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Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States, despite available screening programs, making regular screening essential for early detection and prevention. This study evaluated adherence to repeat multitarget stool DNA (mt-sDNA) testing and follow-up colonoscopy rates among average-risk individuals in the United States This retrospective study used mt-sDNA lab data linked to a national multipayer claims database from 2017 to 2023. Adults aged 45 to 75 years at average risk for CRC who underwent repeat mt-sDNA screening after one or more prior negative results were included. The primary outcome was adherence to repeat mt-sDNA testing, defined as the return of a successfully completed test with valid results within 365 days of shipment. The secondary outcome was the rate of follow-up colonoscopy after a positive mt-sDNA result. Baseline characteristics, adherence rates, and follow-up colonoscopy rates were summarized descriptively. Logistic regression was used to identify factors independently associated with adherence. The study included 326,329 individuals, predominantly female (62.0%) and White (62.5%). Adherence to repeat mt-sDNA screening was high across all racial and ethnic subgroups, exceeding 80% in every group analyzed. White individuals had the highest adherence at 86.6%, followed by Asian individuals at 85.7%, Black individuals at 83.1%, and Hispanic or Latino individuals at 82.7% (P < 0.001).Among those with two prior mt-sDNA tests, adherence increased to 90.6%. The rate of follow-up colonoscopy among those with a positive mt-sDNA result was 76.0%. Logistic regression analysis showed higher odds of mt-sDNA adherence among individuals aged 65–75 years (OR: 1.27; 95% CI: 1.25–1.30; P < 0.001), those residing in rural (OR: 1.21; 95% CI: 1.13–1.28; P < 0.001), patients whose tests were ordered by OB/GYNs (OR: 1.19; 95% CI: 1.13–1.28; P < 0.001), individuals receiving digital outreach (OR: 1.34; 95% CI: 1.30–1.37; P < 0.001), and individuals with two or more prior mt-sDNA tests (OR: 1.44; 95% CI: 1.31–1.58; P < 0.001). The mt-sDNA test was associated with high repeat screening adherence (86.1%) and a follow-up colonoscopy rate of 76.0%, with mt-sDNA adherence exceeding 80% in most subgroups. These findings support its utility as a reliable, home-based CRC screening option.

Background Colorectal cancer (CRC) harboring BRAF V600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAF V600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies. Methods By injecting human CRC stem-like cells isolated from BRAF V600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities’ functional profile was also predicted. Data were compared with Mann-Whitney U, Welch’s t-test for unequal variances and Kruskal-Wallis test with Benjamini–Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed. Results A specific microbial signature distinctive for BRAF status emerged, being the BRAF -mutated cases closer to healthy controls than BRAF wild-type counterpart. In agreement, a considerable score of correlation was also pointed out between bacteria abundance from BRAF -mutated cases and the level of markers distinctive of BRAF V600E pathway, including those involved in inflammation, innate immune response and epithelial-mesenchymal transition. We provide evidence that two candidate bacterial markers, Prevotella enoeca and Ruthenibacterium lactatiformans , more abundant in BRAF V600E and BRAF wild-type subjects respectively, emerged as single factors with the best performance in distinguishing BRAF status (AUROC = 0.72 and 0.74, respectively, 95% confidence interval). Furthermore, the combination of the 10 differentially represented microorganisms between the two groups improved performance in discriminating serrated CRC driven by BRAF mutation from BRAF wild-type CRC cases (AUROC = 0.85, 95% confidence interval, 0.69–1.01). Conclusion Overall, our results suggest that BRAF V600E mutation itself drives a distinctive gut microbiota signature and provide predictive CRC-associated bacterial biomarkers able to discriminate BRAF status in CRC patients and, thus, useful to devise non-invasive patient-selective diagnostic strategies and patient-tailored optimized therapies.

Background Colorectal cancer is a significant public health concern globally, with high incidence and mortality rates. Despite the implementation of CRC screening guidelines, the uptake of screening among adults in the UAE remains low. This study aimed to assess the practice, factors associated, barriers, and knowledge gaps among adults in the UAE. Materials and methods 2100 residents of the UAE, aged > = 40 years, participated in the study. A validated questionnaire was used to collect data. Data was collected through online platforms and face-to-face interviews in healthcare settings. Chi-Square test and binary logistic regression were used for data analysis. Results The study revealed a low CRC screening rate of 9.1%. Factors analyzed included age groups, health insurance coverage, regular physician checkups, family history of CRC, awareness of CRC, and knowledge levels about CRC and its signs and symptoms. Participants in the 50–59 age group showed a slightly higher likelihood of CRC screening, but the difference was not statistically significant. However, individuals in the 60–69 and > = 70 age groups were more likely to undergo screening. Regular physician checkups, family history of CRC, prior knowledge of CRC, and knowledge about the disease and its signs and symptoms were associated with a higher likelihood of screening, with statistically significant OR. Conclusion A low CRC screening rate of 9.1% among adults. Barriers to screening included not being offered a test by physicians, fear of positive results, discomfort with the screening process, perception of pain, and lack of knowledge. Identifying particulate barriers and developing targeted measures requires larger-scale research.

As technology scales down, circuits are more prone to incur in faults and fault detection is necessary to ensure the system reliability. However, fault‐detection circuits are also vulnerable to stuck‐at faults due to, for example, manufacturing defects or ageing; a fault can cause an incorrect output in the fault‐detection scheme; so concurrent fault detection is, therefore, needed. Cyclic redundancy checks (CRCs) are widely used to detect errors in many applications, for example, they are used in communication to detect errors on transmitted frames. In this study, an efficient method to implement concurrent fault detection for parallel CRC computation is proposed. The scheme relies on using a serial CRC computation circuit that is used to periodically check the results obtained from the main module to detect the faults. This introduces a lower circuit overhead than existing schemes. All CRC encoders and decoders that implement the CRC computation in parallel can employ the proposed scheme to detect faults.

The Wnt/β-catenin signaling pathway is a growth control pathway involved in various biological processes as well as the development and progression of cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. The hyperactivation of Wnt signaling is observed in almost all CRC and plays a crucial role in cancer-related processes such as cancer stem cell (CSC) propagation, angiogenesis, epithelial-mesenchymal transition (EMT), chemoresistance, and metastasis. This review will discuss how the Wnt/β-catenin signaling pathway is involved in the carcinogenesis and progression of CRC and related therapeutic approaches.

Instead of “2Tianjin Medical University Cancer Institute and Hospital, Tianjin China, 3National Clinical Research Center for Cancer, Tianjin, China, 4Key Laboratory of Cancer Prevention and Therapy, Tianjin China, 5Tianjin’s Clinical Research Center for Cancer, Tianjin China, 6Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China, 7Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 8Wenzhou Central Hospital, Wenzhou, Zhejiang, China, 9Department of Head and Neck Surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China, 10Department of Pathology, Shanxi Bethune Hospital, Taiyuan, Shanxi, China, 11General Surgery Department, Shanxi Bethune Hospital, Taiyuan, Shanxi, China, 12Haihe Laboratory of Cell Ecosystem, Tianjin, China, 13Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.”, it should be:” 2National Clinical Research Center for Cancer, Tianjin, China, 3Key Laboratory of Cancer Prevention and Therapy, Tianjin, China, 4Tianjin’s Clinical Research Center for Cancer, Tianjin, China, 5Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China, 6Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 7Wenzhou Central Hospital, Wenzhou, Zhejiang, China, 8Department of head and neck surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China, 9Department of Pathology, Shanxi Bethune Hospital, Taiyuan, Shanxi, China, 10General Surgery Department, Shanxi Bethune Hospital, Taiyuan, Shanxi, China, 11Haihe Laboratory of Cell Ecosystem, Tianjin, China, 12Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. In the published article, there was an error regarding the affiliation(s) for Siyuan Zhang, Qiuru Zhou, Fei Han, Gang Du, Lin Wang, Xuena Yang, Xiying Zhang, Wenwen Yu, Feng Wei, Xishan Hao, Xiubao Ren and Hua Zhao.

Background/Objectives: Colorectal cancer (CRC) remains a major global health burden, marked by complex tumor–microenvironment interactions, genetic heterogeneity, and varied treatment responses. Effective preclinical models are essential for dissecting CRC biology and guiding personalized therapeutic strategies. This review aims to critically evaluate current experimental CRC models, assessing their translational relevance, limitations, and potential for integration into precision oncology. Methods: A systematic literature search was conducted across PubMed, Scopus, and Web of Science, focusing on studies employing defined in vitro, in vivo, and emerging integrative CRC models. Studies were included based on experimental rigor and relevance to therapeutic or mechanistic investigation. Models were compared based on molecular fidelity, tumorigenic capacity, immune interactions, and predictive utility. Results: CRC models were classified into in vitro (2D cell lines, spheroids, patient-derived organoids), in vivo (murine, zebrafish, porcine, canine), and integrative platforms (tumor-on-chip systems, humanized mice, AI-augmented simulations). Traditional models offer accessibility and mechanistic insight, while advanced systems better mimic human tumor complexity, immune landscapes, and treatment response. Tumor-on-chip and AI-driven models show promise in simulating dynamic tumor behavior and predicting clinical outcomes. Cross-platform integration enhances translational validity and enables iterative model refinement. Conclusions: Strategic deployment of complementary CRC models is critical for advancing translational research. This review provides a roadmap for aligning model capabilities with specific research goals, advocating for integrated, patient-relevant systems to improve therapeutic development. Enhancing model fidelity and interoperability is key to accelerating the bench-to-bedside translation in colorectal cancer care.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting SDC2 and SEPT9 in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like LINE-1, mSEPT9 and ERCC1 have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of NKX6.1, IGFBP3, and LMX1A has been identified as an independent negative prognostic factor, while SFRP2 hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups.

Chimeric antigen receptor (CAR) T‐cell therapy has shown unprecedented success in haematological cancers but faces challenges in solid tumours. Although carcinoembryonic antigen‐related cell adhesion molecule 5 (CEACAM5) is differentially expressed in many solid tumours, anti‐CEACAM5 CAR T‐cells are ineffective. Here, we have studied the interaction of CEACAM5 targeting primary CAR T‐cells with colorectal cancer (CRC) cells using fluorescence microscopy. We found that CRC cells’ glycocalyx is much thicker than that of the CAR T cell causing delayed activation. Oscillating calcium fluxes, indicative of non‐sustained CAR T cell activation, are observed when CAR T cells interacted with CRC cells, which increased with increasing cell‐seeding time. Significant reduction in cytotoxicity is observed on going from early to longer‐seeded CRC monolayers. Imaging revealed that this effect correlated with a progressive loss of accessible CEACAM5 antigen on the CRC cell surface, possibly due to their sequestration in the intercellular junction, rendering CAR T cell engagement less effective. Local proteolytic treatment with trypsin to disrupt the CRC cell monolayer, using a micropipette, increased CEACAM5 availability, decreased glycocalyx thickness, and restored sustained CAR T cell calcium fluxes. Similar enhanced interaction is observed after treatment of CRC cell monolayer with hyaluronidase, approved for use in humans. Enzymatic treatment significantly enhanced CAR T cell‐mediated cytotoxicity and increased the percentage of TNF‐α–secreting CAR T cells. We observed limited availability of CEACAM5 on human colorectal cancer tissues, whereas treatment with trypsin or hyaluronidase increased accessibility. Our results reveal why CAR T cells targeting CEACAM5 are ineffective and suggest possible routes to improved therapy for CRC.

Increasing evidence has supported dysbiosis in the faecal microbiome along control-adenoma-carcinoma sequence. In contrast, the data is lacking for in situ tumor bacterial community over colorectal cancer (CRC) progression, resulting in the uncertainties of identifying CRC-associated taxa and diagnosing the sequential CRC stages. Through comprehensive collection of benign polyps (BP, N = 45) and the tumors ( N = 50) over the four CRC stages, we explored the dynamics of bacterial communities over CRC progression using amplicons sequencing. Canceration was the primarily factor governing the bacterial community, followed by the CRC stages. Besides confirming known CRC-associated taxa using differential abundance, we identified new CRC driver species based on their keystone features in NetShift, including Porphyromonas endodontalis , Ruminococcus torques and Odoribacter splanchnicus. Tumor environments were less selective for stable core community, resulting in heterogeneity in bacterial communities over CRC progression, as supported by higher average variation degree, lower occupancy and specificity compared with BP. Intriguingly, tumors could recruit beneficial taxa antagonizing CRC-associated pathogens at CRC initiation, a pattern known as “cry-for-help”. By distinguishing age- from CRC stage-associated taxa, the top 15 CRC stage-discriminatory taxa contributed an overall 87.4% accuracy in diagnosing BP and each CRC stage, in which no CRC patients were falsely diagnosed as BP. The accuracy of diagnosis model was unbiased by human age and gender. Collectively, our findings provide new CRC-associated taxa and updated interpretations for CRC carcinogenesis from an ecological perspective. Moving beyond stratifying case-control, the CRC-stage discriminatory taxa could add the diagnosis of BP and the four CRC stages, especially the patients with poor pathological feature and un-reproducibility between two observers.