Tumor stemness is increasingly recognized as a key contributor to tumor heterogeneity, immune regulation, and therapeutic resistance in colorectal cancer (CRC). In this study, we developed a stemness-based risk model using bulk transcriptomic data from The Cancer Genome Atlas and evaluated its prognostic and therapeutic relevance through integrative analyses. The proposed risk score robustly stratified patients into distinct prognostic groups and remained an independent predictor of overall survival after adjustment for clinicopathological variables. Stemness-high tumors exhibited altered immune infiltration patterns and coordinated upregulation of immune checkpoint-related genes. Although the association between stemness score and immune evasion potential was modest, its clinical relevance was supported by validation in independent immunotherapy-treated cohorts, where low-risk patients demonstrated improved survival and higher response rates. Single-cell RNA sequencing (scRNA-seq) analysis further revealed that enhanced stemness and dedifferentiation were predominantly localized within malignant epithelial cells. Together, these findings establish tumor stemness as a central determinant of prognosis, immune regulation, and therapeutic vulnerability in CRC.
Mosaicism, the presence of both euploid and aneuploid cell lines within a single embryo, presents a significant challenge in assisted reproduction. While emerging data support the transfer of mosaic embryos in the absence of euploid alternatives, clinical outcomes are variable. Evidence suggests a correlation between the degree of mosaicism and developmental potential, with higher-level mosaicism generally associated with less favorable outcomes, including reduced implantation and higher miscarriage rates. We present the case of an uneventful liveborn delivery resulting from the intentional transfer of an embryo classified via preimplantation genetic testing for aneuploidy (PGT-A), as exhibiting very high-level mosaicism (75%). This transfer was performed due to the absence of any euploid embryos available for selection. This case demonstrates that even embryos with a very high degree of chromosomal mosaicism can result in healthy, ongoing pregnancies and live births. It contributes to the growing body of evidence on the clinical potential of mosaic embryos and highlights the necessity for nuanced, patient-specific counseling when considering such transfers.
Breast cancer (BC) remains a major health threat, highlighting the need for accessible screening. Characteristics of the cardiovascular system can be altered in BC patients. This study explored a noninvasive method combining arterial pulse-waveform analysis and classification to compare arterial pulse-waveform characteristics between BC patients (n = 51)) and age-matched controls (n = 76)). From one-minute radial waveform recordings, 40 harmonic indices (amplitude proportions, phase angles, and their variability) were derived. Significant differences in pulse-waveform indices were observed between groups, suggesting altered pulse-wave transmission conditions in BC patients. Two classifiers were compared: machine learning and a novel pulse-distribution analysis (PDA). PDA demonstrated an acceptable discrimination with an AUC of 0.74, outperforming machine learning (AUC up to 0.58). Subgroup analysis by clinical factors such as TNM stage showed variable performance, with AUCs ranging from 0.66-0.93. Discrimination appeared to improve with disease progression (AUC 0.86 for stage IV), suggesting that tumor-induced vascular alterations may affect pulse-wave transmission. The primary contribution of this work is the identification of distinct pulse-waveform signatures in BC patients, providing a physiological basis for future development of noninvasive screening tools. The proposed method, characterized by its low cost and ease of use, warrants further validation in larger cohorts.
To investigate the association between chronic upper airway inflammatory diseases, specifically chronic rhinosinusitis (CRS) and allergic rhinitis (AR), and the risk of glaucoma. Two independent reviewers systematically searched PubMed and Embase through December 2025 to identify observational studies evaluating the association between CRS or AR and glaucoma. Risk of bias was assessed using the ROBINS-E tool. Risk estimates, including odds ratios and hazard ratios, as well as glaucoma incidence rates, were extracted. Pooled risk ratio (RR) for glaucoma was calculated using a random-effects model with inverse-variance weighting. Among 1,620 records identified, seven studies met the inclusion criteria, comprising a total of 83,557,354 individuals (three CRS studies and four AR studies), including five retrospective cohort studies, one case–control study, and one cross-sectional study. The incidence of open-angle glaucoma was 5.5 per 1,000 person-years in patients with CRS, while the incidence of glaucoma was 7.1 per 1,000 person-years in patients with AR. CRS was associated with a significantly increased risk of glaucoma (RR 1.49, 95
Importance:Whether maternal use of acetaminophen during pregnancy is associated with offspring's neurodevelopment remains debated. Objective:To evaluate the associations of maternal prenatal prescriptions of acetaminophen with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs) among offspring. Design, Setting, Participants:This cohort study analyzed 2 092 926 singleton births between 2004 and 2015 in Taiwan, with 1 231 819 having at least 1 sibling. Estimated hazard ratios (HRs) and 95% CIs were examined for offspring ADHD or ASDs according to prenatal acetaminophen prescriptions, adjusting for confounding factors. Exposure:Prescriptions of acetaminophen were extracted from the National Health Insurance Research Database (NHIRD). Acetaminophen use was defined as having at least 2 dispense records during pregnancy, and the total number of prescriptions and the estimated mean daily dispensed dose were examined. Main Outcomes and Measures:The primary outcome was ascertaining diagnoses of ADHD and ASDs from the NHIRD. Results:Of the 2 092 926 singleton births between 2004 and 2015, 48.3% (n = 1 012 159) were born to mothers with at least 2 acetaminophen prescriptions during pregnancy. In the full cohort ASD dataset (N = 2 092 926), 23 557 children (1.1%) had ASD, and in the full ADHD dataset (N = 2 079 935), 116 387 children (5.6%) had ADHD. In the full cohort, offspring ADHD and ASDs were associated with prenatal prescriptions to acetaminophen, with associations noted for higher frequencies of acetaminophen use or higher mean daily dispensed doses of acetaminophen. In sibling-matched analyses, the associations between prenatal exposures to acetaminophen and ADHD and ASDs among offspring were null. However, a positive association was observed when only the older sibling was exposed (HR, 1.33 [95% CI, 1.17-1.52] for ADHD; HR, 1.75 [95% CI, 1.29-2.36] for ASDs), and a negative association was observed when only the younger sibling was exposed (HR, 0.75 [95% CI, 0.67-0.84] for ADHD; HR, 0.74 [95% CI, 0.57-0.96] for ASDs). The divergence of associations persisted in the bidirectional analyses of higher frequencies of acetaminophen use or higher mean daily doses of acetaminophen. Conclusions and Relevance:The findings of this cohort study in Taiwan suggest that positive associations were observed between maternal prenatal acetaminophen prescriptions and offspring's ADHD or ASDs in the full cohort but not in the sibling-matched analyses. A substantial divergence in associations in the sibling bidirectional analyses indicates unaddressed sources of bias and prevents firm conclusions from being drawn using the sibling design.
