基本情報
研究キーワード
4研究分野
1委員歴
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2012年 - 2014年
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2014年
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2014年
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2014年
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2012年
受賞
7-
2010年3月
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2009年5月
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2006年11月
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2002年7月
論文
955-
IJC Heart & Vasculature 54 101507-101507 2024年10月
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Hypertension research : official journal of the Japanese Society of Hypertension 2024年9月19日The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.
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International Journal of Cardiology: Cardiovascular Risk and Prevention 22 2024年9月The authors regret that the original version of the article incorrectly stated the study period as “April 2014 to March 2020" in both the Abstract and the Methods section. The correct study period should have been “April 2013 to March 2019". The authors would like to apologise for any inconvenience caused.
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JACC: Advances 3(7) 2024年7月Background: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730)
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JACC. Advances 3(7) 100996-100996 2024年7月BACKGROUND: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. OBJECTIVES: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. METHODS: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. RESULTS: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. CONCLUSIONS: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
MISC
1912-
Clinica chimica acta; international journal of clinical chemistry 428 63-9 2014年1月20日 査読有りOBJECTIVES: Immunoglobulin G4 (IgG4)-related immuno-inflammation may play a role in the development of coronary artery disease (CAD). We analyzed the association of serum IgG4 and soluble interleukin-2 receptor (sIL-2R) levels with epicardial fat volume (EFV) and coronary artery calcification (CAC). METHODS: Serum IgG4 and sIL-2R levels were measured in 267 patients who underwent 320-slice cardiac computed tomography. RESULTS: THE median serum levels of IgG4 and sIL-2R were higher in patients with CAD than in those without. Serum IgG4 levels were significantly greater in patients with EFV within the second and fourth quartile (≥75 mL) than in those with low EFV (b75 mL) (33.5 mg/dL vs. 22.5 mg/dL). On the other hand, serum sIL-2R levels were significantly higher in patients with CAC than in those without (409 U/mL vs. 345 U/mL). In age- and gender-adjusted logistic regression analysis, the fourth quartile of IgG4 (≥56.7 mg/dL) was associated with EFV within the second and fourth quartile (≥75 mL) with an odds ratio of 3.13. CONCLUSION: Serum IgG4 levels were greater in patients with EFV within the second and fourth quartile, whereas serum sIL-2R levels were increased in patients with CAC. These two biomarkers may reflect different mechanisms underlying development of cardiovascular remodeling.
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PloS one 9(4) e95521 2014年 査読有りBACKGROUND: Although periodontitis is a risk factor for cardiovascular disease (CVD), the influence of periodontitis on Marfan syndrome (MFS) with CVD is unclear. The aim of this study was to assess the relationship between periodontal bacterial burden and MSF with CVD. METHODS AND RESULTS: The subjects were patients with MFS with CVD (n = 47); age and gender matched non-MFS CVD patients (n = 48) were employed as controls. Full-mouth clinical measurements, including number of teeth, probing of pocket depth (PD), bleeding on probing (BOP) and community periodontal index (CPI) were recorded. We also evaluated the existence of three periodontal pathogens, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia using polymerase chain reaction assays. Serum antibody titers against the pathogens were also measured. We revealed that MFS with CVD patients had periodontitis more frequently than the age and gender matched non-MFS CVD control subjects. MFS with CVD patients had significantly severer periodontitis, fewer remaining teeth and deeper PD compared to the non-MFS CVD controls. Furthermore, the serum antibody titer level against Prevotella intermedia was significantly lower in MFS plus CVD patients compared to the non-MFS CVD patients. CONCLUSION: Periodontitis may influence the pathophysiology of cardiovascular complications in MFS patients. A specific periodontal pathogen might be a crucial therapeutic target to prevent CVD development.
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9(5) e96286 2014年 査読有り・ Wang JH, Eguchi K, Matsumoto S, Fujiu K, Komuro I, Nagai R, Manabe I. The ω-3polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling. PLoS One. 2014 May 5;9(5):e96286.
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Circulation journal : official journal of the Japanese Circulation Society 78(10) 2483-91 2014年 査読有りBACKGROUND: Indications of implantable cardioverter-defibrillator (ICD) for patients with an old myocardial infarction (OMI) and left ventricular dysfunction (LVD) were expanded in Western countries after the results of MADIT II. However, the prognosis of OMI patients with LVD and the merits of prophylactic implantation of ICD, based on evidence in Japan, have not yet been clarified. This subanalysis of the Japanese Coronary Artery Disease (JCAD) Study focused on MADIT II-compatible patients to clarify the prognosis of OMI patients with LVD in Japan. METHODS AND RESULTS: Consecutive 6,868 OMI patients were prospectively followed up for 3 years or until clinical events occurred. 291 patients had left ventricular ejection fraction (LVEF) ≤30%. Clinical events, congestive heart failure, cardiopulmonary arrest on arrival and vascular events were significantly more frequent in patients with LVEF ≤30% than in those with better LVEF. In the LVEF ≤30% group, cardiopulmonary arrest on arrival comprised 33% of all-cause deaths, and the survival curves at 2 years of the LVEF ≤30% group were almost compatible with those of the MADIT II ICD group. CONCLUSIONS: In this subanalysis, LVD was less frequent than in Western countries. The annual death rate in JCAD was better than for the MADIT II ICD group. The prophylactic use of ICD seemed to be less effective than in Western countries but still expected to be useful for OMI patients with LVD in Japan.
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CIRCULATION 128(22) 2013年11月
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CIRCULATION 128(22) 2013年11月
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International Journal of Cardiology 168(3) 3125-3127 2013年10月3日
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ARTHRITIS AND RHEUMATISM 65 S1156-S1157 2013年10月
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American journal of human genetics 93(2) 289-97 2013年8月8日 査読有りTakayasu arteritis (TAK) is an autoimmune systemic vasculitis of unknown etiology. Although previous studies have revealed that HLA-B*52:01 has an effect on TAK susceptibility, no other genetic determinants have been established so far. Here, we performed genome scanning of 167 TAK cases and 663 healthy controls via Illumina Infinium Human Exome BeadChip arrays, followed by a replication study consisting of 212 TAK cases and 1,322 controls. As a result, we found that the IL12B region on chromosome 5 (rs6871626, overall p = 1.7 × 10(-13), OR = 1.75, 95% CI 1.42-2.16) and the MLX region on chromosome 17 (rs665268, overall p = 5.2 × 10(-7), OR = 1.50, 95% CI 1.28-1.76) as well as the HLA-B region (rs9263739, a proxy of HLA-B*52:01, overall p = 2.8 × 10(-21), OR = 2.44, 95% CI 2.03-2.93) exhibited significant associations. A significant synergistic effect of rs6871626 and rs9263739 was found with a relative excess risk of 3.45, attributable proportion of 0.58, and synergy index of 3.24 (p ≤ 0.00028) in addition to a suggestive synergistic effect between rs665268 and rs926379 (p ≤ 0.027). We also found that rs6871626 showed a significant association with clinical manifestations of TAK, including increased risk and severity of aortic regurgitation, a representative severe complication of TAK. Detection of these susceptibility loci will provide new insights to the basic mechanisms of TAK pathogenesis. Our findings indicate that IL12B plays a fundamental role on the pathophysiology of TAK in combination with HLA-B(∗)52:01 and that common autoimmune mechanisms underlie the pathology of TAK and other autoimmune disorders such as psoriasis and inflammatory bowel diseases in which IL12B is involved as a genetic predisposing factor.
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JOURNAL OF CARDIAC FAILURE 19(8) S29-S29 2013年8月
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JOURNAL OF CARDIAC FAILURE 19(8) S91-S91 2013年8月
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EUROPEAN HEART JOURNAL 34 159-159 2013年8月
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Biological Rhythm Research 44(4) 519-530 2013年8月1日Significant circadian variations exist in the frequency of cardiac arrhythmia, but few studies have examined the relation between cardiac ion channels genes and biological clocks. We investigated this relation using suprachiasmatic nuclei lesion (SCNX) and pharmacological autonomic nervous system block (ANSB) mice. Significant 24-h variations were observed in the expression of clock genes Per2, Bmal1, and Dbp and ion channel genes KCNA5, KCND2, KCHIP2, and KCNK3 in the control mice hearts. In the SCNX mice, all genes examined lost circadian rhythm. In the ANSB mice, the expressions of the three clock genes were dampened significantly but still had circadian rhythm, whereas the four ion channel gene expressions lost rhythm. Heart rate also lost circadian rhythm in both the SCNX and ANSB mice. These results suggest that some ion channel gene expressions might be regulated by the central clock in the SCN through the ANS but not the peripheral clock in the heart. © 2013 Taylor & Francis Group, LLC.
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Circulation research 112(12) 1634-47 2013年6月7日 査読有りAtherosclerosis is a chronic inflammatory disease driven by lipids and other atherogenic factors. It is characterized by a dynamic and complex pathological process of bone marrow-derived cells playing divergent roles. Recent studies have begun unraveling the contribution of growing varieties of subsets of immune cells and other bone marrow-derived cells to atherogenesis. For example, bone marrow-derived vascular progenitor cells have been shown to play an important role in the pathogenesis of atherosclerosis. This review provides an overview of the current understanding of contributions of bone marrow-derived cells to atherosclerosis. Particular focus is placed on myeloid cells and vascular progenitor cells. We also summarize the uncertainty surrounding cellular lineage identity and functions. Expansion of our understanding of pathological roles of various subsets of bone marrow-derived cells in atherosclerosis may lead to identification of novel cellular and molecular targets for development of therapeutic strategies.
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日本心臓血管外科学会雑誌 42(3) (1)-(21) 2013年5月
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Modern rheumatology 64(10) S300-S300 2013年3月30日 査読有りOBJECTIVE: To investigate the clinical significance of flow-mediated dilation (FMD) in systemic sclerosis (SSc). METHODS: Thirty-three SSc patients and 12 healthy controls were studied. Ultrasound assessment of the brachial artery FMD was performed on all subjects. The results were expressed as the percentage of increase in brachial artery diameter following hyperemia. RESULTS: Limited cutaneous SSc (lcSSc) patients had significantly lower FMD values than healthy controls (5.3 ± 2.7 versus 7.7 ± 2.0 %, p < 0.05), while the values in diffuse cutaneous SSc (dcSSc) patients (6.7 ± 4.0 %) were comparable to those in lcSSc patients and healthy controls. Although FMD values did not correlate with any clinical features in dcSSc patients, there was an inverse correlation between FMD values and disease duration in lcSSc patients (r = -0.64, p < 0.05). Furthermore, lcSSc patients with decreased FMD values showed significantly higher prevalence of digital ulcers and elevated right ventricular systolic pressure than those with normal values (for each; 75 versus 10 %, p < 0.05). CONCLUSION: The FMD values represent the severity of vascular damages, which progress along with disease duration and lead to digital ulcers and pulmonary arterial hypertension, in lcSSc patients.
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CIRCULATION JOURNAL 77(2) 519-549 2013年2月
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EMBO Journal 31(23) 4428-4440 2012年11月28日Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE -/- mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1 -/-) mice and atherosclerotic lesions in Mkl1 -/- ApoE -/- mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin β1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1 -/- mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases. © 2012 European Molecular Biology Organization | All Rights Reserved.
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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CIRCULATION 126(21) 2012年11月
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JOURNAL OF CARDIAC FAILURE 18(10) S178-S178 2012年10月
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Current Atherosclerosis Reports 14(5) 484-490 2012年10月Atherosclerosis underlies coronary artery disease (CAD) and cerebrovascular disease, which are the most common forms of life-threatening cardiovascular disorders. To minimize the risk of atherosclerotic complications, primary and secondary prevention strategies seek to control risk factors. Reducing low-density lipoprotein (LDL) cholesterol through lipid-lowering drugs, such as statins, in particular yields a proportional decrease in cardiovascular disease risk. Atherosclerosis is considered to be a complex chronic inflammatory process triggered by cardiovascular risk factors which cause endothelial dysfunction and inflammatory cell infiltration within the artery wall. In this review, we summarize the current understanding of the underling molecular mechanisms of the immune signals in the development and progression of atherosclerosis. Among various molecular mechanisms, toll like receptors (TLRs) are potent proinflammatory cytokines that operate to induce inflammation play an important role in the pathogenesis of atherosclerosis. Moreover, we discuss current knowledge regarding monocyte/macrophage biology that contributes to the progression of atherosclerosis, including macrophage polarization and heterogeneity. Understanding the molecular mechanisms in conjunction with orchestration of monocyte/macrophage biology should provide a basis for novel treatment strategies to prevent the development and progression of atherosclerosis. © Springer Science+Business Media, LLC 2012.
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肥満研究 18(Suppl.) 214-214 2012年9月
書籍等出版物
21-
Springer 2009年 (ISBN: 9784431877745)
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Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
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Signal Transduction and Cardiac Hypertrophy (Naranjan S. Dhalla, Larry Hryshko, Elissavet Kardami, Pawan K. Singal, KLUWER ACADEMIC PUBLISHERS) 2003年
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Rapid Cycle Real-Time PCR : methods and applications 2001年
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in"The Hypertrophied Heart" 2000年
共同研究・競争的資金等の研究課題
91-
日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2020年7月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2018年6月 - 2023年3月