Colorectal cancer (CRC) is the second leading cause of cancer-related death. The tumor immune microenvironment plays a critical role in tumor progression and immune evasion. B7-H3 (CD276), a member of the B7 family of immune checkpoint molecules, is frequently overexpressed in a variety of malignancies, including CRC. A systematic search of the literature was performed to identify studies evaluating B7-H3 in CRC. Data were extracted on study characteristics, B7-H3 expression and detection methods, molecular and signaling pathways, and clinical outcomes. Study quality and risk of bias were assessed using the MASTER scale, and findings were synthesized using a structured narrative approach. Sixty-three studies were included. B7-H3 expression was commonly reported but demonstrated substantial variability, largely driven by differences in detection and scoring methodologies. Preclinical evidence suggests that B7-H3 may contribute to tumor growth, invasion, immune evasion, and resistance to radio- and chemotherapy, potentially through pathways such as PI3K-AKT-mTOR, JAK-STAT, MAPK/ERK, NF-κB, VEGF/hypoxia, and Wnt/β-catenin. Preclinical studies have demonstrated that targeting B7-H3 may improve radiotherapy response and reduce metastatic burden in murine CRC models. However, these findings should be considered preliminary and are not yet supported by clinical evidence in humans. B7-H3 targeting remains an emerging therapeutic approach that requires further clinical validation. However, significant methodological heterogeneity in detection and scoring limits comparability across studies and precludes definitive conclusions regarding its clinical utility. B7-H3 should therefore be considered a candidate biomarker and further standardized. Prospective studies are needed to clarify its diagnostic, prognostic, and therapeutic relevance in CRC.

AIM To determine whether immunohistochemical B7-H3 expression is associated with magnetic resonance imaging (MRI)-derived tumour volume, peritumoral brain oedema volume, and oedema index in adult gliomas. METHODS This retrospective radiopathological correlation study included 99 consecutive patients with histopathologically confirmed intracranial gliomas surgically treated between 2013 and 2021. B7-H3 expression (clone RBT-B7H3, Bio SB, USA) was evaluated using staining intensity, percentage of positive tumour cells, and a composite immunoreactive score (IRS). Tumour volume (TV), peritumoral brain oedema volume (PTBE), and oedema index (EI) were calculated from orthogonal MRI measurements. Spearman correlation and crude and adjusted linear regression were used. Adjusted models included age, sex, tumour grade, and Ki-67. RESULTS Median TV was 29.31 cm3 (IQR 12.17-49.12), median PTBE was 84.51 cm3 (IQR 47.59-178.18), and median EI was 4.56 (IQR 3.83-5.00). B7-H3 IRS correlated strongly with TV (r = 0.921, p < 0.001) and PTBE (r = 0.920, p < 0.001), but not with EI (r = -0.105, p = 0.299). After adjustment, B7-H3 IRS remained associated with ln(TV) (beta = 0.228, 95% CI 0.190-0.265, p < 0.001) and ln(PTBE) (beta = 0.178, 95% CI 0.152-0.204, p < 0.001), but not with EI (beta = 0.001, 95% CI -0.083 to 0.084, p = 0.990). CONCLUSION B7-H3 expression is independently associated with MRI-derived tumour volume and peritumoral brain oedema volume in adult gliomas, but not with oedema index, supporting its relationship with absolute MRI-visible lesion burden.

Abstract Androgen receptor splice variant 7 (AR-V7) is associated with resistance to androgen receptor-targeting therapies in prostate cancer, but its prevalence and clinical relevance in non-prostatic cancers remain incompletely characterized. A systematic review was conducted in accordance with PRISMA guidelines. Thirty-four studies, including 4855 clinical cases and 60 cell lines, were included. Overall, AR-V7 positivity was reported in 948/4855 clinical cases (19.5%); however, this represents a descriptive estimate across heterogeneous tumor types, study designs, and detection methods. Breast cancer accounted for 4057 of 4855 clinical cases (83.6%) and 815 of 948 AR-V7-positive cases (86.0%), with a within-cancer prevalence of 20.1%. However, after excluding the TCGA cohort in which AR-V7 was inferred through splice-junction analysis, the prevalence of AR-V7-positive breast cancer decreased to 9%. Higher tumor-specific proportions were observed in salivary duct carcinoma (55.2%), hepatocellular carcinoma (57.1%), and non-muscle-invasive bladder cancer (82.6%), but these estimates were based on smaller cohorts and should be interpreted cautiously. AR-V7 was present in several treatment-naive non-prostatic cancers, suggesting that it may represent a preexisting molecular feature in selected contexts. Current evidence suggests that AR-V7 warrants further investigation as a candidate biomarker. Standardized detection methods and prospective studies are needed before its clinical utility can be established.

Immunohistochemistry (IHC) is central to precision oncology in advanced non-small cell lung cancer (NSCLC), although its predictive value and the need for molecular confirmation differ across biomarkers. This narrative review aimed to summarize the clinical utility, validated assays, scoring systems, diagnostic performance, and testing algorithms for predictive IHC biomarkers in NSCLC. Recent guidelines, regulatory documents, and selected analytical and clinical studies were reviewed for programmed death-ligand 1 (PD-L1), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), mesenchymal-epithelial transition factor receptor (c-Met), B-Raf proto-oncogene serine/threonine kinase V600E (BRAF V600E), pan-tropomyosin receptor kinase (pan-TRK), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR). PD-L1 and ALK are established IHC-based predictive assays, although PD-L1 interpretation remains assay-, platform-, and cutoff-specific. VENTANA ALK D5F3 and VENTANA MET SP44 RxDx are clinically validated companion diagnostics, whereas HER2 IHC score 3+ may support eligibility for trastuzumab deruxtecan in the tumor-agnostic setting. ROS1, BRAF V600E, pan-TRK, and non-companion-diagnostic c-Met or HER2 assays are best used for screening or triage and generally require molecular confirmation. EGFR mutation-specific IHC is not recommended because of insufficient diagnostic performance. Overall, IHC enables rapid, tissue-sparing biomarker assessment but should be integrated with broad genomic and transcriptomic next-generation sequencing (NGS), particularly when alteration-specific findings are negative, equivocal, or discordant.

OBJECTIVE To investigate reported paper mill involvement among retracted systematic reviews and meta-analyses (SR/MAs), and to compare retracted SR/MAs with and without reported paper mill involvement with respect to temporal patterns, disciplinary profile, country recorded in the database, and retraction characteristics. STUDY DESIGN AND SETTING Cross-sectional study based on the Retraction Watch database. Records were screened to identify retracted SR/MAs. Reported paper mill involvement was assigned only when explicitly stated in the Retraction Watch record or associated retraction information; fake peer review was coded separately. Group comparisons used the Pearson chi-square and Mann-Whitney U tests. Associations with reported paper mill involvement were estimated using univariable Poisson regression with robust variance and reported as prevalence ratios (PRs) with 95% confidence intervals (CIs). These analyses were treated as exploratory, non-inferential internal contrasts within the dataset of already retracted SR/MAs. RESULTS Among 69,163 retracted publications in the Retraction Watch dataset, 1,071 (1.5%) were identified as retracted SR/MAs. Of those, 191 (17.8%) were paper mill-associated and 880 (82.2%) were not. In the database country field, China was recorded for 732/1,071 retracted SR/MAs (68.3%) and 177/191 SR/MAs with reported paper mill involvement (92.7%). The annual number of paper mill-associated SR/MAs peaked in 2023 (n=152). Within this restricted dataset, paper mill-associated SR/MAs had a longer median time to retraction (511 vs 459 days; p=0.024), more frequent results-related concerns (89.0% vs 30.0%), data issues (53.4% vs 17.5%), referencing concerns (53.9% vs 13.6%), and ethical concerns (8.9% vs 2.6%) (all p<0.001), and less frequent multi-country authorship (8.9% vs 17.6%; p=0.004). In univariable Poisson regression analyses restricted to retracted SR/MAs, larger observed proportions of reported paper mill involvement were seen among records linked to China in the database country field (PR 5.86, 95% CI 3.45-9.93), more recent publication years (PR 1.20 per 1-year increase, 95% CI 1.16-1.23), the medical broad domain (PR 3.66, 95% CI 1.66-8.08), and records with results-related concerns (PR 11.88, 95% CI 7.68-18.39). These PRs should not be interpreted as likelihoods, risks, or rates beyond the analyzed Retraction Watch subset. CONCLUSION In this Retraction Watch-based analysis, reported paper mill involvement was identified in 191/1,071 retracted SR/MAs (17.8%). These records were most often linked to China in the database country field (177/191; 92.7%) and clustered in recent years, particularly 2023. These findings should be interpreted as descriptive patterns within detected and retracted records, not as country-level rates, comparative performance indicators, or estimates of the true prevalence of paper mill activity.

Abstract Hemorrhagic cystitis (HC) in children is most associated with infection or treatment-related toxicity, whereas other cases remain uncommon. We report a 5-year-old boy presenting with recurrent painless gross hematuria in whom a structured, stepwise evaluation excluded glomerular, infectious, structural, and systemic causes. Cystoscopy revealed diffuse mucosal inflammation with focal hemorrhagic changes involving the bladder neck and posterior wall, consistent with noninfectious HC. In the absence of an identifiable etiology and with persistent symptoms, management was directed toward restoring urothelial barrier integrity using intravesical hyaluronic acid (HA). The clinical response was rapid, with resolution of gross hematuria after the first instillation, followed by sustained remission and progressive endoscopic improvement. The treatment was well tolerated, and the patient remained disease-free at 12 months of follow-up. This case highlights the diagnostic complexity of unexplained hematuria in children and supports a potential role of urothelial barrier dysfunction in the pathogenesis of noninfectious HC.

Early distinction between perforated and non-perforated acute appendicitis (AA) in children remains challenging. Conventional inflammatory markers have limited accuracy, highlighting the potential value of composite inflammatory indices. Pediatric patients were categorized as having non-perforated or perforated appendicitis based on intraoperative findings and histopathologic confirmation. Laboratory data obtained on hospital admission included C-reactive protein (CRP), white blood cell count, and differential leukocyte percentages. The subjects of this retrospective study were 338 pediatric patients, 48 (14.2%) of whom had perforated AA. The CRP to lymphocyte ratio (CRP/LR) was significantly higher in the patients with perforated AA (p < 0.001). ROC analysis demonstrated good discriminative performance of CRP/LR for predicting appendiceal perforation, with an area under the curve of 0.84 (95% CI 0.78–0.90). A CRP/LR cut-off value of ≥ 7.2 yielded a sensitivity of 83.3% and a specificity of 78.6%. After adjustment for age, symptom duration, and body temperature on admission, CRP/LR remained an independent predictor of appendiceal perforation in the multivariate regression analysis. The CRP/LR showed good diagnostic performance in differentiating perforated from non-perforated AA and may serve as a simple, readily available tool for early risk stratification in pediatric patients.

This response to the letter expands the discussion on the evolving demands of peer review for systematic reviews and meta-analyses. We emphasize that the main concern surrounding artificial intelligence is not its limited and disclosed use for language support, but undisclosed application and insufficient human verification, which may compromise citation accuracy, interpretation, and overall trustworthiness. We also argue that similarity reports should be interpreted contextually, particularly in evidence syntheses where standardized methodological language is unavoidable, and that low similarity does not necessarily exclude manuscript manipulation. Finally, we highlight reference verification as a central research-integrity challenge that should not rest on peer reviewers alone. Preserving the credibility of evidence synthesis requires shared responsibility across authors, reviewers, editors, and publishers.