Noninvasive Prediction of Ki-67 Expression in Hepatocellular Carcinoma Using Machine Learning-Based Ultrasomics: A Multicenter Study.

OBJECTIVES: To investigate the ability of ultrasomics to predict Ki-67 expression in hepatocellular carcinoma (HCC). METHODS: A total of 244 patients from three hospitals were retrospectively recruited (training dataset, n = 168; test dataset, n = 43; and validation dataset, n = 33). Lesion segmentation of the ultrasound images was performed manually by two radiologists. In total, 1409 ultrasomics features were extracted. Feature selection was conducted using the intra-class correlation coefficient, variance threshold, mutual information, and recursive feature elimination plus eXtreme Gradient Boosting. The support vector machine was combined with the learning curve and grid search parameter tuning to construct the clinical, ultrasomics, and combined models. The predictive performance of the models was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy. RESULTS: The ultrasomics model performed well on the training, test, and validation datasets. The AUC (95% confidence interval [CI]) for these datasets were 0.955 (0.912-0.981), 0.861 (0.721-0.947), and 0.665 (0.480-0.819), respectively. The combination of ultrasomics and clinical features significantly improved model performance on all three datasets. The AUC (95% CI), sensitivity, specificity, and accuracy were 0.986 (0.955-0.998), 0.973, 0.840, and 0.869 on the training dataset; 0.871 (0.734-0.954), 0.750, 0.829, and 0.814 on the test dataset; and 0.742 (0.560-0.878), 0.714, 0.808, and 0.788 on the validation dataset, respectively. CONCLUSIONS: Ultrasomics was proved to be a potential noninvasive method to predict Ki-67 expression in HCC.

Ultrasomics prediction for cytokeratin 19 expression in hepatocellular carcinoma: A multicenter study.

Objective: The purpose of this study was to investigate the preoperative prediction of Cytokeratin (CK) 19 expression in patients with hepatocellular carcinoma (HCC) by machine learning-based ultrasomics. Methods: We retrospectively analyzed 214 patients with pathologically confirmed HCC who received CK19 immunohistochemical staining. Through random stratified sampling (ratio, 8:2), patients from institutions I and II were divided into training dataset (n = 143) and test dataset (n = 36), and patients from institution III served as external validation dataset (n = 35). All gray-scale ultrasound images were preprocessed, and then the regions of interest were then manually segmented by two sonographers. A total of 1409 ultrasomics features were extracted from the original and derived images. Next, the intraclass correlation coefficient, variance threshold, mutual information, and embedded method were applied to feature dimension reduction. Finally, the clinical model, ultrasonics model, and combined model were constructed by eXtreme Gradient Boosting algorithm. Model performance was assessed by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: A total of 12 ultrasomics signatures were used to construct the ultrasomics models. In addition, 21 clinical features were used to construct the clinical model, including gender, age, Child-Pugh classification, hepatitis B surface antigen/hepatitis C virus antibody (positive/negative), cirrhosis (yes/no), splenomegaly (yes/no), tumor location, tumor maximum diameter, tumor number, alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyl-transpeptidase, albumin, total bilirubin, conjugated bilirubin, creatinine, prothrombin time, fibrinogen, and international normalized ratio. The AUC of the ultrasomics model was 0.789 (0.621 - 0.907) and 0.787 (0.616 - 0.907) in the test and validation datasets, respectively. However, the performance of the combined model covering clinical features and ultrasomics signatures improved significantly. Additionally, the AUC (95% CI), sensitivity, specificity, and accuracy were 0.867 (0.712 - 0.957), 0.750, 0.875, 0.861, and 0.862 (0.703 - 0.955), 0.833, 0.862, and 0.857 in the test dataset and external validation dataset, respectively. Conclusion: Ultrasomics signatures could be used to predict the expression of CK19 in HCC patients. The combination of clinical features and ultrasomics signatures showed excellent effects, which significantly improved prediction accuracy and robustness.

Preoperative prediction of pathological grading of hepatocellular carcinoma using machine learning-based ultrasomics: A multicenter study.

PURPOSE: The present study investigated the value of ultrasomics signatures in the preoperative prediction of the pathological grading of hepatocellular carcinoma (HCC) via machine learning. METHODS: A total of 193 patients were collected from three hospitals. The patients from two hospitals (n = 160) were randomly divided into training set (n = 128) and test set (n = 32) at a 8:2 ratio. The patients from a third hospital were used as an independent validation set (n = 33). The ultrasomics features were extracted from the tumor lesions on the ultrasound images. Support vector machine (SVM) was used to construct three preoperative pathological grading models for HCC on each dataset. The performance of the three models was evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. RESULTS: The ultrasomics signatures extracted from the grayscale ultrasound images could successfully differentiate between high- and low-grade HCC lesions on the training set, test set, and the independent validation set (p < 0.05). On the test set and the validation set, the combined model's performance was the highest, followed by the ultrasomics model and the clinical model successively (p < 0.05). Their AUC (along with 95 %CI) of these models was 0.874(0.709-0.964), 0.789(0.608-0.912), 0.720(0.534-0.863) and 0.849(0.682-0.949), 0.825(0.654-0.935), 0.770(0.591-0.898), respectively. CONCLUSION: Machine learning-based ultrasomics signatures could be used for noninvasive preoperative prediction of pathological grading of HCC. The combined model displayed a better predictive performance for pathological grading of HCC and had a stronger generalization ability.

Clinical Value of Machine Learning-Based Ultrasomics in Preoperative Differentiation Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Multicenter Study.

OBJECTIVE: This study aims to explore the clinical value of machine learning-based ultrasomics in the preoperative noninvasive differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: The clinical data and ultrasonic images of 226 patients from three hospitals were retrospectively collected and divided into training set (n = 149), test set (n = 38), and independent validation set (n = 39). Manual segmentation of tumor lesion was performed with ITK-SNAP, the ultrasomics features were extracted by the pyradiomics, and ultrasomics signatures were generated using variance filtering and lasso regression. The prediction models for preoperative differentiation between HCC and ICC were established by using support vector machine (SVM). The performance of the three models was evaluated by the area under curve (AUC), sensitivity, specificity, and accuracy. RESULTS: The ultrasomics signatures extracted from the grayscale ultrasound images could successfully differentiate between HCC and ICC (p < 0.05). The combined model had a better performance than either the clinical model or the ultrasomics model. In addition to stability, the combined model also had a stronger generalization ability (p < 0.05). The AUC (along with 95% CI), sensitivity, specificity, and accuracy of the combined model on the test set and the independent validation set were 0.936 (0.806-0.989), 0.900, 0.857, 0.868, and 0.874 (0.733-0.961), 0.889, 0.867, and 0.872, respectively. CONCLUSION: The ultrasomics signatures could facilitate the preoperative noninvasive differentiation between HCC and ICC. The combined model integrating ultrasomics signatures and clinical features had a higher clinical value and a stronger generalization ability.

Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single-cell RNA sequencing.

OBJECTIVE: PE is a pregnancy-specific syndrome that affects 3%-5% of pregnant women. It often presents as new-onset hypertension and proteinuria during the third trimester. PE progresses rapidly and may lead to serious complications, including the death of both mother and fetus. In low-income countries, PE is one of the main causes of maternal and child mortality. While the cause of PE is still debated, clinical and pathological studies suggest that the placenta plays an important role in the pathogenesis of PE. MATERIALS AND METHODS: In this single-cell RNA-sequencing (RNA-seq) study, the placenta was taken from the designated position after cesarean section. We compared placental cell subsets and their transcriptional heterogeneity between preeclampsia and healthy pregnancies using the single-cell RNA-seq technology. A developmental trajectory of human trophoblasts was shown. RESULTS: Gene expression in endoplasmic reticulum signaling pathways in syncytiotrophoblast was upregulated in the PE group. The villi cytotrophoblasts (VCT) and extravillous trophoblasts were mainly involved in immune responses. CONCLUSION: The placental immune function of patients with PE was altered. Proteasomes, spliceosomes, ribosomes, and mitochondria were abnormally active in the new VCT cell type.

Discourse production of mandarin-speaking children with high-functioning autism: The effect of mental and action verbs' semantic-pragmatic features.

The present study investigated the syntactic and pragmatic performance of children with high-functioning autism (HFA) during a discourse production task with mental verbs. Children with HFA and typically developing (TD) children were matched by chronological age, verbal IQ (VIQ) and full-scale IQ (FIQ). We found that children with HFA tended to select a nominal object given a mental verb with either a nominal or clausal object. They committed few syntactic errors but generated syntactic stereotypes with mental verbs. However, this behavior was not observed with action verbs. Thus, children with HFA were specifically impaired in the argument structures of mental verbs. In pragmatic performance, children with HFA produced significantly fewer clauses or sentences with lower syntactic complexity for mental verbs than TD controls. This result might be due to the semantic-pragmatic impairment of children with HFA in the use of mental verbs. This study concludes that children with HFA were able to acquire the syntactic frames of mental verbs but were nevertheless impaired in the acquisition of pragmatic information inherent in those verbs.