Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Unraveling variations and enhancing prediction of successful sphincter-preserving resection for low rectal cancer: A post hoc analysis of the multicenter LASRE randomized clinical trial.

BACKGROUND: Accurate prediction of successful sphincter-preserving resection (SSPR) for low rectal cancer enables peer institutions to scrutinize their own performance and potentially avoid unnecessary permanent colostomy. The aim of this study is to evaluate the variation in SSPR and present the first artificial intelligence (AI) models to predict SSPR in low rectal cancer patients. STUDY DESIGN: This was a retrospective post hoc analysis of a multicenter, noninferiority randomized clinical trial (LASRE, NCT XXXXXX) conducted in 22 tertiary hospitals across China. A total of 604 patients who underwent neoadjuvant chemoradiotherapy (CRT) followed by radical resection of low rectal cancer were included as the study cohort, which was then split into a training set (67%) and a testing set (33%). The primary end point of this post hoc analysis was SSPR, which was defined as meeting all the following criteria: (1) sphincter-preserving resection; (2) complete or nearly complete TME, (3) a clear CRM (distance between margin and tumor of 1 mm or more), and (4) a clear DRM (distance between margin and tumor of 1 mm or more). Seven AI algorithms, namely, support vector machine (SVM), logistic regression (LR), extreme gradient boosting (XGB), light gradient boosting (LGB), decision tree classifier (DTC), random forest (RF) classifier, and multilayer perceptron (MLP), were employed to construct predictive models for SSPR. Evaluation of accuracy in the independent testing set included measures of discrimination, calibration, and clinical applicability. RESULTS: The SSPR rate for the entire cohort was 71.9% (434/604 patients). Significant variation in the rate of SSPR, ranging from 37.7% to 94.4%, was observed among the hospitals. The optimal set of selected features included tumor distance from the anal verge before and after CRT, the occurrence of clinical T downstaging, post-CRT weight and clinical N stage measured by magnetic resonance imaging. The 7 different AI algorithms were developed and applied to the independent testing set. The LR, LGB, MLP and XGB models showed excellent discrimination with AUROC values of 0.825, 0.819, 0.819 and 0.805, respectively. The DTC, RF and SVM models had acceptable discrimination with AUROC values of 0.797, 0.766 and 0.744, respectively. LR and LGB showed the best discrimination, and all 7 AI models had superior overall net benefits within the range of 0.3-0.8 threshold probabilities. Finally, we developed an online calculator based on the LGB model to facilitate clinical use. CONCLUSIONS: The rate of SSPR exhibits substantial variation, and the application of AI models has demonstrated the ability to predict SSPR for low rectal cancers with commendable accuracy.

Fibrosis signature of anastomotic margins for predicting anastomotic stenosis in rectal cancer with neoadjuvant chemoradiotherapy and sphincter-preserving surgery.

Background: Radiation-induced colorectal fibrosis (RICF) is a common pathological alteration among patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (nCRT). Anastomotic stenosis (AS) causes symptoms and negatively impacts patients' quality of life and long-term survival. In this study, we aimed to evaluate the fibrosis signature of RICF and develop a nomogram to predict the risk of AS in patients with rectal cancer undergoing nCRT. Methods: Overall, 335 pairs of proximal and distal margins were collected and randomly assigned at a 7:3 ratio to the training and testing cohorts. The RICF score was established to evaluate the fibrosis signature in the anastomotic margins. A nomogram based on the RICF score for AS was developed and evaluated by using the area under the curve, decision curve analysis, and the DeLong test. Results: The training cohort included 235 patients (161 males [68.51%]; mean age, 59.61 years) with an occurrence rate of AS of 17.4%, whereas the testing cohort included 100 patients (72 males [72.00%]; mean age, 57.17 years) with an occurrence rate of AS of 11%. The RICF total score of proximal and distal margins was significantly associated with AS (odds ratio, 3.064; 95% confidence interval [CI], 2.200-4.268; P < 0.001). Multivariable analysis revealed that the RICF total score, neoadjuvant radiotherapy, and surgical approach were independent predictors for AS. The nomogram demonstrated good discrimination in the training cohort (area under the receiver-operating characteristic curve, 0.876; 95% CI, 0.816-0.937), with a sensitivity of 68.3% (95% CI, 51.9%-81.9%) and a specificity of 85.5% (95% CI, 78.7%-89.3%). Similar results were observed in the testing cohort. Conclusions: This study results suggest that the RICF total score of anastomotic margins is an independent predictor for AS. The prediction model developed based on the RICF total score may be useful for individualized AS risk prediction in patients with rectal cancer undergoing nCRT and sphincter-preserving surgery.

Dysbiosis of gut microbiota and metabolites is associated with radiation-induced colorectal fibrosis and is restored by adipose-derived mesenchymal stem cell therapy.

AIMS: This study aimed to investigate the effects of adipose-derived mesenchymal stem cells (ADSCs) on radiation-induced colorectal fibrosis (RICF) along with the associated dysbiosis of gut microbiota and metabolites. MAIN METHODS: Fecal microbiota were assessed through 16S rRNA gene sequencing, and the fecal metabolome was characterized using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The correlation between microbiota and metabolome data was explored. KEY FINDINGS: ADSC injection demonstrated a significant restoration of radiation-induced intestinal damage in vivo. At the phylum level, irradiated rats exhibited an increase in Bacteroidota and Campilobacterota, and a decrease in Firmicutes and Desulfobacterota, contrasting with the ADSC treatment group. Metabolomic analysis revealed 72 differently expressed metabolites (DEMs) from gas chromatography-mass spectrometry and 284 DEMs from liquid chromatography-mass spectrometry in the radiation group compared to the blank group. In the ADSC treatment group versus the radiation group, 36 DEMs from gas chromatography-mass spectrometry and 341 DEMs from liquid chromatography-mass spectrometry were identified. KEGG enrichment analysis implicated pathways such as steroid hormone biosynthesis, gap junction, primary bile acid biosynthesis, citrate cycle, cAMP signaling pathway, and alanine, aspartate, and glutamate metabolism during RICF progression and after treated with ADSCs. Correlation analysis highlighted the role of ADSCs in modulating the metabolic process of Camelledionol in fecal Bacteroides. SIGNIFICANCE: These findings underscore the potential of ADSCs in reversing dysbiosis and restoring normal colonic flora in the context of RICF, offering valuable insights for therapeutic interventions targeting radiation-induced complications.

Radiological characteristics and diagnostic clues for persistent descending mesocolon in patients with rectal cancer.

PURPOSE: Persistent descending mesocolon (PDM) increases the difficulty and colonic ischemia in the surgery of colorectal cancer, but the preoperative diagnostic criteria have not yet been clearly demonstrated. This study explored the MR imaging features and diagnostic criteria of PDM to improve the preoperative diagnostic rate. METHODS: The clinical data of 54 patients with PDM and 270 patients without PDM who underwent rectal surgery at the Department of Colorectal Surgery, Fujian Medical University Union Hospital, from March 2018 to December 2022 were analyzed, retrospectively. The radiological parameters of PDM from MRI were analyzed. RESULTS: On MRI T2WI axial image, the left edge of the abdominal aorta was defined as the reference line. The shortest vertical distance between the right edge of the descending colon and this line (dN) and the maximum transverse diameter of the peritoneal cavity (dA) at the same level and the maximum vertical distance between the right edge of the descending colon and this line (dW) were measured. There were significant statistical differences in dN, dW, dN/dW, and dN/dA between the PDM group and the non-PDM group. dN, dN/dW, and dN/dA have high diagnostic performance for the PDM. dN < 4.16 cm, dN/dW < 0.52, and dN/dA < 0.15 can all be used as clues to diagnose PDM. CONCLUSIONS: We propose a feasible set of diagnostic criteria for PDM based on abdominal MRI, which can quickly and accurately diagnose PDM, and provide some reference for preoperative planning and surgical decision-making.

The prevention of rectovaginal fistula after rectal cancer surgery by packing with laparoscopic dislocated fat flap containing ovarian vascular pedicle anterior to the anastomotic stoma: a parallel group randomized controlled trial protocol.

BACKGROUND: Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. METHODS: In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10-15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. CONTROL GROUP: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. DISCUSSION: This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.

MRI-based parameters and clinical risk factors to predict lymph node metastasis in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUNDS: The aim of this study was to assess the significant risk factors that predict lymph node metastasis in ypT0 patients with locally advanced rectal cancer following chemoradiotherapy (CRT). Additionally, the study aimed to identify high-risk groups who would not be suitable candidates for a rectal-preserving strategy, despite achieving a complete tumour response. METHODS: Between 2013 and 2021, 226 ypT0 patients with stages II/III rectal cancer underwent CRT and radical surgery were enrolled. Two groups of patients were evaluated: those with lymph nodes metastasis and those without. The selection of variables for multivariable logistic regression was conducted through bivariate logistic regression analysis. Furthermore, the determination of optimal cutoff values for risk factors was achieved using ROC curve analysis. RESULTS: Nearly 8% (18/226) of patients with ypT0 had positive lymph nodes (LN) on final pathology. Four variables resulted as being independent factors of LN metastasis: pre-CRT tumour movability (OR = 8.618, P = 0.003), pre-CRT maximal LN size (OR = 28.474, P = 0.004), post-CRT tumour vertical length (OR = 1.492, P = 0.050), post-CRT anaemia (OR = 10.288, P = 0.001). The optimal cutoff point of pre-CRT maximal LN size and post-CRT tumour vertical length was 7.50 mm and 3.05 cm, respectively. CONCLUSION: The prevalence of lymph node metastasis remains at 8% among patients who achieve pathological complete regression of the primary tumour. In instances where patients are considered appropriate candidates for a rectal-preserving strategy after clinical complete remission, careful consideration should be given to the selection of this strategy if specific risk factors are present. These risk factors encompass a maximal LN size surpassing 7.50 mm prior to CRT, a fixed tumour prior to CRT, a tumour vertical length exceeding 3.05 cm after CRT, and the existence of anaemia subsequent to CRT.

Comparative analysis of preoperative chemoradiotherapy and upfront surgery in the treatment of upper-half rectal cancer: oncological benefits, surgical outcomes, and cost implications.

The value of neoadjuvant chemoradiotherapy (CRT) is not absolutely clear for upper-half (> 7-15 cm) rectal cancer. This study aimed to compare the efficacy and safety of radical surgery with preoperative CRT vs. upfront surgery (US) in Chinese patients with stage II and III upper-half rectal cancer. A total of 809 patients with locally advanced upper-half rectal cancer between 2017 and 2021 were enrolled retrospectively (280 treated with CRT and 529 treated with US). Through 1:1 propensity score matching, the CRT (172 patients) and US (172 patients) groups were compared for short-term postoperative results and long-term oncological and functional outcomes. In the entire cohort, patients in the CRT group had a younger age, lower distance from the anal verge (DAV), and higher rates of cT4 stage, cN2 stage, mrCRM positivity, EMVI positivity, CEA elevation, and CA-199 elevation than those in the US group. The 5-year disease-free survival (DFS) was lower in the CRT group than in the US group (76% vs. 84%, p = 0.022), while the 5-year overall survival (OS) was comparable between the two groups (85% and 88%, p = 0.084). The distant metastasis rate was higher in the CRT group than in the US group (12.5% vs. 7.8%, p = 0.028), though the local recurrence rate was similar between the two groups (1.1% and 1.3%, p = 1.000). After performing PSM, the 5-year OS (86% vs. 88% p = 0.312), the 5-year DFS (79% vs. 80%, p = 0.435), the local recurrence rate (1.2% vs. 1.7%, p = 1.000), and the distant metastasis rate (11.0% vs. 9.3%, p = 0.593) were comparable between the two groups. Notable pathological downstaging was observed in the CRT group, with a pathological complete response (PCR) rate of 14.5%. In addition, patients in the CRT group had a lower proportion of pT3 (61.6% vs. 77.9%, p < 0.001), pN + (pN1, 15.1% vs. 30.2%, pN2, 9.3% vs. 20.3%, p < 0.001), stage III (24.4% vs. 50.6%, p < 0.001), perineural invasion (19.8% vs. 32.0%, p = 0.014), and lymphovascular invasion (9.3% vs. 25.6%, p < 0.001) than those in the US group. Postoperative complications and long-term functional results were similar, yet there was a trend toward a higher conversion to laparotomy rate (5 (2.9%) vs. 0 (0.0%), p = 0.061) and higher rates of robotic surgery (11.6% vs. 4.7%, p < 0.001), open surgery (7.0% vs. 0.6%, p < 0.001), diverting stoma (47.1% vs. 25.6%, p < 0.001), and surgery costs (1473.6 ± 106.5 vs. 1140.3 ± 54.3$, p = 0.006) in the CRT group. In addition, EMVI (OR = 2.516, p = 0.001) was the only independent risk factor associated with poor response to CRT, and in subgroup analysis of EMVI + , CRT group patients presented a lower 5-year DFS (72.9% vs. 80.5%, p = 0.025) compared to US group patients. CRT prior to surgery has no additional oncological benefits over US in the treatment of upper-half rectal cancer. In contrast, CRT is associated with increased rates of conversion to laparotomy, stoma creation and higher surgery costs. Surgeons tend to favor robotic surgery in the treatment of complex cases such as radiated upper-half rectal cancers. Notably, EMVI + patients with upper-half rectal cancer should be encouraged to undergo upfront surgery, as preoperative CRT may not provide benefits and may lead to delayed treatment effects.

Transverse Coloplasty Pouch versus Straight Coloanal Anastomosis Following Intersphincteric Resection for Low Rectal Cancer: the Functional Benefits May Emerge After Two Years.

PURPOSE: This study aimed to compare the oncological and functional outcomes following intersphincteric resection (ISR) with transverse coloplasty pouch (TCP) or straight coloanal anastomosis (SCAA) for low rectal cancer. METHODS: A single-center retrospective analysis was performed on patients with low rectal cancer who received ISR between January 2016 and June 2021. The primary endpoint was to compare the outcomes of bowel function within 1 year, 1 to 2 years, and 2 years after ileostomy closure in patients undergoing two different bowel reconstruction procedures (TCP or SCAA). The postoperative complications and oncological results were also compared between the two groups. RESULTS: A total of 235 patients were enrolled in this study (SCAA group: 166; TCP group: 69). There was no significant difference in complications, including grades A-C anastomotic leakage (9.6% vs 15.9%), 3-year local recurrence rates (6.1% vs 3.9%), disease-free survival (82.4%vs 83.8%), or overall survival (94.1% vs 94.7%) between the two groups. Two years after ileostomy closure, 52.7% of patients in the SCAA group were assessed as having major low anterior resection syndrome (LARS), which was significantly higher than the 25.9% of patients in the TCP group (P = 0.014), but no difference was found prior to 2 years. Similar differences were seen in Wexner scores 2 years after surgery (P = 0.032). Additionally, TCP was an independent protective factor for postoperative bowel function as measured by both the LARS (OR, 0.28; 95% CI, 0.10-0.82; p = 0.020) and Wexner scoring (OR, 0.28; 95% CI, 0.09-0.84; p = 0.023). CONCLUSION: This study suggests that TCP is a safe technique that may decrease bowel dysfunction after ISR for low rectal cancer compared with SCAA 2 years after ileostomy closure.

Transanal local excision versus intersphincteric resection for low rectal cancer with stage ypT0-1ycN0 after neoadjuvant chemoradiotherapy: an inverse probability weighting analysis for oncological and functional outcomes.

OBJECTIVES: This study aimed to compare the efficacy of local excision (LE) and intersphincteric resection (ISR) in patients with locally advanced rectal cancer who achieved a significant or complete pathological response following neoadjuvant chemoradiotherapy. METHODS: We performed a retrospective analysis of data from patients with stage ypT0-1ycN0 low rectal cancer after neoadjuvant chemoradiotherapy who underwent LE or ISR between June 2016 and June 2021. Baseline characteristics, short-term outcomes, long-term oncological outcomes, and functional outcomes, were compared between the two groups. To reduce the selection bias, inverse probability of treatment weighting (IPTW) was performed. RESULTS: This study included 106 patients (LE group: n = 51, ISR group: n = 55). There were significant differences in baseline characteristics between the two groups (P < 0.05). After IPTW, there were almost no significant differences in baseline data between the two groups. The LE group showed less postoperative complications and better function outcomes compared to the ISR group. The LE group had significantly lower rates of complications (13.7% vs. 36.4%, P = 0.014). There were no significant differences between the two groups in terms of long-term oncological outcomes. CONCLUSIONS: For patients with locally advanced low rectal cancer achieving significant or complete pathological response after neoadjuvant therapy, both LE and ISR present comparable oncological outcomes. Yet, LE seems to show more advantages in terms of postoperative complications and functional outcomes. These findings offer important insights for surgical decision-making, emphasizing the necessity to consider both oncological and functional outcomes in selecting the optimal surgical approach.

Construction and validation of stemness-related lncRNA pair signature for predicting prognosis in colorectal cancer.

PURPOSE: The purpose of this study was to identify a prognostic signature based on stemness-related differentially expressed lncRNAs in colorectal cancer (CRC) and to investigate their potential as biomarkers for diagnosis, prognosis, and therapeutic targets. METHODS: Stemness-related genes were collected from the TCGA cohort, and 13 differently expressed stemness-related lncRNAs were identified as prognostic factors for CRC using Kaplan-Meier analysis. A risk model was constructed based on the calculated risk score as a novel independent prognostic factor for CRC patients. The study also investigated the association between the risk model and immune checkpoints and m6A differentiation gene expression. qRT-PCR analysis was performed to validate the expression of differentially expressed stemness-related lncRNAs in CRC cell lines compared to normal colon mucosal cell line. RESULTS: The low-risk lncRNAs were associated with higher survival in CRC patients (Kaplan-Meier analysis, P < 0.001). The risk model was a significant independent prognostic factor for CRC patients. Type I INF response was statistically significant between low- and high-risk groups. CD44, CD70, PVR, TNFSF4, BTNL2, CD40, these immune checkpoints were expressed differently between two risk groups. There was a significant difference between m6A differentiation gene expression such as METTL3, METTL14, WTAP, RBM15, ZC3H13, YTHDC2, YTHDF2, ALKBH5. qRT-PCR analysis validated that there were five up-regulated and eight down-regulated differently expressed stemness-related lncRNAs in CRC cell lines compared to the normal colon mucosal cell line. CONCLUSION: This study suggests that the 13 CRC stemness-related lncRNA signature could become a promising and reliable prognostic factor for colorectal cancer. The risk model based on the calculated risk score may have implications for personalized medicine and targeted therapies for CRC patients. The study also suggests that immune checkpoints and m6A differentiation genes may play important roles in the development and progression of CRC.

Comparison of survival outcomes and survival prediction in patients with primary colorectal MANEC and primary colorectal SRCC: a population-based propensity-score matching study.

PURPOSE: Primary mixed adeno-neuroendocrine carcinoma (MANEC) and primary signet-ring cell cancer (SRCC) are two rare but highly malignant tumors in colorectal cancer. Therefore, we attempted to compare the tumors' survival outcomes, identify risk factors, and ultimately evaluate the prognosis by developing a nomogram. METHODS: We identified 755 MANEC and 5836 SRCC patients of colorectal cancer. PSM was used to balance the influence of baseline clinical and pathological differences. Kaplan-Meier method was used to compare the prognosis of different pathological grades and AJCC stages. Cox proportional hazards model was used to identify potential prognostic factors for the two groups. Finally, we developed a nomogram and evaluated the feasibility of the model. RESULTS: After PSM, the median OS and CSS of MANEC patients were significantly better than those of SRCC patients in stage III-IV (P < 0.001) but similar in stage I-II. The median OS and CSS of MANEC patients in each pathological grade were also greater than those of SRCC patients. Patients with MANEC and SRCC who underwent lymph node dissection in more than four areas had longer survival time. MANEC patients benefited from postoperative chemotherapy and radiotherapy; among SRCC patients, those who received preoperative and postoperative comprehensive chemotherapy and radiotherapy had benefits in OS and CSS. CONCLUSION: Both MANEC and SRCC are often diagnosed in advanced stages, highlighting the importance of early screening. Despite the better prognosis of MANEC compared to SRCC, both types of patients require the formulation of personalized treatment strategies based on different risk factors combined with column charts.

Human intelligence-based metaverse for co-learning of students and smart machines.

This paper proposes a Human Intelligence (HI)-based Computational Intelligence (CI) and Artificial Intelligence (AI) Fuzzy Markup Language (CI&AI-FML) Metaverse as an educational environment for co-learning of students and machines. The HI-based CI&AI-FML Metaverse is based on the spirit of the Heart Sutra that equips the environment with teaching principles and cognitive intelligence of ancient words of wisdom. There are four stages of the Metaverse: preparation and collection of learning data, data preprocessing, data analysis, and data evaluation. During the data preparation stage, the domain experts construct a learning dictionary with fuzzy concept sets describing different terms and concepts related to the course domains. Then, the students and teachers use the developed CI&AI-FML learning tools to interact with machines and learn together. Once the teachers prepare relevant material, students provide their inputs/texts representing their levels of understanding of the learned concepts. A Natural Language Processing (NLP) tool, Chinese Knowledge Information Processing (CKIP), is used to process data/text generated by students. A focus is put on speech tagging, word sense disambiguation, and named entity recognition. Following that, the quantitative and qualitative data analysis is performed. Finally, the students' learning progress, measured using progress metrics, is evaluated and analyzed. The experimental results reveal that the proposed HI-based CI&AI-FML Metaverse can foster students' motivation to learn and improve their performance. It has been shown in the case of young students studying Software Engineering and learning English.

Expression patterns and prognostic value of key regulators associated with m7G RNA modification based on all gene expression in colon adenocarcinoma.

BACKGROUND: N7-methylguanosine (m7G) is present in a wide variety of organisms and has important roles. m7G has been reported to be involved in multiple biological processes, and recent studies have reported that changes in RNA modifications result in tumor cellular transformation and cancer, such as colon adenocarcinoma, lung cancer, and intrahepatic cholangiocarcinoma. However, little is known about the function of the m7G in colon adenocarcinoma. METHODS: We established two clusters based on the expression of all genes associated with m7G to explore the expression pattern of 31 key regulatory factors of m7G RNA and assess the prognostic value of regulatory factors. Wilcoxon test and differential box line plots were applied for bioinformatics analysis. Receiver Operating and Kaplan‒Meier curves were utilized to evaluate the prognostic value. Finally, four genes' expression in the colon cancer cell line was confirmed by qRT-PCR. RESULTS: From The Cancer Genome Atlas database, we found that the expression levels of 25 out of the 31 key N7-methylguanosine RNA modification regulators were significantly different in colon adenocarcinoma. According to 25 methylation regulators' expression, we identified two subgroups by consensus clustering, in which the prognosis was worse in Group 2 than in Group 1 and was significantly correlated with age. Cluster 2 was significantly enriched in tumor-associated pathways, and immune cells were highly infiltrated in Cluster 1 but weakly infiltrated in Cluster 2. Further results indicated that this risk profile may serve as a standalone predictive factor for colon adenocarcinoma, and the four genetic risk profiles' prognostic relatedness was successfully verified through Gene Expression Omnibus dataset. At last, A nomogram for prognosis was created according to age, sex, histological grading, clinicopathological staging, and hazard score to accurately predict patient prognosis in colon adenocarcinoma. We successfully validated the differential expression of four genes using qRT-PCR. CONCLUSIONS: In the present study, we revealed the important contribution of key regulators associated with m7G RNA modifications based on all gene expression in colon adenocarcinoma and developed a signature of risk that serves as a promising prognostic marker for patients with colon adenocarcinoma.

The antitumour effects of caloric restriction are mediated by the gut microbiome.

Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γ+CD8+ T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.

Short peripheral intravenous cannula and straight-tip guide wire in ultrasound-guided neonatal central venous catheterization.

BACKGROUND: Inserting a J-tip guide-wire into a vein's lumen is often difficult when using the Seldinger or modified Seldinger technique for central venous catheterization (CVC) in newborns. This study was designed to compare the efficacy and safety of guide-wire insertion using the combination of a short peripheral intravenous cannula with a straight-tip guide-wire vs. a needle with a J-tip guide-wire for ultrasound-guided (USG) cannulation of the internal jugular vein (IJV) in newborns using an in-plane technique. METHODS: One hundred and thirty newborn patients (weight, 1.4-5.2 kg) scheduled for selective or emergency surgery, were randomly assigned to either the needle group (combined with a J-tip guide-wire) or cannula group (combined with a straight-tip guide-wire). The primary outcome was the rate of successful guide-wire insertion on the first attempt. The puncture attempts, catheter placement attempts, and mechanical complications were also compared between the groups. RESULTS: The rate of successful guide-wire insertion on the first attempt was higher in the cannula group (97%) than in the needle group (76%) (p < 0.05, χ2 = 11.233). Moreover, fewer insertion attempts were needed in the cannula group (1.0 ± 0.2) than in the needle group (1.7 ± 1.1) (p < 0.05, 95% CI [0.449, 1.028]). The time to successful guide-wire insertion was shorter in the cannula group (63 ± 32 s) than in the needle group (92±50 s) (p < 0.05, 95% CI [14.024, 43.063]). No differences were found about other catheterization parameters and complications between the groups. CONCLUSION: The short peripheral cannula combined with a straight-tip guide-wire was superior to the needle combined with a J-tip guide-wire for USG newborn IJV catheterization in terms of successful guide-wire insertion on the first attempt and overall number of insertion attempts.

The global, regional, and national early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global Burden of Disease Study 2019.

PURPOSE: The incidence of early-onset colorectal cancer (EO-CRC), which occurs in people under age 50, has been increasing annually. The aim of this study was to provide an up-to-date estimate of the global EO-CRC burden. METHODS: We used Global Burden of Disease Study data and methodologies to describe changes in the EO-CRC burden from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs). The driving factors for cancer burden variation were further analyzed using decomposition analysis. Frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. RESULTS: The global EO-CRC incidence more than doubled, increasing from 95,737 (95% uncertainty interval (UI): 90,838-101.042) /100,000 in 1990 to 226,782 (95% UI: 207,495-248,604) /100,000 in 2019. Additionally, related deaths increased from 50,997 (95% UI: 47,692-54,410) /100,000 to 87,014 (95% UI: 80,259-94,339) /100,000, and DALYs increased from 256,1842 (95% UI: 239,4962-2,735,823) /100,000 to 4,297,573 (95% UI: 3,965,485-4,650,790) /100,000. Regarding age-standardized rates, incidence and prevalence increased significantly, while mortality and DALYs rate were basically unchanged. Decomposition analysis showed a significant increase in DALYs in the middle sociodemographic index (SDI) quintile region, in which aging and population growth played a major driving role. Frontier analysis showed that countries or regions with a higher SDI quintile tend to have greater improvement potential. CONCLUSION: The current EO-CRC burden was found to be the greatest in the high-middle SDI quintile region and East Asia, which may need to adjust screening guidelines accordingly and introduce more effective interventions.

Research progress of reduced amino acid alphabets in protein analysis and prediction.

Proteins are the executors of cellular physiological activities, and accurate structural and function elucidation are crucial for the refined mapping of proteins. As a feature engineering method, the reduction of amino acid composition is not only an important method for protein structure and function analysis, but also opens a broad horizon for the complex field of machine learning. Representing sequences with fewer amino acid types greatly reduces the complexity and noise of traditional feature engineering in dimension, and provides more interpretable predictive models for machine learning to capture key features. In this paper, we systematically reviewed the strategy and method studies of the reduced amino acid (RAA) alphabets, and summarized its main research in protein sequence alignment, functional classification, and prediction of structural properties, respectively. In the end, we gave a comprehensive analysis of 672 RAA alphabets from 74 reduction methods.