Publications by authors named "Masahiro Nakano"

231 Publications

Acetylation of the influenza A virus polymerase subunit PA in the N-terminal domain positively regulates its endonuclease activity.

FEBS J 2021 Jul 16. Epub 2021 Jul 16.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.

The post-translational acetylation of lysine residues is found in many nonhistone proteins and is involved in a wide range of biological processes. Recently, we showed that the nucleoprotein of the influenza A virus is acetylated by histone acetyltransferases (HATs), a phenomenon that affects viral transcription. Here, we report that the PA subunit of influenza A virus RNA-dependent RNA polymerase is acetylated by the HATs, P300/CREB-binding protein-associated factor (PCAF), and general control nonderepressible 5 (GCN5), resulting in accelerated endonuclease activity. Specifically, the full-length PA subunit expressed in cultured 293T cells was found to be strongly acetylated. Moreover, the partial recombinant protein of the PA N-terminal region containing the endonuclease domain was also acetylated by PCAF and GCN5 in vitro, which facilitated its endonuclease activity. Mass spectrometry analyses identified K19 as a candidate acetylation target in the PA N-terminal region. Notably, the substitution of the lysine residue at position 19 with glutamine, a mimic of the acetyl-lysine residue, enhanced its endonuclease activity in vitro; this point mutation also accelerated influenza A virus RNA-dependent RNA polymerase activity in the cell. Our findings suggest that PA acetylation is important for the regulation of the endonuclease and RNA polymerase activities of the influenza A virus.
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http://dx.doi.org/10.1111/febs.16123DOI Listing
July 2021

Ultrastructure of influenza virus ribonucleoprotein complexes during viral RNA synthesis.

Commun Biol 2021 07 9;4(1):858. Epub 2021 Jul 9.

Laboratory of Ultrastructural Virology, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.

The single-stranded, negative-sense, viral genomic RNA (vRNA) of influenza A virus is encapsidated by viral nucleoproteins (NPs) and an RNA polymerase to form a ribonucleoprotein complex (vRNP) with a helical, rod-shaped structure. The vRNP is responsible for transcription and replication of the vRNA. However, the vRNP conformation during RNA synthesis is not well understood. Here, using high-speed atomic force microscopy and cryo-electron microscopy, we investigated the native structure of influenza A vRNPs during RNA synthesis in vitro. Two distinct types of vRNPs were observed in association with newly synthesized RNAs: an intact, helical rod-shaped vRNP connected with a folded RNA and a deformed vRNP associated with a looped RNA. Interestingly, the looped RNA was a double-stranded RNA, which likely comprises a nascent RNA and the template RNA detached from NPs of the vRNP. These results suggest that while some vRNPs keep their helical structures during RNA synthesis, for the repeated cycle of RNA synthesis, others accidentally become structurally deformed, which likely results in failure to commence or continue RNA synthesis. Thus, our findings provide the ultrastructural feature of vRNPs during RNA synthesis.
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http://dx.doi.org/10.1038/s42003-021-02388-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271009PMC
July 2021

Pathophysiological background and prognosis of common atrial flutter in non-elderly patients: Comparison to Atrial Fibrillation.

J Cardiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL).

Purpose: To investigate the difference between the patient background of both CAFL and AF in the non-elderly.

Methods: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation.

Results: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure.

Conclusions: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.
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http://dx.doi.org/10.1016/j.jjcc.2021.05.008DOI Listing
June 2021

miRNA-93 in Serum Extracellular Vesicles Before and After Low Dose Rate Prostate Brachytherapy.

Anticancer Res 2021 May;41(5):2411-2418

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan;

Background/aim: To identify novel biomarkers for prostate cancer (PC), we evaluated changes of miRNAs contained in serum small extracellular vesicles (EVs) in patients who received low dose rate prostate brachytherapy (BT).

Materials And Methods: EVs were isolated from the pooled serum of 10 PC patients prior to and 1 month after BT. miRNA profiling and quantitation in EVs was performed by microarray analysis and RT-digital PCR, respectively. Expression of miRNA-93 in prostate tissue was evaluated using the TCGA database and its level in EVs was determined in 25 patients before and 1, 3, 6 and 12 months after BT.

Results: Profiling and quantitation identified miRNA-93 as significantly down-regulated in EVs after BT. TCGA database analysis showed that miRNA-93 was increased in PC tissue. miRNA-93 in EVs significantly decreased in 3, 6 and 12 months after BT.

Conclusion: miRNA-93 contained in serum EVs may be a novel diagnostic and monitoring biomarker for PC.
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http://dx.doi.org/10.21873/anticanres.15016DOI Listing
May 2021

Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases.

Cell 2021 May 1;184(11):3006-3021.e17. Epub 2021 May 1.

Research Division, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa 247-8530, Japan.

Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the disease-relevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions.
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http://dx.doi.org/10.1016/j.cell.2021.03.056DOI Listing
May 2021

Selective Extraction of Nonfullerene Acceptors from Bulk-Heterojunction Layer in Organic Solar Cells for Detailed Analysis of Microstructure.

Materials (Basel) 2021 Apr 21;14(9). Epub 2021 Apr 21.

Graduate School of Natural Science and Technology, Kanazawa University, Ishikawa 920-1192, Japan.

Detailed analyses of the microstructures of bulk-heterojunction (BHJ) layers are important for the development of high-performance photovoltaic organic solar cells (OSCs). However, analytical methods for BHJ layer microstructures are limited because BHJ films are composed of a complex mixture of donor and acceptor materials. In our previous study on the microstructure of a BHJ film composed of donor polymers and fullerene-based acceptors, we analyzed donor polymer-only films after selectively extracting fullerene-based acceptors from the film by atomic force microscopy (AFM). Not only was AFM suitable for a clear analysis of the morphology of the donor polymers in the BHJ film, but it also allowed us to approximate the acceptor morphology by analyzing the pores in the extracted films. Herein we report a method for the selective extraction of nonfullerene acceptors (NFAs) from a BHJ layer in OSCs and provide a detailed analysis of the remaining BHJ films based upon AFM. We found that butyl glycidyl ether is an effective solvent to extract NFAs from BHJ films without damaging the donor polymer films. By using the selective extraction method, the morphologies of NFA-free BHJ films fabricated under various conditions were studied in detail. The results may be useful for the optimization of BHJ film structures composed of NFAs and donor polymers.
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http://dx.doi.org/10.3390/ma14092107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122272PMC
April 2021

Ionic Liquid-Assisted MAPbI Nanoparticle-Seeded Growth for Efficient and Stable Perovskite Solar Cells.

ACS Appl Mater Interfaces 2021 May 29;13(18):21194-21206. Epub 2021 Apr 29.

Nanomaterials Research Institute, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.

With the rapid improvement of perovskite solar cells (PSCs), long-life operational stability has become a major requirement for their commercialization. In this work, we devised a pristine cesium-formamidinium-methylammonium (termed as CsFAMA) triple-cation-based perovskite precursor solution into the ionic liquid (IL)-assisted MAPbI nanoparticles (NPs) through a seeded growth approach in which the host IL-assisted MAPbI NPs remarkably promote high-quality perovskite films with large single-crystal domains, enhancing the device performance and stability. The power conversion efficiency (PCE) of the MAPbI NP-seeded growth of MAPbI NPs/CsFAMA-based PSCs is as high as 19.44%, which is superior to those of MAPbI NPs and pristine CsFAMA films as the photoactive layer (9.52 and 17.33%, respectively). The long-term light-soaking and moisture stability of IL-aided MAPbI NPs/CsFAMA-based devices (non-encapsulated) remain above 90 and 80%, respectively, of their initial output after 2 h of light illumination (1 sun) and 6000 h storage at ambient with a relative humidity range of 30-40%. The use of the IL-assisted MAPbI NP-seeded growth for PSCs is a significant step toward developing stable and reliable perovskite photovoltaic devices.
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http://dx.doi.org/10.1021/acsami.1c00677DOI Listing
May 2021

Amplification-free RNA detection with CRISPR-Cas13.

Commun Biol 2021 04 19;4(1):476. Epub 2021 Apr 19.

Molecular Physiology Laboratory, Cluster for Pioneering Research, RIKEN, Saitama, Japan.

CRISPR-based nucleic-acid detection is an emerging technology for molecular diagnostics. However, these methods generally require several hours and could cause amplification errors, due to the pre-amplification of target nucleic acids to enhance the detection sensitivity. Here, we developed a platform that allows "CRISPR-based amplification-free digital RNA detection (SATORI)", by combining CRISPR-Cas13-based RNA detection and microchamber-array technologies. SATORI detected single-stranded RNA targets with maximal sensitivity of ~10 fM in <5 min, with high specificity. Furthermore, the simultaneous use of multiple different guide RNAs enhanced the sensitivity, thereby enabling the detection of the SARS-CoV-2 N-gene RNA at ~5 fM levels. Therefore, we hope SATORI will serve as a powerful class of accurate and rapid diagnostics.
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http://dx.doi.org/10.1038/s42003-021-02001-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055673PMC
April 2021

Transcriptomic studies of systemic lupus erythematosus.

Inflamm Regen 2021 Apr 9;41(1):11. Epub 2021 Apr 9.

Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8 T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.
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http://dx.doi.org/10.1186/s41232-021-00161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033719PMC
April 2021

Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis.

ACS Cent Sci 2021 Mar 23;7(3):476-487. Epub 2021 Feb 23.

School of Chemistry and Bio21 Molecular Science and Biotechnology Institute and University of Melbourne, Parkville, Victoria 3010, Australia.

The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on Earth and is metabolized by bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolizes SQ to produce dihydroxyacetone phosphate and sulfolactaldehyde and is analogous to the classical Embden-Meyerhof-Parnas glycolysis pathway for the metabolism of glucose-6-phosphate, though the former only provides one C3 fragment to central metabolism, with excretion of the other C3 fragment as dihydroxypropanesulfonate. Here, we report a comprehensive structural and biochemical analysis of the three core steps of sulfoglycolysis catalyzed by SQ isomerase, sulfofructose (SF) kinase, and sulfofructose-1-phosphate (SFP) aldolase. Our data show that despite the superficial similarity of this pathway to glycolysis, the sulfoglycolytic enzymes are specific for SQ metabolites and are not catalytically active on related metabolites from glycolytic pathways. This observation is rationalized by three-dimensional structures of each enzyme, which reveal the presence of conserved sulfonate binding pockets. We show that SQ isomerase acts preferentially on the β-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a derepressor for the transcriptional repressor CsqR that regulates SQ-utilization. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex modulation by the metabolites SQ, SLA, AMP, ADP, ATP, F6P, FBP, PEP, DHAP, and citrate, and we show that SFP aldolase reversibly synthesizes SFP. This body of work provides fresh insights into the mechanism, specificity, and regulation of sulfoglycolysis and has important implications for understanding how this biochemistry interfaces with central metabolism in prokaryotes to process this major repository of biogeochemical sulfur.
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http://dx.doi.org/10.1021/acscentsci.0c01285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006165PMC
March 2021

Simultaneous conduction disturbance of an atrioventricular accessory pathway and nodal pathway after a mitral valve replacement: A case report.

HeartRhythm Case Rep 2020 Nov 31;6(11):827-830. Epub 2020 Jul 31.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2020.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653459PMC
November 2020

Efficacy of amiodarone in a case with pre-excited atrial fibrillation with a precarious conduction property of the accessory pathway.

HeartRhythm Case Rep 2020 Nov 17;6(11):823-826. Epub 2020 Jul 17.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653465PMC
November 2020

Efficacy of cabazitaxel and the influence of clinical factors on the overall survival of patients with castration-resistant prostate cancer: A local experience of a multicenter retrospective study.

Asia Pac J Clin Oncol 2021 Jun 24;17(3):238-244. Epub 2020 Sep 24.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

Aim: To date, the optimal sequencing of life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unclear owing to a lack of prospective trials. This study aimed to evaluate the efficacy and safety of cabazitaxel (CBZ) treatment and examine the prognostic factors for oncological outcomes in patients with mCRPC who received CBZ after docetaxel (DOC).

Methods: This multi-institutional retrospective study included 44 patients with mCRPC who received CBZ. All enrolled patients had histologically confirmed prostate cancer (PCa) with distant metastases and had received DOC before CBZ administration. The primary endpoint was the oncological outcomes, including the overall (OS) and progression-free survival (PFS). The secondary endpoints were adverse events due to CBZ and rates of ≥30% reduction in prostate-specific antigen (PSA) levels.

Results: The median follow-up period was 9.2 months (range, 0.2-34 months). During this time, 34 patients (77%) died of PCa. The median OS and PFS were 12.2 (range, 0.2-34 months) and 1.4 months (range, 0.4-17 months), respectively. According to the PSA decline rate, patients who achieved a ≥30% reduction in PSA levels had significantly longer OS than those who showed a <30% reduction in PSA levels (P = 0.002). Regarding the number of cycles of CBZ, patients who received ≥4 cycles of CBZ showed significantly longer OS than those who received <4 cycles of CBZ (P < 0.001). Patients who had visceral metastasis showed significantly shorter OS than those without visceral metastasis (P = 0.012).

Conclusion: This study demonstrated that CBZ was effective and safe in Japanese local patients in a real-world setting. Patients with mCRPC who received ≥4 cycles of CBZ showed a ≥30% reduction in the serum PSA levels, and did not have visceral metastasis might achieve longer OS.
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http://dx.doi.org/10.1111/ajco.13441DOI Listing
June 2021

Naphthalene diimide-incorporated helical thienoacene: a helical molecule with high electron mobility, good solubility, and thermally stable solid phase.

Chem Commun (Camb) 2020 Oct;56(82):12343-12346

Department of Chemistry, Graduate School of Science, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.

A Naphthalene diimide (NDI)-incorporated helical thienoacene was developed. The compound has high electron mobility (1.4 cm2 V-1 s-1) thanks to its two-dimensional π-π interaction assisted by the intermolecular C-HO hydrogen bonding of the NDI moieties. Moreover, its bow-shaped π-skeleton reduces molecular fluctuation and gives the compound a thermally stable solid phase, which enables us to fabricate thermally stable organic devices.
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http://dx.doi.org/10.1039/d0cc04634eDOI Listing
October 2020

Low-Temperature Processed TiO Electron Transport Layer for Efficient Planar Perovskite Solar Cells.

Nanomaterials (Basel) 2020 Aug 26;10(9). Epub 2020 Aug 26.

Nanomaterials Research Institute, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.

The most frequently used n-type electron transport layer (ETL) in high-efficiency perovskite solar cells (PSCs) is based on titanium oxide (TiO) films, involving a high-temperature sintering (>450 °C) process. In this work, a dense, uniform, and pinhole-free compact titanium dioxide (TiO) film was prepared via a facile chemical bath deposition process at a low temperature (80 °C), and was applied as a high-quality ETL for efficient planar PSCs. We tested and compared as-deposited substrates sintered at low temperatures (< 150 °C) and high temperatures (> 450 °C), as well as their corresponding photovoltaic properties. PSCs with a high-temperature treated TiO compact layer (CL) exhibited power conversion efficiencies (PCEs) as high as 15.50%, which was close to those of PSCs with low-temperature treated TiO (14.51%). This indicates that low-temperature treated TiO can be a potential ETL candidate for planar PSCs. In summary, this work reports on the fabrication of low-temperature processed PSCs, and can be of interest for the design and fabrication of future low-cost and flexible solar modules.
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http://dx.doi.org/10.3390/nano10091676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559000PMC
August 2020

Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner.

Virol J 2020 07 16;17(1):107. Epub 2020 Jul 16.

Laboratory of Molecular Genetics, Institute for Frontier Life and Medical Science, Kyoto University, Kyoto, Japan.

Background: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a key player in inhibiting antiviral response in host cells, thereby facilitating its replication. However, other roles of NS1, which are independent of antagonising host cells' antiviral response, are less characterised.

Methods: To investigate these unidentified roles, we used a recombinant virus, which lacks NS1 expression, and observed its phenotypes during the infection of antiviral defective cells (RIG-I KO cells) in the presence or absence of exogeneous NS1. Moreover, we used virus-like particle (VLP) production system to further support our findings.

Results: Our experiments demonstrated that IAV deficient in NS1 replicates less efficiently than wild-type IAV in RIG-I KO cells and this replication defect was complemented by ectopic expression of NS1. As suggested previously, NS1 is incorporated in the virion and participates in the regulation of viral transcription and translation. Using the VLP production system, in which minigenome transcription or viral protein production was unaffected by NS1, we demonstrated that NS1 facilitates viral genome packaging into VLP, leading to efficient minigenome transfer by VLP. Furthermore, the incorporation of NS1 and the minigenome into VLP were impaired by introducing a point mutation (R38A) in the double stranded RNA-binding domain of NS1.

Conclusion: These results suggest a novel function of NS1 in improving genome packaging in a dsRNA binding-dependent manner. Taken together, NS1 acts as an essential pro-viral regulator, not only by antagonizing host immunity but also by facilitating viral replication and genome packaging.
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http://dx.doi.org/10.1186/s12985-020-01357-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367362PMC
July 2020

Predicting therapies in Japanese hypertrophic cardiomyopathy patients with an implantable cardioverter-defibrillator using the 2014 European Society of Cardiology guidelines.

Heart Vessels 2021 Jan 15;36(1):99-104. Epub 2020 Jul 15.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Previous studies have shown that the sudden cardiac death (SCD) prediction model proposed by the 2014 European Society of Cardiology (ESC) guideline (5-Year Risk-SCD) was validated in European patients with hypertrophic cardiomyopathy (HCM). However, there are limited data on Asian patients with HCM. We assessed the validity of the estimated 5-Year Risk-SCD in Japanese HCM patients with an implantable cardioverter-defibrillator (ICD) using the2014 ESC guidelines. We retrospectively examined data of 492 consecutive Japanese patients with an ICD. Sixty-two Japanese HCM patients with an ICD were enrolled in this study, and 50 patients (81%) were followed up for ≥ 5 years. We analyzed the characteristics and outcomes of these 50 patients. We investigated the incidence of appropriate ICD therapy as categorized by the ESC guideline and compared the 5-Year Risk-SCD with the 5-year rate of appropriate shock therapies. Based on the 2012 Japanese Circulation Society guideline and the 2011guidelines of the American Heart Association and American College of Cardiology Foundation, 10 and 40 patients met classes I and IIa of the ICD recommendation, respectively. However, only 18 (36%) patients were classified into class I or IIa of the ESC guideline. Among 50 patients followed up for ≥ 5 years after ICD implantation, the incidences of appropriate ICD therapies for classes I, IIa, IIb, and III indications based on the 2014 ESC guideline were 50%, 38%, 17%, and 0%, respectively. Risk stratification for SCD using 5-Year Risk-SCD is valid in Japanese HCM patients with an ICD, and the 2014 ESC guideline might be useful for the indication of ICD implantation in Japan.
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http://dx.doi.org/10.1007/s00380-020-01668-zDOI Listing
January 2021

Review: transcriptome and trans-omics analysis of systemic lupus erythematosus.

Inflamm Regen 2020 18;40:11. Epub 2020 Jun 18.

Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 113-8655 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Systemic lupus erythematosus (SLE), which was recognized as a defined clinical entity more than 100 years ago, is an archetype for systemic autoimmune diseases. The 10-year survival of SLE patients has shown dramatic improvement during the last half-century. However, SLE patients receiving long-term prednisone therapy are at high risk of morbidity due to organ damage. Identification of key immune pathways is mandatory to develop a suitable therapy and to stratify patients based on their responses to therapy. Recently developed transcriptome and omic analyses have revealed a number of immune pathways associated with systemic autoimmunity. In addition to type I interferon, plasmablast and neutrophil signatures demonstrate associations with the SLE phenotype. Systematic investigations of these findings enable us to understand and stratify SLE according to the clinical and immunological features.
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http://dx.doi.org/10.1186/s41232-020-00123-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301441PMC
June 2020

Successful cryoablation of ventricular extrasystoles originating from the vicinity of the left anterior fascicle.

J Arrhythm 2020 Jun 6;36(3):518-521. Epub 2020 Feb 6.

Department of Cardiovascular Medicine Chiba University Graduate School of Medicine Chiba Japan.

A 32-year-old male received catheter ablation of frequent ventricular extrasystoles (VEs). His electrocardiogram showed monomorphic VEs with an inferior axis and early precordial transitional zone. During electrophysiological testing, a 10-pole catheter positioned in the left ventricular outflow tract recorded sharp pre-potentials just before the ventricular activation during VEs as well as sinus beats. Three-dimensional mapping was performed by annotating the sharp pre-potentials to reveal that the earliest activation site was deemed to be close to the left anterior fascicle. A cryoablation catheter was introduced into the left ventricle and freezing for 240 seconds successfully eliminated the clinical VEs without any complications.
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http://dx.doi.org/10.1002/joa3.12304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280001PMC
June 2020

Implant and Prosthetic Treatment in Esthetic Zone with Alveolar Ridge Preservation and Autotransplantation: Clinical Case Report with 16-year Follow-up.

Bull Tokyo Dent Coll 2020 Jul 5;61(2):145-150. Epub 2020 Jun 5.

Department of Fixed Prosthodontics, Tokyo Dental College.

Occlusal reconstruction comprising orthodontic treatment, autotransplantation, and implant treatment was performed in a 30-year-old woman with missing maxillary anterior teeth. An initial examination revealed marked root resorption of the maxillary anterior teeth. Both the maxillary canines were missing, causing constriction of the dental arch. Conserving the right maxillary central and lateral incisors, which were dislocated due to trauma, was considered to be too difficult, and a bridge was not selected as there was insufficient load bearing capacity in the adjacent abutment teeth, making the prognosis uncertain. Partial dentures were rejected due to the patient's age and esthetic demands. First, the right mandibular lateral incisor was extracted to relieve crowding in the mandibular anterior teeth, leaving the patient with 3 mandibular incisors. Orthodontic treatment was then performed to harmonize the occlusal relationship between the mandibular and maxillary anterior teeth. Next, the right mandibular lateral incisor was transplanted to the extraction site of the right maxillary lateral incisor. After fixation of the autotransplanted tooth, the shape of the bone around the implant site improved. The final prosthesis for the right maxillary central incisor was provided via implant treatment. As seen in a follow-up 16 years later, the interproximal dental papilla was intact, and the patient's esthetic demands were fulfilled. Utilizing the functions of the periodontal ligament of the natural teeth was a useful part of orthodontic treatment and autotransplantation.
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http://dx.doi.org/10.2209/tdcpublication.2019-0018DOI Listing
July 2020

Predictive factors of rectal hemorrhage in patients with localized prostate cancer who underwent low-dose-rate brachytherapy.

Int J Clin Oncol 2020 Sep 5;25(9):1711-1717. Epub 2020 Jun 5.

Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.

Background: This study aimed to evaluate the association between clinical covariates or the prescribed radiation dose for the prostate and rectal hemorrhage in patients with prostate cancer (PCa) who received iodine-125 low-dose-rate brachytherapy (LDR-BT group) or the combination of LDR-BT and external beam radiation therapy (CMT group).

Methods And Materials: In this retrospective study, we reviewed the clinical records of 298 consecutive PCa patients with clinical stage T1c/T2 who underwent LDR-BT between August 2004 and August 2016 at a single institution. The prescribed minimum peripheral doses were 145 Gy for the LDR-BT group and 104 Gy for the CMT group. The dosimetric parameters analyzed were minimal dose received by 90% of the prostate gland, biologically effective dose, and rectal volume receiving 100% (RV100) or 150% of the prescribed dose. The endpoint of this study was the onset of any-grade clinical rectal hemorrhage after treatment.

Results: The median follow-up period was 6.8 years. The 5-year overall survival rate was found to be 98.3%, and two patients (0.7%) reported biochemical recurrence during follow-up period. A total of 33 patients (11%) experienced rectal hemorrhage. However, ≥ grade 2 rectal hemorrhage occurred in eight patients (2.7%). On multivariate analysis, CMT, RV100 ≥ 0.66 mL, and hemorrhoids before treatment were identified as predictors of rectal hemorrhage after radiation therapy.

Conclusions: Maximal reduction of the rectal dose seems very important to prevent serious rectal hemorrhage. In addition, we should consider the risk of rectal toxicities in patients with abnormalities in the rectal mucosa, especially hemorrhoids.
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http://dx.doi.org/10.1007/s10147-020-01713-xDOI Listing
September 2020

Assessment of Long-term Changes in Lower Urinary Tract Symptoms in Patients With Prostate Cancer Who Underwent Low-dose-rate Prostate Brachytherapy.

Urology 2020 Aug 13;142:213-220. Epub 2020 May 13.

Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan. Electronic address:

Objective: To investigate long-term changes in lower urinary tract symptoms in patients with prostate cancer (PCa) who underwent low-dose-rate brachytherapy with iodine-125 (LDR-BT).

Patients And Methods: In this retrospective study, 313 patients with localized PCa underwent LDR-BT at Gifu University hospital between August 2004 and December 2013. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and quality of life due to urinary symptoms (IPSS-QOL) were measured before LDR-BT; at 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after LDR-BT; and annually thereafter. Study endpoints were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values. A multivariable nonlinear regression model with robust sandwich estimator evaluated association between outcomes and time with adjustment for covariates.

Results: All scores worsened immediately after LDR-BT compared to preoperative scores. However, symptoms improved with time and returned to baseline in 18-36 months. After a 5-year follow-up after LDR-BT, OABSS significantly worsened in almost all patients compared to baseline although there were gradual improvements in less than 5 years after LDR-BT.

Conclusions: Our results may be of clinical importance in selecting treatment modalities for patients with localized PCa and long-term survival after definitive therapy.
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http://dx.doi.org/10.1016/j.urology.2020.04.106DOI Listing
August 2020

Metal Oxide Compact Electron Transport Layer Modification for Efficient and Stable Perovskite Solar Cells.

Materials (Basel) 2020 May 11;13(9). Epub 2020 May 11.

Nanomaterials Research Institute, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.

Perovskite solar cells (PSCs) have appeared as a promising design for next-generation thin-film photovoltaics because of their cost-efficient fabrication processes and excellent optoelectronic properties. However, PSCs containing a metal oxide compact layer (CL) suffer from poor long-term stability and performance. The quality of the underlying substrate strongly influences the growth of the perovskite layer. In turn, the perovskite film quality directly affects the efficiency and stability of the resultant PSCs. Thus, substrate modification with metal oxide CLs to produce highly efficient and stable PSCs has drawn attention. In this review, metal oxide-based electron transport layers (ETLs) used in PSCs and their systemic modification are reviewed. The roles of ETLs in the design and fabrication of efficient and stable PSCs are also discussed. This review will guide the further development of perovskite films with larger grains, higher crystallinity, and more homogeneous morphology, which correlate to higher stable PSC performance. The challenges and future research directions for PSCs containing compact ETLs are also described with the goal of improving their sustainability to reach new heights of clean energy production.
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http://dx.doi.org/10.3390/ma13092207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254352PMC
May 2020

Fast Statistical Iterative Reconstruction for Mega-voltage Computed Tomography.

J Med Invest 2020 ;67(1.2):30-39

Department of Radiology, The University of Tokyo Hospital, Japan.

Statistical iterative reconstruction is expected to improve the image quality of computed tomography (CT). However, one of the challenges of iterative reconstruction is its large computational cost. The purpose of this review is to summarize a fast iterative reconstruction algorithm by optimizing reconstruction parameters. Megavolt projection data was acquired from a TomoTherapy system and reconstructed using in-house statistical iterative reconstruction algorithm. Total variation was used as the regularization term and the weight of the regularization term was determined by evaluating signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and visual assessment of spatial resolution using Gammex and Cheese phantoms. Gradient decent with an adaptive convergence parameter, ordered subset expectation maximization (OSEM), and CPU/GPU parallelization were applied in order to accelerate the present reconstruction algorithm. The SNR and CNR of the iterative reconstruction were several times better than that of filtered back projection (FBP). The GPU parallelization code combined with the OSEM algorithm reconstructed an image several hundred times faster than a CPU calculation. With 500 iterations, which provided good convergence, our method produced a 512 × 512 pixel image within a few seconds. The image quality of the present algorithm was much better than that of FBP for patient data. J. Med. Invest. 67 : 30-39, February, 2020.
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http://dx.doi.org/10.2152/jmi.67.30DOI Listing
June 2021

Properties of manual toothbrush that influence on plaque removal of interproximal surface .

J Dent Sci 2020 Mar 31;15(1):14-21. Epub 2019 Dec 31.

Department of Operative Dentistry, Tsurumi University School of Dental Medicine, Yokohama, Japan.

Background/purpose: Few papers were available on the interproximal cleaning efficiency by manual toothbrushes when used alone. The aim was to investigate the efficiency of commercially available toothbrushes on interproximal cleaning and determine the key properties that would make the differences.

Materials And Methods: Artificial-teeth were coated with manicure type experimental dental plaque covering mainly the interproximal surface and fixed in the jaw model of a dental simulator. A modified scrubbing technique was employed to brush out the plaque conducted by one trained dentist using 26 different toothbrushes from the equal number of separate interproximal conditions. The rate of the plaque removal (%) was calculated by measuring the plaque free areas on the post-brush images.

Results: The data analysis using mixed effect modelling showed that stiffness, number of tufts and total length have effect on the rate of the plaque removable from the interproximal surfaces.

Conclusion: This study indicated consideration should be given to toothbrush properties to enhance plaque removal from the interproximal surfaces.
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http://dx.doi.org/10.1016/j.jds.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109512PMC
March 2020

Peak deflection index as a predictor of a free-wall implantation of contemporary leadless pacemakers.

J Interv Card Electrophysiol 2021 Mar 2;60(2):239-245. Epub 2020 Apr 2.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Background: Leadless pacemakers are an effective treatment for bradycardia. However, some cases exhibit pericardial effusions, presumably associated with device implantations on the right ventricular free-wall. The present study was carried out to find the ECG features during ventricular pacing with a Micra, which enabled distinguishing free-wall implantations from septal implantations without using imaging modalities.

Methods: Thirty-one consecutive patients who received Micra implantations in our facility were enrolled. The location of the device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum (Sep group), apex (Apex group), or free-wall (FW group). The differences in the 12-lead ECG during ventricular pacing by the Micra were analyzed between the Sep and FW groups.

Results: The body of the Micra was clearly identifiable in 22 patients. The location of the device was classified into Sep in 12 patients, Apex in 4, and FW in 6. The mean age was highest in the FW and lowest in the Sep group (82.7 ± 6.6 vs. 72.8 ± 8.7 years, p = 0.027). The peak deflection index (PDI) was significantly larger in the FW group than Sep/Apex group in lead V1 (Sep: 0.505 ± 0.010, Apex: 0.402 ± 0.052, FW: 0.617 ± 0.043, p = 0.004) and lead V2 (Sep: 0.450 ± 0.066, Apex: 0.409 ± 0.037, FW: 0.521 ± 0.030, p = 0.011), whereas there was no difference in the QRS duration, transitional zone, and QRS notching.

Conclusion: The PDI in V1 could be useful for predicting implantations of Micra devices on the free-wall and may potentially stratify the risk of postprocedural pericardial effusions.
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http://dx.doi.org/10.1007/s10840-020-00724-yDOI Listing
March 2021

SCN5A mutation and a short coupled variant of Torsades de Pointes originating from the right ventricle: A case report.

J Cardiol Cases 2020 Mar 22;21(3):104-105. Epub 2019 Nov 22.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

A 40-year-old male visited our institute complaining of transient loss of consciousness. He had been implanted with an implantable cardioverter defibrillator (ICD) due to idiopathic ventricular fibrillation for secondary prevention. His past genetic screening detected a single nucleotide SCN5A mutation (pR18Q), while neither QT prolongation nor ST segment elevation in the right precordial leads was observed. An interrogation of the ICD revealed that a shock therapy successfully terminated ventricular fibrillation at the time syncope occurred. His electrocardiogram revealed ventricular premature contractions (VPCs) with a short coupling interval of 250 ms. Since the spontaneous occurrence of non-sustained polymorphic ventricular tachycardia following the same VPCs was observed after admission, he was diagnosed with a short-coupled variant of Torsades de Pointes (ScTdP). Contact mapping on the basal inferior right ventricular free wall, exhibiting the earliest activation, revealed pre-potentials preceding the QRS by 30 ms during the VPCs. Radiofrequency ablation was performed to reduce the triggering VPCs. To the best of our knowledge, this is the first report describing a case of ScTdP harboring an SCN5A mutation. The present N-terminally mutated SCN5A was originally reported in relation to Brugada syndrome, whereas the detailed mechanism remains to be elucidated.

: The fundamental genetic disorders of short-coupled variant of Torsades de Pointes (ScTdP) are not clear. The present case harboring a mutation of SCN5A exhibited no long-QT or Brugada syndrome, which may implicate an unknown mechanism of the development of ScTdP.〉.
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http://dx.doi.org/10.1016/j.jccase.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054653PMC
March 2020

"Disrupt and induce" intermolecular interactions to rationally design organic semiconductor crystals: from herringbone to rubrene-like pitched π-stacking.

Chem Sci 2020 Jan 7;11(6):1573-1580. Epub 2020 Jan 7.

Emergent Molecular Function Research Team, RIKEN Center for Emergent Matter Science (CEMS) 2-1 Hirosawa, Wako Saitama 351-0198 Japan

The packing structures of organic semiconductors in the solid state play critical roles in determining the performances of their optoelectronic devices, such as organic field-effect transistors (OFETs). It is a formidable challenge to rationally design molecular packing in the solid state owing to the difficulty of controlling intermolecular interactions. Here we report a unique materials design strategy based on the β-methylthionation of acenedithiophenes to generally and selectively control the packing structures of materials to create organic semiconductors rivalling rubrene, a benchmark high-mobility material with a characteristic pitched π-stacking structure in the solid state. Furthermore, the effect of the β-methylthionation on the packing structure was analyzed by Hirshfeld surface analysis together with theoretical calculations based on symmetry-adapted perturbation theory (SAPT). The results clearly demonstrated that the β-methylthionation of acenedithiophenes can universally alter the intermolecular interactions by disrupting the favorable edge-to-face manner in the parent acenedithiophenes and simultaneously inducing face-to-face and end-to-face interactions in the β-methylthionated acenedithiophenes. This "disrupt and induce" strategy to manipulate intermolecular interactions can open a door to rational packing design based on the molecular structure.
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http://dx.doi.org/10.1039/c9sc05902dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148081PMC
January 2020

[2019 AAPM Annual Meeting and Exhibition, San Antonio, Texas, USA].

Authors:
Masahiro Nakano

Igaku Butsuri 2019 ;39(4):86-90

Radiation Oncology Department, Cancer Institute Hospital, Japanese Foundation for Cancer Research.

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http://dx.doi.org/10.11323/jjmp.39.4_86DOI Listing
January 2019

A simple microfluidic device for live-imaging of the vertical section of epithelial cells.

Analyst 2020 Jan 4;145(2):667-674. Epub 2019 Dec 4.

Precision Engineering Course, Graduate School of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan. and Dept. Precision Mechanics, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.

We investigated the capability of simple microfluidic devices with trenches having vertical sidewalls for live-cell fluorescence imaging of adherent cells. An epithelial cell line that forms a two-dimensional (2D) sheet was cultured to adhere to the vertical sidewall so that its vertical section can be imaged directly using ordinal inverted-type laser-scanning microscopy. The material and the structure of the device were characterized. We show that the detailed distribution of intracellular organelles, such as microtubules and mitochondria, and of intercellular apparatus, such as claudin and zonula occludens, can be imaged with high spatio-temporal resolution with a single scan.
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http://dx.doi.org/10.1039/c9an02165eDOI Listing
January 2020
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