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  • Ellington posted an update 9 months, 1 week ago

    Our results indicate the importance of correctly using CV to avoid biased results of prediction performance of neuropsychiatric biomarkers.Despite high expectations for lung tumoroids, they have not been applied in the clinic due to the difficulty of their long-term culture. APR246 Here, however, using AO (airway organoid) media developed by the Clevers laboratory, we succeeded in generating 3 lung tumoroid lines for long-term culture (>13 months) from 41 lung cancer cases (primary or metastatic). Use of nutlin-3a was key to selecting lung tumoroids that harbor mutant p53 in order to eliminate normal lung epithelial organoids. Next-generation sequencing (NGS) analysis indicated that each lung tumoroid carried BRAFG469A, TPM3-ROS1 or EGFRL858R/RB1E737*, respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAFG469A, crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFRL858R/RB1E737*) significantly suppressed the growth of each lung tumoroid line. AO media was superior to 3 different media developed by other laboratories. Our experience indicates that long-term lung tumoroid culture is feasible, allowing us to identify NGS-based therapeutic targets and determine the responsiveness to corresponding small molecule drugs.In the hemodynamic study, computational fluid dynamics (CFD) analysis has shown that high wall shear stress (WSS) is an important parameter in cerebral aneurysm formation. However, CFD analysis is not more realistic than fluid-structure interaction (FSI) analysis given its lack of considering the involvement of vascular structures. To investigate the relationship between the hemodynamic parameters and the aneurysm formation, the locations of high WSS and high strain were extracted from the CFD and FSI analyses, respectively. Then the distances between the aneurysm formation site and the locations of high WSS or high strain were calculated. A total of 37 intracranial paraclinoid aneurysms were enrolled for quantitative comparison. Additionally, the dura mater was modeled to facilitate realistic results in FSI analysis. The average distance from the location of the aneurysm formation site to the high strain (1.74 mm [Formula see text] 1.04 mm) was smaller than the average distance to the high WSS (3.33 mm [Formula see text] 1.18 mm). The presence of dura mater also influenced the findings in the aneurysm formation site. High strain extracted by FSI analysis is an important hemodynamic factor related to the formation of cerebral aneurysms. Strain parameter could help to predict the formation of aneurysms and elucidate the appropriate treatment.The aim of this study is to establish the expression of ATP-sensitive potassium channels(KATP) in human umbilical arteries with severe pre-eclampsia. Real-time quantitative PCR and western blotting were used to detect the mRNA and protein expression levels of KATP channel subunits Kir6.1 and SUR2B in human umbilical arteries from normal pregnant and those with severe pre-eclampsia, early onset severe pre-eclampsia and late onset severe pre-eclampsia. The mRNA and protein levels of SUR2B in the severe pre-eclampsia group were lower than those in the normal group (P  0.05). The mRNA and protein expression levels of SUR2B in pregnant women with severe pre-eclampsia were lower than those in normal pregnant women, suggesting that the expression of the SUR2B of the KATP channel may be related to the occurrence and development of severe pre-eclampsia. Compared with late onset severe pre-eclampsia, the mRNA and protein expression levels of SUR2B were lower in the umbilical arteries of women with early onset severe pre-eclampsia, suggesting that the occurrence time of severe pre-eclampsia may be related to the extent reduced expression of the SUR2B of the KATP channel.Pure metallic Co, Ni, and their bimetallic compositions of Co3Ni, CoNi, and CoNi3 nanomaterials were prepared by solution combustion synthesis. Microstructure, phase composition, and crystalline structure of these nanoparticles (NPs) were characterized along with studies of their corrosion and dissolution properties in synthetic freshwater with and without natural organic matter (NOM). The nanomaterials consisted of aggregates of fine NPs (3-30 nm) of almost pure metallic and bimetallic crystal phases with a thin surface oxide covered by a thin carbon shell. The nanomaterials were characterized by BET surface areas ranging from ~ 1 to 8 m2/g for the Ni and Co NPs, to 22.93 m2/g, 14.86 m2/g, and 10.53 m2/g for the Co3Ni, CoNi, CoNi3 NPs, respectively. More Co and Ni were released from the bimetallic NPs compared with the pure metals although their corrosion current densities were lower. In contrast to findings for the pure metal NPs, the presence of NOM increased the release of Co and Ni from the bimetallic NPs in freshwater compared to freshwater only even though its presence reduced the corrosion rate (current density). It was shown that the properties of the bimetallic nanomaterials were influenced by multiple factors such as their composition, including carbon shell, type of surface oxides, and the entropy of mixing.The management of patients with spinal metastases (SM) requires a multidisciplinary team of specialists involved in oncological care. Surgical management has evolved significantly over the recent years, which warrants reevaluation of its role in the oncological treatment concept. Any patient with a SM was screened for study inclusion. We report baseline characteristics, surgical procedures, complication rates, functional status and outcome of a large consecutive cohort undergoing surgical treatment according to an algorithm. 667 patients underwent 989 surgeries with a mean age of 65 years (min/max 20-94) between 2007 and 2018. The primary cancers mostly originated from the prostate (21.7%), breast (15.9%) and lung (10.0%). Surgical treatment consisted of dorsoventral stabilization in 69.5%, decompression without instrumentation in 12.5% and kyphoplasty in 18.0%. Overall survival reached 18.4 months (95% CI 9.8-26.9) and the median KPS increased by 10 within hospital stay. Surgical management of SMs should generally represent the first step of a conclusive treatment algorithm.

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