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JNK-Mediated FOXO Expression Plays a Critical Role in EGFR Tyrosine Kinase Inhibitor-Induced BIM Expression and Apoptosis

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Journal of Cancer Therapy 2012年第4期3卷 424-434页

作者： Kenji Takeuchi Anh Ho Viet katsumi kawasaki Kazuto Nishio Fumiaki Ito Department of Biochemistry Faculty of Pharmaceutical Sciences Setsunan University Osaka Japan Department of Genome Biology Kinki University School of Medicine Osaka Japan

BIM, a key proapoptotic member of the BCL-2 family of proteins, is essential for apoptosis triggered by tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). However, the precise molecular mechanism by which EGFR-TKIs induce BIM expression has remained unclear. A previous study of ours showed that the activetion of c-Jun NH2-terminal kinase (JNK) is critical for the TKI-induced apoptosis in PC-9 cells, a gefitinib-sensitive human NSCLC cell line. In this study, we therefore examined the effect of JNK activation on BIM expression and further investigated the mechanism responsible for TKI-induced apoptosis in PC-9 cells. Northern blotting analysis revealed that the TKI AG1478 induced a substantial increase in the level of BIM mRNA. However, this TKI-induced increase was not observed in dominant-negative JNK overexpressing cell line J12A5 or in the TKI-resistant cell line HP-5R, in which JNK is not activated in response to AG1478. Therefore, JNK activation was correlated with the up-regulation of BIM expression. BIM is known to be a downstream target of forkhead box protein O (FOXO) transcription factors. Immunoblot analysis indicated that the levels of FOXO1, FOXO3a, and FOXO4 transcription factors increased after AG1478 treatment of PC-9 cells but that they were not increased in either J12A5 or HP-5R cells, indicating that FOXO was increased in PC-9 cells through JNK activation. FOXO1 knockdown in PC-9 cells decreased EGFR-TKI-induced BIM expression and apoptosis. These findings provide evidence that JNK activation and subsequent increased FOXO expression play a critical role in EGFR-TKI-induced BIM expression and apoptosis.

关键词： EGFR-TKI FOXO BIM JNK NSCLC

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Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

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World Journal of Diabetes 2024年第5期15卷 935-944页

作者： Eiji kawasaki Hidekazu Tamai Takahiro Fukuyama Yoko Sagara Ryutaro Hidaka Aira Uchida Masayuki Tojikubo Narihito Tatsumoto Yuko Akehi Yuji Hiromatsu The Diabetes Thyroid and Endocrine CenterShin-Koga HospitalKurume 830-8577Japan

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD *** commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical *** To investigate the frequency of anti-islet autoantibodies in AITD *** Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these *** The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two ***,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,***,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for ***,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual *** the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D com

关键词： Anti-islet autoantibodies Autoimmune thyroid disease Real-world practice Retrospective study Type 1 diabetes

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Review Integration of smartphone technology and artificial intelligence for advanced ophthalmic care:A systematic review

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Advances in Ophthalmology Practice and Research 2024年第3期4卷 120-127页

作者： Kai Jin Yingyu Li Hongkang Wu Yih Chung Tham Victor Koh Yitian Zhao Ryo kawasaki Andrzej Grzybowski Juan Ye Eye Center The Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang Provincial Key Laboratory of OphthalmologyZhejiang Provincial Clinical Research Center for Eye DiseasesZhejiang Provincial Engineering Institute on Eye DiseasesHangzhouChina Centre for Innovation and Precision Eye Health National University of SingaporeSingapore Department of Ophthalmology National University of SingaporeSingapore Singapore Eye Research Institute Singapore National Eye CentreSingapore Ophthalmology and Visual Science Academic Clinical Program Duke-NUS Medical SchoolSingapore Cixi Institute of Biomedical Engineering Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboChina Ningbo Eye Hospital NingboChina Zhejiang International Scientific and Technological Cooperative Base of Biomedical Materials and Technology Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboChina Zhejiang Engineering Research Center for Biomedical Materials Ningbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboChina Division of Public Health Department of Social MedicineGraduate School of MedicineOsaka UniversityOsakaJapan Artificial Intelligence Center for Medical Research and Application Osaka University HospitalOsakaJapan Institute for Research in Ophthalmology Foundation for Ophthalmology DevelopmentPoznanPoland A R T I C L

Background:The convergence of smartphone technology and artificial intelligence(AI)has revolutionized the landscape of ophthalmic care,offering unprecedented opportunities for diagnosis,monitoring,and management of ocular ***,there is a lack of systematic studies on discussing the integration of smart-phone and AI in this *** text:This review includes 52 studies,and explores the integration of smartphones and AI in ophthalmology,delineating its collective impact on screening methodologies,disease detection,telemedicine initiatives,and patient *** collective findings from the curated studies indicate promising performance of the smartphone-based AI screening for various ocular diseases which encompass major retinal diseases,glaucoma,cataract,visual impairment in children and ocular surface ***,the utilization of smartphone-based imaging modalities,coupled with AI algorithms,is able to provide timely,efficient and cost-effective screening for ocular *** modality can also facilitate patient self-monitoring,remote patient monitoring and enhancing accessibility to eye care services,particularly in underserved *** involving data pri-vacy,algorithm validation,regulatory frameworks and issues of trust are still need to be ***,evaluation on real-world implementation is imperative as well,and real-world prospective studies are currently ***:Smartphone ocular imaging merged with AI enables earlier,precise diagnoses,personalized treat-ments,and enhanced service accessibility in eye *** is crucial to navigate ethical and data security challenges while responsibly leveraging these innovations,promising a potential revolution in care access and global eye health equity.

关键词： Artificial intelligence Smartphone imaging Ophthalmology Telemedicine Ocular disease management

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多元文化共生时代的“简明日语”

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语言战略研究 2024年第4期9卷 8-9页

作者：河崎深雪日本《社会语言科学》杂志

“简明日语”(Yasashii Nihongo)是1995年阪神淡路大地震后,作为应紧急状态下向外国人传达信息的需要而诞生的。“简明日语”已有20多年的历史,在理论和实践上取得了丰硕的成果和多样化发展,主要表现在6个方面。一、应急领域应用。弘前... 详细信息

“简明日语”(Yasashii Nihongo)是1995年阪神淡路大地震后,作为应紧急状态下向外国人传达信息的需要而诞生的。“简明日语”已有20多年的历史,在理论和实践上取得了丰硕的成果和多样化发展,主要表现在6个方面。一、应急领域应用。弘前大学佐藤和之等学者1999年发表了《在发生灾害时为向外国人使用的日语文本方案:在广播、海报等上使用的简明日语表达方式》,接下来又发布了一系列研究成果,并研制了日语简化标准。东北大学伊藤彰则开发了日语简化支援系统“Yansisu”。

关键词：日语表达支援系统多样化发展传达信息紧急状态多元文化共生研究成果东北大学

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日本法人处罚的现状与课题——组织模式并用说与企业系统过失责任的提案

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北京社会科学 2024年第2期 55-61页

作者：川崎友巳段宇衡(译) 同志社大学京都大学

日本对法人犯罪采“两罚制”,但该制度存在着处罚标准不明确、处罚根据不明晰及预期效果难以达成的问题,故应考虑代替方案。但作为传统立法论的企业组织体责任论与法人行为责任说均存在着缺陷。作为因应,应提倡组织模式并用说。该说在... 详细信息

日本对法人犯罪采“两罚制”,但该制度存在着处罚标准不明确、处罚根据不明晰及预期效果难以达成的问题,故应考虑代替方案。但作为传统立法论的企业组织体责任论与法人行为责任说均存在着缺陷。作为因应,应提倡组织模式并用说。该说在考虑法人作为“被认可为在法律上具有与自然人同样权限与能力的存在”及“组织体之性质”的基础上,承认个人模式与组织模式的各自意义并一并采用。一方面,该说基于对责任主义中主观责任之原则的尊重,将能与法人等同的自然人的意思与行为视为法人的意思与行为,并追究法人的故意、过失责任;另一方面,该说基于企业系统过失责任,赋予企业法人建设相应系统的法律义务。

关键词：法人处罚个人模式组织模式企业系统过失责任

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Functionally Graded Dual-nanoparticulate-reinforced Aluminium Matrix Bulk Materials Fabricated by Spark Plasma Sintering

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Journal of Materials Science & Technology 2014年第8期30卷 736-742页

作者： Hansang Kwon Marc Leparoux Akira kawasaki Department of Materials System Engineering Pukyong National University365 Sinsenro608-759 BusanKorea Empa Swiss Federal Laboratories for Materials Science and TechnologyAdvanced Materials ProcessingFeuerwerkerstrasse 39CH-3602 ThunSwitzerland Department of Materials Processing Engineering Graduate School of EngineeringTohoku University980-8579 SendaiJapan

Functionally graded（FG） carbon nanotubes（CNT） and nano-silicon carbide（nSiC） reinforced aluminium（Al）matrix composites have been successfully fabricated using high-energy ball milling followed by solid-state spark plasma sintering *** CNTs were well-dispersed in the Al particles using the nSiC as a solid mixing *** different types of multi-walled CNTs were used to add different amounts of CNTs in the same *** ball milled Al—CNT—nSiC and Al—CNT powder mixtures were fully densified and demonstrated good adhesion with no serious microcracks and pores within an FG multilayer *** layer contained different amounts of the CNTs,and the nSiC additions showed different microstructures and *** is possible to control the characteristics of the FG multilayer composite through the efficient design of an Al—CNT—nSiC gradient *** concept offers a feasible approach for fabricating the dualnanoparticulate-reinforced Al matrix nanocomposites and can be applied to other scenarios such as polymer and ceramic systems.

关键词： Carbon nanotubes(CNT) Silicon carbide High-energy ball milling Spark plasma sintering(SPS) Functionally graded materials(FGM)

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Endoscopic findings can predict the efficacy of leukocytapheresis for steroid-naive patients with moderately active ulcerative colitis

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World Journal of Gastroenterology 2008年第34期14卷 5316-5321页

作者： Yasushi Umehara Masatoshi Kudo Masanori kawasaki Division of Gastroenterology and Hepatology Department of Internal Medicine Kinki University School of Medicine

AIM:To investigate the therapeutic usefulness of leukocytapheresis (LCAP; Cellsoba) in steroid-naive patients with moderately active ulcerative colitis (UC). METHODS: Eighteen steroid-naive patients with moderately active UC received one LCAP session every week for fi ve consecutive weeks. RESULTS: The remission rate 8 weeks after the last LCAP session was 61.1% (11/18). All three patients with deep ulcers showed worsening after LCAP. For the remaining 15 patients, who had erosions or geographic ulcers, the average clinical activity index (CAI) score dropped significantly from 9.4 to 3.8 eight weeks after the last LCAP session (t = 4.89, P = 0.001). The average C-reactive protein (CRP) levels before and after LCAP were 1.2 mg/dL and 1.0 mg/dL, respectively. Of the patients with erosions, geographic ulcers, and deep ulcers, 100% (9/9), 33.3% (2/6), and 0% (0/3) were in remission 8 weeks after the last LCAP session, respectively (χ2 = 7.65, P < 0.005). Forty- eight weeks after the last LCAP session, the remission rates for patients with erosions and geographic ulcers were 44.4% (4/9) and 16.7% (1/6), respectively. Only one patient suffered a mild adverse event after LCAP (nausea). CONCLUSION: LCAP is a useful and safe therapyfor steroid-naive UC patients with moderate disease activity. Moreover, the effi cacy of the treatment can be predicted on the basis of endoscopic fi ndings.

关键词： Ulcerative colitis Steroid-naive Leukocytapheresis Efficacy Endoscopic findings

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Media Preference, Information Needs, and the Language Proficiency of Foreigners in Japan after the 2011 Great East Japan Earthquake

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International Journal of Disaster Risk Science 2018年第1期9卷 1-15页

作者： Akiyuki kawasaki Michael Henry Kimiro Meguro Department of Civil Engineering The University of Tokyo Division of Field Engineering for the Environment Faculty of Engineering Hokkaido University International Center for Urban Safety Engineering Institute of Industrial Science The University of Tokyo

After the 2011 Great East Japan Earthquake, the Japanese government identified the lack of proficiency in the Japanese language as one characteristic of foreigners that should be considered in disaster prevention *** article seeks to understand how proficiency in a local language affects disaster information gathering behavior by using the results of a questionnaire survey conducted after the 2011 Great East Japan Earthquake. Respondents were categorized based on their Japanese and English language abilities. Their media mode, language preferences, information importance, and information-gathering difficulties also were examined. It was found that foreigners skilled in Japanese demonstrated similar information gathering behavior as Japanese respondents, but foreigners unskilled in Japanese showed little usage of Japanese-language media. This group also encountered difficulties due to a lack of Japanese proficiency, but many members were able to acquire some level of Japanese-language information through Internet-based methods. To address language proficiency in disaster prevention planning, information provision in languages other than Japanese should be increased, and Japanese information should be shared in a way that facilitates translation. Although this survey wassignificant in its scope, the results should be considered within the limitations of the Internet-based response collection and focus only on the less-affected area of Japan.

关键词： 2011 Great East Japan Earthquake Disaster information Foreign population Internet-based media Language proficiency

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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Hemodynamic Profiling Using a Cardiac Index–Systemic Vascular Resistance Plot in Patients with Fontan Circulation

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Congenital Heart Disease 2023年第4期18卷 431-445页

作者： Yuki kawasaki Takeshi Sasaki Daisuke Kobayashi Division of Pediatric Cardiology Osaka City General Hospital Pediatric Medical CenterOsaka5340021Japan Division of Cardiology St.Louis Children’s HospitalDepartment of PediatricsWashington University in St.LouisSt.LouisMO 63130USA

Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.

关键词： Cardiac index systemic vascular resistance perfusion pressure hemodynamic category fontan circulation prognosis

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