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BackgroundUbiquitination, a major post-translational modification, significantly impacts tumorigenesis, progression, and prognosis. This study aims to classify colon cancer at the molecular level and create a reliable signature using ubiquitination-related genes (URGs) to assess the immune microenvironment and prognosis.MethodsWe employed non-negative matrix factorization to subtype colon cancer based on ubiquitination-related gene (URG) expression patterns. Quantitative scores for 28 immune cell infiltrates and the tumor microenvironment were computed using single-sample gene set enrichment analysis (ssGSEA) and the Estimate algorithm. Subtype feature genes were selected through Lasso logistic regression and SVM-RFE algorithm. The ubiquitination-related signature was constructed using univariate Cox, Lasso, and stepwise regression methods to categorize patients into high and low-risk groups. Validation included log-rank tests, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and external dataset validation. Immune therapy response was compared using Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenoscore (IPS), and submap analyses. Clinical variables and risk scores were integrated into an enhanced nomogram. The early diagnostic value of four URGs was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The cell proliferation was assessed through colony formation, EdU staining, and xenograft tumorigenesis assays.ResultsPrognostic ubiquitination-related genes (URGs) stratified patients into subtypes, revealing differences in survival, immune cell infiltration, and pathological staging. A signature of 6 URGs (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified from 57 subtype-related genes. The high-risk group exhibited characteristics indicative of enhanced epithelial-mesenchymal transition, immune escape, immunosuppressive myeloid-derived suppressor cells, regulatory T cell infiltration, and lower immunogenicity. In contrast, the low-risk group demonstrated the opposite trend but showed a better response to CTLA4 checkpoint inhibitors. The predictive performance of the nomogram significantly improved with the integration of risk score, stage, and age. ARHGAP4 and SIAH2 exhibit promising early diagnostic capabilities. Additionally, WDR72 knockdown significantly inhibited CRC cell proliferation both in vitro and in vivo.ConclusionOur developed ubiquitination-related signature and genes serve as promising biomarkers for colon cancer prognosis, immune microenvironment, and diagnosis.

In this paper, we address a blind frame synchronization problem where the receiver acts as an eavesdropper in the wiretap channel. A challenging condition is considered, where the receiver has completely no prior information except that an unknown synchronization word (SW) is repeated in a nonperiodic fashion. Although an autocorrelation method was proposed for the fixed frame length scenario, the scheme is not applicable to the variable-length scenario. To solve the problem, we propose a deep learning-aided blind SW estimation method where recurrent neural networks (RNNs) are used as a symbol predictor that predicts a symbol from an observation of preceding symbols. The prediction confidence of the RNN-based predictor is used for the localization of the SW symbols in the received signal. Two RNNs fed with the received signal forward and backward are used for accurate SW localization. It has been verified by simulation that the proposed schemes estimate the SW well when the amount of the received signal is sufficiently large. It is straightforward to get synchronization to the received signal with the correctly estimated SW.

INTRODUCTION: The management of childhood constipation is challenging. Pelvic floor dysfunction (PFD) is one of the most common causes of childhood constipation. Percutaneous tibial nerve stimulation (PTNS) with pelvic floor exercises (PFE) has achieved a satisfactory outcome in the elderly individuals and women with PFD. The efficacy of PTNS with PFE in childhood constipation has not been established. METHODS: A randomized, double-blind, controlled trial with 84 childrenwho met the inclusion criteriawas conducted. All participantswere randomly assigned toPTNSwithPFEorshamPTNSwithPFEgroups and received their individual interventionfor4weekswitha 12-week follow-up evaluation. The spontaneousbowelmovements (SBM) -3 per week were themain outcomes, and the risk ratio (RR) with 95%confidence interval (CI) were calculated. High-resolution anorectal manometry and surface electromyography were used for the assessment of pelvic floor function, and the adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 26 patients (61.9%) in the PTNS with PFE group and 15 patients (35.7%) in the sham group had -3 SBM per week compared with baseline (net difference 26.2%, 95% CI 5.6%-46.8%; RR 2.750, 95% CI 1.384-5.466; P < 0.05). PFD remission occurred in 49 children, 33 (78.6%) in the PTNS with PFE group and 16 (38.1%) in the sham group (RR 2.063, 95% CI 1.360-3.128, P < 0.05). No adverse effects occurred. DISCUSSION: PTNS with PFE is a safe and effective method in the treatment of childhood constipation, particularly in children with PFD or dyssynergic defecation. [ABSTRACT FROM AUTHOR]

Background: The Brief COPE instrument has been utilized to conduct research on various populations, including people living with HIV (PLWH). However, the questionnaire constructs when applied to PLWH have not been subjected to thorough factor validation. Methods: A total of 258 PLWH were recruited from two provinces of China. They answered questions involving the scales of three instruments: the Brief COPE, the Perceived Social Support Scale, and the Perceived Discrimination Scale for PLWH. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. Results: The CFA found a poor goodness of fit to the data. The subsequent EFA identified six preliminary factors, forming subscales with Cronbach's alphas, which ranged from 0.61 to 0.80. Significant correlation coefficients between the subscales and measures of perceived social support and perceived discrimination were reported, giving preliminary support to the validity of the new empirical factor structure. Conclusion: This study showed that the original factor structure of the Brief COPE instrument, when applied to PLWH in China, did not fit the data. Thus, the Brief COPE should be applied to various populations and cultures with caution. The new factor structure established by the EFA is only preliminary and requires further validation. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. Methods: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. Results: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). Conclusions: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To examine E1AF mRNA expression and to determine whether it is correlated with tumor progression and matrilysin in human rectal cancer. Methods: Real-time RT-PCR was used to determine E1AF and matrilysin expression in 100 matched rectal cancers and normal tissues. Results: Among the 100 rectal cancers, 69 cases of E1AF mRNA overexpression were observed. E1AF mRNA overexpression correlated well with matrilysin. In carcinomas, E1AF mRNA overexpression correlated significantly with depth of invasion, lymph node metastasis, venous involvement and advanced pTNM stage. Conclusions: E1AF was correlated significantly with tumor progression of human rectal cancer and may be an important factor in rectal cancer progression. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]