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Deep-learning classifier with ultrawide-field fundus ophthalmoscopy for detecting branch retinal vein occlusion

International Journal of Ophthalmology(English edition) 2019年第1期12卷 94-99页

作者： Daisuke Nagasato Hitoshi Tabuchi Hideharu Ohsugi Hiroki Masumoto Hiroki Enno naofumi ishitobi Tomoaki Sonobe Masahiro Kameoka Masanori Niki Yoshinori Mitamura Department of Ophthalmology Saneikai Tsukazaki Hospital Rist Inc Department of Ophthalmology Institute of Biomedical SciencesTokushima University Graduate School

AIM: To investigate and compare the efficacy of two machine-learning technologies with deep-learning(DL) and support vector machine(SVM) for the detection of branch retinal vein occlusion(BRVO) using ultrawide-field fundus images. METHODS: This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6 y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4 y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and area under the curve(AUC) were calculated to compare the diagnostic abilities of the DL and SVM models. RESULTS: For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0%(95%CI: 93.8%-98.8%), 97.0%(95%CI: 89.7%-96.4%), 96.5%(95%CI: 94.3%-98.7%), 93.2%(95%CI: 90.5%-96.0%) and 0.976(95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5%(95%CI: 77.8%-87.9%), 84.3%(95%CI: 75.8%-86.1%), 83.5%(95%CI: 78.4%-88.6%), 75.2%(95%CI: 72.1%-78.3%) and 0.857(95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters(P<0.001). CONCLUSION: These results indicate that the combination of the DL model and ultrawide-field fundus ophthalmoscopy may distinguish between healthy and BRVO eyes with a high level of accuracy. The proposed combination may be used for automatically diagnosing BRVO in patients residing in remote areas lacking access to an ophthalmic medical center.

关键词： automatic diagnosis branch retinal vein occlusion deep learning machine-learning technology ultrawide-field fundus ophthalmoscopy

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Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma

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World Journal of Gastroenterology 2018年第17期24卷 1839-1858页

作者： naofumi Mukaida Yasunari Nakamoto Division of Molecular Bioregulation Cancer Research Institute Kanazawa University Second Department of Internal Medicine Faculty of Medical Sciences University of Fukui

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.

关键词： natural killer T cell natural killer cell chimeric antigen receptor T cell T cell receptor cytokine-induced killer cell program death-1 cytotoxic lymphocyte antigen-4 regulatory T cell dendritic cell myeloid-derived suppressor cell PD-ligand 1 peptide vaccine tumor-associated antigen tumor infiltrating lymphocyte

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Reduction behaviors of permanganate by microbial cells and concomitant accumulation of divalent cations of Mg2+, Zn2+, and Co2+

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Journal of Environmental Sciences 2019年第12期31卷 78-86页

作者： Tomoaki Kato Qianqian Yu Kazuya Tanaka naofumi Kozai Takumi Saito Toshihiko Ohnuki School of Environment and Society Tokyo Institute of Technology2-12-1 OofcayamaMeguro-fcuTokyo 152-8550Japan School of Earth Science China University of GeosciencesWuhan 430074China Advanced Science Research Center Japan Atomic Energy AgencyTokaiIbaraki 319-1195Japan Institute of Innovative Research Tokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8550Japan The University of Tokyo 7-3-1 HongoBunkyo-kuTokyo 113-8654Japan

Permanganate treatment is widely used for disinfection of bacteria in surface-contaminated water.In this paper,the fate of the dissolved permanganate in aqueous solution after contact with cells of Pseudomonas fluorescens was studied.Concomitant accumulation of divalent cations of Mg2+,Zn2+,and Co2+during precipitation of Mn oxides was also studied.The time course of the Mn concentration in solution showed an abrupt decrease after contact of Mn(VII)with microbial cells,followed by an increase after^24 hr.XRD analysis of the precipitated Mn oxides,called biomass Mn oxides,showed the formation of low-crystalline birnessite.Visible spectroscopy and X-ray absorption near edge structure(XANES)analyses indicated that dissolved Mn(VII)was reduced to form biomass Mn oxides involving Mn(IV)and Mn(III),followed by reduction to soluble Mn(II).The numbers of electron transferred from microbial cells to permanganate and to biomass Mn oxides for 24 hr after the contact indicated that the numbers of electron transfer from microbial cell was approximately 50 times higher to dissolved permanganate than to the biomass Mn oxides in present experimental conditions.The 24 hr accumulation of divalent cations during formation of biomass Mn oxides was in the order of Co2+>Zn2+>Mg2+.XANES analysis of Co showed that oxidation of Co2+to Co3+resulted in higher accumulation of Co than Zn and Mg.Thus,treatment of surface water by KMnO4 solution is effective not only for disinfection of microorganisms,but also for the elimination of metal cations from surface water.

关键词： Permanganate Cobalt Zinc Biomass Mn oxides Bimessite XANES

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Implicit Discontinuous Galerkin Method for RANS Simulation Utilizing Pointwise Relaxation Algorithm

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Communications in Computational Physics 2010年第3期7卷 510-533页

作者： Kanako Yasue Michiko Furudate naofumi Ohnishi Keisuke Sawada Department of Aerospace Engineering Graduate School of EngineeringTohoku UniversitySendai 980-8579Japan

An efficient implicit procedure for the Discontinuous Galerkin (DG) methodis developed utilizing a pointwise relaxation algorithm. In the pointwise relaxation,those contributions from the degrees of freedom in own computational cell are accounted for in the implicit matrix inversion. The resulting scheme is shown to be stablewith very large CFL numbers for both the Euler and the Navier-Stokes equations fortypical test problems. In order to achieve a faster convergence, efforts are also madeto reduce computing time of the present method by utilizing a p-multigrid schemeand also by solving a simplified matrix instead of a fully loaded dense matrix in theimplicit matrix inversion. A superior performance of the present implicit DG methodon the parallel computer using up to 128 PEs is shown in terms of readily achievablescalability and high parallel efficiency. The RANS simulation of turbulent flowfieldover AGARD-B model is carried out to show the convergence property and numericalstability of the present implicit DG method for engineering applications.

关键词： Discontinuous Galerkin method pointwise relaxation implicit scheme viscous compressible flow

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Fibroblasts, an inconspicuous but essential player in colon cancer development and progression

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World Journal of Gastroenterology 2016年第23期22卷 5301-5316页

作者： naofumi Mukaida Soichiro Sasaki Division of Molecular Bioregulation Cancer Research InstituteKanazawa University

Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.

关键词： Angiogenesis Drug resistance extracellular matrix immune evasion Transforming growth factor-β invasion Metastasis

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CCR5 gene expression in fulminant hepatitis and DTH in mice

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World Journal of Gastroenterology 1998年第1期4卷 19-23页

作者： GUO Bao-Yu ZHANG Su-Ying naofumi Mukaida Akihisa Harada Kouji Kuno WANG Jian-Bin SUN Shu-Han Kouji Matsushima 不详

ＣＣＲ５ｇｅｎｅｅｘｐｒｅｓｓｉｏｎｉｎｆｕｌｍｉｎａｎｔｈｅｐａｔｉｔｉｓａｎｄＤＴＨｉｎｍｉｃｅＧＵＯＢａｏＹｕ１，ＺＨＡＮＧＳｕＹｉｎｇ２，ＮａｏｆｕｍｉＭｕｋａｉｄａ３，ＡｋｉｈｉｓａＨａｒａｄａ３，Ｋｏ... 详细信息

ＣＣＲ５ｇｅｎｅｅｘｐｒｅｓｓｉｏｎｉｎｆｕｌｍｉｎａｎｔｈｅｐａｔｉｔｉｓａｎｄＤＴＨｉｎｍｉｃｅＧＵＯＢａｏＹｕ１，ＺＨＡＮＧＳｕＹｉｎｇ２，ＮａｏｆｕｍｉＭｕｋａｉｄａ３，ＡｋｉｈｉｓａＨａｒａｄａ３，ＫｏｕｊｉＫｕｎｏ３，ＷＡＮＧＪｉａｎ...

关键词： CCR5 gene DNA,complementary gene expression cloning,molecular hepatitis hypersensitivity,delayed disease models,animal polymerase chain reaction immunohistochemistry

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Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression

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World Journal of Gastroenterology 2014年第28期20卷 9392-9404页

作者： Ying-Yi Li naofumi Mukaida Cancer Research Institute Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical CollegeFudan University Division of Molecular Bioregulation Cancer Microenvironment Research ProgramCancer Research InstituteKanazawa University

Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase activity.Similar to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involved in many cellular processes,including cell proliferation,survival,and protein synthesis.Although Pim-3is expressed in normal vital organs,it is overexpressed particularly in tumor tissues of endoderm-derived organs,including the liver,pancreas,and colon.Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular,pancreatic,and colon carcinoma cell lines by promoting cell apoptosis.Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack,and therefore,Pim-3 can exhibit its kinase activity once it is expressed.Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors(e.g.,Ets-1)and post-translational modifiers(e.g.,translationally-controlled tumor protein),respectively.Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model.Furthermore,a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice,without inducing any major adverse effects.Thus,Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer.

关键词： Serine/threonine kinase Pancreatic cancer Ets-1 Tr

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High Concentration of Spermine Induces the Dedifferentiation of Somatic Cells into Pluripotent Stem Cells

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Journal of Biomedical Science and Engineering 2019年第2期12卷 92-110页

作者： naofumi Shiomi School of Human Sciences Kobe College Nishinomiya Japan

Cancer tissues contain cancer stem cells (CSCs), which play important roles in cancer metastasis. However, the mechanisms through which cancer cells dedifferentiate into stem cells have not yet been elucidated. In this study, the effects of high concentrations of polyamines produced in cancer cells on dedifferentiation were examined. The results showed that when normal human fibroblasts were cultured with high concentrations of spermine, the obtained polyamine-induced cells expressed alkaline phosphatase and marker proteins of pluripotent stem cells, although apoptosis occurred in most cells. In contrast, another polyamine-induced stem (PIS) cell line (Spe-2 PIS cells), obtained by culture in medium containing Rock, p53, and Bax inhibitors plus spermine, did not show signs of apoptosis. These Spe-2 PIS cells expressed marker proteins of pluripotent stem cells and differentiated into cardiomyocytes, brown adipocytes, and nerve cells. These results suggest that a high concentration of spermine, which often induces apoptosis in normal cells, has the capacity to dedifferentiate somatic cells into pluripotent stem cells and may be associated with the dedifferentiation of cancer cells, which continuously produce high concentrations of spermine. Moreover, the procedure to obtain Spe-2 PIS cells, which is simple and efficient, may have potential applications in regenerative medicine.

关键词： Polyamine Spermine Pluripotent Stem Cells Dedifferentiation Cancer Stem Cells Regenerative Medicine

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Development of nanocrystal formulation of mebendazole with improved dissolution and pharmacokinetic behaviors

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 122-123页

作者： naofumi Hashimoto Kayo Yuminoki Haruka Takeuchi Chiaki Okada Setsunan University

Nanosizing by wet beads milling is a method to improve the solubility of poorly water soluble compounds[1,2].Mebendazole(MBZ)is a well-known anthelmintic drug in wide clinical use.There were some reports that MBZ had the anticancer effect in preclinical study.However,the bioavailability of MEB is low(<10%)due to the poor solubility in water(0.5μg/mL).The present study aimed to develop the nanocrystal formulations of MEB to improve dissolution behavior and enhance oral absorption.

关键词： Mebendazole Nanocrystal Wet beads milling Oral absorption

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Synthesis and Properties of Organic-Inorganic Hybrid Porous Polymers Obtained with Click Addition Reactions of Thiol-Functionalized Random Type Silsesquioxane by and Diacrylate or Diisocyanate Compounds

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Open Journal of Polymer Chemistry 2020年第1期10卷 1-20页

作者： Tomoharu Miyanaga naofumi Naga Graduate School of Engineering and Science Shibaura Institute of Technology Tokyo Japan Department of Applied Chemistry College of Engineering Shibaura Institute of Technology Tokyo Japan

Organic-inorganic hybrid network polymers have been synthesized by addition reaction of a thiol-functionalized random type silsesquioxane (SQ109) and alkyl diacrylate or diisocyanate compounds. Thiol-ene reaction of SQ109 and 1,4-butanediol diacrylate (BDA) successfully yield porous polymer in toluene initiated by azobis(isobutyronitrile) (AIBN) at 60°C. Morphology of the porous polymers was composed by connected globules, and the diameter of the globules decreased with increasing in the monomer concentration of the reaction system. By contrast, the reaction with 1,6-hexanediol diacrylate or 1,5-hexadiene yielded homogeneous clear gels. Thermal analyses of SQ109-BDA porous polymers indicated that thermal degradation of ester groups of BDA in the polymer network occurred at around 300°C. The porous polymer was also obtained by the reaction using a photo-initiator (Irugacure184) at room temperature, and showed higher Young’s modulus than the corresponding porous polymer obtained with the reaction with AIBN due to the small size of the globules. Young’s modulus of SQ109-BDA porous polymer increased

关键词： Silsesquioxane Thiol Diacrylate Diisocyanate Gel Porous Polymer Morphology

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