Human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR) proteins, claudin-18 isoform 2 (CLDN18.2), and the programmed cell death ligand-1 combined positive score (PD-L1 CPS) are predictive biomarkers for the efficacy of combination chemotherapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. However, only a small proportion of these patients are positive for at least two of these predictive biomarkers.

We present a rare case of HER2-positive, CLDN18.2-positive, MMR-deficient gastric cancer. A 72-year-old man was initially diagnosed with clinical stage IVB gastric cancer (cT4aN0, M1 PUL). Immunohistochemical analysis of endoscopic biopsy specimens revealed HER2-negative, CLDN18.2-negative, and MMR-proficient gastric cancer. He underwent surgery to remove the hemorrhagic gastric cancer before chemotherapy, and immunohistochemical analysis of surgical specimens revealed HER2-positive, CLDN18.2-positive, and MMR-deficient gastric cancer. Moreover, a transbronchial lung biopsy after surgery showed that one of the bilateral multiple lung nodules was lung adenocarcinoma, and he was ultimately diagnosed with pathological stage IIB gastric cancer and clinical stage IVB lung cancer. He died of lung cancer without any signs of gastric cancer recurrence during 17 months of follow-up.

HER2-positive, CLDN18.2-positive, MMR-deficient gastric cancer is extremely rare. Adequate endoscopic biopsy sampling from different areas of a tumor is essential for accurate predictive biomarker assessment in patients with gastric or gastroesophageal junction cancer because of intratumoral heterogeneity.

Primary meningeal melanocytic tumors (PMMTs) are rare neoplasms currently stratified by the World Health Organization (WHO) into three grades of malignancy based exclusively on histopathological criteria, while the prognostic significance of molecular alterations remains poorly defined. This study aimed to investigate the prognostic relevance of histopathological and molecular features in PMMTs and to assess the diagnostic utility of immunohistochemical and molecular markers for distinguishing PMMTs from malignant melanotic nerve sheath tumors (MMNSTs). Thirty-six primary central nervous system (CNS) melanocytic tumors, including 24 PMMTs (10 grade 1, 12 grade 2, and 2 grade 3) and 12 MMNSTs, were analyzed through integrated histopathological, immunohistochemical, genetic, and epigenetic characterization. Among grade 2 PMMTs, descriptively defined CNS-invasive otherwise benign melanocytomas defined a clinically favorable subgroup, whereas SF3B1 mutations and chromosome 8q gains were associated with higher recurrence rates and shorter recurrence-free survival. Losses of chromosome 17 or 21q were observed exclusively in MMNSTs, supporting their potential diagnostic utility in distinguishing MMNSTs from PMMTs. These findings demonstrate biological heterogeneity among intermediate-grade PMMTs and identify molecular markers associated with adverse clinical outcomes. Integrated histopathological and molecular characterization may enhance prognostic stratification and diagnostic accuracy in primary CNS melanocytic tumors.

Magnetic Resonance Cholangiopancreatography (MRCP) is the gold standard for evaluating ductal pathologies, particularly Intraductal Papillary Mucinous Neoplasms (IPMN) and common bile duct (CBD) stones. However, image quality can be limited by noise, artifacts, and acquisition constraints. Deep learning (DL) reconstruction algorithms may improve image quality and diagnostic confidence. This study aims to compare DL and non-DL reconstructions in MRCP regarding diagnostic confidence for IPMN evaluation and CBD stone detection.

This single-center retrospective study included 91 patients who underwent MRCP between March 2024 and January 2025 for IPMN assessment (51 patients) or suspected CBD stones (40 patients). Four sequence types were analyzed (2D and 3D, with and without DL reconstruction). Image quality was objectively assessed (SNR, CR, CNR). Subjective criteria (overall image quality, artifacts, noise, contrast) and diagnostic confidence scores for specific IPMN and CBD stone features were independently evaluated by two radiologists.

DL reconstruction significantly improved SNR, contrast, and CNR for the CBD, particularly in 2D sequences. For the pancreatic duct, improvement was more limited and variable. Subjectively, DL images received higher ratings, notably for contrast, with significant noise reduction and better overall quality. Diagnostic confidence was enhanced for IPMN typing, malignancy criteria, and CBD stone detection.

Deep learning reconstruction improves MRCP image quality and reader diagnostic confidence for evaluating IPMNs and CBD stones. While prospective studies with procedural standards are needed to evaluate direct impacts on diagnostic accuracy and patient outcomes, these findings support integrating DL technology into routine clinical protocols.

Intraductal papillary mucinous neoplasms of the pancreas are heterogenous lesions with variable malignant potential, suggesting underlying biologic diversity. Although inflammation has been implicated in pancreatic carcinogenesis, its contribution to intraductal papillary mucinous neoplasm biology remains poorly understood. We hypothesized that a subset of intraductal papillary mucinous neoplasms may arise in a pancreatitis-associated biologic background.

Whole-exome sequencing was performed in 11 intestinal-type intraductal papillary mucinous neoplasms to explore unrecognized genetic alterations. The PRSS1 germline variant was subsequently validated by Sanger sequencing in 131 patients with intraductal papillary mucinous neoplasm and 50 control patients with pancreatic neuroendocrine neoplasms. Clinical features and imaging findings suggestive of early chronic pancreatitis were compared between variant carriers and noncarriers.

Whole-exome sequencing identified a pancreatitis-related germline mutation of PRSS1^A16V as a candidate variant in intraductal papillary mucinous neoplasm. In the validation cohort, 12 of 131 patients with intraductal papillary mucinous neoplasm (9.2%) harbored the PRSS1^A16V variant, whereas none of the controls did (P = .018). Clinicopathologic analysis revealed significantly higher frequencies of preoperative clinical symptoms (6/12, 50%; P = .041) and body weight loss (2/12, 16.7%; P = .0078) in the mutation-positive cohort. Imaging features suggestive of early chronic pancreatitis were observed more frequently in the mutation-positive cohort than in the mutation-negative cohort (6/12 [50%] vs 14/119 [11.8%]; P = .0031).

A subset of intraductal papillary mucinous neoplasms is characterized by a pancreatitis-associated biologic background defined by the PRSS1^A16V germline variant and imaging features of early chronic pancreatitis. These findings suggest that microinflammatory processes may contribute to intraductal papillary mucinous neoplasm heterogeneity and highlight a potential link between pancreatitis-related genetic susceptibility and pancreatic neoplasia.

Chondrosarcoma is a common bone sarcoma in adults with limited therapeutic options due to frequent chemoresistance. Cisplatin (CDDP) is a key chemotherapeutic agent, but resistance often develops. This study investigated the role and mechanism of circular RNA HMGB2 (circHMGB2) in cisplatin resistance of chondrosarcoma. Clinically, circHMGB2 was upregulated in chondrosarcoma tumors and associated with cisplatin resistance and poor patient survival. Functionally, exogenous overexpression of circHMGB2 elevated cisplatin resistance in chondrosarcoma cells (SW1353, OUMS-27) in vitro, while its silencing re-sensitized resistant cells. Mechanistically, circHMGB2 did not function as a miRNA sponge but acted as a competitive molecular decoy for the RNA-binding protein IGF2BP1. We demonstrated that circHMGB2 directly binds IGF2BP1, competitively impairing IGF2BP1's binding to and stabilization of Grb10 mRNA, leading to its destabilization and subsequent downregulation of Grb10 protein. This suppression of Grb10, a known negative regulator of the PI3K/Akt pathway, resulted in constitutive Akt phosphorylation, driving resistance. Crucially, co-overexpression of IGF2BP1 rescued circHMGB2-induced Grb10 downregulation, Akt activation, and cisplatin resistance, validating the decoy mechanism. Furthermore, in a cisplatin-resistant xenograft model, silencing circHMGB2 synergized with cisplatin to significantly inhibit tumor growth, improve host survival, and upregulate intratumoral Grb10 while suppressing Akt phosphorylation. Our results delineate a novel circHMGB2/IGF2BP1/Grb10/Akt axis that drives cisplatin resistance in chondrosarcoma. Targeting circHMGB2 could therefore serve as a promising therapeutic strategy to overcome chemoresistance and enhance treatment efficacy.

The aim of this study was to reveal the histopathological results of Prostate Imaging Reporting and Data System 3 lesions and to investigate whether targeted biopsy is essential in these lesions.

One hundred and twenty-seven patients with 176 lesions, being categorized as Prostate Imaging Reporting and Data System 3 according to Prostate Imaging Reporting and Data System version 2.1, who underwent transrectal ultrasound-magnetic resonance imaging fusion biopsy were included in the study.

The mean age of the patients was 62.4 years. The median of prostate-specific antigen, prostate-specific antigen density, free prostate-specific antigen, and free/total prostate-specific antigen were 6.64 ng/mL, 0.10 ng/mL2, 1.24 ng/mL, and 0.18 ng/mL, respectively. In patient- and lesion-based analysis, the prevalence of adenocarcinoma was 12.7 and 9%, and clinically significant prostate cancer was 2.3 and 1.7%, respectively. The rate of prostate cancer detected by systematic biopsy alone was 7.8%, and 1.5% of these were clinically significant. There was no significant difference in prostate-specific antigen or prostate-specific antigen density between patients with histopathologically malignant and benign Prostate Imaging Reporting and Data System 3 lesions (p≥0.233). prostate-specific antigen density was higher in malignant patients, considering only 89 patients with index lesion P3 (p=0.046). Family history was significantly higher in malignant patients (p=0.028).

Since clinically significant prostate cancer is very low in Prostate Imaging Reporting and Data System 3 lesions, clinical findings and risk factors should be considered in the biopsy decision in patients with index lesion Prostate Imaging Reporting and Data System 3. However, in patients with index lesions Prostate Imaging Reporting and Data System 4 and 5, targeting these Prostate Imaging Reporting and Data System 3 areas might be important with regard to the extent of the disease.

Diffuse Gastric Cancer (DGC) is an aggressive subtype with a poor prognosis and a lack of specific biomarkers, representing a critical unmet need in oncology. This study aimed to elucidate the key molecular drivers of DGC by integrating RNA-seq data with a multi-faceted bioinformatics approach.

We analyzed RNA-seq data from young-onset DGC and normal tissues (GSE113255, GSE122401). Machine learning (ML) feature selection (ReliefF algorithm) was used to prioritize genes, followed by protein-protein interaction network analysis to identify hub genes. Their roles were further investigated through Gene Ontology, KEGG pathway analysis, tumor microenvironment immune infiltration, miRNA-regulatory network analysis, transcription factor prediction, and computational drug repurposing analyses.

Our ML‑driven approach identified seven hub genes central to DGC pathogenesis including CCL5, CXCR4, MMP9, FOXP3, IL18, TNFSF11, and TNFSF13B. Among these, three prioritized core hub genes (CXCR4, MMP9, and TNFSF13B) were selected based on statistically significant overexpression and complementary functional roles. Specifically, CXCR4 showed a Fold Change of 3.12 (Log2FC = 1.64, FDR = 0.01), MMP9 exhibited the highest magnitude of upregulation (Fold Change = 16.58, Log2FC = 4.05), and TNFSF13B demonstrated the most statistically significant differential expression (Fold Change = 2.32, Log2FC = 1.21, FDR < 0.000001). High CXCR4 expression was identified as a potential prognostic indicator associated with poorer overall survival in the TCGA‑STAD cohort (HR = 1.5, p = 0.0072). We delineated a core regulatory circuitry where NF‑κB (NFKB1/RELA) masterfully regulates the hub gene network. Drug repurposing analysis nominated several FDA‑approved agents, including the VEGF‑A inhibitor Bevacizumab, which indirectly suppresses CXCR4 and MMP9.

This pilot study establishes a robust integrative framework that synergizes ML with network biology. It nominates CXCR4 and TNFSF13B as candidate therapeutic targets and highlights the potential of ML‑based feature selection for discovering biologically relevant, context‑dependent prognostic indicators in DGC. However, we emphasize that these findings are exploratory and hypothesis‑generating, requiring independent validation through experimental studies and larger cohorts before any clinical translation.

Colorectal cancer (CRC) is the second most common cancer across the globe, accounting for 10% cancer-related deaths annually. CRC has been recognized as a consequence of microbial (such as F. nucleatum, E. coli (pks⁺ strains) biofilms, inflammatory signaling, and redox imbalance in the human gut. Hence, natural bioactive substances as a part of the daily diet are crucial for the downregulation of biofilm-mediated CRC. Dietary alkaloids, nitrogen-containing secondary metabolites, have been identified as potential chemotherapeutic agents that can inhibit biofilm formation through quorum-sensing inhibition, modulating the tumor microenvironment, including redox and inflammatory pathway regulation. The present review primarily focuses on the alkaloids' structure-function relationships, microbial biotransformation, and inhibition of pathogenic biofilms, through downregulation of NF-κB, IL-6, STAT3-mediated inflammatory cascades, apoptosis, induction of autophagy, and balancing the redox-oxidative homeostasis. Further, the synergistic effect of alkaloids with dietary fiber, short-chain fatty acid (SCFA)-mediated synergy, and polyphenol compounds is essential for microbial-epithelial barrier activity and metabolic homeostasis regulation. However, the integration of dose windows, dietary patterns, and regulatory landscapes is essential to establish dietary alkaloids as a functional food in biofilm-mediated CRC prevention. Moreover, bioavailability of dietary alkaloids is a potential challenge, and nano-enabled delivery, specifically lipid and polymeric nano carriers, is considered for the controlled delivery, mucosal bioactivity, and reduced systemic exposure of alkaloid carriers for colon mucosa bioactivity. Overall, the integration of microbiome with dietary alkaloids as bioactive food components, to modulate biofilm and tumor micro-niches, underlines the translational potential of dietary alkaloids for CRC prevention.

As the most common malignant renal tumor in children, the progression of Wilms' tumor is frequently driven by abnormal alternative splicing (AS), cell death imbalance, and an immunosuppressive microenvironment. However, the precise regulatory chain connecting these three critical elements remains largely unexplored. This study aimed to systematically construct and characterize an "AS-cell death-immunity" regulatory network in Wilms' tumor.

We performed a comprehensive in silico analysis using matched paired Wilms' tumor and adjacent normal RNA-seq data from the GSE138869 cohort. The SUVA algorithm was employed to identify cell death-related regulated alternative splicing events (RASEs). A tripartite regulatory network was constructed via correlation analysis to link these RASEs with upstream differentially expressed splicing factors (DESFs). Immune cell infiltration was quantified using CIBERSORT. Finally, the HNRNPD knockout and FLASH-seq multi-omics dataset (GSE212767) was utilized to computationally validate the predicted regulatory axis.

Our analysis identified 118 cell death-related host genes undergoing significant alternative splicing in Wilms' tumor. Network integration highlighted a critical regulatory axis where the overexpressed splicing factor HNRNPD is strongly correlated with an aberrant AS event (clualt5p51764) in the apoptosis-related kinase MAP4K4. Further immune deconvolution demonstrated that both HNRNPD upregulation and the MAP4K4 splicing shift were significantly correlated with increased monocyte infiltration in the tumor microenvironment. Moreover, cross-validation utilizing the GSE212767 dataset confirmed that HNRNPD perturbation directly alters MAP4K4 splicing.

Our computational framework proposes that the HNRNPD-MAP4K4 splicing axis links apoptotic dysregulation to immune microenvironment remodeling in Wilms' tumor. These correlative in silico findings provide a robust, hypothesis-generating basis for discovering novel prognostic biomarkers and developing targeted therapeutic strategies directed at the splicing machinery.

Music interventions by listening to recorded music have been associated with the alleviation of breathlessness and the improvement of physical outcomes in the context of pulmonary rehabilitation. Results of these studies, however, should be interpreted carefully since study protocols have been heterogeneous and findings inconsistent. Studies are subject to selection bias and the effect of music interventions is assumed to depend partly on a placebo effect, increasing effectiveness when pre-treatment expectations are higher. In combination with low costs and negligible side effects, implementation of music interventions would be feasible, but they have not been structurally implemented in pulmonary rehabilitation settings yet. Before making efforts on implementing an appropriate music intervention, current use, demands and treatment expectations on music interventions of the target population and their healthcare professionals are to be explored. This study aims to explore the current use of music interventions among patients enrolled in pulmonary rehabilitation and gain insight into the expectations of patients and their caregivers regarding its effect on breathlessness and exercise tolerance.

This paper describes the protocol for a cross-sectional survey consisting of a single questionnaire among patients and their healthcare professionals. The questionnaire into expectations regarding music interventions was developed and validated through a systematic and iterative process. After data collection, descriptive statistics will be performed. Cronbach's alpha will be calculated to measure the questionnaire's internal consistency. Correlation analysis will be performed between baseline characteristics and level of expectation for music interventions.

This study received approval of the institutional review board of the Erasmus Medical Center, The Netherlands (reference number MEC-2025-0703). Results will be disseminated through a peer-reviewed scientific publication, and raw data will be made available on reasonable request to support implementation.