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Background: The recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. Materials and Methods: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). Results: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10). Conclusion: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web‐based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: "oncologist characteristics," "oncologist attitude toward influenza vaccines and the current status of influenza vaccination for cancer patients undergoing chemotherapy," "incidence of influenza infection and associated treatment complications," and "treatment policy for influenza infection." In total, 153 (36.9%) physicians replied that they did not actively encourage influenza vaccination for patients undergoing chemotherapy. The primary reasons given were lack of evidence (48/153, 31.4%) and uncertainty of appropriate timing (46/153, 30.1%). There was diverse variation in the timing of vaccination and in the levels of encouragement based on the cancer location and medication type. Two hundred eighty‐three (68.2%) oncologists reported that their cancer patients had experienced influenza infection while undergoing chemotherapy, and 169 (40.7%) responded that their patients had experienced an administration delay or discontinuation of medication because of influenza infection. Our surveillance revealed some oncologists considered evidence regarding the administration of influenza vaccine to cancer patients undergoing chemotherapy (particularly the optimal timing and level of recommendation by cancer location and medication) to be lacking. It also exposed the adverse impact of influenza infection in cancer patients. [ABSTRACT FROM AUTHOR]

Histone H3 lysine‐9 di‐methylation (H3K9me2) and lysine‐27 tri‐methylation (H3K27me3) are linked to repression of gene expression, but the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. Here, we report that lysine demethylases 7A (KDM7A) and 6A (UTX) play crucial roles in tumor necrosis factor (TNF)‐α signaling in endothelial cells (ECs), where they are regulated by a novel TNF‐α‐responsive microRNA, miR‐3679‐5p. TNF‐α rapidly induces co‐occupancy of KDM7A and UTX at nuclear factor kappa‐B (NF‐κB)‐associated elements in human ECs. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and are both required for activation of NF‐κB‐dependent inflammatory genes. Chromosome conformation capture‐based methods furthermore uncover increased interactions between TNF‐α‐induced super enhancers at NF‐κB‐relevant loci, coinciding with KDM7A and UTX recruitments. Simultaneous pharmacological inhibition of KDM7A and UTX significantly reduces leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF‐κB‐dependent regulation of genes that control inflammatory responses of ECs. Synopsis: Comprehensive analysis of epigenetic responses during early inflammation in endothelial cells reveals that lysine demethylase 7A and 6A act cooperatively to rapidly erase repressive histone marks, which is required for activation of the pro‐inflammatory TNF‐α/NF‐κB‐signaling pathway. Lysine demethylase 7A (KDM7A) and 6A (UTX) cooperatively control NF‐κB‐dependent transcription in mammalian vascular endothelial cells.Demethylation of repressive histone marks by KDM7A and UTX is critical for early inflammatory responses.KDM7A and UTX are associated with TNF‐α‐induced chromatin looping of super enhancers.Pharmacological inhibition of KDM7A and UTX reduces leucocyte adhesive interactions with endothelial cells in mice. [ABSTRACT FROM AUTHOR]

Abstract: Solubility and local structure of transmission elements in calcium silicate compounds has not been well understood. We investigate the local structure of chromium ions dissolved in merwinite (3CaO·MgO·2SiO2) of a monoclinic crystal structure. The acceptance of doping elements into merwinite has not been reported before. We found that chromium ions are soluble in merwinite in air and that chemical valence of the dissolved Cr ions varies with annealing temperature. The absorption edge in the x‐ray absorption near edge structure (XANES) of Cr‐doped merwinite indicated that octahedrally coordinated Cr3+ ions were mainly formed when annealed at 1673 K in air. A pre‐edge peak was also detected, indicating the existence of tetrahedrally coordinated high‐valence Cr ions. Conversely, through annealing of merwinite at 1123 K in air, tetrahedrally coordinated Cr6+ ions were found to be the main form of chromium. XANES spectra simulated by first‐principle calculations were used to explain the structural features in the observed spectra. We propose the coexistence of Cr3+ ions in octahedral Mg2+ sites and high‐valence Cr ions in tetrahedral Si4+ sites. In addition, a change in the chromium ion oxidation state in tetrahedral coordination sites was suggested by XANES spectroscopy of Cr‐doped merwinite synthesized at 1673 K and reannealed at 1123 K. [ABSTRACT FROM AUTHOR]

Background Evidence of eribulin therapy for metastatic breast cancer ( MBC) in clinical practice is not well documented. Methods We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. Results The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m2, and 75%, respectively. One patient achieved a complete response, ( CR) six a partial response ( PR), eight stable disease ( SD) and 14 patients exhibited progressive disease. The objective response rate ( ORR: CR + PR) was 24.1%, and the clinical benefit rate ( CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [ CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment. Conclusion Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy. [ABSTRACT FROM AUTHOR]

Dicalcium silicate (2CaO·SiO2) is a typical silicate compound that exists even at elevated temperatures. Different types of elements can be dispersed in dicalcium silicate to form a solid solution phase. However, the dispersion behavior of transition elements that can display different ionic valences is not well understood. Herein, we investigate the local structure of chromium ions dispersed in dicalcium silicate of different phase states under inert and air atmospheres using Cr K-edge X-ray absorption near-edge structure ( XANES) spectroscopy and first-principle calculations. The measured XANES spectra indicated that Cr ions exist as high-valence states when dispersed in dicalcium silicate in air atmosphere. Specifically, Cr6+ ions were detected in γ-dicalcium silicate, which was prepared by annealing a mixture of 2CaO·SiO2 and Cr2O3 at 973 K in air atmosphere. In addition, the XANES spectra obtained via first-principle calculations revealed that Cr ions, with high-valence states between Cr4+ and Cr6+, in dicalcium silicate, occupy the tetrahedral Si4+ sites. [ABSTRACT FROM AUTHOR]

The authors have been engaged in the development of a phosphorus recovery system capable of maintaining high recovery efficiencies, with the chemical cost suppressed. This time, they conducted demonstration tests of a fluidized bed magnesium ammonium phosphate reactor provided with a seeder reactor for the supernatant from anaerobic digestion using a pilot experimental plant with a wastewater treatment capacity of 20 m3/d. For the digestion supernatant with a phosphorus concentration of approximately 300 mg/L, the treated water phosphorus concentration was 10 to 25 mg/L, and the phosphorus recovery efficiency was more than 90%. Relative to the chemical cost in the case of magnesium chloride, the chemical cost in the case of magnesium hydroxide is approximately 40%. Thus, with the new system, it was possible to reduce the running cost while maintaining high recovery efficiencies. [ABSTRACT FROM AUTHOR]

The epidermis of higher plants generates the cuticle layer that covers the outer surface of each plant. The cuticle plays a crucial role in plant development, and some mutants with defective cuticle exhibit morphological abnormalities, such as the fusion of organs. The way in which the cuticle forms and its contribution to morphogenesis are poorly understood. Conventional detection of the cuticle by transmission electron microscopy (TEM) requires laborious procedures, which include fixation, staining with osmium, and preparation of ultra-thin sections. It is also difficult to survey entire surfaces of expanded leaves because of the limited size of specimens that can be examined. Thus, TEM is unsuitable for large-scale screening for mutants with defective cuticle. We describe here a rapid and inexpensive method, designated the toluidine-blue (TB) test, for detection of cuticular defects in whole leaves. We demonstrated the validity of the TB test using mutants of Arabidopsis thaliana, including abnormal leaf shape1 ( ale1), fiddlehead ( fdh), and five e cer iferum ( cer) mutants, in which the structure and/or function of the cuticle is abnormal. Genetic screening for mutants using the TB test allowed us to identify seven loci. The cuticle-defective regions of leaves of the mutants revealed five intrinsic patterns of surface defects (classes I through V), suggesting that formation of functional cuticle on leaves involves various spatially regulated factors. [ABSTRACT FROM AUTHOR]

Determination of the mRNA start site is the first step in identifying the promoter region, which is of key importance for transcriptional regulation of gene expression. The 'oligo-capping' method enabled us to introduce a sequence tag to the first base of an mRNA by replacing the cap structure of the mRNA. Using cDNA libraries made from oligo-capped mRNAs, we could identify the transcriptional start site of an individual mRNA just by sequencing the 5'-end of the cDNA. The fine mapping of transcriptional start sites was performed for 5880 mRNAs in 276 human genes. Contrary to our expectations, the majority of the genes showed a diverse distribution of transcriptional start sites. They were distributed over 61.7 bp with a standard deviation of 19.5. Our finding may reflect the dynamic nature of transcriptional initiation events of human genes in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Solubility and local structure of transmission elements in calcium silicate compounds has not been well understood. We investigate the local structure of chromium ions dissolved in merwinite (3CaO·MgO·2SiO2) of a monoclinic crystal structure. The acceptance of doping elements into merwinite has not been reported before. We found that chromium ions are soluble in merwinite in air and that chemical valence of the dissolved Cr ions varies with annealing temperature. The absorption edge in the x‐ray absorption near edge structure (XANES) of Cr‐doped merwinite indicated that octahedrally coordinated Cr3+ ions were mainly formed when annealed at 1673 K in air. A pre‐edge peak was also detected, indicating the existence of tetrahedrally coordinated high‐valence Cr ions. Conversely, through annealing of merwinite at 1123 K in air, tetrahedrally coordinated Cr6+ ions were found to be the main form of chromium. XANES spectra simulated by first‐principle calculations were used to explain the structural features in the observed spectra. We propose the coexistence of Cr3+ ions in octahedral Mg2+ sites and high‐valence Cr ions in tetrahedral Si4+ sites. In addition, a change in the chromium ion oxidation state in tetrahedral coordination sites was suggested by XANES spectroscopy of Cr‐doped merwinite synthesized at 1673 K and reannealed at 1123 K. [ABSTRACT FROM AUTHOR]

Background: Mutations in the coding sequence of SCN5A, which encodes the cardiac Na(+) channel α subunit, have been associated with inherited susceptibility to various arrhythmias. Variable expression of SCN5A is a possible mechanism responsible for this pleiotropic effect; however, it is unknown whether variants in the promoter and regulatory regions of SCN5A also modulate the risk of arrhythmias., Methods and Results: We resequenced the core promoter region of SCN5A and the regulatory regions of SCN5A transcription in 1298 patients with arrhythmia phenotypes (atrial fibrillation, n=444; sinus node dysfunction, n=49; conduction disease, n=133; Brugada syndrome, n=583; and idiopathic ventricular fibrillation, n=89). We identified 26 novel rare variants in the SCN5A promoter in 29 patients affected by various arrhythmias (atrial fibrillation, n=6; sinus node dysfunction, n=1; conduction disease, n=3; Brugada syndrome, n=14; idiopathic ventricular fibrillation, n=5). The frequency of rare variants was higher in patients with arrhythmias than in controls. In the alignment with chromatin immunoprecipitation sequencing data, the majority of variants were located at regions bound by transcription factors. Using a luciferase reporter assay, 6 variants (Brugada syndrome, n=3; idiopathic ventricular fibrillation, n=2; conduction disease, n=1) were functionally characterized, and each displayed decreased promoter activity compared with the wild-type sequences. We also identified rare variants in the regulatory region that were associated with atrial fibrillation, and the variant decreased promoter activity., Conclusions: Variants in the core promoter region and the transcription regulatory region of SCN5A were identified in multiple arrhythmia phenotypes, consistent with the idea that altered SCN5A transcription levels modulate susceptibility to arrhythmias., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)