Anatomical Prior and Inter-Slice Consistency for Semi-Supervised Vertebral Structure Detection in 3D Ultrasound Volume.

Three-dimensional (3D) ultrasound imaging technique has been applied for scoliosis assessment, but the current assessment method only uses coronal projection images and cannot illustrate the 3D deformity and vertebra rotation. The vertebra detection is essential to reveal 3D spine information, but the detection task is challenging due to complex data and limited annotations. We propose VertMatch to detect vertebral structures in 3D ultrasound volume containing a detector and classifier. The detector network finds the potential positions of structures on transverse slice globally, and then the local patches are cropped based on detected positions. The classifier is used to distinguish whether the patches contain real vertebral structures and screen the predicted positions from the detector. VertMatch utilizes unlabeled data in a semi-supervised manner, and we develop two novel techniques for semi-supervised learning: 1) anatomical prior is used to acquire high-quality pseudo labels; 2) inter-slice consistency is used to utilize more unlabeled data by inputting multiple adjacent slices. Experimental results demonstrate that VertMatch can detect vertebra accurately in ultrasound volume and outperforms state-of-the-art methods. Moreover, VertMatch is also validated in automatic spinous process angle measurement on forty subjects with scoliosis, and the results illustrate that it can be a promising approach for the 3D assessment of scoliosis.

A clinicopathologic study of 13 cases of primary lymphoma in soft tissue and review of literature.

Primary lymphoma in soft tissue is very rare. In order to understand the clinicopathological features of primary lymphoma in soft tissue, we found 13 cases (0.3%) of primary lymphoma in soft tissue by reviewing 4303 lymphomas diagnosed in our institution from 2010 to 2019. Tumors were found in the following sites: 8 in lower extremity (2 in leg, 1 in calf, 1 in knee and 4 in buttock), 1 in upper extremity (left shoulder) and 4 in the trunk (3 in waist and 1 in thoracolumbar). The most common histologic type was DLBCL (7/13, 54.8%). 6 cases of which had follow-up information. 25 patients were also selected by screening the English literature search (from Jan 2010 to December 2019) including 1102 studies. Compared to the results of literature review, our results are similar with them. The tumor sites were as follows: 10 in lower extremity, 4 in upper extremity, 9 in the trunk and 2 in masticatory muscle. The most common histological type was also DLBCL (n=11/25, 44%). Overall survival analysis of all 31 patients including our 6 cases with primary lymphoma in soft tissue showed no significant difference between different histological type (Log Rank P=0.120, Breslow P=0.157). The differential diagnosis includes malignant melanoma, rhabdomyosarcoma and metastatic carcinoma in soft tissue.

Self-Assembly of a Multifunction DNA Tetrahedron for Effective Delivery of Aptamer PL1 and Pcsk9 siRNA Potentiate Immune Checkpoint Therapy for Colorectal Cancer.

Compared with the traditional single therapy, nanomedicine has promoted a multimodal combination treatment for various carcinomas, especially the development of corresponding intelligent multifunctional biomaterials based on advanced DNA nanotechnology has great potential in cancer combination therapy. Herein, we describe a strategy to "backpack" aptamer PL1, which specifically binds to PD-L1 and Pcsk9 siRNA on well-defined DNA tetrahedral nanoparticles (TDNs) via DNA hybridization, which collectively contributes to the effective therapy for colorectal cancer (CRC). In addition, we designed a targeted TDN upon folic acid (FA) recognition, limiting its release to the sites of tumors where folic acid receptor (FAR) is encountered. Our results demonstrated that the TDN-FA/PL1/Pcsk9-siRNA could free immune cells to target CRC cells and attenuate 83.48% tumor growth in mouse models of CT26 CRC. Mechanically, the cancer-targeting FA guided TDN-FA/PL1/Pcsk9-siRNA into tumor cells, thereby ensuring that the aptamer PL1 could choke the mutual effects between PD-1 and PD-L1, followed by a 1.69-fold increase in T cell number and a 1.9-fold suppression of T cell activity by the PD-1/PD-L1 pathway, while Pcsk9 siRNA decreased Pcsk9 expression averagely to the extent of 65.13% and then facilitated intratumoral infiltration of cytotoxic T cells robustly with IFN-γ and Granzyme B expression. Our results reveal that the multifunctional TND-FA/PL1/Pcsk9-siRNA is effective and safe for CRC therapy, thereby expanding the application of DNA nanotechnology for innovative therapies of various cancers.

Pathological and Prognostic Characterization of Craniopharyngioma Based on the Expression of TrkA, ß-Catenin, Cell Cycle Markers, and BRAF V600E Mutation.

We collected 61 craniopharyngioma (CP) specimens to investigate the expression of TrkA, ß-catenin, BRAF gene mutation, and NTRK1 fusion in CP. There were 37 male and 24 female individuals with a median age of 34 years (range, 4-75 years). Histologically, there were 46 cases of adamantinomatous craniopharyngioma (ACP), 14 cases of papillary craniopharyngioma (PCP), and 1 case with a mixed adamantinomatous and papillary pattern. By immunohistochemistry, we found that moderate/high TrkA expression was detected in 47% (28/60) CP and was significantly higher in adult patients (p = 0.018). Interestingly, TrkA is more expressed in "whorled epithelium" cells in ACP, similar to the localization of abnormal ß-catenin. The abnormal expression rate of ß-catenin was 70% (43/61), and the medium/high cyclin D1 expression rate was 73% (44/60), both of which were significantly higher in ACP than in PCP. Of the CP, 41% (21/51) had a moderate/strong P16-positive signal; 58% (34/59) showed a high Ki-67 expression, and there was a significant correlation between high Ki-67 L.I. and high tumor recurrence (p = 0.021). NTRK1 fusion was not found in CP by fluorescence in situ hybridization (FISH). By PCR, 26% (15/58) CP showed BRAF V600E gene mutation, which mainly occurred in PCP (100%, 14/14) except one case of mixed CP. Moreover, TrkA expression was negatively correlated with Ki-67 index and positively correlated with P16 expression. There was a significantly negative correlation between BRAF V600E mutation and abnormal ß-catenin expression. Our results demonstrate for the first time that TrkA expression might occur in CP, especially in adult CP patients, and suggest that cyclin D1 could be used for ACP histological classification in addition to ß-catenin and BRAF V600E mutation, while Ki-67 could be used as a marker to predict CP recurrence.

Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer.

BACKGROUND: Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear. METHODS: Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers. RESULTS: Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells. CONCLUSIONS: Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

Automatic Detection and Measurement of Spinous Process Curve on Clinical Ultrasound Spine Images.

The ultrasound (US) imaging technique has been applied to scoliosis assessment, and the proxy Cobb angle can be acquired on the US coronal images. The spinous process angle (SPA) is a valuable parameter to indicate 3-D deformity of spine. However, the SPA cannot be measured on US images since the spinous process (SP) is merged in the soft tissue layer and impossible to be identified on the coronal view directly. A new method based on the gradient vector flow (GVF) snake model was proposed to automatically locate SP position on the US transverse images, and the density-based spatial clustering of application with noise (DBSCAN) was used to remove the outliers out of the detected location results. With marking the SP points on the US coronal image, the SP curve was interpolated and the SPA was measured. The algorithm was evaluated on 50 subjects with various severity of scoliosis, and two raters measured the SPA on both US images and radiographs manually. The mean absolute differences (MADs) of SPAs obtained from the two modalities were 3.4° ± 2.4° and 3.6° ± 2.8° for the two raters, respectively, which were less than the clinical acceptance error (5°), and the results reported a good linear correlation ( ) between the US method and radiography. It indicates that the proposed method can be a promising approach for SPA measurement using the US imaging technique.

Automatic Measurement of Spinous Process Angles on Ultrasound Spine Images.

Ultrasound (US) imaging technique has been applied to measure the proxy Cobb angle and spinous process angle (SPA) for spinal curvatures of scoliosis. However manual measurement of ultrasound images is time consuming and greatly relying on the experience of raters. The objectives of this work are to develop an automatic measurement method to assess SPA of spine curves and to evaluate the accuracy and reliability of the method. The spinous process curves were identified and fitted on US images, and the automatically measured SPA were compared with the results from US manual and radiographic measurements. It illustrates that the US-auto measurement of SPA presents higher correlation and smaller difference with clinical standard radiographic results than the US-manual measurement.