Deep Learning for Virtual Histological Staining of Bright-Field Microscopic Images of Unlabeled Carotid Artery Tissue

Molecular Imaging and Biology - Histological analysis of artery tissue samples is a widely used method for diagnosis and quantification of cardiovascular diseases. However, the variable and...     

唇腭裂相关基因的关键信号通路

唇腭裂是一种常见的出生缺陷,其发生的分子机制是近年来的研究热点。目前已有超过100个唇腭裂相关基因被发现,但这些基因的致病机制还有待阐明。基因携带的遗传信息通过信号通路来影响表型,信号通路的顺利传递是机体正常发育的必要条件。唇腭裂的形成过程中亦有信号通路的异常表达。一系列信号因子参与基因表达的调控,它们之间又相互作用,构成信号通路及复杂精细的信号调控网络,共同参与指导细胞活动及组织形成。本文就目前研究较多的与唇腭裂相关的几个重要信号通路进行概括,综述了唇腭裂发展过程中的重要分子机制,以期为唇腭裂的病因学及遗传学研究提供参考。     

Effects of concentrated ambient ultrafine particulate matter on hallmarks of Alzheimer’s disease in the 3xTgAD mouse model

BackgroundExposure to air pollution has been identified as a possible environmental contributor to Alzheimer’s Disease (AD) risk. As the number of people with AD worldwide continues to rise, it becomes vital to understand the nature of this potential gene-environment interaction. This study assessed the effects of short-term exposures to concentrated ambient ultrafine particulates (UFP, <100 nm) on measurements of amyloid-β, tau, and microglial morphology.MethodsTwo cohorts of aged (12.5–14 months) 3xTgAD and NTg mice were exposed to concentrated ambient UFP or filtered air for 2 weeks (4-h/day, 4 days/week). Bronchoalveolar lavage fluid and brain tissue were collected twenty-four hours following the last exposure to evaluate lung inflammation, tau pathology, amyloid-β pathology, and glial cell morphology.ResultsNo exposure- or genotype-related changes were found with any of the measures of lung inflammation or in the hippocampal staining density of astrocyte marker glial fibrillary acidic protein. The microglia marker, ionized calcium binding adaptor molecule 1, and amyloid-β marker, 6E10, exhibited significant genotype by exposure interactions such that levels were lower in the UFP-exposed as compared to filtered air-exposed 3xTgAD mice. When microglia morphology was assessed by Sholl analysis, microglia from both NTg mouse groups were ramified. The 3xTgAD air-exposed mice had the most ameboid microglia, while the 3xTgAD UFP-exposed mice had microglia that were comparatively more ramified. The 3xTgAD air-exposed mice had more plaques per region of interest as measured by Congo red staining as well as more plaque-associated microglia than the 3xTgAD UFP-exposed mice. The number of non-plaque-associated microglia was not affected by genotype or exposure. Levels of soluble and insoluble human amyloid-β₄₂ protein were measured in both 3xTgAD groups and no exposure effect was found. In contrast, UFP-exposure led to significant elevations in phosphorylated tau in 3xTgAD mice as compared to those that were exposed to air, as measured by pT205 staining.ConclusionsExposure to environmentally relevant levels of ultrafine particulates led to changes in tau phosphorylation and microglial morphology in the absence of overt lung inflammation. Such changes highlight the need to develop greater mechanistic understanding of the link between air pollution exposure and Alzheimer’s disease.     

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

Acetylsalicylic acid for metal stent in malignant distal common bile duct obstruction: A randomized controlled trial

BackgroundEndoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction. Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid (ASA) use. The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo.MethodsThis prospective, multicenter, double-blinded, and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea. Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled, and allocated to ASA treatment or placebo. The study outcomes were the rate of stent dysfunction at 6 months, duration of stent patency, risk factors for stent dysfunction, and any adverse events.ResultsInterim analysis included 24 and 28 patients in the ASA and placebo groups, respectively. There was no significant difference between the ASA and placebo groups in stent dysfunction (25.0% vs. 20.7%, P = 0.761) or the duration of stent patency (150.97 ± 10.55 vs. 158.07 ± 8.70 days, P = 0.497). Six patients experienced suspected ASA-related adverse events, and there was one lethal case.ConclusionsASA did not prolong stent patency. This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care.