Abstract
Two-dimensional coordination nanosheets (CONASHs) are grown at the spherical liquid–liquid interface of a dichloromethane droplet in water to form zero-dimensional nano- and micro-capsules ...using a simple dropping method, a syringe-pump method, and an emulsion method. Reaction of 1,3,5-tris4-(4′-2,2′:6′,2″-terpyridyl)phenylbenzene (1) with Fe(BF
4
)
2
affords electrochromic Fe(tpy)
2
CONASH capsules and that of ligand 1 with ZnSO
4
does photoluminescent Zn
2
(μ-O
2
SO
2
)
2
(tpy)
2
CONASH capsules. Fe(tpy)
2
CONASH capsules containing magnetite particles were produced by the syringe-pump method by adding magnetite to the aqueous phase, with the assembly and dispersion of the magnetite-containing CONASH capsules being easily controlled with a magnet. This indicates that physicochemically functional CONASH capsules are suitable for incorporating other functional materials to develop hybrid systems.
Silyl radicals are valuable species to prepare diverse organosilicon compounds. However, unlike stable tertiary silyl radicals, the use of secondary silyl radicals has been problematic in silylation ...reactions due to their instability. Here, we present photocatalytic in situ generations of both secondary and tertiary silyl radicals by one-electron oxidation of ate complexes, formed from silylboranes and an alkoxide cocatalyst, achieving highly efficient hydrosilylation and deuterosilylation of electron-rich alkenes and dienes as well as electron-deficient alkenes. The theoretical studies show that anionic borate complexes activated with an alkoxide have lower oxidation potentials than neutral borate complexes, allowing the formation of secondary silyl radicals. The calculated reaction pathways reveal that anionic conditions using the conjugate acid–base pair of NaOEt (cocatalyst) and EtOH (solvent) are the key to expanding the scope of silyl radicals and alkenes.
The hydrogen embrittlement (HE) characteristics of Fe–0.33C–1.2Mn–xNb–xMo steels were investigated experimentally using various samples with differing microstructural characteristics. HE in steels ...was affected by hydrogen trapping sites:
ε
-carbide-based, Nb-based, and Mo-based precipitates, which were effective at enhancing HE resistance. In contrast, the prior austenite (
γ
) grain boundary within steel could act as hydrogen trapping sites and accelerate HE. In addition, hydrogen trapping occurred around the crack, leading to an acceleration of crack growth rate. There are various trapping sites in the steels with negative and positive effects on HE. The extent of the HE was clarified via tensile strength and resistance of delayed failure. Furthermore, the HE characteristics were analyzed using the samples with different quantity of hydrogen charged with two different methods. Based upon the above work, high HE resistance of the steel was proposed as Fe–0.33C–1.2Mn–0.05Nb–0.5Mo steels after a bake-hardening process at 170 °C for 20 min.
This paper discusses energy behaviors in hydraulic cylinder dynamics, which are important for model-based control of agriculture scale excavators. First, we review hydraulic cylinder dynamics and ...update our physical parameter identification method to agriculture scale experimental excavators in order to construct a nominal numerical simulator. Second, we analyze the energy behaviors from the port-Hamiltonian point of view which provides many links to model-based control at laboratory scale at least. At agriculture scale, even though the nominal numerical simulator is much simpler than an experimental excavator, the analytical, experimental, and numerical energy behaviors are very close to each other. This implies that the port-Hamiltonian point of view will be applicable in agriculture scale against modeling errors.
Backgrounds
Cycle-consistent generative adversarial network (CycleGAN) is a deep neural network model that performs image-to-image translations. We generated virtual indigo carmine (IC) ...chromoendoscopy images of gastric neoplasms using CycleGAN and compared their diagnostic performance with that of white light endoscopy (WLE).
Methods
WLE and IC images of 176 patients with gastric neoplasms who underwent endoscopic resection were obtained. We used 1,633 images (911 WLE and 722 IC) of 146 cases in the training dataset to develop virtual IC images using CycleGAN. The remaining 30 WLE images were translated into 30 virtual IC images using the trained CycleGAN and used for validation. The lesion borders were evaluated by 118 endoscopists from 22 institutions using the 60 paired virtual IC and WLE images. The lesion area concordance rate and successful whole-lesion diagnosis were compared.
Results
The lesion area concordance rate based on the pathological diagnosis in virtual IC was lower than in WLE (44.1% vs. 48.5%,
p
< 0.01). The successful whole-lesion diagnosis was higher in the virtual IC than in WLE images; however, the difference was insignificant (28.2% vs. 26.4%,
p
= 0.11). Conversely, subgroup analyses revealed a significantly higher diagnosis in virtual IC than in WLE for depressed morphology (41.9% vs. 36.9%,
p
= 0.02), differentiated histology (27.6% vs. 24.8%,
p
= 0.02), smaller lesion size (42.3% vs. 38.3%,
p
= 0.01), and assessed by expert endoscopists (27.3% vs. 23.6%,
p
= 0.03).
Conclusions
The diagnostic ability of virtual IC was higher for some lesions, but not completely superior to that of WLE. Adjustments are required to improve the imaging system’s performance.
Background
Osimertinib is recommended for T790M mutation‐positive advanced non‐small cell lung cancer (NSCLC) resistant to first‐ and second‐generation epidermal growth factor receptor ...(EGFR)‐tyrosine kinase inhibitors (TKIs). Recently, some reports exist on the real‐world use of osimertinib; however, reports involving third/later‐line use are few. Hence, this study was conducted to evaluate the efficacy and safety of osimertinib used in various treatment lines for T790M‐positive NSCLC patients.
Methods
This retrospective, observational, multicenter study included T790M‐positive advanced/recurrent NSCLC patients treated with osimertinib from May 2016 to March 2018. The clinical characteristics, efficacy, and adverse events were retrospectively investigated. The Kaplan‐Meier method was used to analyze progression‐free survival (PFS) and overall survival (OS). PFS‐associated clinical characteristics were evaluated using the Cox proportional hazards model.
Results
The objective response rate (ORR) and disease control rate (DCR) were 60.7% and 91.1%, respectively; the median PFS was 11.0 months. There were no significant differences in the median PFS for patients treated with osimertinib as second‐line and third−/later‐line (14.5 vs. 11.0 months respectively, P = 0.327). Analysis using the Cox proportional hazards model for clinical features affecting PFS also revealed no significant factors. Adverse events of grade ≥ 3 were reported in 15 patients (26.8%); the most common were anemia (n = 3) and cutaneous toxicity (n = 3). Grade 4 neutropenia was observed in one patient; any‐grade pneumonitis was observed in six patients (10.7%), including one with grade 3 pneumonitis.
Conclusions
Osimertinib demonstrated efficacy even when administered as third−/later‐line treatment to NSCLC patients. Osimertinib‐related pneumonitis was observed more frequently than previously reported.
Key points
Significant findings of the study
Osimertinib shows efficacy even as later‐line treatment in T790M mutation‐positive NSCLC patients previously treated with EGFR‐TKIs. However, the incidence of ≥ grade 3 adverse events, especially pneumonitis, was higher than that previously reported by other studies.
What this study adds
Osimertinib was approved for previously EGFR‐TKI‐treated EGFR T790M‐positive NSCLC. With the increasing frequency of its use as first‐line treatment, this study provides valuable evidence for the efficacy and safety of osimertinib for previously EGFR‐TKI‐treated NSCLC.
We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer ...patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed.
Endothelial cells (EC) are involved in regulating several aspects of lipid metabolism, with recent research revealing the clinicopathological significance of interactions between EC and lipids. ...Induced pluripotent stem cells (iPSC) have various possible medical uses, so understanding the metabolism of these cells is important. In this study, endothelial phenotype cells generated from human iPSC formed cell networks in co-culture with fibroblasts. Changes of plasmalogen lipids and sphingomyelins in endothelial phenotype cells generated from human iPSC were investigated by reverse-phase ultra-high-pressure liquid chromatography mass spectrometry (UHPLC-MS/MS) analysis. The levels of plasmalogen phosphatidylethanolamines (38:5) and (38:4) increased during differentiation of EC, while sphingomyelin levels decreased transiently. These changes of plasmalogen lipids and sphingomyelins may have physiological significance for EC and could be used as markers of differentiation.
Vascular endothelial cell disorders are closely related to cardiovascular disease (CVD) and pulmonary diseases. Abnormal lipid metabolism in the endothelium leads to changes in cell signalling, and ...the expression of genes related to immunity and inflammation. It is therefore important to investigate the pathophysiology of vascular endothelial disorders in terms of lipid metabolism, using a disease model of endothelium.
Human induced pluripotent stem cell-derived endothelial cells (iECs) were cultured on a matrigel to form an iEC network. Lipids in the iEC network were investigated by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) analysis. Ion fragments obtained by mass spectrometry were analysed using an infusion method, involving precursor ion scanning with fragment ion.
The MALDI TOF IMS analysis revealed co-localized intensity of peaks at m/z 592.1 and 593.1 in the iEC network. Tandem mass spectrometry (MS/MS) analysis by MALDI-imaging, in conjunction with precursor ion scanning using an infusion method with lipid extracts, identified that these precursor ions were lysophosphatidylcholine (LPC) (22:5) and its isotype.
The MALDI-imaging analysis showed that LPC (22:5) was abundant in an iEC network. As an in vitro test model for disease and potential therapy, present analysis methods using MALDI-imaging combined with, for example, mesenchymal stem cells (MSC) to a disease derived iEC network may be useful in revealing the changes in the amount and distribution of lipids under various stimuli.
Background: The purpose of this study is to clarify the changes in peripheral blood eosinophil (PBE) counts and eosinophilic granulomatosis with polyangiitis (EGPA) onset in patients with asthma who ...were treated with dupilumab in clinical practice. Methods: The primary outcome of this study is to determine the onset of EGPA in patients whose PBE counts continued to rise within 6 months of dupilumab initiation (rising group) and in patients whose PBE counts peaked and subsequently declined within 6 months (peaked and declined group). As a secondary outcome, the incidence of developing EGPA in patients with PBE counts greater than 1500 cells/μL at 3 or 6 months after dupilumab administration is investigated. Results: A total of 37 individual were enrolled (male/female = 14/23, median age = 57.0 years old). The development of EGPA was significantly more frequent in the rising group compared with the peaked and declined group (p = 0.042, effect size = 0.455, moderate association). Patients with PBE counts greater than 1500 cells/μL showed a significantly higher risk of developing EGPA (p = 0.017, effect size = 0.678, strong association). Conclusions: Physicians should check for the onset of EGPA by monitoring the elevation of eosinophils within 6 months after dupilumab administration, especially in patients with PBE counts greater than 1500 cells/μL at 3 months.
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