Identification of non-coding RNAs embracing microRNA-143/145 cluster

In a variety of cancers, altered patterns of microRNA (miRNA) expression are reported and may affect the cell cycle and cell survival. Recent studies suggest that the expression level of miRNAs that act as tumor suppressors is frequently reduced in cancers because of chromosome deletions, epigenetical changes, aberrant transcription and disturbances in miRNA processing. miR-143 and -145, which are located approximately 1.3 kb from each other at chromosome 5q33, are highly expressed in several tissues, but down-regulated in most cancers. However, the mechanism of this down-regulation has not been investigated in detail. Here, we show that both miRNAs were expressed well under the same control program in human tissues, but were down-regulated equally in the most of the cancer cell lines tested. Then we identified the host gene encoding both miRNAs. The transcripts of this gene were approximately 11, 7.5, and 5.5 kb long; and the expression of these transcripts was coordinated with that of its resident miRNAs and down-regulated in the cancer cell lines tested as well as in colorectal cancer tissue samples. These data demonstrate that the host gene can function as a primary miRNA transcript and suggest that the down-regulation of host gene expression caused the low-expression of its encoded microRNAs-143 and -145 in human cancer cell lines and in cancer tissues

Deep variational quantum eigensolver for excited states and its application to quantum chemistry calculation of periodic materials

A programmable quantum device that has a large number of qubits without fault-tolerance has emerged recently. Variational quantum eigensolver (VQE) is one of the most promising ways to utilize the computational power of such devices to solve problems in condensed matter physics and quantum chemistry. As the size of the current quantum devices is still not large for rivaling classical computers at solving practical problems, Fujii et al. proposed a method called “Deep VQE”, which can provide the ground state of a given quantum system with the smaller number of qubits by combining the VQE and the technique of coarse graining [K. Fujii, K. Mitarai, W. Mizukami, and Y. O. Nakagawa, arXiv:2007.10917]. In this paper, we extend the original proposal of Deep VQE to obtain the excited states and apply it to quantum chemistry calculation of a periodic material, which is one of the most impactful applications of the VQE. We first propose a modified scheme to construct quantum states for coarse graining in Deep VQE to obtain the excited states. We also present a method to avoid a problem of meaningless eigenvalues in the original Deep VQE without restricting variational quantum states. Finally, we classically simulate our modified Deep VQE for quantum chemistry calculation of a periodic hydrogen chain as a typical periodic material. Our method reproduces the ground-state energy and the first-excited-state energy with the errors up to O(1)% despite the decrease in the number of qubits required for the calculation by two or four compared with the naive VQE. Our result will serve as a beacon for tackling quantum chemistry problems with classically-intractable sizes by smaller quantum devices in the near future

Investigation of the feasibility of a simple method for verifying the motion of a binary multileaf collimator synchronized with the rotation of the gantry for helical tomotherapy

In this paper, we suggest a new method for verifying the motion of a binary multileaf collimator (MLC) in helical tomotherapy. For this we used a combination of a cylindrical scintillator and a general-purpose camcorder. The camcorder records the light from the scintillator following photon irradiation, which we use to track the motion of the binary MLC. The purpose of this study is to demonstrate the feasibility of this method as a binary MLC quality assurance (QA) tool. First, the verification was performed using a simple binary MLC pattern with a constant leaf open time; secondly, verification using the binary MLC pattern used in a clinical setting was also performed. Sinograms of simple binary MLC patterns, in which leaves that were open were detected as "open" from the measured light, define the sensitivity which, in this case, was 1.000. On the other hand, the specificity, which gives the fraction of closed leaves detected as "closed", was 0.919. The leaf open error identified by our method was -1.3 +/- 7.5%. The 68.6% of observed leaves were performed within +/- 3% relative error. The leaf open error was expressed by the relative errors calculated on the sinogram. In the clinical binary MLC pattern, the sensitivity and specificity were 0.994 and 0.997, respectively. The measurement could be performed with -3.4 +/- 8.0% leaf open error. The 77.5% of observed leaves were performed within +/- 3% relative error. With this method, we can easily verify the motion of the binary MLC, and the measurement unit developed was found to be an effective QA tool.ArticleJOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS. 13(1):27-43 (2012)journal articl

慢性肺疾患の早産児におけるプロテインC経路 : 前向き研究

Background: Chronic lung disease (CLD) is a major neonatal pulmonary disorder associated with inflammation. Recent studies have shown that protein C anticoagulant pathways, such as those for protein C (PC), protein S (PS), and thrombomodulin (TM), could be useful indices for reflecting pulmonary injury. However, the involvement of these factors in preterm infants with very low birthweight (VLBW) who have developed CLD remains to be investigated. Here, we investigated whether PC pathway-related factors could predict the development of CLD in preterm infants with VLBW. Methods: We collected plasma samples from 26 preterm infants with VLBW (13 each from those with and without CLD) at the time of birth and measured TM, PC, and PS levels in their plasmas. We analyzed prospectively the relationship between these factors in infants with and without CLD. Results: There were significant differences in gestational age, birthweight, Apgar score (5 min), and duration of mechanical ventilation between the CLD and non-CLD groups. No significant differences in the PC and PS levels at birth were observed between the two groups, whereas the TM levels in the CLD group were significantly higher than those in the non-CLD group (P = 0.013). The TM levels correlated with gestational age and duration of mechanical ventilation. However, covariance analysis demonstrated that gestational age was significantly associated with TM levels, and consequently, development of CLD was not associated with TM level at birth. Conclusions: Thrombomodulin, PC, and PS levels at birth could not predict the development of CLD in preterm infants with VLBW.博士（医学）・甲第850号・令和4年9月28日© 2022 Japan Pediatric Society.This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/ped.15221], which has been published in final form at [https://doi.org/10.1111/ped.15221]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.発行元が定める登録猶予期間終了の後、本文を登録予定（2023.01

Antitumor effects of α-bisabolol against pancreatic cancer.

In the present study, we investigated whether α-bisabolol, a sesquiterpene alcohol present in essential oils derived from a variety of plants, has antitumor effects against pancreatic cancer. α-Bisabolol induced a decrease in cell proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1, MIA Paca2), but not in pancreatic epithelial cells (ACBRI515). α-Bisabolol treatment induced apoptosis and suppressed Akt activation in pancreatic cancer cell lines. Furthermore, α-bisabolol treatment induced the overexpression of early growth response-1 (EGR1), whereas EGR1 siRNA decreased the α-bisabolol-induced cell death of KLM1 cells. Tumor growth in both subcutaneous and peritoneal xenograft nude mouse models was significantly inhibited by intragastric administration of 1000 mg/kg of α-bisabolol, once a week for three weeks. The results indicate that α-bisabolol could be a novel therapeutic option for the treatment of pancreatic cancer

日本における非代償性急性心不全患者の30日および90日以内の心不全再入院の発生率と臨床的意義 : NARA-HF研究より

Background: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. Conclusions: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.博士（医学）・甲第735号・令和2年3月16日日本循環器学会の許諾を得て登録（2020年9月2日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

A New Electrophysiological Method for the Diagnosis of Extraforaminal Stenosis at L5-S1

Study DesignA retrospective study.PurposeTo examine the effectiveness of using an electrodiagnostic technique as a new approach in the clinical diagnosis of extraforaminal stenosis at L5-S1.Overview of LiteratureWe introduced a new effective approach to the diagnosis of extraforaminal stenosis at the lumbosacral junction using the existing electrophysiological evaluation technique.MethodsA consecutive series of 124 patients with fifth lumbar radiculopathy were enrolled, comprising a group of 74 patients with spinal canal stenosis and a second group of 50 patients with extraforaminal stenosis at L5-S1. The technique involved inserting a pair of needle electrodes into the foraminal exit zone of the fifth lumbar spinal nerves, which were used to provide electrical stimulation. The compound muscle action potentials from each of the tibialis anterior muscles were recorded.ResultsThe distal motor latency (DML) of the potentials ranged from 11.2 to 24.6 milliseconds in patients with extraforaminal stenosis. In contrast, the DML in patients with spinal canal stenosis ranged from 10.0 to 17.2 milliseconds. After comparing the DML of each of the 2 groups and at the same time comparing the differences in DML between the affected and unaffected side of each patient, we concluded there were statistically significant differences (p<0.01) between the 2 groups. Using receiver operating characteristic curve analysis, the cutoff values were calculated to be 15.2 milliseconds and 1.1 milliseconds, respectively.ConclusionsThis approach using a means of DML measurement enables us to identify and localize lesions, which offers an advantage in diagnosing extraforaminal stenosis at L5-S1

急性心不全における退院時の尿素窒素分画排泄率の予後判定への有用性

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.博士（医学）・甲第814号・令和4年3月15日Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made