ABSTRACT
INTRODUCTION: The International Association for the Study of Lung Cancer (IASLC) grading system predicts early lung adenocarcinoma outcomes. METHODS: The purpose of this study is to examine prognostic value of the IASLC grading system and its association with the tumor microenvironment (TME) in Stage I EGFR-muted lung adenocarcinoma. Based on the IASLC grading system, we compared the clinicopathological characteristics of EGFR-mutated lung adenocarcinoma (n = 296). In addition, we examined the expression level of E-cadherin in tumor cells and counted the number of tumor-infiltrating lymphocytes (TILs; CD8, CD20, CD138, and Foxp3), tumor-associated macrophages (TAMs; CD204), and cancer-associated fibroblasts (CAFs; podoplanin) using semi-automatic digital pathology image analysis. RESULTS: Recurrence-free survival (RFS) curve showed that survival of grade 3 was significantly shorter than that of grade 1 (P < 0.01) and grade 2 (P = 0.03). Multivariate analysis of RFS revealed the invasive size, lymphatic permeation, and grade 3 (P < 0.01) as independent poor prognostic factors. The number of CD204 +TAMs and PDPN+CAFs was significantly higher in grade 3 than in grade 1 or 2 (all P < 0.01). Among the intermediate grade by the predominant subtype based classification, cases classified as grade 3 by the new classification had higher number of CD204 +TAMs (P < 0.01) and PDPN+CAFs (P = 0.02) than those classified as grade 2. CONCLUSION: The IASLC grading system correlated with the outcomes of EGFR-mutated lung adenocarcinoma. Grade 3 was found to have the TME that most contributes to tumor progression, which probably explained their poor prognosis.
Subject(s)
Adenocarcinoma of Lung , ErbB Receptors , Lung Neoplasms , Mutation , Tumor Microenvironment , Humans , Male , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Prognosis , Middle Aged , Aged , Neoplasm Staging , Neoplasm Grading , Lymphocytes, Tumor-Infiltrating/pathology , Cancer-Associated Fibroblasts/pathology , Cancer-Associated Fibroblasts/metabolism , Adult , Tumor-Associated Macrophages , Aged, 80 and over , Retrospective StudiesABSTRACT
CONTEXT: Nonpharmacologic distraction (NPD) during medical procedures in children is known to be beneficial to patients; however, no reviews have assessed their benefits to medical providers. OBJECTIVES: We aimed to assess the benefits of NPD to medical providers. DATA SOURCES: We searched 5 databases for relevant articles. STUDY SELECTION: Peer-reviewed published randomized controlled trials comparing NPD with standard care that included children who had undergone medical procedures were included. DATA EXTRACTION: Primary outcomes were procedure time, number of medical staff involved, and initial success rate of venipuncture. Two reviewers assessed the risk of bias by using the Cochrane Collaboration (Oxford, United Kingdom)'s Randomized Controlled Trials Risk of Bias Tool, and we performed a meta-analysis to assess efficacy. RESULTS: We included 22 trials with 1968 participants. The main NPD was audiovisual distraction, such as tablets. No significant difference was found in venipuncture procedure time (mean difference: -9.79; 95% confidence interval: -22.38 to 2.81; low certainty). We found no studies on the number of medical staff. CONCLUSIONS: Our review did not find any clear NPD-associated benefit for the medical provider. The review included a small amount of literature, analyzed a small number of cases, and had a low certainty of evidence regarding procedure duration; therefore, further studies are needed to conclude the benefits to clinicians of NPD.
Subject(s)
Phlebotomy , Child , Humans , United Kingdom , Phlebotomy/psychology , AttentionABSTRACT
Quantitative analysis of behaviors shown by interacting multiple animals can provide a key for revealing high-order functions of their nervous systems. To resolve these complex behaviors, a video tracking system that preserves individual identity even under severe overlap in positions, i.e., occlusion, is needed. We developed GroupTracker, a multiple animal tracking system that accurately tracks individuals even under severe occlusion. As maximum likelihood estimation of Gaussian mixture model whose components can severely overlap is theoretically an ill-posed problem, we devised an expectation-maximization scheme with additional constraints on the eigenvalues of the covariance matrix of the mixture components. Our system was shown to accurately track multiple medaka (Oryzias latipes) which freely swim around in three dimensions and frequently overlap each other. As an accurate multiple animal tracking system, GroupTracker will contribute to revealing unexplored structures and patterns behind animal interactions. The Java source code of GroupTracker is available at https://sites.google.com/site/fukunagatsu/software/group-tracker.
Subject(s)
Crowding , Oryzias/physiology , Video Recording , Algorithms , Animal Identification Systems , Animals , Normal Distribution , Software , SwimmingABSTRACT
A new procedure for constructing monocyclic five- and six-membered azacycles by the endo-mode ring-closing reaction of allenylazido derivatives under neutral conditions has been developed. The azabicyclo[m.n.0] compounds were prepared by applying this newly developed procedure. The seven-membered azacycle was prepared when the allene possessing an unsubstituted carboxyl amido functionality was submitted to the basic conditions. In addition, indole and quinoline skeletons were synthesized using this procedure.
