Research progress on the protective effect of hormones and hormone drugs in myocardial ischemia-reperfusion injury.

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.

Artificial intelligence-based classification of breast lesion from contrast enhanced mammography: a multicenter study.

PURPOSE: The authors aimed to establish an artificial intelligence (AI)-based method for preoperative diagnosis of breast lesions from contrast enhanced mammography (CEM) and to explore its biological mechanism. MATERIALS AND METHODS: This retrospective study includes 1430 eligible patients who underwent CEM examination from June 2017 to July 2022 and were divided into a construction set (n=1101), an internal test set (n=196), and a pooled external test set (n=133). The AI model adopted RefineNet as a backbone network, and an attention sub-network, named convolutional block attention module (CBAM), was built upon the backbone for adaptive feature refinement. An XGBoost classifier was used to integrate the refined deep learning features with clinical characteristics to differentiate benign and malignant breast lesions. The authors further retrained the AI model to distinguish in situ and invasive carcinoma among breast cancer candidates. RNA-sequencing data from 12 patients were used to explore the underlying biological basis of the AI prediction. RESULTS: The AI model achieved an area under the curve of 0.932 in diagnosing benign and malignant breast lesions in the pooled external test set, better than the best-performing deep learning model, radiomics model, and radiologists. Moreover, the AI model has also achieved satisfactory results (an area under the curve from 0.788 to 0.824) for the diagnosis of in situ and invasive carcinoma in the test sets. Further, the biological basis exploration revealed that the high-risk group was associated with the pathways such as extracellular matrix organization. CONCLUSIONS: The AI model based on CEM and clinical characteristics had good predictive performance in the diagnosis of breast lesions.

NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

Multitask Deep Learning-Based Whole-Process System for Automatic Diagnosis of Breast Lesions and Axillary Lymph Node Metastasis Discrimination from Dynamic Contrast-Enhanced-MRI: A Multicenter Study.

BACKGROUND: Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience. PURPOSE: To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis. STUDY TYPE: Retrospective. POPULATION: 1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets. FIELD STRENGTH/SEQUENCE: 3.0T/dynamic contrast-enhanced (DCE)-MRI sequence. ASSESSMENT: DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data. STATISTICAL TESTS: Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value. RESULTS: The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation. DATA CONCLUSION: The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Detection and classification of breast lesions using multiple information on contrast-enhanced mammography by a multiprocess deep-learning system: A multicenter study.

Objective: Accurate detection and classification of breast lesions in early stage is crucial to timely formulate effective treatments for patients. We aim to develop a fully automatic system to detect and classify breast lesions using multiple contrast-enhanced mammography (CEM) images. Methods: In this study, a total of 1,903 females who underwent CEM examination from three hospitals were enrolled as the training set, internal testing set, pooled external testing set and prospective testing set. Here we developed a CEM-based multiprocess detection and classification system (MDCS) to perform the task of detection and classification of breast lesions. In this system, we introduced an innovative auxiliary feature fusion (AFF) algorithm that could intelligently incorporates multiple types of information from CEM images. The average free-response receiver operating characteristic score (AFROC-Score) was presented to validate system's detection performance, and the performance of classification was evaluated by area under the receiver operating characteristic curve (AUC). Furthermore, we assessed the diagnostic value of MDCS through visual analysis of disputed cases, comparing its performance and efficiency with that of radiologists and exploring whether it could augment radiologists' performance. Results: On the pooled external and prospective testing sets, MDCS always maintained a high standalone performance, with AFROC-Scores of 0.953 and 0.963 for detection task, and AUCs for classification were 0.909 [95% confidence interval (95% CI): 0.822-0.996] and 0.912 (95% CI: 0.840-0.985), respectively. It also achieved higher sensitivity than all senior radiologists and higher specificity than all junior radiologists on pooled external and prospective testing sets. Moreover, MDCS performed superior diagnostic efficiency with an average reading time of 5 seconds, compared to the radiologists' average reading time of 3.2 min. The average performance of all radiologists was also improved to varying degrees with MDCS assistance. Conclusions: MDCS demonstrated excellent performance in the detection and classification of breast lesions, and greatly enhanced the overall performance of radiologists.

Intra- and Peritumoral Radiomics of Contrast-Enhanced Mammography Predicts Axillary Lymph Node Metastasis in Patients With Breast Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: This multicenter study aimed to explore the feasibility of radiomics based on intra- and peritumoral regions on preoperative breast cancer contrast-enhanced mammography (CEM) to predict axillary lymph node (ALN) metastasis. MATERIALS AND METHODS: A total of 809 patients with preoperative breast cancer CEM images from two centers were retrospectively recruited. Least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features extracted from CEM images in regions of the tumor and peritumoral area of five and ten mm as well as construct radiomics signature. A nomogram, including the optimal radiomics signature and clinicopathological factors, was then constructed. Nomogram performance was evaluated using AUC and compared with breast radiologists directly. RESULTS: In the internal testing set, AUCs of peritumoral signatures decreased when the peritumoral area increased and signaturetumor + 10mm demonstrated the best performance with an AUC of 0.712. The nomogram incorporating signaturetumor + 10mm, tumor diameter, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and CEM-reported lymph node status yielded maximum AUCs of 0.753 and 0.732 in internal and external testing sets, respectively. Moreover, the nomogram outperformed radiologists and improved diagnostic performance of radiologists. CONCLUSION: The nomogram based on CEM intra- and peritumoral regions may provide a noninvasive auxiliary tool to guide treatment strategy of ALN metastasis in breast cancer.

Radiomics of contrast-enhanced spectral mammography for prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been regarded as one of the standard treatments for patients with locally advanced breast cancer. No previous study has investigated the feasibility of using a contrast-enhanced spectral mammography (CESM)-based radiomics nomogram to predict pathological complete response (pCR) after NAC. OBJECTIVE: To develop and validate a CESM-based radiomics nomogram to predict pCR after NAC in breast cancer. METHODS: A total of 118 patients were enrolled, which are divided into a training dataset including 82 patients (with 21 pCR and 61 non-pCR) and a testing dataset of 36 patients (with 9 pCR and 27 non-pCR). The tumor regions of interest (ROIs) were manually segmented by two radiologists on the low-energy and recombined images and radiomics features were extracted. Intraclass correlation coefficients (ICCs) were used to assess the intra- and inter-observer agreements of ROI features extraction. In the training set, the variance threshold, SelectKBest method, and least absolute shrinkage and selection operator regression were used to select the optimal radiomics features. Radiomics signature was calculated through a linear combination of selected features. A radiomics nomogram containing radiomics signature score (Rad-score) and clinical risk factors was developed. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate prediction performance of the radiomics nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the radiomics nomogram. RESULTS: The intra- and inter- observer ICCs were 0.769-0.815 and 0.786-0.853, respectively. Thirteen radiomics features were selected to calculate Rad-score. The radiomics nomogram containing Rad-score and clinical risk factor showed an encouraging calibration and discrimination performance with area under the ROC curves of 0.906 (95% confidence interval (CI): 0.840-0.966) in the training dataset and 0.790 (95% CI: 0.554-0.952) in the test dataset. CONCLUSIONS: The CESM-based radiomics nomogram had good prediction performance for pCR after NAC in breast cancer; therefore, it has a good clinical application prospect.

Intra- and peritumoral radiomics for predicting malignant BiRADS category 4 breast lesions on contrast-enhanced spectral mammography: a multicenter study.

OBJECTIVE: To construct and test a nomogram based on intra- and peritumoral radiomics and clinical factors for predicting malignant BiRADS 4 lesions on contrast-enhanced spectral mammography. METHODS: A total of 884 patients with BiRADS 4 lesions were enrolled from two centers. For each lesion, five ROIs were defined using the intratumoral region (ITR), peritumoral regions (PTRs) of 5 and 10 mm around the tumor, and ITR plus PTRs of 5 mm and 10 mm. Five radiomics signatures were established by LASSO after selecting features. A nomogram was built using selected signatures and clinical factors by multivariable logistic regression analysis. The performance of the nomogram was assessed with the AUC, decision curve analysis, and calibration curves, and also compared with the radiomics model, clinical model, and radiologists. RESULTS: The nomogram built by three radiomics signatures (constructed from ITR, 5 mm PTR, and ITR + 10 mm PTR) and two clinical factors (age and BiRADS category) showed powerful predictive ability in internal and external test sets with AUCs of 0.907 and 0.904, respectively. The calibration curves, decision curve analysis, showed favorable predictive performance of the nomogram. In addition, radiologists improved the diagnostic performance with the help of nomogram. CONCLUSION: The nomogram established via intratumoral and peritumoral radiomics features and clinical risk factors had the best performance in distinguishing benign and malignant BiRADS 4 lesions, which could help radiologists improve diagnostic capabilities. KEY POINTS: • Radiomics features from peritumoral regions in contrast-enhanced spectral mammography images may provide valuable information for the diagnosis of benign and malignant breast imaging reporting and data system category 4 breast lesions. • The nomogram incorporated intra- and peritumoral radiomics features and clinical variables have good application prospects in assisting clinical decision-makers.

Attention-based Deep Learning for the Preoperative Differentiation of Axillary Lymph Node Metastasis in Breast Cancer on DCE-MRI.

BACKGROUND: Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear. PURPOSE: To investigate the potential of the proposed attention-based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 941 breast cancer patients who underwent DCE-MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts. FIELD STRENGTH/SEQUENCE: A 3.0 T MR scanner, DCE-MRI sequence. ASSESSMENT: A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor-ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.). STATISTICAL TESTS: Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification. RESULTS: The optimal RCNet model, that is, RCNet-tumor+ALN , achieved an AUC of 0.907, an accuracy of 0.831, a sensitivity of 0.824, and a specificity of 0.837 in the internal test cohort, as well as an AUC of 0.852, an accuracy of 0.828, a sensitivity of 0.792, and a specificity of 0.853 in the external test cohort. Additionally, with the assistance of RCNet-tumor+ALN , the radiologists' performance was improved (external test cohort, P < 0.05). DATA CONCLUSION: DCE-MRI-based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Intratumoral and peritumoral radiomics for preoperatively predicting the axillary non-sentinel lymph node metastasis in breast cancer on the basis of contrast-enhanced mammography: a multicenter study.

OBJECTIVE: To develop and test a contrast-enhanced mammography (CEM)-based radiomics model using intratumoral and peritumoral regions to predict non-sentinel lymph node (NSLN) metastasis in breast cancer before surgery. METHODS: This multicenter study included 365 breast cancer patients with sentinel lymph node metastasis. Intratumoral regions of interest (ROIs) were manually delineated, and peritumoral ROIs (5 and 10 mm) were automatically obtained. Five models, including intratumoral model, peritumoral (5 and 10 mm) models, and intratumoral+peritumoral (5 and 10 mm) models, were constructed by support vector machine classifier on the basis of optimal features selected by variance threshold, SelectKbest, and least absolute shrinkage and selection operator algorithms. The predictive performance of radiomics models was evaluated by receiver operating characteristic curves. An external testing set was used to test the model. The Memorial Sloan Kettering Cancer Center (MSKCC) model was used to compare the predictive performance with radiomics model. RESULTS: The intratumoral ROI and intratumoral+peritumoral 10-mm ROI-based radiomics model achieved the best performance with an area under the curve (AUC) of 0.8000 (95% confidence interval [CI]: 0.6871-0.8266) in the internal testing set. In the external testing set, the AUC of radiomics model was 0.7567 (95% CI: 0.6717-0.8678), higher than that of MSKCC model (AUC = 0.6681, 95% CI: 0.5148-0.8213) (p = 0.361). CONCLUSIONS: The intratumoral and peritumoral radiomics based on CEM had an acceptable predictive performance in predicting NSLN metastasis in breast cancer, which could be seen as a supplementary predicting tool to help clinicians make appropriate surgical plans. ADVANCES IN KNOWLEDGE: The intratumoral and peritumoral CEM-based radiomics model could noninvasively predict NSLN metastasis in breast cancer patients before surgery.

Current Progress of CAR-NK Therapy in Cancer Treatment.

CD8+ T cells and natural killer (NK) cells eliminate target cells through the release of lytic granules and Fas ligand (FasL)-induced target cell apoptosis. The introduction of chimeric antigen receptor (CAR) makes these two types of cells selective and effective in killing cancer cells. The success of CAR-T therapy in the treatment of acute lymphoblastic leukemia (ALL) and other types of blood cancers proved that the immunotherapy is an effective approach in fighting against cancers, yet adverse effects, such as graft versus host disease (GvHD) and cytokine release syndrome (CRS), cannot be ignored for the CAR-T therapy. CAR-NK therapy, then, has its advantage in lacking these adverse effects and works as effective as CAR-T in terms of killing. Despite these, NK cells are known to be hard to transduce, expand in vitro, and sustain shorter in vivo comparing to infiltrated T cells. Moreover, CAR-NK therapy faces challenges as CAR-T therapy does, e.g., the time, the cost, and the potential biohazard due to the use of animal-derived products. Thus, enormous efforts are needed to develop safe, effective, and large-scalable protocols for obtaining CAR-NK cells. Here, we reviewed current progress of CAR-NK therapy, including its biological properties, CAR compositions, preparation of CAR-NK cells, and clinical progresses. We also discussed safety issues raised from genetic engineering. We hope this review is instructive to the research community and a broad range of readers.

Association between quantitative and qualitative image features of contrast-enhanced mammography and molecular subtypes of breast cancer.

BACKGROUND: The molecular subtype of breast cancer is one of the most important factors affecting patient prognosis. The study aimed to analyze the association between quantitative and qualitative features of contrast-enhanced mammography (CEM) images and breast cancer molecular subtypes. METHODS: This retrospective double-center study included women who underwent CEM between November 2017 and April 2020. Each patient had at least 1 malignant lesion confirmed by pathology. The CEM images were evaluated by 2 radiologists to obtain quantitative and qualitative image features. The molecular subtypes were studied as dichotomous outcomes, including luminal versus non-luminal, human epidermal growth factor receptor (HER2)-enriched versus non-HER2-enriched, and triple-negative breast cancer (TNBC) versus non-TNBC subtypes. The association between the image features and molecular subtypes was analyzed by multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) provided. RESULTS: A total of 151 patients with 160 malignant lesions were included in the study. For quantitative features, a higher standard deviation of lesion density was associated with non-luminal (OR =0.88, 95% CI: 0.81 to 0.96, P=0.004) and HER2-enriched breast cancers (OR =1.16, 95% CI: 1.04 to 1.28, P=0.006). The relative degree of enhancement (RDE) and contrast-to-noise ratio (CNR) were not associated with molecular subtypes. However, a higher CNR/lesion size (OR =1.06, 95% CI: 1.01 to 1.12, P=0.012) was associated with luminal subtype cancers, and a higher RDE/lesion size (OR =0.94, 95% CI: 0.88 to 1.00, P=0.035) or a higher CNR/lesion size (OR =0.94, 95% CI: 0.88-1.00, P=0.038) was associated with non-TNBCs. For qualitative features, the presence of calcification was associated with HER2-enriched breast cancers (OR =2.91, 95% CI: 1.10 to 7.67, P=0.031). The presence of architectural distortion was associated with luminal cancer (OR =14.50, 95% CI: 1.91 to 110.14, P=0.010) and non-TNBC (OR =0.05, 95% CI: 0.00 to 0.43, P=0.022). Non-mass enhancement (OR =2.78, 95% CI: 1.08 to 7.14, P=0.033) was associated with HER2-enriched breast cancers. An association remained after adjustments for age, breast thickness, and breast density (all adjusted P<0.050). CONCLUSIONS: The quantitative and qualitative imaging features of CEM could contribute to distinguishing breast cancer molecular subtypes.

Intratumoral and peritumoral radiomics for preoperative prediction of neoadjuvant chemotherapy effect in breast cancer based on contrast-enhanced spectral mammography.

OBJECTIVE: To investigative the performance of intratumoral and peritumoral radiomics based on contrast-enhanced spectral mammography (CESM) to preoperatively predict the effect of the neoadjuvant chemotherapy (NAC) of breast cancers. MATERIALS AND METHODS: A total of 118 patients with breast cancer who underwent preoperative CESM and NAC from July 2017 to June 2020 were retrospectively analyzed, and the patients were grouped into training (n = 81) and test sets (n = 37) according to the CESM examination time. NAC effect for each patient was assessed by pathology. Intratumoral and peritumoral radiomics features were extracted from CESM images, and feature selection was performed through the Mann-Whitney U test and least absolute shrinkage and selection operator regression (LASSO). Five radiomics signatures based on intratumoral regions, 5-mm peritumoral regions, 10-mm peritumoral regions, intratumoral regions + 5-mm peritumoral regions, and intratumoral regions + 10-mm peritumoral regions were calculated through a linear combination of selected features weighted by their respective coefficients. The prediction performance of radiomics signatures was assessed by the area under the receiver operator characteristic (ROC) curve, the precision-recall (P-R) curve, the calibration curve, and decision curve analysis (DCA). RESULTS: Ten radiomics features were selected to establish the radiomics signature of intratumoral regions + 5-mm peritumoral regions, which yielded a maximum AUC of 0.85 (95% CI, 0.72-0.98) in the test set. The calibration curves, P-R curves, and DCA showed favorable predictive performance of the five radiomics signatures. CONCLUSION: The intratumoral and peritumoral radiomics based on CESM exhibited potential for predicting the NAC effect in breast cancer, which could guide treatment decisions. KEY POINTS: • The intratumoral and peritumoral CESM-based radiomics signatures show good performance in predicting the NAC effect in breast cancer.

LncRNA LINC00924 upregulates NDRG2 to inhibit epithelial-mesenchymal transition via sponging miR-6755-5p in hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a life-threatening cancer. Long noncoding RNAs participate in HBV-related HCC progression. Based on the bioinformatics analysis, LINC00924 downregulation is positively related to unfavorable outcomes in patients with HBV-related HCC. Herein, we detected the biological functions and regulatory system of LINC00924 in HCC. The LINC00924 downregulation in HBV-related HCC tissues and cells was revealed by reverse transcription-quantitative polymerase chain reaction. Functionally, as Transwell assays and western blotting indicated, LINC00924 elevation inhibited HCC cell invasion and epithelial-mesenchymal transition (EMT). The binding site between LINC00924 and miR-6755-5p was determined by luciferase reporter assays. miR-6755-5p was confirmed to target NDRG2. miR-6755-5p upregulation decreased NDRG2 messenger RNA (mRNA) and protein levels. The mRNA and protein levels of NDRG2 were downregulated in tissues and cells. NDRG2 knockdown attenuated the inhibition induced by LINC00924 overexpression on invasion and EMT of HCC cells. In summary, LINC00924 increases NDRG2 expression to inhibit EMT by targeting miR-6755-5p in HBV-related HCC.

Incorporating the clinical and radiomics features of contrast-enhanced mammography to classify breast lesions: a retrospective study.

BACKGROUND: Contrast-enhanced mammography (CEM) is a promising breast imaging technique. A limited number of studies have focused on the radiomics analysis of CEM. We intended to explore whether a model constructed with both clinical and radiomics features of CEM can better classify benign and malignant breast lesions. METHODS: This retrospective, double-center study included women who underwent CEM between August 2017 and February 2020. The data from Center 1 were used as training set and the data from Center 2 were used as external testing set (training: testing =2:1). Models were constructed with the clinical, radiomics, and clinical + radiomics features of CEM. The clinical features included patient age and clinical image features interpreted by the radiologists. The radiomics features were extracted from high-energy (HE), low-energy (LE), and dual-energy subtraction (DES) images of CEM. The Mann-Whitney U test, Pearson correlation and Boruta's approach were used to select the radiomics features. Random Forest (RF) and logistic regression were used to establish the models. For the testing set, the areas under the curve (AUCs) and 95% confidence intervals (CIs) were employed to evaluate the performance of the models. For the training set, the mean AUCs were obtained by performing internal validation for 100 iterations and then compared by the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: A total of 226 women (mean age: 47.4±10.1 years) with 226 pathologically proven breast lesions (101 benign; 125 malignant) were included. For the external testing set, the AUCs were 0.964 (95% CI: 0.918-1.000) for the combined model, 0.947 (95% CI: 0.891-0.997) for the radiomics model, and 0.882 (95% CI: 0.803-0.962) for the clinical model. In the internal validation process, the combined model achieved a mean AUC of 0.934±0.030, which was significantly higher than those of the radiomics (mean AUC =0.921±0.031, adjusted P<0.050) and clinical models (mean AUC =0.907±0.036; adjusted P<0.050). CONCLUSIONS: Incorporating both clinical and radiomics features of CEM may achieve better classification results for breast lesions.

Graphitization and Performance of Deadman Coke in a Large Dissected Blast Furnace.

The graphitization and performance of deadman coke in the blast furnace hearth have an essential influence on the longevity of the blast furnace. In this paper, coke samples were obtained from various heights in a hearth during the overhaul of the blast furnace. The voidage, particle size, graphitization degree, microstructure, and structure evolution of multiple cokes were analyzed through digital image processing, XRD, Raman spectra, scanning electron microscopy, and energy-dispersive X-ray spectroscopy (SEM-EDS). The graphitization results were compared with feed coke, tuyere coke, cohesive zone coke, and deadman coke in reference, and the main findings were analyzed. The following results were obtained. First, the voidage of deadman coke increased and then decreased with the increase of the depth while the particle size continued to decrease. In addition, the consumption rate of coke as a carburizer, reductant, and heart source was 8.47, 30.95, and 60.58%, respectively. Second, the graphitization degree of deadman coke was extremely high and showed a trend of first increasing and then decreasing. Finally, the evolution mechanism of coke graphitization was proposed. Molten iron, alkali metal, temperature, and mineral were the crucial factors that affect the graphitization of coke. The turning point of the graphitization degree was related to the buoyancy of the hearth.

Radiomic Analysis of Contrast-Enhanced Mammography With Different Image Types: Classification of Breast Lesions.

Objective: A limited number of studies have focused on the radiomic analysis of contrast-enhanced mammography (CEM). We aimed to construct several radiomics-based models of CEM for classifying benign and malignant breast lesions. Materials and Methods: The retrospective, double-center study included women who underwent CEM between November 2013 and February 2020. Radiomic analysis was performed using high-energy (HE), low-energy (LE), and dual-energy subtraction (DES) images from CEM. Datasets were randomly divided into the training and testing sets at a ratio of 7:3. The maximum relevance minimum redundancy (mRMR) method and least absolute shrinkage and selection operator (LASSO) logistic regression were used to select the radiomic features and construct the best classification models. The performances of the models were assessed by the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI). Leave-group-out cross-validation (LGOCV) for 100 rounds was performed to obtain the mean AUCs, which were compared by the Wilcoxon rank-sum test and the Kruskal-Wallis rank-sum test. Results: A total of 192 women with 226 breast lesions (101 benign; 125 malignant) were enrolled. The median age was 48 years (range, 22-70 years). For the classification of breast lesions, the AUCs of the best models were 0.931 (95% CI: 0.873-0.989) for HE, 0.897 (95% CI: 0.807-0.981) for LE, 0.882 (95% CI: 0.825-0.987) for DES images and 0.960 (95% CI: 0.910-0.998) for all of the CEM images in the testing set. According to LGOCV, the models constructed with the HE images and all of the CEM images showed the highest mean AUCs for the training (0.931 and 0.938, respectively; P < 0.05 for both) and testing sets (0.892 and 0.889, respectively; P = 0.55 for both), which were significantly higher than those of the two models constructed with the LE and DES images in the training (0.912 and 0.899, respectively; all P < 0.05) and testing sets (0.866 and 0.862, respectively; all P < 0.05). Conclusions: Radiomic analysis of CEM images was valuable for classifying benign and malignant breast lesions. The use of HE images or all three types of CEM images can achieve the best performance.

Contrast-Enhanced Spectral Mammography-Based Radiomics Nomogram for the Prediction of Neoadjuvant Chemotherapy-Insensitive Breast Cancers.

PURPOSE: We developed and validated a contrast-enhanced spectral mammography (CESM)-based radiomics nomogram to predict neoadjuvant chemotherapy (NAC)-insensitive breast cancers prior to treatment. METHODS: We enrolled 117 patients with breast cancer who underwent CESM examination and NAC treatment from July 2017 to April 2019. The patients were grouped randomly into a training set (n = 97) and a validation set (n = 20) in a ratio of 8:2. 792 radiomics features were extracted from CESM images including low-energy and recombined images for each patient. Optimal radiomics features were selected by using analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation, to develop a radiomics score in the training set. A radiomics nomogram incorporating the radiomics score and independent clinical risk factors was then developed using multivariate logistic regression analysis. With regard to discrimination and clinical usefulness, radiomics nomogram was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC) and decision curve analysis (DCA). RESULTS: The radiomics nomogram that incorporates 11 radiomics features and 3 independent clinical risk factors, including Ki-67 index, background parenchymal enhancement (BPE) and human epidermal growth factor receptor-2 (HER-2) status, showed an encouraging discrimination power with AUCs of 0.877 [95% confidence interval (CI) 0.816 to 0.924] and 0.81 (95% CI 0.575 to 0.948) in the training and validation sets, respectively. DCA revealed the increased clinical usefulness of this nomogram. CONCLUSION: The proposed radiomics nomogram that integrates CESM-derived radiomics features and clinical parameters showed potential feasibility for predicting NAC-insensitive breast cancers.

Role and dynamics of vacuolar pH during cell-in-cell mediated death.

The nonautonomous cell death by entosis was mediated by the so-called cell-in-cell structures, which were believed to kill the internalized cells by a mechanism dependent on acidified lysosomes. However, the precise values and roles of pH critical for the death of the internalized cells remained undetermined yet. We creatively employed keima, a fluorescent protein that displays different excitation spectra in responding to pH changes, to monitor the pH dynamics of the entotic vacuoles during cell-in-cell mediated death. We found that different cells varied in their basal intracellular pH, and the pH was relatively stable for entotic vacuoles containing live cells, but sharply dropped to a narrow range along with the inner cell death. In contrast, the lipidation of entotic vacuoles by LC3 displayed previously underappreciated complex patterns associated with entotic and apoptotic death, respectively. The pH decline seemed to play distinct roles in the two types of inner cell deaths, where apoptosis is preceded with moderate pH decline while a profound pH decline is likely to be determinate for entotic death. Whereas the cancer cells seemed to be lesser tolerant to acidified environments than noncancerous cells, manipulating vacuolar pH could effectively control inner cell fates and switch the ways whereby inner cell die. Together, this study demonstrated for the first time the pH dynamics of entotic vacuoles that dictate the fates of internalized cells, providing a rationale for tuning cellular pH as a potential way to treat cell-in-cell associated diseases such as cancer.