analysis. Benjamini–Hochberg false-discovery-rate (FDR) correction and an exploratory multivariable logistic model were applied. Results: Preoperative TSH and the conventional platelet-to-lymphocyte ratio (PLR) were higher in PTC (p = 0.002, q = 0.013; and p = 0.004, q = 0.023), whereas the fT4/TSH and fT3/TSH ratios were lower (both q = 0.013). The fT3 difference was nominal (p = 0.018, q = 0.076), and MCV was not significant (p = 0.076). In 126 complete cases, each doubling of TSH was associated with higher odds of PTC (adjusted odds ratio [aOR] 1.51, 95% CI 1.08–2.13), whereas higher fT3 was associated with lower odds (aOR 0.41, 95% CI 0.19–0.87). Conclusions: TSH and fT3 were independently associated with PTC in the exploratory model, while the PLR and TSH-normalized hormone ratios differed between groups but lacked validated diagnostic performance. These measures should not be used in isolation; prospective multicenter studies are needed to determine whether they add clinically meaningful information to ultrasonographic, cytological, and molecular assessments. Full article

Purpose: To characterize the messenger RNA (mRNA) and microRNA (miRNA) expression profiles of the normal human cornea and conjunctiva using impression cytology (IC) samples and to investigate their molecular characteristics and regulatory networks. Methods: Corneal and conjunctival IC samples were collected from healthy subjects. Whole-transcriptome and miRNA sequencing were performed, followed by differential expression and bioinformatics analyses. Regulatory networks, protein interaction networks, and functional enrichment analyses were constructed. Selected genes and miRNAs were validated by RT-qPCR. Results: A total of 1676 differentially expressed genes and 175 differentially expressed miRNAs were identified between the cornea and conjunctiva. Functional analyses revealed that genes showing higher expression in the cornea were mainly associated with epithelial structure, barrier function, and antiviral immune responses. In contrast, genes showing higher expression in the conjunctiva were primarily involved in immune regulation, secretion, metabolic detoxification, and tissue remodeling. PPI network analysis showed that hub genes in the cornea were predominantly interferon-stimulated genes related to antiviral responses, while those in the conjunctiva were mainly involved in cell cycle regulation and metabolic detoxification. GO and KEGG analyses further supported these functional distinctions. RT-qPCR validation generally supported the expression patterns identified by RNA sequencing. Conclusions: Our findings reveal that the cornea is characterized by gene expression programs supporting epithelial homeostasis, barrier function, and antiviral immunity, whereas the conjunctiva exhibits transcriptional signatures related to immune surveillance, secretion, metabolic processing, and tissue remodeling. The miRNA–mRNA regulatory networks constructed in this study provide new insights into the molecular regulatory mechanisms of the ocular surface and offer a theoretical basis for future research into disease mechanisms and targeted therapeutic strategies. Full article

Anther length is a crucial agronomic trait that directly correlates with pollen number and pollination efficiency, thereby affecting rice grain yield and hybrid seed production. However, the specific molecular mechanisms regulating rice anther length remain largely unclear. In this study, we identified a short anther (san) mutant generated by CRISPR/Cas9, which exhibited significantly shortened anthers and reduced pollen number, without affecting other agronomic traits or pollen viability. Cytological observations revealed that the shortened anther phenotype in san mutants was caused by reduced epidermal cell number, rather than altered cell size. SAN was highly expressed in spikelets and developing anthers and encodes a nucleus-localized C1-1iG subclass C₂H₂ zinc finger protein with a conserved QALGGH motif and a C-terminal EAR motif. Further assays demonstrated that SAN functions as a transcriptional repressor, and could interact with the corepressor TPR2 in the nucleus. RNA-seq analysis indicated that SAN influences expression of genes associated with cell cycle and cytokinin, which are critical for epidermal cell division during anther development. Phylogenetic analysis showed that SAN was evolutionarily conserved in plants and was closely related to Arabidopsis SUP/ZFP11 and rice SRO. Collectively, our findings revealed that SAN specifically modulated rice anther length by promoting epidermal cell division and providing new insights into the molecular mechanism of anther size regulation. Full article

Eucommia ulmoides leaf extract (ELE) boasts a high concentration of bioactive components including flavonoids, chlorogenic acid, and polysaccharides. It exhibits multiple biological functions, including antioxidant, anti-inflammatory, and gut microbiota-modulating properties, showing great potential in enhancing immunity, maintaining intestinal health, and delaying cellular senescence. This study investigated the protective effects and underlying mechanisms of ELE against D-galactose-induced senescence in chick embryo primary intestinal epithelial cells (IECs). Using an in vitro model (200 mmol/L D-galactose), we found that 100 µg/mL ELE pretreatment significantly preserved cell viability, mitigated apoptosis, and delayed cellular senescence, as evidenced by cytological and biochemical assays. Furthermore, RNA-seq transcriptomic analysis identified seven key differentially expressed genes (DEGs) mediating these anti-aging effects. Mechanistic investigations revealed that ELE modulates ATP6V0D2 and NCF2 to activate autophagy signaling pathways. This ELE-induced promotion of autophagy effectively suppresses inflammatory responses in IECs, thereby delaying senescence progression. These findings elucidate the molecular mechanisms by which ELE antagonizes intestinal cellular senescence, providing a solid theoretical foundation for its development as a functional anti-aging additive in the food industry. Full article

Background/Objectives: Cytological analysis of pleural and peritoneal effusions is minimally invasive but may show limited sensitivity for malignancy detection because tumor cells can be scarce or morphologically difficult to identify. Proteomics-based mass spectrometry imaging (MSI) enables direct molecular profiling of cytological specimens and may improve the distinction between malignant and benign samples. This study investigated whether MALDI-based MSI profiling of formalin-fixed paraffin-embedded (FFPE) cytology cell blocks could discriminate high-grade serous ovarian carcinoma (HGSOC) from benign effusions and identify discriminatory peptide signatures. Methods: Forty-one FFPE cytological specimens derived from pleural and peritoneal effusions were analyzed, including 18 malignant samples and 23 benign control specimens with reactive or inflammatory cytological backgrounds. MALDI-MSI analyses were performed using proteomic profiling. In a preliminary comparative experiment, two section thicknesses (3 µm and 5 µm) were evaluated to optimize ion peak intensity yield. Classification analyses using linear discriminant analysis (LDA) and support vector machine (SVM) models were performed to identify discriminatory peptide signatures. Results: Comparative analysis of average mass spectra identified multiple differentially expressed ions with significant discriminatory performance (AUROC ≥ 0.7 or ≤0.3; Wilcoxon/Kruskal–Wallis, p < 0.001). Classification analyses achieved accuracy ranged from 91% to 94% for the discrimination of malignant and benign samples. Differential proteomic profiling identified Complement C3, Perilipin-3, arachidonate 5-lipoxygenase, Leukotriene A-4 hydrolase, fibrinogen beta and gamma chains, and serotransferrin as discriminatory proteins associated with immune modulation, lipid metabolism, cytoskeletal and extracellular matrix organization, and metabolic regulation. Notably, Complement C3 was found to be overexpressed in malignant tumor cells, supporting its potential role as a marker of tumor presence and progression. Conclusions: Proteomics-based mass spectrometry imaging enabled reliable discrimination of HGSOC from benign cytological specimens and revealed cancer-associated proteins linked to relevant biological processes. These findings support MALDI-MSI as a complementary molecular approach for the classification of challenging cytological specimens in routine diagnostic pathology. Full article

Non-Hodgkin lymphomas (NHL) are lymphoproliferative neoplasms with a heterogenous genetic landscape that require multiple assays to be characterized. Cytological samples are frequently utilized in the diagnosis of NHL. An RNA-based assay was utilized to detect translocations and identify mutations in fine-needle aspiration cytology (FNAC) samples of NHL. Fragmentation index and RNA concentration were evaluated in 54 FNAC and eight corresponding histological samples of NHL to establish first the material adequacy before sequencing. To sequence FusionPlex Lymphoma (ArcherDX, Boulder, USA), an anchored multiplex polymerase chain reaction-based RNA targeting 125 genes was used. The sequencing data processing was entirely carried out on the ArcherDX online platform. Mutations were detected in 21 of 62 samples (34%), and in 41 of 62 samples (66%), no genomic alterations were found. The FusionPlex assay detected five BCL6 translocations (three IGH-BCL6 and two EIF4A2-BCL6), six IGH-BCL2 translocations, two IGH-CCND1 translocations, two TP53 point mutations, two MYD88 mutation and four uncommon translocations (two EIF4E3-FOXP1, one TBL1XR1-TP63, one LOC105370537-FUT8). In eight out of eight cases, there was NGS (Next Generation Sequencing) results concordance between corresponding cytological and histological samples (100% concordance). FNAC samples of NHL are suitable for molecular assessment by NGS and FusionPlex Lymphoma assay is an effective method for this purpose. NGS allows the detection of mutations and the identification of translocations on cytological samples also with scanty diagnostic material. Full article

Background: Urothelial carcinoma requires frequent surveillance because of its high recurrence rate, particularly in patients with non-muscle-invasive disease. Although cystoscopy remains the standard method for diagnosis and follow-up, it is invasive, costly, and associated with patient discomfort. Urinary biomarkers have emerged as potential tools for improving surveillance and reducing unnecessary cystoscopies. Methods: We performed a narrative review of studies published between 2017 and 2026 evaluating urinary biomarkers in urothelial carcinoma. Particular attention was given to assay mechanisms, diagnostic performance, clinical applications, and integration into surveillance techniques. Results: The most extensively studied biomarkers were Xpert Bladder Cancer Monitor, Bladder EpiCheck, ADXBLADDER, and Cxbladder. Most molecular assays demonstrated higher sensitivity than urinary cytology, particularly for the detection of high-grade recurrence. Reported negative predictive values frequently exceeded 95%, suggesting potential utility in identifying patients at low risk of clinically significant recurrence. Xpert Bladder Cancer Monitor and Bladder EpiCheck were supported by the largest body of surveillance evidence, whereas Cxbladder and mutation-enhanced platforms showed promise for risk stratification and individualized follow-up. Evidence supports the use of urinary biomarkers as adjuncts to cystoscopy rather than replacements. Conclusions: Modern urinary biomarkers provide clinically useful information during the surveillance of urothelial carcinoma, especially for excluding high-grade recurrence and assisting the interpretation of equivocal findings. Future biomarker-guided surveillance strategies may reduce the burden of cystoscopy while maintaining oncological safety. Further studies are required to improve specificity and sensitivity in order to fully integrate these biomarkers into diagnostic and follow-up protocols. Full article

Background/Objectives: Oral cavity squamous cell carcinoma (OSCC) remains a major global health burden, with outcomes strongly dependent on stage at diagnosis. Although the oral cavity is directly accessible to clinical examination, many cases are still detected at advanced stages. This narrative review aimed to summarize current trends in OSCC diagnosis and early monitoring, with emphasis on non-invasive and minimally invasive techniques and biomarkers. Methods: A semi-systematic narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science using predefined combinations of OSCC-, early-detection-, imaging-, cytology-, liquid-biopsy-, salivaomics-, artificial-intelligence-, and biosensor-related terms. English-language systematic reviews, meta-analyses, reviews of reviews, translational studies, and clinically relevant original articles were prioritized, with explicit attention to oral cavity-specific evidence and clearly identified extrapolation from broader head-and-neck or oropharyngeal cancer settings. Results: Conventional oral examination and histopathological assessment of biopsy specimens remain the diagnostic foundation. Adjunctive methods may support lesion triage, biopsy-site selection, risk stratification, and early monitoring, but cannot replace tissue diagnosis. Narrow-band imaging, optical coherence tomography, and molecular brush cytology appear particularly promising for specialist assessment and surveillance. Liquid biopsy and saliva-based biomarker platforms offer translational potential, particularly for repeatable monitoring, but clinical implementation is limited by methodological heterogeneity, pre-analytical variability, inconsistent thresholds, and insufficient external validation. Artificial intelligence and biosensor platforms remain promising but largely developmental. Conclusions: Progress in early OSCC diagnosis and monitoring will most likely depend on integrated diagnostic models combining clinical examination, adjunctive imaging, minimally invasive sampling, molecular biomarkers, and computational decision-support tools, validated in prospective multicenter studies. Full article

Proliferative nodules (PNs) are benign, well-limited melanocytic proliferations that can occur within congenital nevi, particularly larger ones. Although they may mimic melanoma clinically and histologically, PNs are characterized by a monomorphic, well-defined cell population with peripheral blending with the adjacent nevus cells, and a lack of severe atypias, numerous mitoses (in most instances), necrosis, or inflammation. They generally present at birth or early childhood, and even with cytological atypia, they do not undergo malignant transformation. The risk of malignancy associated with a large/giant congenital nevus is low but increases with size and the presence of multiple satellite lesions. Diagnostic tools, including immunohistochemistry and, in selected cases, molecular techniques such as CGH-array or RNA-seq, can help differentiate atypical PNs from melanoma. Awareness of this entity and its diverse histological features is crucial to avoid over-diagnosis of malignancy and unnecessary interventions. Here we report a case of atypical PNs in a giant congenital nevus and discuss the literature. Full article

Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article

Background/Objectives: This study aimed to evaluate the association between the clinical parameters of vaginal infection—specifically the presence, type, number of concurrent symptoms, and recurrence frequency—and cervical cytology findings, including inflammation severity, Candida, bacterial vaginosis, cellular abnormalities, and Human Papillomavirus (HPV) positivity. Methods: This prospective, cross-sectional, observational study included 458 women attending our gynecology outpatient clinic for Pap smear screening. Vaginal symptoms were documented through face-to-face interviews using a structured data collection form. Cervical samples were evaluated via liquid-based cytology by a single, experienced cytopathologist, who was blinded to the clinical data; cellular abnormalities, the degree of inflammation and cytomorphological findings indicative of infection were reported. HPV analysis was performed on the 218 women for whom results were available. Chi-square and trend chi-square tests were used in the statistical analysis. Results: No significant association was found between the clinical parameters of vaginal symptoms—specifically presence, concurrency, and recurrence frequency—and cytological abnormalities, HPV positivity and bacterial vaginosis (p > 0.05). In contrast, the prevalence of moderate-to-severe inflammation was significantly higher in women with vaginal discharge and a greater symptom burden (p < 0.05). Pruritus, dysuria, and vaginal burning were significantly associated with Candida positivity (p < 0.05). However, no significant association was found between the severity of cervical inflammation and abnormal cytology or HPV positivity (p > 0.05). In multivariable logistic regression analyses, neither symptom burden nor cervical inflammation severity was independently associated with abnormal cytology or HPV positivity. Conclusions: Our findings indicate that vaginal symptoms and the severity of cervical inflammation may not serve as definitive or independent discriminatory markers for cellular abnormalities or HPV positivity in this context. Nevertheless, specific symptom patterns may assist clinicians in evaluating localized infectious processes. Consequently, while standard cytological and molecular protocols remain essential for oncogenic screening, evaluating the overall symptom burden provides clinicians with a valuable framework for identifying benign dysbiotic and inflammatory processes. These findings remained consistent after adjustment for major clinical confounders. Full article

Background: Accurate preoperative risk stratification of intraductal papillary mucinous neoplasms (IPMNs) remains a major challenge in pancreatic surgery. Cytology obtained through endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) demonstrates high specificity but limited sensitivity, whereas molecular analysis of cyst fluid—particularly KRAS and GNAS mutations—has emerged as a promising complementary diagnostic tool. Methods: We conducted a narrative review combined with a retrospective single-center observational study of patients evaluated for suspected IPMN between 2018 and 2025 who underwent EUS-FNA with cytology and KRAS/GNAS testing followed by surgical resection. Histology was used as the reference standard. Given the limited number of resected cases (n = 25), results should be interpreted with caution. Results: A total of 105 patients were included, of whom 70 underwent EUS-FNA and 25 surgical resection. Final histology showed low-grade dysplasia in 12 cases (48%) and high-grade dysplasia in 13 cases (52%), with no invasive carcinoma detected, limiting the evaluation of diagnostic performance for invasive disease. Cytology demonstrated a sensitivity of 38.5% and specificity of 75% for advanced neoplasia. Molecular testing achieved 100% sensitivity but low specificity. A combined diagnostic strategy increased sensitivity to 92.3% compared with 38.5% for cytology alone, although with reduced specificity. Conclusions: A multimodal diagnostic approach integrating morphology, cytology, and molecular testing improves risk stratification of IPMNs and may supports surgical decision-making within multidisciplinary pancreatic teams, particularly in indeterminate cases, although its impact should be interpreted in the context of limited sample size. Full article

Human cervical cancer and pre-cancer research relies on datasets scattered across modality-specific archives, imaging repositories, benchmark platforms, trial registries, and controlled-access catalogs. This fragmentation—combined with heterogeneous metadata, ambiguous use of “cervical” terminology, and inconsistent indexing of pre-cancer and screening/triage resources—limits reproducible discovery, access planning, and cross-modal benchmarking. We present the Cervical Cancer Dataset Catalog (CCDCAT), a machine-readable, versioned dataset of datasets that enumerates host-specific dataset-instance records anchored to stable identifiers and resolvable landing records within an explicitly declared discoverable source universe (U_v1.0) and a frozen discovery/labeling lexicon (Q_v1.0). The CCDCAT spans invasive cervical cancer, pre-cancer/dysplasia, and cervix-focused screening and triage phenotypes, and it covers molecular omics, imaging and microscopy (including cervix photography, cytology, and digital pathology), trial registry records, benchmark resources, and controlled-access catalogs represented as metadata with explicit access pathways. Eligibility and labels are assigned conservatively from source-provided metadata; when evidence is insufficient, the CCDCAT abstains rather than infers. In the initial release (CCDCAT-U_v1.0; v0.1), we enumerate 14 eligible dataset instances across 11 host systems within a declared universe of 21 sources. Releases include manuscript-ready tables and interoperable artifacts (schema, controlled vocabularies, provenance logs, abstention ledgers, and a queryable database), enabling reproducible filtering, linkage, and auditable reuse planning. Full article

Pediatric brain and other central nervous system (CNS) tumors remain a leading cause of cancer-related death in children, while contemporary management increasingly depends on molecular classification, risk stratification, and longitudinal disease assessment. Yet tissue-based profiling has major limitations in pediatric neuro-oncology, particularly for deep-seated, eloquent, or surgically hazardous tumors and when repeat sampling is impractical. For primary CNS tumors, cerebrospinal fluid is generally more informative than plasma because it is anatomically closer to the tumor and more enriched for tumor-derived material. This narrative review summarizes current and emerging applications of cerebrospinal fluid in pediatric neuro-oncology, from conventional staging to molecular diagnosis, methylation-based classification, measurable residual disease detection, pharmacodynamic monitoring, and relapse surveillance. We discuss the biological rationale for cerebrospinal fluid analysis, major pre-analytical and technical determinants of assay performance, and the strengths and limitations of key analyte classes, including cytology, circulating tumor cells, cell-free DNA, RNA, extracellular vesicles, proteins, and metabolites. We also summarize how these approaches are being applied across major pediatric central nervous system tumor entities. Cerebrospinal fluid liquid biopsy is unlikely to replace tissue or imaging, but is increasingly positioned to complement both in precision pediatric neuro-oncology. Full article