Efficacy and safety of tegoprazan (LXI-15028) vs. esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase â ¢ trial.

BACKGROUND: An evidence gap still exists regarding the efficacy and safety of tegoprazan in Chinese patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. METHODS: This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. RESULTS: A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7, 95% confidence interval [CI]: -8.5, 5.0, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. CONCLUSION: Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03615677.

The diagnostic value of serum trefoil factor 3 and pepsinogen combination in chronic atrophic gastritis: a retrospective study based on a gastric cancer screening cohort in the community population.

BACKGROUND: Chronic atrophic gastritis (CAG) is an important precursor of gastric cancer(GC), and there is currently a lack of reliable non-invasive diagnostic markers. This study aims to find a biomarker for non-invasive screening of CAG in the community. METHODS: A total of 540 individuals were enrolled (test set = 385, validation set = 155). ROC curve analysis was used to evaluate the diagnostic significance of serum Trefoil Factor 3 (TFF3) alone or in combination with pepsinogen (PG) for CAG in the test and validation set. Furthermore, the diagnostic value of TFF3 and PG in different Helicobacter pylori (H. pylori) infection states was studied. RESULTS: When compared with chronic superficial gastritis (CSG), the expression level of serum TFF3 in the CAG was higher (27 ng/ml vs 19.61, P < 0.001). ROC curve analysis found that the sensitivity, specificity, and area under the curve (AUC) of CAG diagnosis using serum TFF3 alone at the optimal cut-off value of 26.55 ng/ml were 0.529, 0.87, and 0.739, respectively. When TFF3 was combined with The Ratio of PGI to PGII (PGR), the AUC and specificity reached 0.755 and 0.825, respectively. TFF3 individual or combined with PGR had good predictive value, especially in the H. Pylori negative patients. CONCLUSION: TFF3 combined with PGR can effectively predict CAG, especially in patients with H. pylori negative.

Machine learning identifies a 5-serum cytokine panel for the early detection of chronic atrophy gastritis patients.

BACKGROUND: Chronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized. METHODS: Blood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm. RESULTS: Five serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59). CONCLUSION: Using state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions. FUNDING: Supported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).

Characteristic abnormal expression of galectin-3 in serrated colon lesions and its pathological significance.

Serrated lesions are precursors of some colon cancers. The expression of galectin-3 has been reported to be involved in BRAF and KRAS mutations (the key pathogenic drivers of serrated lesions). This study aimed to investigate the expression intensity and subcellular localization of galectin-3 in serrated colon lesions by immunohistochemistry. The results demonstrated that, regarding expression intensity, galectin-3 expression in serrated colon lesions was significantly upregulated; regarding subcellular localization, the membrane expression of hyperplastic polyps/ sessile serrated lesions (HP/SSL) was weakened, the structure was disorganized and that of traditional serrated adenoma (TSA) was significantly weakened or disappeared, and the nuclear expression of both was positive; in the dysplasia of SSL (SSL-D) and TSA (TSA-HD), galectin-3 expression intensity remained high, and was weakened or disappeared in some nuclei, the expression disorder of the SSL-D cell membrane was reduced, the polarity of the cell was restored, weak expression appeared in the local cell membrane of TSA-HD, and the "serrated" structure of both was reduced or disappeared and seemed to revert more to that seen in common adenomas. In summary, abnormal galectin-3 expression occurs in the early stages of serrated lesions, its expression is characteristic, the dynamic changes in galectin-3 expression are closely related to the histopathological changes and progression of serrated lesions, and further accumulated molecular alterations contribute to this process.

Effects of Cu2O nanoparticles on the kinetic characteristics of rapid chlorophyll fluorescence induction and related genes in wheat seedlings.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu2O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSⅡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Rapid Endoscopic Diagnosis of Benign Ulcerative Colorectal Diseases With an Artificial Intelligence Contextual Framework.

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

The highly selective and sensitive fluorescence probe for detection of copper (II) ions and its bioimaging in vitro and vivo.

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.

Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells.

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.

Dominance of plasma-induced modulation in terahertz generation from gas filament.

In this paper, we revisit the fundamental mechanism responsible for terahertz generation from laser-induced plasma filament based on the photocurrent model by employing a blend of analytical calculation and numerical simulation. By using the frequency-decomposed finite-difference time-domain (FD-FDTD) method, the role of two-color field and photocurrent radiation in terahertz generation from plasma filament is visually separated, and the driving effect of photocurrent radiation is confirmed pretty significant within the process. Then, a pair of numerical experiments are taken to further analyze the driving effect of photocurrent radiation, and it is revealed that plasma-induced modulation to photocurrent radiation is actually the underlying physical mechanism of terahertz generation from plasma filament. Furthermore, a three-step diagram is introduced to reillustrate the overall physical process and provides a more comprehensive explanation. In addition, the mechanism of plasma-induced modulation to photocurrent radiation in terahertz generation is substantiated by taking theoretical prediction and numerical simulation of minimal filament length required for achieving stable backward terahertz emission, which directly confirms the validity and significance of plasma-induced modulation to photocurrent radiation in terahertz generation from laser-induced plasma filament.

Comparison of the characteristics of the CF-H290I and PCF-Q260JI colonoscopes in non-sedated patients with a history of abdominal or pelvic surgery: a randomized controlled study.

BACKGROUND AND AIM: The purpose of this randomized controlled study was to compare the characteristics of the CF-H290I (high-definition) colonoscope with those of the PCF-Q260JI (high-resolution) colonoscope in non-sedated patients with a history of abdominal or pelvic surgery in an effort to help endoscopists to select more effectively and objectively between the various colonoscopes. METHODS: A total of 397 patients who underwent colonoscopy at the Affiliated Wuxi People's Hospital of Nanjing Medical University, between August 2022 and October 2022 were randomized to a CF-H290I group (n = 198) or a PCF-Q260JI group (n = 199) using a computer-generated allocation method. We compared the adenoma detection rate (ADR), patient satisfaction with the examination, discomfort associated with colonoscopy including abdominal distension and pain, cecal intubation time, and patient willingness to undergo colonoscopy in the future between the CF-H290I and PCF-Q260JI groups. RESULTS: There was no statistically significant difference in the overall ADR between the CF-H290I and PCF-Q260JI groups (81 [40.9%] vs 63 [31.7%], Z = 3.674, P = 0.055). However, the ADRs in the transverse colon and left colon were significantly higher in the CF-H290I group (22 [11.1%] vs 6 [3.0%], Z = 9.588, P = 0.002 and 57 [28.8%] vs 37 [18.6%], Z = 5.212, P = 0.017, respectively). More sessile serrated lesions were detected in the CF-H290I group (52 [26.3] vs 30 [15.1%], Z = 7.579, P = 0.006). Patient satisfaction with colonoscopy was better in the PCF-Q260JI group (8.91 ± 1.09 vs 8.51 ± 1.44, t = -3.158, P < 0.01) with less likelihood of discomfort (23 [11.6%] vs 41 [20.7%], Z = 6.144, P = 0.013), The number of patients willing to undergo colonoscopy in the future was significantly greater in the PCF-Q260JI group (168 [84.4%] vs 149 [75.3%], Z = 5.186, P = 0.023). The cecal intubation time was significantly shorter in the CF-H290I group (256.09 ± 155.70 s vs 315.64 ± 171.64 s, P = 0.004). There were no complications such as perforation or bleeding in either group. CONCLUSION: The CF-H290I and PCF-Q260JI colonoscopes each have advantages when used in patients with a history of abdominal or pelvic surgery. The CF-H290I has higher ADRs in the transverse and left colon whereas the PCF-Q260JI is less painful and better accepted by patients. This study was approved by the Clinical Research Ethics Committee of Wuxi People's Hospital and was registered in the Chinese Clinical Trial Registry (ChiCTR2200063092).

Formin protein FMNL1 is a biomarker for tumor-infiltrating immune cells and associated with well immunotherapeutic response.

Background: Increased studies on the basis of bulk RNA-sequencing (RNA-seq) data of cancer identify numbers of immune-related genes which may play potential regulatory roles in the tumor microenvironment (TME) without in-depth validation. Methods: In the current study, the immunological correlation and cell subpopulation expression pattern of FMNL1 were analyzed using public data. In addition, the cell subpopulation expression pattern of FMNL1 was also deeply validated using single-cell RNA-sequencing (scRNA-seq) and multiplexed quantitative immunofluorescence (mQIF). Results: Bulk FMNL1 mRNA was related to better prognosis in hepatocellular carcinoma (HCC) and was able to identify immuno-hot tumor in not only HCC but also multiple cancer types. Bulk FMNL1 mRNA also predicted the response to immunotherapy in multiple cancers. Further validation using scRNA-seq and mQIF revealed that FMNL1 was a biomarker for immune cells. Conclusions: FMNL1 is a biomarker for immune cells in not only hepatocellular carcinoma, but also multiple cancer types. Moreover, immune infiltration analysis using the bulk RNA-seq data would be further validated using scRNA-seq and/or mQIF to describe the cell subpopulation expression pattern in tumor tissues for more in-depth and appropriate understanding.

GBP2 is a prognostic biomarker and associated with immunotherapeutic responses in gastric cancer.

BACKGROUND: The interferon-induced protein known as guanylate-binding protein 2 (GBP2) has been linked to multiple different cancer types as an oncogenic gene. Although the role of GBP2 in cancer has been preliminarily explored, it is unclear how this protein interacts with tumor immunity in gastric cancer. METHODS: The expression, prognostic value, immune-correlations of GBP2 in gastric cancer was explored in multiple public and in-house cohorts. In addition, the pan-cancer analysis was performed to investigate the immunological role of GBP2 based on The Cancer Genome Atlas (TCGA) dataset, and the predictive value of GBP2 for immunotherapy was also examined in multiple public cohorts. RESULTS: GBP2 was highly expressed in tumor tissues and associated with poor prognosis in gastric cancer. In addition, GBP2 was associated with the immune-hot phenotype. To be more specific, GBP2 was positively related to immuno-modulators, tumor-infiltrating immune cells (TIICs), immunotherapy biomarkers, and even well immunotherapeutic response. In addition to gastric cancer, GBP2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, GBP2 could predict the immunotherapeutic responses in at least four different cancer types, including melanoma, urothelial carcinoma, non-small cell lung cancer, and breast cancer. CONCLUSIONS: To sum up, GBP2 expression is a promising pan-cancer biomarker for estimating the immunological characteristics of tumors and may be utilized to detect immuno-hot tumors in gastric cancer.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

A superficial esophageal cancer with a diverticulum cured by endoscopic submucosal dissection.

Esophageal diverticulum are rare. However, Esophageal cancer that involves diverticula is relatively rare. Here we reported a rare case of a superficial esophageal cancer with an esophageal diverticulum, which was invisible before the endoscopic submucosal dissection. The cancer was successfully removed by ESD with no perforation.

Protein tyrosine phosphatase nonreceptor type 2 exerts antimetastatic functions in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive tumor with a dismal prognosis. Recent studies have demonstrated PTPN2 (protein tyrosine phosphatase nonreceptor type 2) as a potential target for cancer therapy. However, the functions of PTPN2 in PDAC progression remain poorly understood. In this study, we found PTPN2 expression was downregulated in PDAC tissues, and decreased PTPN2 expression was associated with unfavorable prognosis. Functional studies indicated that PTPN2 knockdown promoted the migration and invasion abilities of PDAC cells in vitro, and the liver metastasis in vivo through epithelial-mesenchymal transition process. Mechanistically, MMP-1 was identified as a downstream target of PTPN2 via RNA-seq data and was responsible for the enhanced metastasis of PDAC cells upon PTPN2 knockdown. Moreover, according to chromatin immunoprecipitation and electrophoretic mobility shift assay, PTPN2 depletion transcriptionally activated MMP-1 via regulating the interaction of p-STAT3 with its distal promoter. This study, for the first time, demonstrated that PTPN2 inhibited PDAC metastasis, and presented a novel PTPN2/p-STAT3/MMP-1 axis in PDAC progression.

Silicon-mediated alleviation of cadmium toxicity in soil-plant system: historical review.

The contamination of crops by Cd is a worldwide problem that needs to be addressed for minimizing risk for human health. Today, numerous investigations have demonstrated that Si plays a role in reducing Cd toxicity and accumulation in cultivated plants. The evolution of scientific understanding - the Cd behavior in soil and in plant is discussed for the first time. Our analysis evidences that the research on Si-Cd interactions in the soil-plant system has quickened only in recent years, although basic interactions between silicic acid and Cd cations in aqueous systems were studied over 40-50 years ago. Today, numerous direct and indirect mechanisms of the Si impact on mobility and translocation of Cd in soil and in plants are reported. More productive studies in this area are those that considered the soil-plant system as a whole. Analysis of the development of the Cd-Si-related ideas suggests the prospects of further studies aimed at finding synergetic action of Si and other substances on Cd behavior in the soil-plant system.

A real-time interpretable artificial intelligence model for the cholangioscopic diagnosis of malignant biliary stricture (with videos).

BACKGROUND AND AIMS: It is crucial to accurately determine malignant biliary strictures (MBSs) for early curative treatment. This study aimed to develop a real-time interpretable artificial intelligence (AI) system to predict MBSs under digital single-operator cholangioscopy (DSOC). METHODS: A novel interpretable AI system called MBSDeiT was developed consisting of 2 models to identify qualified images and then predict MBSs in real time. The overall efficiency of MBSDeiT was validated at the image level on internal, external, and prospective testing data sets and subgroup analyses, and at the video level on the prospective data sets; these findings were compared with those of the endoscopists. The association between AI predictions and endoscopic features was evaluated to increase the interpretability. RESULTS: MBSDeiT can first automatically select qualified DSOC images with an area under the curve (AUC) of .963 and .968 to .973 on the internal testing data set and the external testing data sets, and then identify MBSs with an AUC of .971 on the internal testing data set, an AUC of .978 to .999 on the external testing data sets, and an AUC of .976 on the prospective testing data set, respectively. MBSDeiT accurately identified 92.3% of MBSs in prospective testing videos. Subgroup analyses confirmed the stability and robustness of MBSDeiT. The AI system achieved superior performance to that of expert and novice endoscopists. The AI predictions were significantly associated with 4 endoscopic features (nodular mass, friability, raised intraductal lesion, and abnormal vessels; P < .05) under DSOC, which is consistent with the endoscopists' predictions. CONCLUSIONS: The study findings suggest that MBSDeiT could be a promising approach for the accurate diagnosis of MBSs under DSOC.

FMNL3 is Overexpressed in Tumor Tissues and Predicts an Immuno-Hot Phenotype in Pancreatic Cancer.

Background: FMNL3 (Formin-like protein 3) is involved in the tumorigenesis of multiple cancers. The critical role of FMNL3 in malignancies has been preliminarily explored, but its immunological correlation is not clear. Methods: A pan-cancer analysis was performed to investigate the expressions, prognostic values, and immunological roles of FMNL3 across cancer types in The Cancer Genome Atlas (TCGA) database. Next, the correlations between FMNL3 and immunological features in the tumor microenvironment (TME) of pancreatic cancer (PAAD) were assessed. Besides, the role of FMNL3 in predicting the clinical characteristics and the responses to various therapies in PAAD was evaluated as well. Besides, the correlations between FMNL3 and the emerging immune-related biomarkers were also evaluated. Results: The pan-cancer analysis uncovered inconsistent expression status and prognostic values in several cancers. Besides, FMNL3 exhibited positive correlations with a majority of immunomodulators and tumor-infiltrating immune cells (TIICs) in several cancer types, including PAAD. In addition, FMNL3 was associated with an inflamed phenotype in the TME and predicted significantly higher responses to multiple anti-cancer therapies. In addition, FMNL3 was notably correlated with immune-related microbiota and N6-methyladenosine (m6A) genes. Conclusion: In summary, FMNL3 predicts an immuno-hot phenotype, which could be a promising indicator for identifying high immunogenicity in PAAD.