Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Recent research of BTK inhibitors: Methods of structural design, pharmacological activities, manmade derivatives and structure-activity relationship.

Protein kinases constitute the largest group within the kinase family, and mutations and translocations of protein kinases due to genetic alterations are intimately linked to the pathogenesis of numerous diseases. Bruton's tyrosine kinase (BTK) is a member of the protein kinases and plays a pivotal role in the development and function of B cells. BTK belongs to the tyrosine TEC family. The aberrant activation of BTK is closely associated with the pathogenesis of B-cell lymphoma. Consequently, BTK has always been a critical target for treating hematological malignancies. To date, two generations of small-molecule covalent irreversible BTK inhibitors have been employed to treat malignant B-cell tumors, and have exhibited clinical efficacy in hitherto refractory diseases. However, these drugs are covalent BTK inhibitors, which inevitably lead to drug resistance after prolonged use, resulting in poor tolerance in patients. The third-generation non-covalent BTK inhibitor Pirtobrutinib has obtained approval for marketing in the United States, thereby circumventing drug resistance caused by C481 mutation. Currently, enhancing safety and tolerance constitutes the primary issue in developing novel BTK inhibitors. This article systematically summarizes recently discovered covalent and non-covalent BTK inhibitors and classifies them according to their structures. This article also provides a detailed discussion of binding modes, structural features, pharmacological activities, advantages and limitations of typical compounds within each structure type, providing valuable references and insights for developing safer, more effective and more targeted BTK inhibitors in future studies.

Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy: A Histopathological Comparison of Pediatric and Adult Patients.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic cardiomyopathy characterized by microvascular ischemia and myocardial fibrosis. Microvessels play an important role in myocardial fibrosis in HOCM. However, the changes of myocardial microvessels and myocardial fibrosis in pediatric and adult patients with HOCM remain unclear. This study was to investigate the changes in myocardial microvessel density (MVD) and myocardial fibrosis in pediatric and adult patients with HOCM. METHODS: We analyzed the changes in MVD and myocardial fibrosis in myectomy left ventricular (LV) septal wall specimens in 12 adult patients and five pediatric patients with HOCM. Control myocardium from the LV septal wall was collected at autopsy of 5 adults and 4 pediatric individuals, who died of non-cardiac causes. RESULTS: There was no significant difference in MVD between pediatric HOCM patients and control subjects (706.4±187.5 vs. 940.2±491.1, P > 0.05), but the myocardial fibrosis area ratio was significantly increased in HOCM than in control subjects (10.6±3.5 vs. 4.9±1.2, P < 0.01). MVD was significantly reduced, and myocardial fibrosis area ratio was significantly higher in adult HOCM patients than in control subjects (i.e. 523.3± 209.4 vs. 845.7±260.7, P < 0.05; 12.8±5.1 vs. 4.4±1.3, P < 0.05). There was no significant difference in MVD and myocardial fibrosis between pediatric and adult HOCM patients (706.4±187.5 vs. 523.3±209.4, P > 0.05; 10.6±3.5 vs. 12.8±5.1, P > 0.05).  Conclusions: Pediatric and adult patients with HOCM have high myocardial fibrosis. The present findings suggest that myocardial microvascular density lesions contribute to myocardial fibrosis during childhood.

Development and validation of a preoperative CT-based radiomic nomogram to predict pathology invasiveness in patients with a solitary pulmonary nodule: a machine learning approach, multicenter, diagnostic study.

OBJECTIVES: To develop and validate a preoperative CT-based nomogram combined with radiomic and clinical-radiological signatures to distinguish preinvasive lesions from pulmonary invasive lesions. METHODS: This was a retrospective, diagnostic study conducted from August 1, 2018, to May 1, 2020, at three centers. Patients with a solitary pulmonary nodule were enrolled in the GDPH center and were divided into two groups (7:3) randomly: development (n = 149) and internal validation (n = 54). The SYSMH center and the ZSLC Center formed an external validation cohort of 170 patients. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to feature signatures and transform them into models. RESULTS: The study comprised 373 individuals from three independent centers (female: 225/373, 60.3%; median [IQR] age, 57.0 [48.0-65.0] years). The AUCs for the combined radiomic signature selected from the nodular area and the perinodular area were 0.93, 0.91, and 0.90 in the three cohorts. The nomogram combining the clinical and combined radiomic signatures could accurately predict interstitial invasion in patients with a solitary pulmonary nodule (AUC, 0.94, 0.90, 0.92) in the three cohorts, respectively. The radiomic nomogram outperformed any clinical or radiomic signature in terms of clinical predictive abilities, according to a decision curve analysis and the Akaike information criteria. CONCLUSIONS: This study demonstrated that a nomogram constructed by identified clinical-radiological signatures and combined radiomic signatures has the potential to precisely predict pathology invasiveness. KEY POINTS: • The radiomic signature from the perinodular area has the potential to predict pathology invasiveness of the solitary pulmonary nodule. • The new radiomic nomogram was useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection in patients with early-stage non-small-cell lung cancer.

Preoperative CT-based peritumoral and tumoral radiomic features prediction for tumor spread through air spaces in clinical stage I lung adenocarcinoma.

OBJECTIVES: This study aims to develop and evaluate preoperative CT-based peritumoral and tumoral radiomic features to predict tumor spread through air space (STAS) status in clinical stage I lung adenocarcinoma (LUAD). MATERIALS AND METHODS: From June 2018 to December 2019, a retrospective diagnostic investigation was done. Patients with pathologically confirmed STAS status (N = 256) were eventually enrolled. The development cohort consisted of 191 patients (74.6%) chosen randomly in a 7:3 ratio, whereas the validation group consisted of 65 patients (25.4%). The performance of models was assessed using receiver operating characteristic analysis, accuracy, sensitivity, specificity, negative predictive values, and positive predictive values. RESULTS: The STAS positive status was found in 85 (33.2%) of the 256 patients (female: 53.2%; median [IQR] age: 62.0, [53.0-79.0] years), while the STAS negative status was found in 171 patients (66.8%) (female:50.6%; median [IQR] age: 62.0, [53.0-87.0] years). The combined TRS and PRS-15 mm model had an AUC of 0.854 (95% CI, 0.799-0.909) in the development cohort and 0.870 (95% CI, 0.781-0.958) in the validation cohort, indicating that the tumor radiomic signature (TRS) model and different peritumoral radiomic signature (PRS) models were used to build the optimal gross radiomic signature (GRS) model. The radiomic nomogram achieves superior discriminatory performance than GRS and clinical and radiological signatures (CRS), with an AUC of 0.871 (95% CI, 0.820-0.922) in the development cohort and AUC of 0.869 (95% CI, 0.776-0.961) in the validation cohort. Based on the Akaike information criterion (AIC) and decision curve analysis (DCA), the radiomic nomogram provided greater clinical predictive capacity than clinical or any radiomic signatures alone. CONCLUSION: In conclusion, we discovered that peritumoral characteristics were substantially related to STAS status. This study revealed the unit of radiomic signature and clinical signatures may have a better performance in STAS status.

The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs.

OBJECTIVE: This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. METHODS: A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). RESULTS: High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. CONCLUSION: The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.

Glycothermal Synthesis of VO2(B) Nanoparticles for Gas Sensing Application.

This study represents a facile but efficient glycothermal method for synthesis of vanadium dioxide, VO2(B) nanoparticles with various geometries from spheres to rods, flakes or their agglomeration structures, by controlling reaction conditions (e.g., vanadium resources, reducing agents and surfactants). The as-prepared VO2(B) nanoparticles were characterized in microstructure and composition, and also examined in terms of gas sensing performance. It was found that the VO2(B) nanoparticles exhibit a good sensitivity towards alcohols (ethanol, isopropanol, and butanol) and acetone at the optimised operating temperature of 300 °C. The gas sensing performance was further compared with other vanadium oxides investigated previously, such as V2O5, Na1.08V3O8. The plausible gas sensing mechanism of the as-prepared nanoparticles was discussed in detail. This study would expand the family of vanadium oxides that can be made as potential sensors for applications in detecting environmental safety and human health.

Crystal plane-dependent gas-sensing properties of zinc oxide nanostructures: experimental and theoretical studies.

The sensitivity of a metal oxide gas sensor is strongly dependent on the nature of the crystal surface exposed to the gas species. In this study, two types of zinc oxide (ZnO) nanostructures: nanoplates and nanorods with exposed (0001) and (10̄10) crystal surfaces, respectively, were synthesized through facile solvothermal methods. The gas-sensing results show that sensitivity of the ZnO nanoplates toward ethanol is two times higher than that of the ZnO nanorods, at an optimum operating temperature of 300 °C. This could be attributed to the higher surface area and the exposed (0001) crystal surfaces. DFT (Density Functional Theory) simulations were carried out to study the adsorption of ethanol on the ZnO crystal planes such as (0001), (10̄10), and (11̄20) with adsorbed O(-) ions. The results reveal that the exposed (0001) planes of the ZnO nanoplates promote better ethanol adsorption by interacting with the surface oxygen p (O2p) orbitals and stretching the O-H bond to lower the adsorption energy, leading to the sensitivity enhancement of the nanoplates. These findings will be useful for the fabrication of metal oxide nanostructures with specifically exposed crystal surfaces for improved gas-sensing and/or catalytic performance.