Search

PURPOSE Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT). METHODS The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value 16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups. RESULTS We found that there was no significant difference between the groups with index value

Key Clinical Message In Japan and worldwide, the increase in educational interventions about resuscitation training significantly increases favorable neurological survival in out‐of‐hospital cardiopulmonary arrest cases treated with bystander cardiopulmonary resuscitation (BCPR) each year. This case with Bland‐White‐Garland syndrome having high‐quality BCPR by nurses demonstrates the importance of education about BCPR.

Yukari Sugiyama, Kazuhisa Asai, Kazuhiro Yamada, Yuko Kureya, Naoki Ijiri, Tetsuya Watanabe, Hiroshi Kanazawa, Kazuto Hirata Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan Background: Cigarette smoking-induced oxidant–antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis. Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus. However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown. Subjects and methods: Forty patients with COPD were enrolled in this study. Pulmonary function tests and measurements of the percentage of low-attenuation area on high-resolution computed tomography images were performed, and the results were evaluated for correlation with serum irisin levels. The effect of irisin on cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a transcription factor for antioxidants, was also examined in vitro. Results: Serum irisin levels were significantly correlated with lung diffusing capacity for carbon monoxide divided by alveolar volume (r=0.56, P

The present study investigates the efficiency of haptic search facilitated by the division of the searchable area. Previous studies have shown that scales provided around tactile maps for blind persons can shorten the search time for tactile symbols on the maps, but the optimum number of divisions has not been found. We conducted an experiment in which maps with different numbers of divisions were presented to blindfolded participants. The search times for tactile targets on the maps were measured and a movie that recorded searching behavior was analyzed. Our results indicate that scales with 3 × 4 divisions minimize search time, and the movie analysis reveals that this optimization is determined by the time of both scale-counting and target-searching. This finding elucidates the manner of human haptic search and should be utilized for the optimization of automated tactile map creation.

Purpose: To identify lower limb 2-dimensional (2D) perfusion angiographic parameters that are related to skin perfusion pressure (SPP), a predictor of wound healing in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) endovascular treatment (EVT). Materials and Methods: Thirty-three consecutive patients (mean age 74.5 years; 18 men) with 47 isolated BTK lesions in 33 limbs (Rutherford category 3–5) underwent EVT. Dorsal and plantar SPPs were measured before EVT and the day after. The indexed blood flow below the ankle was measured using 2D perfusion angiography before and after EVT to determine changes in perfusion parameters [arrival time (AT), time to peak, wash-in rate, mean transit time, and width and area under the time-density curve] at rest vs during hyperemia induced with a 20-mg intra-arterial papaverine infusion. Correlations between the 2D perfusion parameters and SPPs were assessed using the Pearson coefficient. The cutoff points to predict mean SPPs >40 mm Hg were analyzed using a receiver operating characteristic curve; outcomes are reported as the area under the curve (AUC) with 95% confidence interval (CI). Results: After EVT at rest and during hyperemia, only AT was significantly changed, although hyperemia produced significant changes in all the pre-/post-EVT 2D perfusion parameters except the wash-in rate. Dorsal and plantar SPPs after EVT were significantly increased and correlated with hyperemic AT and the AT ratio (hyperemia/at rest values) below the ankle. Hyperemic ATs 40 mm Hg, with AUCs of 0.83 (95% CI 0.67 to 0.99) and 0.78 (95% CI 0.61 to 0.95), respectively. Conclusion: Hyperemic ATs

Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

The index for a target that can lead to improved prognoses and more reliable therapy in each heterogeneous patient with heart failure with preserved ejection fraction (HFpEF) remains to be defined. We examined the heterogeneity in the cardiac performance of patients with HFpEF by clarifying the relationship between the indices of left atrial (LA) volume (LAV) overload and pressure overload with echocardiography. We enrolled patients with HFpEF (N = 105) who underwent transthoracic echocardiography during stable sinus rhythm. Relative LAV overload was evaluated using the LAV index or stroke volume (SV)/LAV ratio. Relative LA pressure overload was estimated using E/e’ or the afterload-integrated index of left ventricular (LV) diastolic function: diastolic elastance (Ed)/arterial elastance (Ea) ratio = (E/e’)/(0.9 × systolic blood pressure). The logarithmic value of the N-terminal pro-brain natriuretic peptide was associated with SV/LAV (r = −0.214, p = 0.033). The pulmonary capillary wedge pressure was positively correlated to Ed/Ea (r = 0.403, p = 0.005). SV/LAV was negatively correlated to Ed/Ea (r = −0.292, p = 0.002), with no observed between-sex differences. The correlations between the LAV index and E/e’ and Ed/Ea and between SV/LAV and E/e’ were less prominent than the abovementioned relationships. SV/LAV and Ed/Ea, showing relative LAV and LA pressure respectively, were significantly but modestly correlated in patients with HFpEF. There may be considerable scatter in the relationships between these indices, which could possibly affect the selection of medications or efforts to improve the prognoses of patients with HFpEF.

Solar-C (EUVST) is the next Japanese solar physics mission to be developed with significant contributions from US and European countries. The mission carries an EUV imaging spectrometer with slit-jaw imaging system called EUVST (EUV High-Throughput Spectroscopic Telescope) as the mission payload, to take a fundamental step towards answering how the plasma universe is created and evolves and how the Sun influences the Earth and other planets in our solar system. In April 2020, ISAS (Institute of Space and Astronautical Science) of JAXA (Japan Aerospace Exploration Agency) has made the final down-selection for this mission as the 4th in the series of competitively chosen M-class mission to be launched with an Epsilon launch vehicle in mid 2020s. NASA (National Aeronautics and Space Administration) has selected this mission concept for Phase A concept study in September 2019 and is in the process leading to final selection. For European countries, the team has (or is in the process of confirming) confirmed endorsement for hardware contributions to the EUVST from the national agencies. A recent update to the mission instrumentation is to add a UV spectral irradiance monitor capability for EUVST calibration and scientific purpose. This presentation provides the latest status of the mission with an overall description of the mission concept emphasizing on key roles of the mission in heliophysics research from mid 2020s.

著者人数: 35名 (所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 坂尾, 太郎; 清水, 敏文), Number of authors: 35 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS): Sakao, Taro; Shimizu, Toshifumi), Accepted: 2019-08-01, 資料番号: SA1190166000

Background: Chronic Obstructive Pulmonary Disease (COPD) is a pulmonary disease caused by long-term inhalation exposure of harmful substances, mainly cigarette smoke. Oxidative stress is considered as one of the important mechanisms of COPD. Irisin is a kind of myokine secreted from muscle by exercise. Recent studies have shown that irisin acts defensively against oxidative stress via Nrf2, a transcription factor responsible for antioxidant capacity. In this study, we examined emphysema suppression effect of exercise in mice. Methods: Mice were divided into three groups: control, smoking, and exercise+smoking. All mice in smoking and exercise+smoking groups were exposed to cigarette smoking for 60 minutes per session once a day. All mice in exercise+smoking group were adapted to treadmill for 30 minutes per session once a day. After 12 weeks intervention, serum irisin concentration, expression of Nrf2 mRNA and protein in lung homogenate, number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and Mean Liner Intercept (MLI) in lung tissue were examined. Results: Serum irisin concentration and expression of Nrf2 (mRNA and protein) in lung homogenate were significantly elevated in exercise+smoking group compared to control group and smoking group. Proportion of neutrophils in BALF was significantly lower in exercise+smoking group than that in smoking group. MLI was significantly smaller in exercise+smoking group than that in smoking group. Conclusions: Our results suggested that irisin secreted from muscle by exercise might act defensively against oxidative stress via Nrf2, and ameliorate emphysema in lung. Exercise-irisin axis might be a novel target for COPD treatment.

Solar-C EUVST (EUV High-Throughput Spectroscopic Telescope) is a solar physics mission concept that was selected as a candidate for JAXA competitive M-class missions in July 2018. The onboard science instrument, EUVST, is an EUV spectrometer with slit-jaw imaging system that will simultaneously observe the solar atmosphere from the photosphere/chromosphere up to the corona with seamless temperature coverage, high spatial resolution, and high throughput for the first time. The mission is designed to provide a conclusive answer to the most fundamental questions in solar physics: how fundamental processes lead to the formation of the solar atmosphere and the solar wind, and how the solar atmosphere becomes unstable, releasing the energy that drives solar flares and eruptions. The entire instrument structure and the primary mirror assembly with scanning and tip-tilt fine pointing capability for the EUVST are being developed in Japan, with spectrograph and slit-jaw imaging hardware and science contributions from US and European countries. The mission will be launched and installed in a sun-synchronous polar orbit by a JAXA Epsilon vehicle in 2025. ISAS/JAXA coordinates the conceptual study activities during the current mission definition phase in collaboration with NAOJ and other universities. The team is currently working towards the JAXA final down-selection expected at the end of 2019, with strong support from US and European colleagues. The paper provides an overall description of the mission concept, key technologies, and the latest status.

概要：抗酸化物質で大豆などに含まれるイソフラボンがCOPD(慢性閉塞性肺疾患)の予防効果を有することを明らかにしました。COPDは日本では約500万人以上が罹患しており、進行すると咳や痰、息切れを自覚し、在宅酸素療法を必要とする患者さんもいます。COPDによる死亡者数は年々増加しており、WHO(世界保健機関)の報告ではCOPDは世界の死因第3位の疾患で、COPD患者の肺では、マクロファージや好中球などの炎症細胞の増加、肺胞壁の破壊による肺気腫が見られます。現時点では破壊された肺を元に戻す有効な治療法はなく、予防が肝要とされています。これまで疫学研究では大豆摂取によるCOPD発症リスク低減が報告されていましたが、そのメカニズムは解明されていませんでした。そこで、喫煙曝露によりCOPDを発症するマウスにイソフラボンを投与したところ、炎症細胞の減少や肺気腫の抑制効果を認めました。また、肺組織中の炎症形成に関わるサイトカイン等の上昇を抑制することも確認しました。本研究は、イソフラボンが抗炎症作用によりCOPD予防を果たすことを実験的に明らかにしたもので、今後のCOPD治療確立に向けて重要な知見であるといえます。, Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.

Objectives Low-frequency epidermal growth factor receptor (EGFR) T790M mutation could be detected by ultrasensitive methods in EGFR tyrosine kinase inhibitor (TKI)-naive non-small cell lung cancer (NSCLC). However, the impact of pretreatment T790M (preT790M) on the efficacy of EGFR-TKIs and on resistance remains unclear. Materials and methods Two independent cohorts consisting of advanced EGFR-mutated NSCLC patients treated with first-line EGFR-TKIs, a derivation cohort that started treatment between August 2013 and July 2016 (cohort A, n = 44) and a validation cohort between August 2016 and December 2017 (cohort B, n = 22), were examined in this study. Among these, 28 patients underwent re-biopsy at disease progression. DNAs from pretreatment tumor biopsy samples and re-biopsy samples were assessed to detect T790M by the Cobas EGFR Mutation Test v2 (Cobas) and for quantitating T790M by droplet digital polymerase chain reaction (ddPCR). Results Detection rates of preT790M were 40.9% (18/44) in cohort A and 45.5% (10/22) in cohort B by ddPCR, and none by Cobas. A cutoff value of 0.3% for dividing into high- vs. low-preT790M allele frequency was determined by receiver operating characteristic curve analysis in cohort A. Progression-free survival (PFS) was significantly shorter in the high- preT790M group (n = 12) than in the low-preT790M (n = 6) and negative (n = 26) groups (combined low-preT790M) (median: 6.9 vs. 13.8 months, P = 0.00073). These observations were validated in cohort B [median: 6.2 (n = 5) vs. 15.3 months (n = 17), P = 0.0029]. In 28 paired biopsies, Cobas detected post-progression T790M in 60% (3/5) of the high-preT790M, in 57% (4/7) of the low-preT790M, and in 56% (9/16) of the negative-preT790M groups. Conclusion EGFR-mutated NSCLC with high preT790M had significantly shorter PFS on EGFR-TKIs. However, preT790M abundance may not necessarily confer post-TKI T790M resistance.

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

In order to assist blind people in using a flat touchscreen, “virtual” tactile dots which feedback either of or both speech and vibration when touched have been proposed. In this paper, we investigated their effectiveness in map reading application. We conducted two experiments with eight blind participants in which participants perceived the distance and direction between two virtual tactile dots. Their results show that the perception of distance and direction by virtual tactile dots was accurate enough. However, the search time for these dots was significantly longer than that for real tactile dots. This search time issue made us conclude that the reading and vibrating tactile map is not practical.

The klotho gene was originally identified as a putative aging-suppressor gene. Klotho-depleted mice display a shortened life span and exhibit a variety of premature aging-related phenotypes such as pulmonary emphysema and sarcopenia. This study was designed to determine the roles of secreted-type klotho protein on lung and skeletal muscle in chronic obstructive pulmonary disease (COPD). Serum α-klotho and irisin levels were assayed in 16 non-smokers, 13 smokers without COPD, and 24 smokers with COPD. Moreover, we examined correlations between soluble α-klotho levels and the results of lung function test, cardiopulmonary exercise test (CPET), and skeletal muscle function in smokers with COPD. Soluble α-klotho levels were significantly lower in smokers with COPD compared to non-smokers and smokers without COPD. In smokers with COPD, those levels did not significantly correlate with any parameters of lung function test. In CPET, peak VO2 significantly correlated with FEV1 (% predicted) (r = 0.76, p = 0.0003) and DLCO (% predicted) (r = 0.62, p = 0.003). In contrast, soluble α-klotho levels did not significantly correlate with peak VO2. Irisin levels were also significantly lower in smokers with COPD. Moreover, there was a significant correlation between soluble α-klotho and serum irisin levels (r = 0.61, p = 0.004). Our findings could provide a critical first step to understanding the impacts of soluble α-klotho on skeletal muscle in COPD and may lead to the identification of new molecular targets for the treatment of COPD.

我々は視覚障害者向けの鍼灸、特に経絡と経穴に関する教育材料の研究に取り組んだ。この教材では、鍼灸分野における概念間の関係の体系的な理解を可能にすべく、オントロジーを用いた。オントロジーの概念図によりオントロジー教材を作成し、これを鍼灸の講義で使用した群とオントロジー教材未使用群とで経絡・経穴の試験の結果を比較し、その有効性を解析した。その結果、オントロジー教材を使用した学生の経絡・経穴の試験の得点は、オントロジー教材未使用群の学生の得点よりも有意(P < 0.001)に高く、経絡と経穴の学習にオントロジー教材有効である事が明らかになった。この結果は、オントロジーの視覚障害者教育への利用が視覚障害者の鍼灸理論の学習へも有効であることを示唆している。, In this study we developed learning material of acupuncture - acupoints and meridians - for visually impaired people. For this learning material, we used ontology to construct the relations between the concepts in the acupuncture and moxibustion field which also enables tactical understanding similarly as visual understanding. We then used our learning material in the acupuncture lecture for the visually impaired students, and quantitatively analysed its efficacy to compare the results with the group which did not use the learning material. As a result, the students, who used our learning material, scored significantly higher in the examination than the students of non-use group (P < 0.001), suggesting that our learning material was effective for learning of acupuncture theory.

We present extreme ultraviolet spectra of highly charged Fe ions observed with a compact electron beam ion trap as a function of monoenergetic electron beam energy. For 3 s 3 p – 3 s 3 d lines in Fe XV, strong intensity enhancement at a specific electron energy is confirmed. The enhancement is assigned as the resonant excitation via dielectronic capture followed by autoionization. The resonance contribution to line intensity ratio, which is important for the diagnostics of astrophysical plasmas, is discussed.

Background: Multiple primary lung cancers (MPLC) are reported to occur in 0.2-20 % of all primary lung cancer cases. MPLC are considered to harbor various genetic profiling patterns among the tumors even within the same individuals, though they developed from the same occupational and environmental exposure. In this study, we performed paired mutational analyses to clarify genetic mutations in MPLC and its relationship with environmental factors. Materials and methods: We obtained 38 surgical specimens from 17 patients who were pathologically diagnosed as MPLC and underwent surgery at Osaka City University Hospital between October 2007 and March 2019. In addition to the clinicopathological features, the patients' age, sex, smoking history, body mass index, radiologic features and surgical procedures were reviewed. Four of the 17 MPLC patients had metachronous lesions, whereas 13 patients only had synchronous lesions. For genetic profiling of MPLC patients, the extracted DNAs were deep-sequenced on Ion S5 sequencer (Thermo Fisher) for somatic mutations in 409 cancer-associated genes (Ion AmpliSeq Comprehensive Cancer Panel). The study was approved by institutional review board of Osaka City University Hospital and written informed consent was obtained from all of the patients. For statistically analyses, we assumed genetic mutations occurred by chance and calculated the frequency of concomitant mutations in multiple tumors within the same individuals based on a previous study (JME study; Kawaguchi T et al, J Clin Oncol 2016). Comparing the assumed frequency of mutations with the actual data, statistically analyses whether mutations would occur concomitantly or randomly were performed using an exact test. Results: Deep sequencing was successfully performed in all of the specimens with the mean coverage of 823. Results from comprehensive genetic analyses suggested that the mutation profiles differed among the tumors within the same individuals, whereas EGFR, KRAS, TP53, and PARP1 mutations were concomitantly detected in multiple tumors within the same individuals. In this study, the frequency of EGFR mutations was significantly higher in never or light -smokers and females. The occurrence of concomitant EGFR or KRAS mutations in multiple tumors within the same individuals was significantly more frequent than expected by chance (EGFR, P = .0023; KRAS, P = .0049), suggesting environmental factors play more role in EGFR and KRAS mutations than the other mutations including TP53 which occurred more randomly in individual tumors. Concomitant EGFR or KRAS mutations were particularly prominent in never or light-smokers and males. Conclusions: Results from our MPLC study confirmed that the development of EGFR or KRAS-mutated tumors were strongly related to environmental factors such as sex and smoking history, and suggested that the other mutations may occur randomly. Citation Format: Motohiro Izumi, Jun Oyanagi, Kenji Sawa, Mitsuru Fukui, Koichi Ogawa, Yoshiya Matsumoto, Yoko Tani, Tomohiro Suzumura, Tetsuya Watanabe, Hiroyasu Kaneda, Shigeki Mitsuoka, Kazuhisa Asai, Tatsuo Kimura, Nobuyuki Yamamoto, Tomoya Kawaguchi, Yasuhiro Koh. Mutational landscape of multiple primary lung cancers and its correlation with environmental factors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2333.

e21035 Background: The role of estrogen receptor status in the carcinogenesis of lung cancer remains elusive. A census of clonal and sub-clonal mutations has been defined through the analyses of evolutionary histories of cancers. We previously reported a prospective multicenter molecular epidemiology study (JME study; Kawaguchi T, J Clin Oncol 2016), which included the expression levels of estrogen receptors β (ER) using immunohistochemistry(IHC) and the mutational profile using next generation sequencing as well as solid smoking information and reproductive/ hormonal risk factors from the detailed questionnaire. Methods: Utilizing the data of the JME study, the impact of ER in lung cancer development was explored. All the patients underwent surgery. In 441 ever- and 435 never-smokers, ER were observed in 46.4% and 53.5%, respectively. The cancer-associated 72 gene mutations and 5 gene amplifications examined in this study included EGFR, SMAD4, APC, FBXW7, BRAF, STK11, PIK3CA, TP53, PTEN, KRAS, CTNNB1, NFE2L2, NF1, and MET. ALK fusion was detected by IHC. Patients were enrolled between July 2012 and December 2013, with follow up until November 30th, 2017.Cox proportional hazards models were used to assess the ER expression on relapse free survival (RFS) and overall survival (OS). A logistic regression model was applied to assess the impact of ER (positive vs. negative) on gene alterations, using sex, smoking history, age and stage as independent variables. Results: ER expression was significantly higher in never smokers (vs. ever smokers; p = 0.022) and earlier stage (stage I vs. II-IV; p = 0.002). Patients with ER positive tumors had a longer RFS than those with negative tumors (RFS rate at 4 years: 33.7 vs. 26.5%; p = 0.021), however, there was no significant difference in OS between the two groups (p = 0.108). In the impact of ER status on the gene alterations, mutations in EGFR (p = 0.003), TP53 (p = 0.007) and CTNNB1 (p = 0.027) were significantly associated with ER expression. Multivariate analysis showed that EGFR mutations (OR = 1.394, 95%CI: 1.029-1.890, p = 0.032) and CTNNB1 mutations (OR = 0.272, 95%CI: 0.087-0.853, p = 0.026) were significantly associated with ER expression, while there was a trend for significance with TP53 mutations (OR = 0.737, 95%CI: 0.537-1.011, p = 0.059). Conclusions: ER positive status triggered the clonal EGFR mutations and suppressed the sub-clonal mutations of TP53 and CTNNB1. It is suggested that ER plays a critical role in the alterations of EGFR/TP53/ CTNNB1 axis in lung cancer evolution.

Background Impaired exercise capacity is one of the most important prognostic factors for patients with chronic obstructive pulmonary disease (COPD). The 6-min walk test (6MWT) is a widely used method for assessing exercise capacity in patients with COPD. However, the 6MWT requires considerable effort from patients. Therefore, a less physically demanding, but also noninvasive, method is warranted. The objective of this study was to determine the predictors of the 6MWT distance (6MWD) in patients with COPD. Methods This retrospective observational study enrolled 133 Japanese patients with COPD. All patients underwent the 6MWT, COPD assessment test (CAT), spirometry, respiratory muscle strength evaluation, body composition assessment, and handgrip strength (HGS) measurement. We examined the associations between the 6MWD and evaluated parameters. Results From single regression analysis, the 6MWD was significantly correlated with age, CAT score, several spirometric measurements (e.g., percentages of forced vital capacity, forced expiratory volume in 1 s, and carbon monoxide diffusing capacity of the lungs [%DLCO]), respiratory muscle strength parameters (e.g., percentages of maximal expiratory and inspiratory pressures), skeletal muscle mass index, and HGS. In multiple regression analysis, age, CAT score, %DLCO, and HGS were independent predictors of the 6MWD. The %DLCO and HGS were strongly correlated as predictors of the 6MWD (p Conclusions We found that HGS was significantly correlated with the 6MWD compared with spirometric measurements or respiratory muscle strength parameters in Japanese patients with COPD, suggesting that HGS could be a simple and noninvasive predictor of the 6MWD in patients with COPD.

BACKGROUND: We previously reported that an index of afterload‐related left ventricular diastolic function, operant diastolic elastance (Ed)/effective arterial elastance (Ea) = E/e’/(0.9 × systolic blood pressure), was significantly higher in elderly hypertensive women. We aimed to determine sex‐related differences in the E/e’‐related indices for left ventricular diastolic function and their related factors during admission in patients with heart failure with preserved ejection fraction (HFpEF). HYPOTHESIS: Elderly HFpEF women exhibit severe left ventricular diastolic dysfunction associated with different left atrioventricular volume ratio. METHODS: We divided 267 patients with HFpEF (men/women, 116/151) into two groups by age (≥75 years, n = 212

Background Although extensive substrate modification in addition to pulmonary vein isolation (PVI) has been recommended in catheter ablation for persistent atrial fibrillation (AF), recent randomized controlled trials have not demonstrated efficacy of such additional ablations. Methods and study design The Osaka Cardiovascular Conference will conduct a multicenter, randomized, open-label trial aiming to examine whether PVI alone is non-inferior to PVI plus additional ablation such as linear ablation and/or complex fractionated atrial electrogram ablation in patients with persistent AF. The primary outcome is recurrence of AF documented by scheduled or symptom-driven electrocardiogram tests during a 1-year follow-up period after the index ablation. The key secondary endpoints include all-cause death, occurrence of symptomatic stroke, complications related to the procedure, and quality of life assessment using the 36-item Short-Form Health Survey. The clinical impact of the presence or absence of AF trigger foci, and their origins in cases with them, on the results of catheter ablation will also be investigated as an exploratory endpoint. A total of 512 patients will be enrolled and followed up to 1 year. Conclusions The EARNEST-PVI trial is a randomized controlled trial designed to assess whether PVI alone is non-inferior to extended substrate ablation for patients with persistent AF undergoing a first catheter ablation.

Background Airway microvascular system participates in the airway inflammation that is central to the pathophysiology of inflammatory lung disorders. Objective To examine the role of airway microvascular permeability on airway obstruction in patients with chronic obstructive pulmonary disease (COPD). Methods We measured the airway microvascular permeability index (AMPI) separately in the central or peripheral airways using a bronchoscopic microsampling technique in 9 non-smokers, 18 smokers without COPD (10 former smokers and 8 current smokers), and 26 smokers with COPD (12 former smokers and 14 current smokers). Results AMPI in the central airways was relatively low, and this index was comparable among the five groups. In contrast, AMPI in the peripheral airways was significantly higher in smokers with or without COPD compared with non-smokers. Moreover, AMPI in the peripheral airways was significantly higher in current smokers than in former smokers with COPD. Especially, AMPI in the peripheral airways, but not in the central airways, showed a significant correlation with the degree of airway obstruction in former or current smokers with COPD. However, AMPI in the peripheral airways was not correlated with the diffusing capacity of the lung in former or current smokers with COPD. Conclusion Airway microvascular permeability in the peripheral airways is increased in patients with COPD, and is associated with the severity of airway obstruction. We may need to consider this characteristic feature as a target in any therapeutic strategy for the treatment of the disease. (237 words).

Integration of laser sintering of plastic powder and laser direct structuring using CO 2 laser for the both of laser sintering and laser activation is discussed. Feasibility of activation by CO 2 laser is investigated, and chromium copper oxide can be used as an agent for the integrated system. Activation can be enhanced by adding active carbon. It is revealed that surface of a part is melted on activation, and flow of the melt affects the activation quality while high flowability of the melt preferable for improvement of relative density.

BACKGROUND: In patients with atrial fibrillation, ablation decreases left atrial (LA) compliance, which may lead to left ventricular (LV) diastolic dysfunction. We aimed to examine serial changes in LV diastolic function after 2 ablation procedures and their related factors in patients with paroxysmal atrial fibrillation (PAF). HYPOTHESIS: LV diastolic function is different after 2 ablation procedures. METHODS: We enrolled 132 patients with PAF (76 males, mean age 67 years; cryoballoon [CB] ablation/radiofrequency [RF] ablation 60/72) who underwent a single ablation procedure. The transthoracic echocardiographic parameters were obtained before, 3 days after, and 6 months after ablation. RESULTS: The afterload‐related index of LV diastolic function, Ed/Ea = E/e' / (0.9 × systolic blood pressure), increased significantly at 3 days after ablation, especially after CB ablation (P

Background Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST‐monitoring function in coronary artery disease patients. Methods and Results We conducted a prospective study of implantable cardioverter defibrillator patients with the ST‐monitoring function. One hundred seventy‐three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12‐lead ECGs and device checks that included analysis of the ST‐monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow‐up. The mean follow‐up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (−) group (28.6% versus 7.2%, P =0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (−) group (13.5% versus 33.5%, P =0.01). Conclusions If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients. Clinical Trial Registration URL: upload.umin.ac.jp . Unique identifier: UMIN000011824.

Aim: Maximal hyperemic response, leading to examination of microvascular resistance in lower-limb lesions is not well understood. This study aimed to investigate the infrainguinal arterial physiological response through a hyperemic condition and the pathophysiological significance of microvascular resistance in peripheral artery disease. Methods: Sixteen limbs with focal stenosis of the superficial femoral artery (SFA) and 16 control limbs were analyzed. We assessed the fractional flow reserve (FFR), vascular flow reserve (VFR), and hyperemic microvascular resistance (h-MR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT). Skin perfusion pressure (SPP) on both the dorsal and the plantar sides of the foot was measured at baseline before and after the endovascular procedures. Results: FFR (p < 0.05) and VFR (p < 0.05), but not h-MR, improved after EVT. There was no association between h-MR and FFR or VFR before EVT. h-MR was negatively correlated with the dorsal SPP before EVT (r = −0.589, p < 0.05). h-MR in patients with high h-MR before EVT significantly decreased after EVT (p < 0.05). Patients with high, but not those with low, h-MR before EVT exhibited a significant increase in dorsal and plantar SPP after EVT (p < 0.05, each). Conclusion: EVT for SFA stenosis improved FFR and VFR comprehensively, with no apparent change in h-MR. However, high h-MR before EVT may play a predictive role for limb perfusion improvement associated with h-MR reduction after EVT.

We have developed software that uses the R statistics software environment to automatically generate tactile graphs — i.e. graphs that can be read by blind people using their sense of touch. We released this software as a Web application to make it available to anyone, from anywhere. This Web application can automatically generate images for tactile graphs from numerical data in a CSV file. It is currently able to generate four types of graph — scatter plots, line graphs, bar charts and pie charts. This paper describes the Web application's functions, operating procedures and the results of evaluation experiments

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%]; the maximum dose to the small bowel [cGy]; and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

Concealed sinus node dysfunction (SND) may become manifest after restoration of sinus rhythm by ablation in patients with persistent atrial fibrillation (AF). The purpose of this study was to investigate the predictors of SND after catheter ablation of persistent AF.Two hundred two consecutive patients who underwent ablation for persistent AF were enrolled. Ipsilateral pulmonary vein isolation followed by, if necessary, electrical cardioversion were performed in all patients. SND was defined when temporary and/or permanent pacemakers were needed due to sinus bradycardia after ablation.SND developed in 12 (5.9 %) patients. There was no difference between the patients with and without SND in terms of the age (with SND, 67 ± 9 and without, 66 ± 10 years old, P = 0.599) and sex (male; 58 vs. 79 %, P = 0.186). However, the patients with SND had a lower amplitude of the fibrillatory waves (0.115 ± 0.086 vs. 0.176 ± 0.077 mV, P = 0.009) and larger left atrial volume index (LAVI; 66 ± 31 vs. 34 ± 13, P = 0.007) than those without. A receiver operating characteristic curve identified a fibrillatory wave amplitude of 0.145 mV (AUC = 0.742; sensitivity = 65 %; specificity = 83 %) and LAVI of 47.5 ml/m(2) (AUC = 0.837; sensitivity = 82 %; specificity = 87 %) as the optimal cutoff values for predicting SND. A multivariate analysis revealed that the amplitude of the fibrillatory waves (odds ratio = 0.84 for 0.010 mV increase, 95 % CI = 0.71-0.98, P = 0.031) and LAVI (odds ratio = 1.08 for 1.0 cm(3)/m(2) increase, 95 % CI = 1.04-1.12, P 0.001) were independent risk factors for SND.A low amplitude of the fibrillatory waves and a large LAVI were predictors of SND after restoration of sinus rhythm by ablation in patients with persistent AF.

A survey was conducted on the use of ICT by visually impaired people. Among 304 respondents, 81 used smartphones and 44, tablets. Blind people used feature phones at a higher rate and smartphones and tablets at lower rates than people with low vision. The most popular smartphone model was iPhone and the most popular tablet model was iPad. While almost all blind users used the speech output accessibility feature and only a few of them used visual features, low vision users used both visual features such as Zoom, Large text, and Invert colors and speech output at high rates both on smartphones and tablets. The most popular text entry methods were different between smartphones and tablets. For smartphones flick and numeric keypad input were popular among low vision users while voice input was the most popular among blind users. For tablets a software QWERTY keyboard was the most popular among both blind and low vision users. The advantages of smartphones were access to geographical information, quick Web browsing, voice input, and extensibility for both blind and low vision users, object recognition for blind users, and readability for low vision users. Tablets also work as a vision aid for people with low vision. The drawbacks of smartphones and tablets were text entry and touch operation difficulties and inaccessible apps for both blind and low vision users, problems in speech output for blind users, and problems in readability for low vision users. Researchers and makers of operating systems (OS) and apps should assume responsibility for solving these problems.

Gas chromatography-olfactometry (GC-O) analyses of the aroma components extracted from Pilsner-type beer were performed. The concentrations of all 76 components, that were identified after the GC-O analyses, were accurately quantitated. The aroma compounds were then used in the following aroma simulation experiments, with ethanol and water as matrices. The odorants with higher odor intensity in GC-O analysis and odor activity values (OAVs) were selected first, and the selected 25 odorants were used in an aroma simulation experiment. The results of sensory analysis showed that the simulation model using 25 odorants exhibited unbalanced characteristics and lacked the malty/cereal, estery characteristics, the total amount of aroma, and the similarity compared to the reference Pilsner-type beer. Addition of the 24 odorants, which were identified through the fractionations of whole aroma extract of beer and expected to complement the malty/cereal characteristic, could not improve the aroma quality of the simulation model. The aroma simulation experiments using 76 odorants indicated that the synergistic contributions of the multiple odorants, with no independent contribution to the overall characteristics (including sub-threshold components) and with no reminiscence of beer aroma, were necessary for the construction of beer aroma.