Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole Slide Images in Adult Patients with Diffuse Glioma.

Isocitrate dehydrogenase gene (IDH) mutation is one of the most important molecular markers of glioma. Accurate detection of IDH status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. Herein, a clustering-based hybrid of a convolutional neural network and a vision transformer deep learning model was developed to detect IDH mutation status from annotation-free hematoxylin and eosin-stained whole slide pathologic images of 2275 adult patients with diffuse gliomas. For comparison, a pure convolutional neural network, a pure vision transformer, and a classic multiple-instance learning model were also assessed. The hybrid model achieved an area under the receiver operating characteristic curve of 0.973 in the validation set and 0.953 in the external test set, outperforming the other models. The hybrid model's ability in IDH detection between difficult subgroups with different IDH status but shared histologic features, achieving areas under the receiver operating characteristic curve ranging from 0.850 to 0.985 in validation and test sets. These data suggest that the proposed hybrid model has a potential to be used as a computational pathology tool for preliminary rapid detection of IDH mutation from whole slide images in adult patients with diffuse gliomas.

Habitat Imaging With Tumoral and Peritumoral Radiomics for Prediction of Lung Adenocarcinoma Invasiveness on Preoperative Chest CT: A Multicenter Study.

Background: Tumors' growth processes result in spatial heterogeneity, with the development of tumor subregions (i.e., habitats) having unique biologic characteristics. Objective: To develop and validate a habitat model combining tumor and peritumoral radiomics features on chest CT for predicting invasiveness of lung adenocarcinoma. Methods: This retrospective study included 1156 patients (mean age, 57.5 years; 464 male, 692 female) from three centers and a public dataset, who underwent chest CT before lung adenocarcinoma resection (variable date ranges across datasets). Patients from one center formed training (n=500) and validation (n=215) sets; patients from the other sources formed three external test sets (n=249, 113, 79). For each patient, a single nodule was manually segmented on chest CT. The nodule segmentation was combined with an automatically generated 4-mm peritumoral region into a whole-volume volume-of-interest (VOI). A Gaussian mixture model (GMM) identified voxel clusters with similar first-order energy across patients. GMM results were used to divide each patient's whole-volume VOI into multiple habitats, defined consistently across patients. Radiomic features were extracted from each habitat. After feature selection, a habitat model was developed for predicting invasiveness, using pathologic assessment as a reference. An integrated model was constructed, combining features extracted from habitats and whole-volume VOIs. Model performance was evaluated, including in subgroups based on nodule density (pure ground-glass, part-solid, solid). Results: Invasive cancer was diagnosed in 625/1156 patients. GMM identified four as the optimal number of voxel clusters and thus of per-patient tumor habitats. The habitat model had AUC of 0.932 in the validation set, and 0.881, 0.880, and 0.764 in the three external test sets. The integrated model had AUC of 0.947 in the validation set and 0.936, 0.908, and 0.800 in the three external test sets. In the three external test sets combined, across nodule densities, AUCs for the habitat model were 0.836-0.969 and for the integrated model were 0.846-0.917. Conclusions: Habitat imaging combining tumoral and peritumoral radiomic features could help predict lung adenocarcinoma invasiveness. Prediction is improved when combining information on tumor subregions and the tumor overall. Clinical Impact: The findings may aid personalized preoperative assessments to guide clinical decision-making in lung adenocarcinoma.

Radiomic features from multiparametric magnetic resonance imaging predict molecular subgroups of pediatric low-grade gliomas.

BACKGROUND: We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI. METHODS: 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation. RESULTS: We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set. CONCLUSIONS: The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov (NCT04217018).

Image-based deep learning identifies glioblastoma risk groups with genomic and transcriptomic heterogeneity: a multi-center study.

OBJECTIVES: To develop and validate a deep learning imaging signature (DLIS) for risk stratification in patients with multiforme (GBM), and to investigate the biological pathways and genetic alterations underlying the DLIS. METHODS: The DLIS was developed from multi-parametric MRI based on a training set (n = 600) and validated on an internal validation set (n = 164), an external test set 1 (n = 100), an external test set 2 (n = 161), and a public TCIA set (n = 88). A co-profiling framework based on a radiogenomics analysis dataset (n = 127) using multiscale high-dimensional data, including imaging, transcriptome, and genome, was established to uncover the biological pathways and genetic alterations underpinning the DLIS. RESULTS: The DLIS was associated with survival (log-rank p < 0.001) and was an independent predictor (p < 0.001). The integrated nomogram incorporating the DLIS achieved improved C indices than the clinicomolecular nomogram (net reclassification improvement 0.39, p < 0.001). DLIS significantly correlated with core pathways of GBM (apoptosis and cell cycle-related P53 and RB pathways, and cell proliferation-related RTK pathway), as well as key genetic alterations (del_CDNK2A). The prognostic value of DLIS-correlated genes was externally confirmed on TCGA/CGGA sets (p < 0.01). CONCLUSIONS: Our study offers a biologically interpretable deep learning predictor of survival outcomes in patients with GBM, which is crucial for better understanding GBM patient's prognosis and guiding individualized treatment. KEY POINTS: • MRI-based deep learning imaging signature (DLIS) stratifies GBM into risk groups with distinct molecular characteristics. • DLIS is associated with P53, RB, and RTK pathways and del_CDNK2A mutation. • The prognostic value of DLIS-correlated pathway genes is externally demonstrated.

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of Axially Chiral α-Carbolinones via Heterocycle Formation.

An NHC-catalyzed atroposelective synthesis of axially chiral α-carbolinones from α,ß-unsaturated iminoindole derivatives and α-chloroaldehydes was developed. The reaction proceeds through a cascade process including [4 + 2] annulation and then oxidative dehydrogenation with concomitant central-to-axial chirality conversion under mild conditions. The developed method opens a new avenue to efficiently access axially chiral α-carbolinones in moderate to good enantioselectivities.

Predicting 1p/19q co-deletion status from magnetic resonance imaging using deep learning in adult-type diffuse lower-grade gliomas: a discovery and validation study.

Determination of 1p/19q co-deletion status is important for the classification, prognostication, and personalized therapy in diffuse lower-grade gliomas (LGG). We developed and validated a deep learning imaging signature (DLIS) from preoperative magnetic resonance imaging (MRI) for predicting the 1p/19q status in patients with LGG. The DLIS was constructed on a training dataset (n = 330) and validated on both an internal validation dataset (n = 123) and a public TCIA dataset (n = 102). The receiver operating characteristic (ROC) analysis and precision recall curves (PRC) were used to measure the classification performance. The area under ROC curves (AUC) of the DLIS was 0.999 for training dataset, 0.986 for validation dataset, and 0.983 for testing dataset. The F1-score of the prediction model was 0.992 for training dataset, 0.940 for validation dataset, and 0.925 for testing dataset. Our data suggests that DLIS could be used to predict the 1p/19q status from preoperative imaging in patients with LGG. The imaging-based deep learning has the potential to be a noninvasive tool predictive of molecular markers in adult diffuse gliomas.

Glioma survival prediction from whole-brain MRI without tumor segmentation using deep attention network: a multicenter study.

OBJECTIVES: To develop and validate a deep learning model for predicting overall survival from whole-brain MRI without tumor segmentation in patients with diffuse gliomas. METHODS: In this multicenter retrospective study, two deep learning models were built for survival prediction from MRI, including a DeepRisk model built from whole-brain MRI, and an original ResNet model built from expert-segmented tumor images. Both models were developed using a training dataset (n = 935) and an internal tuning dataset (n = 156) and tested on two external test datasets (n = 194 and 150) and a TCIA dataset (n = 121). C-index, integrated Brier score (IBS), prediction error curves, and calibration curves were used to assess the model performance. RESULTS: In total, 1556 patients were enrolled (age, 49.0 ± 13.1 years; 830 male). The DeepRisk score was an independent predictor and can stratify patients in each test dataset into three risk subgroups. The IBS and C-index for DeepRisk were 0.14 and 0.83 in external test dataset 1, 0.15 and 0.80 in external dataset 2, and 0.16 and 0.77 in TCIA dataset, respectively, which were comparable with those for original ResNet. The AUCs at 6, 12, 24, 26, and 48 months for DeepRisk ranged between 0.77 and 0.94. Combining DeepRisk score with clinicomolecular factors resulted in a nomogram with a better calibration and classification accuracy (net reclassification improvement 0.69, p < 0.001) than the clinical nomogram. CONCLUSIONS: DeepRisk that obviated the need of tumor segmentation can predict glioma survival from whole-brain MRI and offers incremental prognostic value. KEY POINTS: • DeepRisk can predict overall survival directly from whole-brain MRI without tumor segmentation. • DeepRisk achieves comparable accuracy in survival prediction with deep learning model built using expert-segmented tumor images. • DeepRisk has independent and incremental prognostic value over existing clinical parameters and IDH mutation status.

Quantitative detection of parasitic ciliate Cryptocaryon irritans in seawater with an optimized sample processing method.

The protozoan Cryptocaryon irritans is one of the most important ectoparasites of marine fish, causing 'white spot disease' and mass mortality in aquaculture. To accurately predict disease outbreaks and develop prevention strategies, improved detection methods are required that are sensitive, convenient and rapid. In this study, a pair of specific primers based on the C. irritans 18S rRNA gene was developed and used in a real-time PCR (qPCR) assay. This assay was able to detect five theronts in 1 L of natural seawater. Furthermore, a linear model was established to analyse the log of Ct value and parasite abundance in seawater (y = -2.9623x + 24.2930), and the coefficient of determination (R2 ) value was 0.979. A lysis buffer was optimized for theront DNA extraction and used for storage sample. This method was superior to the commercial water DNA kit, and there was no significant degradation of DNA at room temperature for 24-96 hr. A dilution method was developed to manage qPCR inhibitors and used to investigate natural seawater samples in a net cage farm with diseased fish, and the findings were consistent with the actual situation. This study provides a valuable tool for assisting in the early monitoring and control of cryptocaryoniasis in aquaculture.

Biologic Pathways Underlying Prognostic Radiomics Phenotypes from Paired MRI and RNA Sequencing in Glioblastoma.

Background The biologic meaning of prognostic radiomics phenotypes remains poorly understood, hampered in part by lack of multicenter reproducible evidence. Purpose To uncover the biologic meaning of individual prognostic radiomics phenotypes in glioblastomas using paired MRI and RNA sequencing data and to validate the reproducibility of the identified radiogenomics linkages externally. Materials and Methods This retrospective multicenter study included four data sets gathered between January 2015 and December 2016. From a radiomics analysis set, a 13-feature radiomics signature was built using preoperative MRI for overall survival prediction. Using a radiogenomics training set with both MRI and RNA sequencing, biologic pathways were enriched and correlated with each of the 13 radiomics phenotypes. Radiomics-correlated key genes were identified to derive a prognostic radiomics gene expression (RadGene) score. The reproducibility of identified pathways and genes was validated with an external test set and a public data set (The Cancer Genome Atlas [TCGA]). A log-rank test was performed to assess prognostic significance. Results A total of 435 patients (mean age, 55 years ± 15 [standard deviation]; 263 men) were enrolled. The radiomics signature was associated with overall survival (hazard ratio [HR], 3.68; 95% CI: 2.08, 6.52; P < .001) in the radiomics validation subset. Four types of prognostic radiomics phenotypes were correlated with distinct pathways: immune, proliferative, treatment responsive, and cellular functions (false-discovery rate < 0.10). Thirty radiomics-correlated genes were identified. The prognostic significance of the RadGene score was confirmed in an external test set (HR, 2.02; 95% CI: 1.19, 3.41; P = .01) and a TCGA test set (HR, 1.43; 95% CI: 1.001, 2.04; P = .048). The radiomics-associated pathways and key genes can be replicated in an external test set. Conclusion Individual radiomics phenotypes on MRI scans predictive of overall survival were driven by distinct key pathways involved in immune regulation, tumor proliferation, treatment responses, and cellular functions in glioblastoma, which could be reproduced externally. © RSNA, 2021 Online supplemental material is available for this article.

Validation of CT radiomics for prediction of distant metastasis after surgical resection in patients with clear cell renal cell carcinoma: exploring the underlying signaling pathways.

OBJECTIVES: To develop a radiomics model using preoperative multiphasic CT for predicting distant metastasis after surgical resection in patients with localized clear cell renal cell carcinoma (ccRCC) and to identify key biological pathways underlying the predictive radiomics features using RNA sequencing data. METHODS: In this multi-institutional retrospective study, a CT radiomics metastasis score (RMS) was developed from a radiomics analysis cohort (n = 184) for distant metastasis prediction. Using a gene expression analysis cohort (n = 326), radiomics-associated gene modules were identified. Based on a radiogenomics discovery cohort (n = 42), key biological pathways were enriched from the gene modules. Furthermore, a multigene signature associated with RMS was constructed and validated on an independent radiogenomics validation cohort (n = 37). RESULTS: The 9-feature-based RMS predicted distant metastasis with an AUC of 0.861 in validation set and was independent with clinical factors (p < 0.001). A gene module comprising 114 genes was identified to be associated with all nine radiomics features (p < 0.05). Four enriched pathways were identified, including ECM-receptor interaction, focal adhesion, protein digestion and absorption, and PI3K-Akt pathways. Most of them play important roles in tumor progression and metastasis. A 19-gene signature was constructed from the radiomics-associated gene module and predicted metastasis with an AUC of 0.843 in the radiogenomics validation cohort. CONCLUSIONS: CT radiomics features can predict distant metastasis after surgical resection of localized ccRCC while the predictive radiomics phenotypes may be driven by key biological pathways related to cancer progression and metastasis. KEY POINTS: • Radiomics features from primary tumor in preoperative CT predicted distant metastasis after surgical resection in patients with localized ccRCC. • CT radiomics features predictive of distant metastasis were associated with key signaling pathways related to tumor progression and metastasis. • Gene signature associated with radiomics metastasis score predicted distant metastasis in localized ccRCC.

Differentiation of clear cell and non-clear cell renal cell carcinomas by all-relevant radiomics features from multiphase CT: a VHL mutation perspective.

OBJECTIVES: To develop a radiomics model with all-relevant imaging features from multiphasic computed tomography (CT) for differentiating clear cell renal cell carcinoma (ccRCC) from non-ccRCC and to investigate the possible radiogenomics link between the imaging features and a key ccRCC driver gene-the von Hippel-Lindau (VHL) gene mutation. METHODS: In this retrospective two-center study, two radiomics models were built using random forest from a training cohort (170 patients), where one model was built with all-relevant features and the other with minimum redundancy maximum relevance (mRMR) features. A model combining all-relevant features and clinical factors (sex, age) was also built. The radiogenomics association between selected features and VHL mutation was investigated by Wilcoxon rank-sum test. All models were tested on an independent validation cohort (85 patients) with ROC curves analysis. RESULTS: The model with eight all-relevant features from corticomedullary phase CT achieved an AUC of 0.949 and an accuracy of 92.9% in the validation cohort, which significantly outperformed the model with eight mRMR features (seven from nephrographic phase and one from corticomedullary phase) with an AUC of 0.851 and an accuracy of 81.2%. Combining age and sex did not benefit the performance. Five out of eight all-relevant features were significantly associated with VHL mutation, while all eight mRMR features were significantly associated with VHL mutation (false discovery rate-adjusted p < 0.05). CONCLUSIONS: All-relevant features in corticomedullary phase CT can be used to differentiate ccRCC from non-ccRCC. Most subtype-discriminative imaging features were found to be significantly associated with VHL mutation, which may underlie the molecular basis of the radiomics features. KEY POINTS: • All-relevant features in corticomedullary phase CT can be used to differentiate ccRCC from non-ccRCC with high accuracy. • Most RCC-subtype-discriminative CT features were associated with the key RCC-driven gene-the VHL gene mutation. • Radiomics model can be more accurate and interpretable when the imaging features could reflect underlying molecular basis of RCC.

Multiregional radiomics features from multiparametric MRI for prediction of MGMT methylation status in glioblastoma multiforme: A multicentre study.

OBJECTIVES: To build a reliable radiomics model from multiregional and multiparametric magnetic resonance imaging (MRI) for pretreatment prediction of O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status in glioblastoma multiforme (GBM). METHODS: In this retrospective multicentre study, 1,705 multiregional radiomics features were automatically extracted from multiparametric MRI. A radiomics model with a minimal set of all-relevant features and a radiomics model with univariately-predictive and non-redundant features were built for MGMT methylation prediction from a primary cohort (133 patients) and tested on an independent validation cohort (60 patients). Predictive models combing clinical factors were built and evaluated. Both radiomics models were assessed on subgroups stratified by clinical factors. RESULTS: The radiomics model with six all-relevant features allowed pretreatment prediction of MGMT methylation (AUC=0.88, accuracy=80 %), which significantly outperformed the model with eight univariately-predictive and non-redundant features (AUC=0.76, accuracy=70 %). Combing clinical factors with radiomics features did not benefit the prediction performance. The all-relevant model achieved significantly better performance in stratified analysis. CONCLUSIONS: Radiomics model built from multiregional and multiparameter MRI may serve as a potential imaging biomarker for pretreatment prediction of MGMT methylation in GBM. The all-relevant features have the potential of offering better predictive power than the univariately-predictive and non-redundant features. KEY POINTS: • Multiregional and multiparametric MRI features reliably predicted MGMT methylation in multicentre cohorts. • All-relevant imaging features predicted MGMT methylation better than univariately-predictive and non-redundant features. • Combing clinical factors with radiomics features did not benefit the prediction performance.

[Association of Serum Soluble CD36 with Clinical Variables in Diabetic Patients with Chronic Kidney Diseas].

OBJECTIVE: To investigate the levels of serum soluble CD36 (sCD36) in patients of diabetes mellitus (DM) with chronic kidney disease (CKD),and to analyze its correlation with clinical indicators. METHODS: A total of 161 patients with CKD were enrolled in this study. The patients were divided into two groups according to whether they had DM or not: DM+CKD group and non-DM CKD group. The levels of carotid intima-media thickness (IMT) and the combination of atherosclerotic plaques were measured by color Doppler ultrasonography. Serum fasting serum samples were collected and serum sCD36 level was measured by ELISA. the status of serum sCD36 was analyzed with the progress of renal disease,and the correlation of sCD36 level with clinical indicators were analyzed. RESULTS: Among the 161 patients,87 (54%) were DM+CKD and 74 (46%) were non-DM CKD. There was no significant difference in the levels of urea nitrogen (BUN),serum creatinine (sCr),estimated glomerular filtration rate (eGFR),cystatin C (Cys-C),triglyceride (TG),cholesterol (Chol),low density lipoprotein-chol (LDL-C),urinary albumin/creatinine and IMT in the two groups (P>0.05). Compared with non-DM CKD group,the serum sCD36 level (U/L) in DM+CKD group was lower (4.58±1.06 vs. 4.97±1.28,P<0.05). In DM+CKD group,serum sCD36 was negatively correlated with BUN,sCr and Cys-C (r=⁻0.355,⁻0.336,⁻0.323; P<0.01),and positively correlated with eGFR (r= 0.399; P<0.01),but not with TG,Chol,LDL-C or IMT (P>0.05). In non-DM CKD group,there was a positive correlation between sCD36 and TG,Chol and LDL-C (r= 0.251, 0.298, 0.292; P<0.05),and negatively correlated with Cys-C (r=⁻0.287; P<0.05),but not with eGFR,BUN,sCr or IMT (P>0.05). With the progress of CKD,serum sCD36 levels gradually decreased (P>0.05). CONCLUSION: Serum sCD36 level is associated with renal function in the patients with DM complicated with CKD,but not with lipid indicators.

Diagnostic value of renal perfusion in patients with chronic kidney disease using 3D arterial spin labeling.

PURPOSE: To evaluate the diagnostic value of 3D arterial spin labeling (ASL) for noninvasive quantification of renal blood flow (RBF) in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: CKD patients (n = 27) and healthy volunteers (n = 36) underwent renal 3T ASL magnetic resonance imaging, with inversion times from 1200 to 2000 msec for volunteers in the preliminary test, and 1800 to 2000 msec for volunteers and CKD patients in the formal experiments. The cortical RBFs were compared, and a correlation between RBF and estimated glomerular filtration rate (eGFR) was evaluated. RESULTS: For healthy volunteers, RBF values increased with TIs from 1200 to 1600 msec, but were almost constant at TIs from 1600 to 2000 msec. The cortical RBF values of CKD patients were lower than that of healthy volunteers at TIs from 1800 to 2000 msec. In addition, the CKD patients had lower cortical RBF values than the healthy volunteers (P < 0.01 for both), and their RBF values positively correlated with eGFR. CONCLUSION: 3D ASL is a potential noninvasive method for measuring renal perfusion that can provide valuable information for clinical CKD diagnosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:589-594.

Neighborhood evaluator for efficient super-resolution reconstruction of 2D medical images.

BACKGROUND: Deep learning-based super-resolution (SR) algorithms aim to reconstruct low-resolution (LR) images into high-fidelity high-resolution (HR) images by learning the low- and high-frequency information. Experts' diagnostic requirements are fulfilled in medical application scenarios through the high-quality reconstruction of LR digital medical images. PURPOSE: Medical image SR algorithms should satisfy the requirements of arbitrary resolution and high efficiency in applications. However, there is currently no relevant study available. Several SR research on natural images have accomplished the reconstruction of resolutions without limitations. However, these methodologies provide challenges in meeting medical applications due to the large scale of the model, which significantly limits efficiency. Hence, we suggest a highly effective method for reconstructing medical images at any desired resolution. METHODS: Statistical features of medical images exhibit greater continuity in the region of neighboring pixels than natural images. Hence, the process of reconstructing medical images is comparatively less challenging. Utilizing this property, we develop a neighborhood evaluator to represent the continuity of the neighborhood while controlling the network's depth. RESULTS: The suggested method has superior performance across seven scales of reconstruction, as evidenced by experiments conducted on panoramic radiographs and two external public datasets. Furthermore, the proposed network significantly decreases the parameter count by over 20× and the computational workload by over 10× compared to prior researches. On large-scale reconstruction, the inference speed can be enhanced by over 5×. CONCLUSION: The novel proposed SR strategy for medical images performs efficient reconstruction at arbitrary resolution, marking a significant breakthrough in the field. The given scheme facilitates the implementation of SR in mobile medical platforms.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Supine lithotomy versus prone position in minimally invasive percutaneous nephrolithotomy for upper urinary tract calculi.

OBJECTIVE: To compare operative time, safety and effectiveness of minimally invasive percutaneous nephrolithotomy (MPCNL) in the supine lithotomy versus prone position. METHODS: Between January 2008 and December 2010, a total of 109 consecutive patients with upper urinary tract calculi were enrolled and randomly divided into group A (53 patients, supine lithotomy position) and group B (56 patients, prone position). The MPCNL procedures were performed under the guidance of real-time grayscale ultrasound system. The preoperative characteristics, intraoperative and postoperative parameters were analyzed and compared. RESULTS: All patients were successfully operated. There was no significant difference between the two groups in stone-free rate (group A 90.1 vs. group B 87.5%, p = 0.45), mean blood loss, number of access tracts, calyx puncture, mean hospital stay (group A 6 ± 1.1 vs. group B 6 ± 1.5 days, p = 0.38) and complications. But the operative time was significantly shortened in supine lithotomy position (group A 56 ± 15 vs. group B 86 ± 23 min, p < 0.001). CONCLUSIONS: The effectiveness and safety of the supine lithotomy position for MPCNL were similar to the prone position. However, the supine lithotomy position has an important advantage of reducing the operative time. The supine lithotomy position could be a good choice to perform MPCNL.

Semi-supervised Medical Image Segmentation with Multiscale Contrastive Learning and Cross-Supervision.

We propose a semi-supervised segmentation method based on multiscale contrastive learning to solve the problem of shortage of annotations in medical image segmentation tasks. We apply perturbations to the input image and encoded features and make the output as consistent as possible by cross-supervision, which is a way to improve the generalizability of the model. Two scales of contrastive learning, patch-level and pixel-level, are employed to enhance the intra-class compactness and inter-class separability of the features. We evaluate the proposed model using three public datasets for brain tumor,left atrial, and cellular nuclei segmentation. The experiments showed that our model outperforms state-of-the-art methods.Clinical relevance- The proposed method can be used for medical image segmentation with limited annotated data and achieve comparable performance to the fully annotated situation. Such an approach can be easily extended to other clinical applications.

Imaging-proteomic analysis for prediction of neoadjuvant chemotherapy responses in patients with breast cancer.

BACKGROUND: Optimizing patient selection for neoadjuvant chemotherapy in patients with breast cancer remains an unmet clinical need. Quantitative features from medical imaging were reported to be predictive of treatment responses. However, the biologic meaning of these latent features is poorly understood, preventing the clinical use of such noninvasive imaging markers. The study aimed to develop a deep learning signature (DLS) from pretreatment magnetic resonance imaging (MRI) for predicting responses to neoadjuvant chemotherapy in patients with breast cancer and to further investigate the biologic meaning of the DLS by identifying its underlying pathways using paired MRI and proteomic sequencing data. METHODS: MRI-based DLS was constructed (radiogenomic training dataset, n = 105) and validated (radiogenomic validation dataset, n = 26) for the prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy. Proteomic sequencing revealed biological functions facilitating pCR (n = 139). Their associations with DLS were uncovered by radiogenomic analysis. RESULTS: The DLS achieved a prediction accuracy of 0.923 with an AUC of 0.958, higher than the performance of the model trained by transfer learning. Cellular membrane formation, endocytosis, insulin-like growth factor binding, protein localization to membranes, and cytoskeleton-dependent trafficking were differentially regulated in patients showing pCR. Oncogenic signaling pathways, features correlated with human phenotypes, and features correlated with general biological processes were significantly correlated with DLS in both training and validation dataset (p.adj < 0.05). CONCLUSIONS: Our study offers a biologically interpretable DLS for the prediction of pCR to neoadjuvant chemotherapy in patients with breast cancer, which may guide personalized medication.