BPAT-UNet: Boundary preserving assembled transformer UNet for ultrasound thyroid nodule segmentation.

BACKGROUND AND OBJECTIVE: Accurate and efficient segmentation of thyroid nodules on ultrasound images is critical for computer-aided nodule diagnosis and treatment. For ultrasound images, Convolutional neural networks (CNNs) and Transformers, which are widely used in natural images, cannot obtain satisfactory segmentation results, because they either cannot obtain precise boundaries or segment small objects. METHODS: To address these issues, we propose a novel Boundary-preserving assembly Transformer UNet (BPAT-UNet) for ultrasound thyroid nodule segmentation. In the proposed network, a Boundary point supervision module (BPSM), which adopts two novel self-attention pooling approaches, is designed to enhance boundary features and generate ideal boundary points through a novel method. Meanwhile, an Adaptive multi-scale feature fusion module (AMFFM) is constructed to fuse features and channel information at different scales. Finally, to fully integrate the characteristics of high-frequency local and low-frequency global, the Assembled transformer module (ATM) is placed at the bottleneck of the network. The correlation between deformable features and features-among computation is characterized by introducing them into the above two modules of AMFFM and ATM. As the design goal and eventually demonstrated, BPSM and ATM promote the proposed BPAT-UNet to further constrain boundaries, whereas AMFFM assists to detect small objects. RESULTS: Compared to other classical segmentation networks, the proposed BPAT-UNet displays superior segmentation performance in visualization results and evaluation metrics. Significant improvement of segmentation accuracy was shown on the public thyroid dataset of TN3k with Dice similarity coefficient (DSC) of 81.64% and 95th percentage of the asymmetric Hausdorff distance (HD95) of 14.06, whereas those on our private dataset were with DSC of 85.63% and HD95 of 14.53, respectively. CONCLUSIONS: This paper presents a method for thyroid ultrasound image segmentation, which achieves high accuracy and meets the clinical requirements. Code is available at https://github.com/ccjcv/BPAT-UNet.

Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most frequent type of primary liver cancer. ICC is among the deadliest malignancies, highlighting that novel treatments are urgently needed. Studies have shown that CD44 variant isoforms, rather than the CD44 standard isoform, are selectively expressed in ICC cells, providing an opportunity for the development of an antibody-drug conjugate (ADC)-based targeted therapeutic strategy. In this study, we observed the specific expression of CD44 variant 5 (CD44v5) in ICC tumors. CD44v5 protein was expressed on the surface of most ICC tumors (103 of 155). A CD44v5-targeted ADC, H1D8-DC (H1D8-drug conjugate), was developed that comprises a humanized anti-CD44v5 mAb conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) via a cleavable valine-citrulline-based linker. H1D8-DC exhibited efficient antigen binding and internalization in cells expressing CD44v5 on the cell surface. Because of the high expression of cathepsin B in ICC cells, the drug was preferentially released in cancer cells but not in normal cells, thus inducing potent cytotoxicity at picomolar concentrations. In vivo studies showed that H1D8-DC was effective against CD44v5-positive ICC cells and induced tumor regression in patient-derived xenograft models, whereas no significant adverse toxicities were observed. These data demonstrate that CD44v5 is a bona fide target in ICC and provide a rationale for the clinical investigation of a CD44v5-targeted ADC-based approach. SIGNIFICANCE: Elevated expression of CD44 variant 5 in intrahepatic cholangiocarcinoma confers a targetable vulnerability using the newly developed antibody-drug conjugate H1D8-DC, which induces potent growth suppressive effects without significant toxicity.

Study on Room-Temperature Wet Oxidation of Silicon Catalyzed by Copper.

The anomalously fast growth of the silicon oxide layer at room temperature has been reported for the Cu/Si system. However, the systematical exploration of such a reaction under humidity conditions has not yet been carried out. Through one combination of the experiments and first-principle density functional theory (DFT) simulations, here, we investigate the influence of the imparted Cu atoms in Cu/Si on the oxidation of Si with the presence of H2O. The Cu addition causes the geometric distortion of the Si lattice, which alters the charge transfer to absorbed H2O and decreases its dissociation energy. This results in the experimental formation of much defective SiOx for the Cu/Si system than bare Si under humidity conditions. Furthermore, the presence of such an oxide structure and the catalytic effect of Cu provide the suitable diffusion channels and adsorption sites for the H2O transport and its dissociation. This enhances the oxidation rate of Si consequently and results in the fast growth of the oxide layer on Cu/Si at room temperature.

Scalable synthesis of hydroxyl-functionalized boron nanosheets for high ion-conductive solid-state electrolyte applications.

A hydroxyl-functionalized boron nanosheet is developed as the filler material for the solid-state electrolyte (SSE) of lithium batteries. The nanosheet exhibits good oxidation resistance and thermal stability. Its composite SSE shows high ionic conductivity, and the resulting batteries present much enhanced capacities, rate capability and cycling performance, proving the electrochemical advances of the boron nanosheet.

Triple signal amplification strategy for the ultrasensitive electrochemical detection of human papillomavirus 16 E6/E7 mRNA.

Human papilloma virus (HPV) is the primary causative agent of cervical, vaginal, and vulvar cancers. HPV E6/E7 mRNA detection has been proven to improve the specificity and positive predictive value compared with HPV DNA testing in screening, whereby, it may possess higher diagnostic potential. Herein, to establish the ultrasensitive and specific detection of HPV E6/E7 mRNA, we developed a novel triple signal amplification strategy, combined with gold nanoparticles (AuNPs), reverse transcription loop-mediated isothermal amplification (RT-LAMP) and high affinity biotin-avidin system. This novel proposed signal amplification strategy exhibits the desired detection limit of 0.08 fM (approximately 100 copies) and a wide linear range from 0.1 pmol/mL to 100 nmol/mL for HPV16 E6/E7 mRNA detection. Importantly, the present novel biosensor is 10-100 times more sensitive than conventional RT-PCR in detecting HPV16 E6/E7 mRNA positive clinical samples. Conclusively, this biosensor shows good stability, selectivity, and reproducibility, which demonstrates its potential in future clinical diagnosis with desirable sensitivity and specificity.

Circular RNA hsa_circ_0072309 inhibits non-small cell lung cancer progression by sponging miR-580-3p.

OBJECTIVE: Non-small cell lung cancer (NSCLC) continues to top the list of cancer mortalities worldwide. Early diagnosis and therapeutic interventions targeting NSCLC is becoming the world's significant challenge. Circular RNAs (circRNAs) are emerging as a group of potential cancer biomarkers. MATERIALS AND METHODS: Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of circ_0072309 in NSCLC tissues and cell lines. Cell counting kit 8 (CCK-8), wound healing and Transwell assays were used to analyze cell proliferation, migration and invasion in A549 and H1299 cells. The relationship between circ_0072309 and miR-580-3 was analyzed by Luciferase reporter and RNA pull down assays. RESULTS: We screened circ_0072309 from Gene Expression Omnibus and found that circ_0072309 was lowly expressed in NSCLC tissues and cell lines. The transfection of circ_0072309-overexpressing vector significantly suppressed the cell proliferation, migration and invasion in A549 and H1299 cells. We predicted that miR-580-3p is a target of circ_0072309 by using publicly available bioinformatic algorithms Circinteractome tool and confirmed that circ_0072309 directly bound to miR-580-3p. Furthermore, the addition of miR-580-3p mitigated the blockage of cell proliferation, migration and invasion induced by circ_0072309. CONCLUSIONS: These data showed that circ_0072309 inhibits the progression of NSCLC progression via blocking the expression of miR-580-3p. These findings revealed the anti-tumor role of circ_0072309 during the development of NSCLC and provided a novel diagnostic biomarker and potential therapy for NSCLC.

Surgical treatment for primary pulmonary lymphoepithelioma-like carcinoma.

OBJECTIVES: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare but unique subtype of non-small-cell lung cancer (NSCLC). Our study aimed to evaluate clinicopathological characteristics and the value of surgical treatment for LELC and explore the relevant prognostic factors in a relatively large cohort. METHODS: We retrospectively reviewed the medical records of 39 lung LELC patients who underwent pulmonary resection with curative intent between January 2009 and December 2013. The clinical and pathological characteristics, survival data and relevant prognostic factors were analysed. RESULTS: The median age of lung LELC patients was 47 years (36-81), and 32 of 39 patients were non-smokers (82.1%). Positive expression of P63 and CK5/6 was shown in all the tested LELC specimens. In situ hybridization of Epstein-Bar virus-encoded RNA (EBER) was performed in 36 patients and all of them were positive. However, epidermal growth factor receptor (EGFR) mutational analysis was done in 19 patients and all of them were wild-type. The median follow-up time was 26.0 months in our cohort, and 6-, 12-, 24- and 36-month recurrence-free survival (RFS) rates were 92, 82, 73 and 73%, respectively. Patients with positive lymph nodes experienced significantly worse postoperative RFS than those with negative ones (P = 0.002). Multivariate survival analysis confirmed that only lymph node involvement [RR 0.051; 95% confidence interval, 0.003-0.991, P = 0.049] was an independent prognostic factor. CONCLUSIONS: Primary lung LELC is closely associated with Epstein-Bar virus infection but not involved in EGFR mutation pathway. Radical surgery could achieve a good outcome for resectable pulmonary LELC, and regional lymph node status is a vital prognostic factor.

[The analysis on the misdiagnosis of solitary fibrous tumor of the pleura].

OBJECTIVE: To report the characteristics of solitary fibrous tumor of the pleura (SFTP), and to analyze the factors associated with the misdiagnosis of this disease. METHODS: A retrospective review of the clinical records of 21 cases of SFTP in our hospital from June 2000 to September 2008 was conducted. The follow-up data were also reviewed. RESULTS: The preoperative diagnosis was pleural mesothelioma in 7 cases, neurogenic tumor in 6, lung cancer in 4, SFTP in 2, hilar lymph node tuberculosis in 1 and inflammatory granuloma in 1 case. All the cases underwent radical resection, and postoperative pathology and immunohistochemical study were performed, and the diagnosis of benign solitary fibrous tumor of the pleura was confirmed. Follow-up periods ranged from 3 months to 8 years (median, 43 months). Two cases were lost, and the remaining 19 cases reported no recurrence or metastasis. CONCLUSION: The recognition of the clinical characteristics of pleural solitary fibrous tumor is essential for improving the diagnosis of this uncommon disease.

Establishment and characterization of a new drug surviving cell line Am1010, derived directly from muscle metastases of a human lung adenocarcinoma patient with multi-drug-resistance to cisplatin, taxol, and gefitinib.

AIM: To Characterize a new human lung cancer cell line Am1010, derived from drug-surviving cells (DSCs). METHODS: The Am1010 cell line was established after 4 cycles of chemotherapy from an arm muscle metastatic tumor of a patient diagnosed with lung adenocarcinoma. The cell line has been remained in continuous culture for more than one year during this study. RESULTS: The Am1010 cell line demonstrated in vitro multi-drug-resistance to cisplatin, taxol, and gefitinib. The Am1010 cell doubling time without drug treatment was 42.395 h. The IC(50) value of cisplatin was 4.299 micromol/L and >10 micromol/L for the Am1010 and P0318 (a cell line derived from non-DSCs) cells, respectively. The IC(50) value of taxol was 0.067 micromol/L and >1 micromol/L for the Am1010 and P0318 cells, respectively. The IC(50) value of gefitinib was 15.233 micromol/L and >70 micromol/L for Am1010 and P0318 cells, respectively. 11 genes involved in the focal adhesion and cell adhesion pathways were found to be differentially expressed. The cells of Am1010 have a significantly larger chromosome number than most lung cancer cell lines. CONCLUSION: This novel DSCs derived lung cancer cell line will be a valuable in vitro tool for the investigation of lung cancer drug resistance and metastasis.

Video-assisted thoracoscopic surgery (VATS) for patients with solitary fibrous tumors of the pleura.

OBJECTIVES: To present our experience of video-assisted thoracoscopic surgery (VATS) for patients with solitary fibrous tumors of the pleura (SFTPs) and to discuss the treatment of choice of such neoplasms. METHODS: Between June 2000 and September 2008, 21 patients with SFTPs (9 men and 12 women) underwent VATS at our department. The mean age was 52.5 years (range, 33-76 years). RESULTS: Surgical excision was performed in all patients. Surgical excision was performed by VATS in 15 patients (71.4%), by VATS plus a small thoracotomy (<5 cm) in 4 patients (19.0%), and by posterolateral thoracotomy accompanied by VATS in 2 patients (9.5%). Mean chest drain duration was 2.3 days (range, 1-4 days), and the mean hospital stay was 7.2 days (range, 4-15 days). There were 18 pathologically benign SFTP cases (85.7%) and 3 malignant SFTP cases (14.3%). There was no operative morbidity or mortality. No recurrence or metastasis of SFTPs developed during postoperative median follow-up period of 43 months. CONCLUSIONS: Complete resection and close follow-up for years after operation is recommended for SFTPs. VATS may play an important role in reducing the size of the thoracotomy incision in the treatment of SFTPs, which results in less invasive surgery.