Author: "Jun Fujita" / Database: OpenAIRE - Searchworks@Jio Institute Digital Library Search Results

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370 results on '"Jun Fujita"'

1. Consideration of the contribution of operating a firefighting robot system for large fires to prevent COVID-19 infection among firefighters

Author: Jun Fujita, Hisanori Amano, Kazunori Ohno, and Satoshi Tadokoro
Subjects: Human-Computer Interaction, Hardware and Architecture, Control and Systems Engineering, Software, Computer Science Applications
Published: 2022
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2. Enhancing the multi-encoder-based cutting force estimation along the stationary axis of a machine tool with multiple inertia dynamics

Author: Keisuke Yamamoto, Aya Kamba, Kazuhiro Takeuchi, Jun Fujita, Yusuke Fujimagari, and Yasuhiro Kakinuma
Subjects: Control and Systems Engineering, Mechanical Engineering, Industrial and Manufacturing Engineering, Software, Computer Science Applications
Abstract: Wideband cutting force sensing is a key technology for process monitoring. Sensorless cutting force estimation using the internal servo information of a machine tool with ball-screw-driven stages has been studied owing to its high maintainability and ease of introduction. In the motor current-based method, the cutting force estimation along the stationary axis is challenging, and the estimation bandwidth is significantly limited owing to the low sensitivity of the motor current in the high-frequency range. The dual-inertia model-based load-side disturbance observer (LDOB) can estimate the cutting force along the stationary axis using the relative position obtained from the rotary encoder and linear encoder, which is installed relatively near the cutting point and has a high sensitivity in the high-frequency range. However, this approach is not applicable to machine tools with complicated structural dynamics. To address this challenge, we propose a cutting force estimation method along the stationary axis using the Kalman filter (KF) based on a multiple inertia model derived solely from the relative position signal. The dynamics, depending on the stage position of the feed drive, were modeled using linear interpolation. Through end milling tests, we confirmed that the cutting force estimation accuracy along the stationary axis of a machine tool with multiple inertia dynamics was significantly improved by the proposed method compared to the current and LDOB-based methods. Additionally, the wideband cutting force could be estimated using the proposed method for bandwidths up to 1000 Hz.
Published: 2022
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3. Nuclear Ceramide Is Associated with Ataxia Telangiectasia Mutated Activation in the Neocarzinostatin-Induced Apoptosis of Lymphoblastoid Cells

Author: Jun Fujita, Makoto Taniguchi, Chieko Hashizume, Yoshibumi Ueda, Shota Sakai, Tadakazu Kondo, Mayumi Hashimoto-Nishimura, Kentaro Hanada, Takeo Kosaka, and Toshiro Okazaki
Subjects: Pharmacology, DNA Repair, Tumor Suppressor Proteins, Apoptosis, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Ceramides, DNA-Binding Proteins, Ataxia Telangiectasia, Sphingomyelin Phosphodiesterase, Zinostatin, Humans, Molecular Medicine
Abstract: Ceramide is a bioactive sphingolipid that mediates ionizing radiation- and chemotherapy-induced apoptosis. Neocarzinostatin (NCS) is a genotoxic anti-cancer drug that induces apoptosis in response to DNA double-strand breaks (DSBs) through ataxia telangiectasia mutated (ATM) activation. However, the involvement of ceramide in NCS-evoked nuclear events such as DSB-activated ATM has not been clarified. Here, we found that nuclear ceramide increased by NCS-mediated apoptosis through the enhanced assembly of ATM and the meiotic recombination 11/double-strand break repair/Nijmengen breakage syndrome 1 (MRN) complex proteins in human lymphoblastoid L-39 cells. NCS induced an increase of ceramide production through activation of neutral sphingomyelinase (nSMase) and suppression of sphingomyelin synthase (SMS) upstream of DSB-mediated ATM activation. In ATM-deficient lymphoblastoid AT-59 cells compared with L-39 cells, NCS treatment showed a decrease of apoptosis even though ceramide increase and DSBs were observed. Expression of wild-type ATM, but not the kinase-dead mutant ATM, in AT-59 cells increased NCS-induced apoptosis despite similar ceramide accumulation. Interestingly, NCS increased ceramide content in the nucleus through nSMase activation and SMS suppression and promoted colocalization of ceramide with phosphorylated ATM and foci of MRN complex. Inhibition of ceramide generation by the overexpression of SMS suppressed NCS-induced apoptosis through the inhibition of ATM activation and assembly of the MRN complex. In addition, inhibition of ceramide increased by the nSMase inhibitor GW4869 prevented NCS-mediated activation of the ATM. Therefore, our findings suggest the involvement of the nuclear ceramide with ATM activation in NCS-mediated apoptosis. SIGNIFICANCE STATEMENT: This study demonstrates that regulation of ceramide with neutral sphingomyelinase and sphingomyelin synthase in the nucleus in double-strand break-mimetic agent neocarzinostatin (NCS)-induced apoptosis. This study also showed that ceramide increase in the nucleus plays a role in NCS-induced apoptosis through activation of the ataxia telangiectasia mutated/meiotic recombination 11/double-strand break repair/Nijmengen breakage syndrome 1 complex in human lymphoblastoid cells.
Published: 2022
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4. Supplementary Figure S2 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S2. Association between Cirp and IL-17, Bcl-2, Bcl-xL or Sox2 in the colonic mucosa of patients with Crohn's disease (CD). Scatter plot of relative mRNA levels of Cirp and respective genes in human colonic mucosa.
Published: 2023
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5. Supplementary Figure S3 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S3. (A) Representative immunostaining images of colonic mucosa of controls and patients with refractory UC using anti-Sox2 antibody. Scale bar, 50 microm. (B) Representative immunostaining images of colonic mucosa of patients with refractory UC with anti-Cirp and anti-E-cadherin antibodies. (C) Representative immunostaining images of well-moderately differentiated colorectal cancer tissues with anti-Cirp antibody. Scale bar, 100 microm. (D) Representative immunostaining images of colonic mucosa of patients with refractory UC using anti-Dclk1 antibody. Scale bar, 20 microm.
Published: 2023
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6. Supplementary Figure S6 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S6. (A) Representative images of immunohistochemical detection of E-cadherin, a marker for epithelial cells, and TUNEL staining of tumors from AOM + DSS-treated mice. (B) Representative immunostaining images of colonic mucosa of non-treated (DSS -), DSS-treated (DSS) and AOM + DSS-treated mice (AOM + DSS) using anti-PCNA antibody. Scale bar, 100 microm.
Published: 2023
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7. Supplementary Figure S4 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S4. (A) Colonic lysates from DSS-treated WT and Cirp-/- mice were immunoblotted with antibodies against the indicated proteins. (B) Relative mRNA levels in colonic tissues from mice treated with DSS, as determined by real-time qPCR (n = 4 per group). Expression level in colonic tissues from non-treated WT mice was set as 1. Results are expressed as means + SEM. *P < 0.05 compared with WT mice. (C) TNF-B mRNA level extracted from BM-derived macrophages was analyzed by real-time qPCR. (D) BM-derived macrophages were isolated from WT and Cirp-/- mice and cell lysates were immunoblotted with antibodies against the indicated proteins.
Published: 2023
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8. Supplementary Figure S5 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S5. Representative immunostaining images of colonic mucosa of non-treated (DSS -), DSS-treated (DSS) and AOM+DSS-treated mice (AOM+DSS) using anti-Sox2 (A) and anti-Cirp(B) antibody. Scale bar, 100 microm.
Published: 2023
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9. Supplementary Figure Legends from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Supplementary Figure Legends
Published: 2023
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10. Supplementary Figure S1 from Stress Response Protein Cirp Links Inflammation and Tumorigenesis in Colitis-Associated Cancer

Author: Masatoshi Kudo, Jun Fujita, Hiroaki Higashitsuji, Naoshi Nishida, Hideki Iijima, Tsunekazu Mizushima, Satoru Hagiwara, Tomohiro Watanabe, Hiroshi Kashida, and Toshiharu Sakurai
Abstract: Figure S1. Association between Cirp and TNF-B, IL-17, IL-23, Bcl-xL or Dclk1 in the colonic mucosa of patients with ulcerative colitis (UC). Scatter plot of relative mRNA levels of Cirp and respective genes in human colonic mucosa.
Published: 2023
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11. Internal Translation of p53 Oncoproteins During Integrated Stress Response Confers Survival Advantage on Cancer Cells

Author: Maria José López-Iniesta, Rafaela Lacerda, Ana Catarina Ramalho, Shrutee N. Parkar, Ana Marques-Ramos, Bruna Pereira, Lina Miyawaki, Jun Fujita, Roman Hrstka, Luísa Romão, and Marco M Candeias
Abstract: p53is the most known and studied tumour suppressor gene. Yet we have recently shown thatp53is also a proto-oncogene, as it encodes the Δ160p53 oncoprotein. Integrated stress response (ISR) is a survival pathway frequently activated in cancers, marked by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2α) and a defined reprogramming in mRNA translation. Here we identified ISR as a powerful trigger of p53 oncogene, leading to the induction of not only Δ160p53 but also Δ133p53, another protein variant of thep53gene. Upon ISR the two isoforms were translated internally from p53 full-length (FL) transcript through an internal regulator of expression site (IRES) located in the vicinity of codon 160. Frameshift mutations upstream of codons 133 and 160 demonstrated that FLp53 protein synthesis is not required for making Δ133p53 and Δ160p53. Instead, targeting IRES(160) with an antisense oligo was sufficient to efficiently and specifically impair the expression of these isoforms without affecting FLp53 levels. This in turn averted ISR’s protective program culminating in cancer cell cycle arrest and death. Mechanistically, FLp53 showed 3 times more affinity to Δ160p53 than to other isoforms, Δ40p53 or Δ133p53. During ISR Δ160p53 localized to the nucleus and strongly inhibited FLp53-mediated activation of pro-apoptotic genep53 upregulated modulator of apoptosis(PUMA). Our results uncover a new branch of the ISR network essential for cancer cell survival and growth and establish the proof of concept for a new strategy to target cancer.
Published: 2023
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12. The role of torsional stress in the development of subchondral insufficiency fracture of the femoral head: A finite element model analysis

Author: Jun Fujita, Koichi Kinoshita, Tetsuya Sakamoto, Hajime Seo, Kenichiro Doi, and Takuaki Yamamoto
Subjects: Orthopedics and Sports Medicine, Surgery
Published: 2023
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13. Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort

Author: Itaru Naitoh, Terumi Kamisawa, Atsushi Tanaka, Takahiro Nakazawa, Kensuke Kubota, Hajime Takikawa, Michiaki Unno, Atsushi Masamune, Shigeyuki Kawa, Seiji Nakamura, Kazuichi Okazaki, Keisuke Furumatsu, Shigeaki Sawai, Takuma Goto, Toshikatsu Okumura, Daisuke Suzuki, Masayuki Otsuka, Ikuhiro Kobori, Masaya Tamano, Mitsuhito Koizumi, Yoichi Hiasa, Naoto Kawabe, Yoshiki Hirooka, Satoshi Yamamoto, Yukio Asano, Kazuo Inui, Akihiko Horiguchi, Hiroyuki Watanabe, Daishu Toya, Katsuko Hatayama, Toshiharu Ueki, Norikatsu Kinoshita, Mitsuru Sugimoto, Hiromasa Ohira, Tsuyoshi Mukai, Eiichi Tomita, Keisuke Iwata, Shogo Shimizu, Jun Suetsugu, Masahito Shimizu, Keiji Tsuji, Ryoko Ishida, Masanori Ito, Ryutaro Furukawa, Naoya Sakamoto, Masahiro Araki, Satoshi Tanno, Yasunari Sakamoto, Tetsuhide Ito, Satoshi Takai, Shinichi Ikeya, Takanori Yamada, Norihiko Kudara, Akinori Shimizu, Keiji Hanada, Yasunori Ichiki, Hideki Kitada, Michio Hifumi, Hiroyuki Kimura, Masayuki Kurosaki, Namiki Izumi, Hajime Sumi, Jun-ichi Haruta, Katsumi Hayashi, Ryo Harada, Masafumi Inoue, Shinichiro Nakamura, Tetsuya Ito, Ko Tomishima, Hiroyuki Isayama, Kyoko Oura, Tsutomu Masaki, Naoto Shimokawahara, Shirou Tanoue, Kousei Maemura, Akio Ido, Ichiro Mizushima, Mitsuhiro Kawano, Katsunori Yoshida, Makoto Naganuma, Miki Murata, Akiyoshi Nishio, Yuji Fujita, Takuma Teratani, Shohei Matsubara, Hironao Tamai, Yuu Yoshida, Ryousaku Azemoto, Ken Kamata, Tomohiro Watanabe, Takahiro Kurosu, Wasaburou Koizumi, Jun Fujita, Hideyuki Seki, Yasuhiro Ueda, Takumi Fukumoto, Takuhiro Kousaki, Kazushige Uchida, Toshimasa Ochiai, Takeshi Kawasaki, Motohiko Tanaka, Etsuji Ishida, Kenji Notohara, Hideaki Mori, Toshiyuki Mori, Hideaki Kawabata, Masatoshi Miyata, Junichi Sakagami, Yoshito Itoh, Masahiro Shiokawa, Hiroshi Seno, Noriko Watanabe, Hiromi Kataoka, Toshinori Aoki, Mitsuhiro Fujishiro, Toru Niihara, Hiroto Nishimata, Akira Mitoro, Hitoshi Yoshiji, Motoyuki Yoshida, Masafumi Ikeda, Kengo Tomita, Ryota Hokari, Kenji Hayasaka, Yuji Amano, Kazuhiko Shioji, Kazunao Hayashi, Shuji Terai, Michiko Nakajima, Junya Yamahana, Ryusuke Matsumoto, Hideaki Kikuchi, Akira Kanamori, Seiki Kiriyama, Shinichi Iwatsu, Yuji Kato, Shigeru Horiguchi, Takahito Yagi, Hiroyuki Okada, Kazuyoshi Ohkawa, Motohiro Hirao, Naoki Hiramatsu, Noriko Oza, Haruo Imamura, Takeshi Baba, Shigeru Nakano, Tetsuya Shinobi, Shomei Ryozawa, Masayo Motoya, Hiroshi Nakase, Noboru Kinoshita, Kei Ito, Tatsuya Miyake, Naruaki Kohge, Hiroshi Tobita, Satoru Joshita, Takeji Umemura, Shinya Kawaguchi, Kazuya Ohno, Koichi Sonobe, Akihiko Satoh, Tooru Shimosegawa, Fumihiko Miura, Minami Yagi, Keiji Sano, Toshifumi Kin, Akio Katanuma, Kazuhiko Koike, Shin Miura, Youhei Kawashima, Tatehiro Kagawa, Seishin Azuma, Mamoru Watanabe, Mitsuyoshi Honjyo, Takao Itoi, Akira Honda, Katsumasa Kobayashi, Toru Asano, Suguru Mizuno, Takayoshi Nishino, Hideaki Taniguchi, Kazuto Tajiri, Ichiro Yasuda, Yoshiya Tanaka, Shinji Oe, Masaru Harada, Masanao Kurata, Mituharu Fukasawa, Nobuyuki Enomoto, Yuki Kawaji, Masayuki Kitano, Yuko Nishise, Hidetoshi Hirakawa, Tetsuya Ishizawa, Yoshiyuki Ueno, Miyuki Kaino, Yuko Fujimoto, and Isao Sakaida
Subjects: Male, medicine.medical_specialty, Autoimmune Pancreatitis, Cholangitis, Sclerosing, Gastroenterology, Primary sclerosing cholangitis, Serology, 03 medical and health sciences, 0302 clinical medicine, Japan, Surveys and Questionnaires, Internal medicine, Humans, Medicine, Retrospective Studies, Autoimmune pancreatitis, Hepatology, medicine.diagnostic_test, business.industry, Bile duct, Ultrasound, Magnetic resonance imaging, Histology, medicine.disease, medicine.anatomical_structure, Immunoglobulin G, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, IgG4-related disease, Bile Ducts, Immunoglobulin G4-Related Disease, business, Cholangiography
Abstract: Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.
Published: 2021
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14. Pulmonary tumor thrombotic microangiopathy caused by metastatic ovarian high-grade serous carcinoma: a case report and literature review

Author: Jun Fujita, Kelsey Hummel, and Ya Xu
Subjects: General Medicine, Cardiology and Cardiovascular Medicine, Pathology and Forensic Medicine
Published: 2023
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15. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre 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S.G., Ruzyllo W., Gosselin G., Maggioni A.P., White H.D., Bhargava B., Min J.K., John Mancini G.B., Berman D.S., Picard M.H., Kwong R.Y., Ali Z.A., Mark D.B., Spertus J.A., Krishnan M.N., Elghamaz A., Moorthy N., Hueb W.A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T.D., Szwed H., Doerr R., Keltai M., Selvanayagam J.B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N.O., Harrell F.E., Rockhold F.W., Broderick S., Bruce Ferguson T., Williams D.O., Harrington R.A., Stone G.W., Rosenberg Y, and ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, 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Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider 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Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, 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Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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16. Onecut1partially contributes to the liver progenitor cell transition and acquisition of metastatic potential in hepatocellular carcinoma

Author: Yu Liu, Hiroaki Higashitsuji, Katsuhiko Itoh, Kanji Yamaguchi, Atsushi Umemura, Yoshito Itoh, and Jun Fujita
Abstract: Metastasis-initiating cells are considered to originate from stem cell-like cancer cells. In hepatocellular carcinoma, liver progenitor-like cells are reported to be derived from hepatocytes, indicating the possible acquisition of metastatic potential during hepatocyte-to-cholangiocyte transdifferentiation. Consistent with the expression pattern observed during ductal plate formation, we revealed an LPC transition withOnecut1accumulation both during hepatocyte-to-cholangiocyte transdifferentiation and in a cell model. This event may be associated with transient acquisition of metastatic potential.
Published: 2022
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17. Laparoscopic intraperitoneal mesh repair of a large incisional hernia in a kidney transplantation patient: A case report

Author: Tomoharu Miyashita, Ryosuke Kin, Yoritaka Fujii, Hiroyuki Takamura, Akifumi Hashimoto, Takashi Miyata, Daisuke Kaida, Seiko Miura, Hisashi Nishiki, Yasuto Tomita, Naohiko Nakamura, Nobuhiko Ueda, Jun Fujita, and Hideto Fujita
Subjects: medicine.medical_specialty, Mesh repair, Incisional hernia, business.industry, Abdominal wall defect, Transplanted kidney, General Medicine, 030230 surgery, medicine.disease, Surgery, Abdominal wall, 03 medical and health sciences, surgical procedures, operative, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine, Abdomen, Hernia, business, Kidney transplantation
Abstract: A 73-year-old woman presented to our hospital because of painful bulging in the right lower abdomen, and developed a 17 × 12 cm incisional hernia after kidney transplantation using right oblique incision. Laparoscopic intraperitoneal onlay mesh (IPOM) repair was performed. Since a transplanted kidney is close to the abdominal wall defect, the space between the transplanted kidney and the abdominal wall was peeled off to secure enough space for the mesh to be place. After that the fascial defect was detected precisely, and the polypropylene-polyglycolic acid composite mesh was fixed with 3 cm overlapping of the hernia ring by non-absorbable tacks. The patient was discharged 9 days after surgery. In general, abdominal incisional hernias after kidney transplantation are relatively large with boundary defect of abdominal wall ensuing between the abdominal and allograft. However, laparoscopic IPOM repair of incisional hernia after kidney transplantation can be performed safely and effectively.
Published: 2021
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18. Heart-derived collagen promotes maturation of engineered heart tissue

Author: Hidenori Tani, Eiji Kobayashi, Shinomi Yagi, Keisuke Tanaka, Kotaro Kameda-Haga, Shinsuke Shibata, Nobuko Moritoki, Kaworu Takatsuna, Taijun Moriwaki, Otoya Sekine, Tomohiko Umei, Yuika Morita, Yusuke Soma, Yoshikazu Kishino, Hideaki Kanazawa, Jun Fujita, Shunji Hattori, Keiichi Fukuda, and Shugo Tohyama
Subjects: Biomaterials, Mechanics of Materials, Biophysics, Ceramics and Composites, Bioengineering
Published: 2023
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19. Correlation between cerebral blood flow and olfactory function in mild cognitive impairment and Alzheimer's disease

Author: Naoto Kamimura, Tetsuo Kashibayashi, Ryuichi Takahashi, Hiroaki Kazui, Ryoko Fujito, Jun Fujita, and Fumino Okutani
Subjects: Olfactory system, medicine.medical_specialty, business.industry, Neuropsychology, Brain, Disease, Neuropsychological Tests, Correlation, Psychiatry and Mental health, Odor, Cerebral blood flow, Alzheimer Disease, Cerebrovascular Circulation, Internal medicine, Cardiology, medicine, Humans, Cognitive Dysfunction, Geriatrics and Gerontology, business, Cognitive impairment, Frontal Pole
Abstract: OBJECTIVE Olfactory dysfunction is common in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We sought to elucidate brain regions associated with olfactory dysfunction in patients with MCI and early AD by using 123I-IMP-SPECT to detect regional cerebral blood flow (CBF). METHODS We included 218 patients diagnosed with AD or MCI, who underwent a comprehensive battery of neuropsychiatric and neuropsychological tests, Alzheimer's Disease Assessment Scale-Cognitive Part (ADAS-Cog), and forward- and backward-digit span. Olfactory function was assessed using TT patients stated whether they experienced any smell (detection test) and identified the odor (identification test). The association between single-photon emission computerized tomography based regional CBF and olfactory function was examined by voxel-by-voxel multiple regression analysis, considering sex, age, and education as covariate parameters. RESULTS Of the 218 patients, 78 had mildly impaired olfactory detection and 15 had olfactory detection loss; additionally, 213 had mild olfactory identification impairment. The odor detection score correlated significantly with the ADAS-Cog word recall score (r = 0.193, p = 0.004). The odor identification score correlated significantly with the ADAS memory (r = 0.408, p
Published: 2021
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20. Intramyocardial Transplantation of Human iPS Cell–Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals

Author: Ryota Tabei, Yujiro Kawai, Kazuaki Nakajima, Satoshi Kunita, Shota Someya, Jun Fujita, Hidenori Tani, Keiichi Fukuda, Yoshikazu Kishino, Hideaki Kanazawa, Shugo Tohyama, Takumi Teratani, Akira Ito, Noriko Handa, Akinori Hirano, Rei Shibata, Sho Tanosaki, Eiji Kobayashi, Shuji Hishikawa, Marina Okada, Hideyuki Shimizu, Masataka Yamazaki, Shigeo Okuda, Yoshitake Yamada, Yusuke Soma, Yasuhiko Tabata, Yuika Morita, Shinji Kawaguchi, and Toyoaki Murohara
Subjects: 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, LVEDV, left ventricular end-diastolic volume, Cell, heart failure, cardiomyocyte, 030204 cardiovascular system & hematology, HF, heart failure, human iPS cells, 03 medical and health sciences, 0302 clinical medicine, sCM, single cardiomyocyte, CMR, cardiac magnetic resonance, Internal medicine, hiPSC, human induced pluripotent stem cell, medicine, dp/dtmax, maximum rate of left ventricular pressure rise, EF, ejection fraction, CM, cardiomyocyte, Induced pluripotent stem cell, cell transplantation, LV, left ventricular, Ejection fraction, business.industry, Spheroid, medicine.disease, FAC, fractional area change, VEGF, vascular endothelial growth factor, Transplantation, 030104 developmental biology, medicine.anatomical_structure, GH, gelatin hydrogel, hPSC, human pluripotent stem cell, cardiac spheroids, Heart failure, Cardiology, LVESV, left ventricular end-systolic volume, ECG, electrocardiogram, Teratoma, Preclinical Research, Cardiology and Cardiovascular Medicine, business, CS, cardiac spheroid
Abstract: Visual Abstract, Highlights • hiPSCs are differentiated into CMs with large-scale 2-dimensional culture system, and refined by metabolic purification. • hiPSC-derived CMs are developed into CSs in special microwell plates. • Intramyocardial transplantation of CSs and GH improves cardiac function in small and large animal models. • Engraftment of CMs and angiogenesis are mechanisms for improvement of cardiac function. • Intramyocardial transplantation of CSs with a transplant injection device is a safe, effective, and feasible strategy for the treatment of HF., Summary The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.
Published: 2021

21. Predictive factors for developing acute cholangitis and/or cholecystitis in patients undergoing delayed cholecystectomy: A retrospective study

Author: Hideto Fujita, Takashi Miyata, Daisuke Matsui, Nobuhiko Ueda, Fumio Futagami, Hiroyuki Takamura, Daisuke Kaida, Yasuto Tomita, Tomoharu Miyashita, Koji Nishijima, Naohiko Nakamura, Yuta Fujiwara, Takashi Nakamura, Yoshinao Ohbatake, Jun Fujita, and Hiroto Saito
Subjects: Adult, Male, Risk, medicine.medical_specialty, Cholangitis, medicine.medical_treatment, Cholecystitis, Acute, Operative Time, lcsh:Surgery, Gallstones, Severity of Illness Index, Group B, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Risk Factors, Elective surgical procedure, medicine, Humans, In patient, Cholecystectomy, Risk factor, Intraoperative Complications, Watchful Waiting, Aged, Aged, 80 and over, business.industry, Retrospective cohort study, lcsh:RD1-811, Middle Aged, medicine.disease, Surgery, Acute cholangitis, Acute cholecystitis, Treatment Outcome, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Acute Disease, Cholecystitis, 030211 gastroenterology & hepatology, Female, Elective Surgical Procedure, business
Abstract: Background: /Objective: We evaluated the risk of acute cholangitis and/or cholecystitis while waiting for cholecystectomy for gallstones. Methods: We retrospectively enrolled 168 patients who underwent cholecystectomy for gallstones after conservative therapy. We compared clinical data of 20 patients who developed acute cholangitis and/or cholecystitis while waiting for cholecystectomy (group A) with 148 patients who did not develop (group B). We investigated surgical outcomes and risk factors for developing acute cholangitis and/or cholecystitis. Results: Preoperatively, significant numbers of patients with previous history of acute grade II or III cholecystitis (55.0% vs 10.8%; p
Published: 2021

22. Novel exterior cover design for radiant heat resistance of firefighting robots in large-scale petrochemical complex fires

Author: Jun Fujita, Yoshihiro Tamura, Hisanori Amano, Kazunori Ohno, and Satoshi Tadokoro
Subjects: Control and Optimization, Artificial Intelligence, Mechanical Engineering, Modeling and Simulation, Instrumentation
Abstract: Fires in petrochemical complexes are inaccessible because of the intense radiant heat from flames. Therefore, water cannon robots require radiant heat countermeasures to perform firefighting safely. Conventional radiant heat countermeasures employ a self-spraying method, wherein the water cannon robot requires a water tank of capacity 1.5 m3 (= 1500 L) to function for 7–8 min in an environment with a 20 kW/m2 radiation heat. However, the water cannon robot has size limitations because it is transported on one transport vehicle (10 t truck) to the site, and only a tank of capacity ~ 0.02 m3 can be installed on the robot. To overcome these drawbacks, this study proposes a method that utilizes a mountable radiant heat-resistant exterior cover that works with a small amount of water. The cover is made of radiant heat-shielding fireproof clothing with an aluminum coating that reflects 90% of the radiant heat on the surface and a mist nozzle that sprays water on the back surface. The remaining 10% is removed by the heat of vaporization of water sprayed on the back of the clothing and natural convection. The amount of water required for cooling was reduced to 1/80th of that compared to self-spraying because of the use of the developed cover. The proposed method of radiation reflection via vaporization and natural convection can be employed to protect firefighting robots.
Published: 2022
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23. Purification of cardiomyocytes and neurons derived from human pluripotent stem cells by inhibition of

Author: Sho, Tanosaki, Tomohiko, Akiyama, Sayaka, Kanaami, Jun, Fujita, Minoru S H, Ko, Keiichi, Fukuda, and Shugo, Tohyama
Subjects: Neurons, Pluripotent Stem Cells, Fatty Acids, Induced Pluripotent Stem Cells, Humans, Cell Differentiation, Myocytes, Cardiac
Abstract: Here we describe a protocol to obtain highly pure cardiomyocytes and neurons from human induced pluripotent stem cells (hiPSCs) via metabolic selection processes. Compared to conventional purification protocols, this approach is easier to perform and scale up and more cost-efficient. The protocol can be applied to hiPSCs and human embryonic stem cells. For complete details on the use and execution of this protocol, please refer to Tohyama et al. (2016) and Tanosaki et al. (2020).
Published: 2022

24. Mammalian cold-inducible RNA-binding protein facilitates wound healing through activation of AMP-activated protein kinase

Author: Jun Fujita, Takanori Fujita, Hiroaki Higashitsuji, and Hisako Higashitsuji
Subjects: 0301 basic medicine, Biophysics, Motility, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Biochemistry, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, AMP-Activated Protein Kinase Kinases, AMP-activated protein kinase, Cell Movement, Skin Physiological Phenomena, Animals, Humans, Protein kinase A, Molecular Biology, Barrier function, Mice, Knockout, Wound Healing, integumentary system, biology, Chemistry, RNA-Binding Proteins, AMPK, Cell migration, Cell Biology, Cell biology, Enzyme Activation, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Phosphorylation, Wound healing
Abstract: The skin is usually maintained within a temperature range that induces cold-inducible RNA-binding protein (Cirp). To determine whether Cirp plays a role in barrier function of the skin, we analyzed the skin wound healing in cirp-knockout (KO) mice. They exhibited delayed wound healing compared with wild-type littermates in the absence as well as presence of skin contraction. Dermal fibroblasts and keratinocytes from cirp-KO mice migrated slower than those from wild-type mice. When expression of Cirp was downregulated in cultured cells, migration rate was decreased. Cirp bound liver-kinase-B1 (LKB1) in the nucleus and was suggested to enhance its translocation to the cytoplasm, resulting in enhanced phosphorylation of AMP-activated protein kinase (AMPK) and cell motility. Stimulation of AMPK ameliorated the delayed wound healing in cirp-KO mice. These findings suggest that Cirp facilitates skin wound healing by enhancing cell migration via AMPK, indicating roles for Cirp in linking skin temperature with metabolism and defense mechanism.
Published: 2020
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25. Chronological Changes in Neutrophil/lymphocyte Ratio in Advanced Gastric Cancer Patients Treated with Nivolumab: a Report of Nine Cases

Author: Jun Fujita, Daisuke Kaida, Nobuhiko Ueda, Naohiko Nakamura, Yasuto Tomita, Hiroyuki Takamura, Shinichi Kinami, Takashi Miyata, Hideto Fujita, and Takeo Kosaka
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Neutrophils, medicine.medical_treatment, Lymphocyte, Tumor response, Gastroenterology, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, Biomarkers, Tumor, medicine, Humans, In patient, Lymphocytes, Aged, Retrospective Studies, nivolumab, Chemotherapy, business.industry, Clinical course, General Medicine, Advanced gastric cancer, Prognosis, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, neutrophil/lymphocyte ratio, Female, Nivolumab, Gastric cancer, business, Progressive disease, Follow-Up Studies, Research Article
Abstract: Background Nivolumab has been approved for use in advanced gastric cancer (GC) after third-line chemotherapy in Japan. However, it remains difficult to predict favorable nivolumab response before treatment. Methods We evaluated the clinical course with a focus on the chronological changes in neutrophil/lymphocyte ratio (NLR) throughout the chemotherapy and assessed the relationship between nivolumab response and chronological changes in NLR before nivolumab administration. Results We experienced nine cases who received nivolumab monotherapy for unresectable advanced or postoperative recurrent GC. Nivolumab was used as third-line chemotherapy in all patients, and partial response (PR) and stable disease (SD) were observed in two patients each. Nivolumab treatment resulted in progressive disease (PD) in five patients. In patients with PR or SD, changes in the NLR tended to correspond to the response of target metastatic lymph nodes to first- and second-line chemotherapy. In the four cases with PR or SD following nivolumab, ∆NLRresponses that was the difference in the degree of decline during the most effective pretreatment chemotherapy were 1.39, 0.73, 1.62, and 1.22. However, the patients with PD showed lower ∆NLRresponses, at 0.66, 0.66, 0.25, 0.13, and -0.05 in the five cases. Mean ∆NLRresponses in the patients with PR or SD and patients with PD were 1.17 and 0.33, respectively (P = 0.0008). Conclusions We experienced nine GC cases treated with nivolumab and assessed the association between chronological NLR changes throughout chemotherapy and tumor response to nivolumab. Changes in NLR during pretreatment chemotherapy might predict tumor response to nivolumab monotherapy in patients with advanced GC. .
Published: 2020
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26. Spleen Volume as a Predictive Biomarker for Thrombocytopenia and Liver Dysfunction After Oxaliplatin-based Chemotherapy

Author: Takeo Kosaka, Hisashi Nishiki, Shinichi Kinami, Daisuke Kaida, Seiko Miura, Hideto Fujita, Naohiko Nakamura, Ryosuke Kin, Takashi Miyata, Hiroyuki Takamura, Yoritaka Fujii, Akifumi Hashimoto, Yasuto Tomita, Nobuhiko Ueda, and Jun Fujita
Subjects: Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Aspartate transaminase, Antineoplastic Agents, Gastroenterology, Group A, Group B, Capecitabine, Internal medicine, medicine, Humans, Retrospective Studies, Chemotherapy, biology, business.industry, Liver Diseases, Retrospective cohort study, General Medicine, medicine.disease, Thrombocytopenia, Oxaliplatin, Oncology, biology.protein, Female, business, Biomarkers, Spleen, medicine.drug
Abstract: Background/aim We evaluated whether splenic volume (SV) predicts sinusoidal obstruction syndrome (SOS) in colorectal cancer (CRC) patients receiving capecitabine plus oxaliplatin (CapeOX) therapy. Patients and methods In this retrospective study, we measured SV in 41 patients receiving adjuvant CapeOX for CRC at five different time points. We compared the clinical data of the 18 patients who experienced ≥30% increases in SV immediately after vs. before CapeOX (group A) with data for the remaining 23 patients (group B). Results Platelet numbers decreased and the levels of hepatobiliary enzymes increased significantly 1 year after CapeOX compared with before CapeOX in group A. However, in group B, significantly decreased platelet numbers and significantly increased aspartate transaminase levels were confirmed only immediately after CapeOX, with no significant subsequent changes. Conclusion SV was significantly associated with thrombocytopenia and liver dysfunction in CRC patients, and predicted SOS.
Published: 2020
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27. A Case of Advanced Gastroesophageal Junction Cancer with Bulky Lymph Node Metastases Treated with Nivolumab

Author: Jun Fujita, Takashi Miyata, Hiroyuki Takamura, Nobuhiko Ueda, Takeo Kosaka, Naohiko Nakamura, Shinichi Kinami, Hideto Fujita, Daisuke Kaida, and Yasuto Tomita
Subjects: 0301 basic medicine, medicine.medical_specialty, Case Report, lcsh:RC254-282, Ramucirumab, 03 medical and health sciences, 0302 clinical medicine, Medicine, Lymph node, nivolumab, adenocarcinoma, business.industry, gastroesophageal junction cancer, Cancer, Mediastinum, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Primary tumor, Oxaliplatin, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Radiology, Lymph, Nivolumab, business, medicine.drug
Abstract: A 71-year-old woman was diagnosed with advanced gastroesophageal junction cancer with bulky lymph nodes along the cardiac region and the lower mediastinum (GE-Circ type 3 T3 N3 M0 H0 stage III) and received treatment with S-1 and oxaliplatin (SOX) as first-line chemotherapy. After 3 cycles of SOX, severe anorexia and diarrhea were observed. We converted from this regimen of systemic chemotherapy to ramucirumab (RAM) monotherapy as second-line chemotherapy. This treatment resulted in a reduction in size of the metastatic lymph nodes along the cardiac region and the lower mediastinum. However, progression of lymph node metastasis and the primary tumor was observed following 7 months of RAM monotherapy. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the initial treatment. After 3 months of nivolumab administration, a 47% reduction in metastatic lymph nodes was achieved and a regression of the primary gastric tumor as seen on an enhanced computed tomography scan. After 7 months of nivolumab monotherapy, the diameter of the target lymph nodes had reduced by 81% from baseline, and there was no evidence of malignancy upon pathological assessment of the primary tumor site biopsy. The patient survived with nivolumab monotherapy for approximately 2 years after her first visit, without any adverse reaction to nivolumab.
Published: 2020

28. Rate of Return to Work After Periacetabular Osteotomy and Its Influencing Factors

Author: Jun Fujita, Nobunao Doi, Koichi Kinoshita, Tetsuya Sakamoto, Hajime Seo, and Takuaki Yamamoto
Subjects: Return to Work, Treatment Outcome, Hip Dislocation, Humans, Orthopedics and Sports Medicine, Surgery, Acetabulum, Hip Joint, General Medicine, Osteotomy, Retrospective Studies
Abstract: Periacetabular osteotomy (PAO) has been reported as a treatment for patients with symptomatic developmental dysplasia of the hip (DDH). Several studies have investigated the rate of return to sports activities after PAO, but few studies have evaluated the rate of return to work. In the present study, we aimed to identify the rate of return to work at 1 year after PAO and its affecting factors.We retrospectively evaluated 83 patients (85 hips) with symptomatic DDH who had undergone PAO between December 2015 and June 2020. Patients who had returned to work at 1 year after PAO were classified into the returnee group, and those who had not were classified into the non-returnee group. The returnee group included patients who could return to their original job (original) or to a different job (non-original). The non-returnee group included patients who could not return to work because of hip symptoms (hip) and those who did not return for reasons other than hip symptoms (non-hip). We analyzed clinical parameters, including the Harris hip score, Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire, 36-Item Short Form Survey, and radiographic parameters, as well as the type of work.Sixty-eight patients (70 hips; 82.4%) returned to work at 1 year after PAO (returnee group), and 15 patients (15 hips; 17.6%) were in the non-returnee group. Among the 15 patients in the non-returnee group, 7 were classified into the non-hip subgroup and 8 were classified into the hip subgroup. No significant differences were observed between the returnee group and the hip subgroup in terms of clinical parameters or type of work.One year after PAO, 8 patients (8 hips; 9.4%) could not return to work because of hip symptoms; both clinical parameters and the type of work showed no direct relationship with postoperative working status.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Published: 2022

29. Duct Attachment on Improving Breaking Wave Zone Energy Extractor Device Performance

Author: Krisna Adi Pawitan, Hanley Andrean, Jun Fujita, Shuji Misumi, Hideki Takebe, and Tsumoru Shintake
Subjects: Technology, Total internal reflection, Impact pressure, Control and Optimization, Renewable Energy, Sustainability and the Environment, Water flow, business.industry, Energy Engineering and Power Technology, Breaking wave, structural response, wave energy converter, coastal engineering, renewable energy, Turbine, Renewable energy, Environmental science, Duct (flow), Electricity, Electrical and Electronic Engineering, business, Engineering (miscellaneous), Energy (miscellaneous), Marine engineering
Abstract: A challenging wave energy converter design that utilized the denser energy part of the nearshore breaking wave zone to generate electricity was introduced in 2016 by Shintake. The Okinawa Institute of Science and Technology Graduate University’s project aims to take advantage of breaking wave energy to harness electricity. The 2016 version of the device consisted only of a bare turbine and power generator. Early exploration of the design recorded short periods and high impact wave pressures were experienced by the structure, with the turbine unable to harvest energy effectively. Additional structure to not only reduce incoming impact pressure but also increase the duration of water flow through the turbine was needed. These are the main reasons behind incorporating the duct attachment into the design. This paper show that the duct is capable of halving the impact pressure experienced by the turbine and can increase the energy exposure by up to 1.6 times the bare turbine configuration. Furthermore, it is also said that wave angle (β) = 40° is the critical angle, although the duct still increases wave energy exposure to the power take-off up to β = 60°.
Published: 2021
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30. Early gastric mixed neuroendocrine‐non‐neuroendocrine neoplasm with early poor prognosis after endoscopic submucosal dissection: A case report

Author: Emi Matsuzono, Yusuke Tomita, Susumu Sogabe, Nozomu Sugai, Hideyuki Seki, Yoshimitsu Kobayashi, Jun Fujita, and Akira Suzuki
Subjects: medicine.medical_specialty, Poor prognosis, business.industry, Internal medicine, Neuroendocrine neoplasm, medicine, Endoscopic submucosal dissection, business, Gastroenterology, Early Gastric Cancer
Published: 2021
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31. Relationship between fatty liver change and nutritional status after total gastrectomy in gastric cancer patients: a retrospective study

Author: Daisuke Kaida, Jun Fujita, Tomoharu Miyashita, Naohiko Nakamura, Nobuhiko Ueda, Shinichi Kinami, Hiroyuki Takamura, Hideto Fujita, Yasuto Tomita, and Takashi Miyata
Subjects: medicine.medical_specialty, RD1-811, medicine.medical_treatment, Nutritional Status, Gastroenterology, Gastrectomy, Stomach Neoplasms, Internal medicine, medicine, Humans, Retrospective Studies, business.industry, Research, Significant difference, Fatty liver, Albumin, Cancer, Retrospective cohort study, Nutritional status, General Medicine, University hospital, medicine.disease, Surgery, Fatty Liver, Total gastrectomy, Gastric cancer, business
Abstract: Background The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG. Methods We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups. Results Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006). Conclusions We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG.
Published: 2021
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32. A Method for Cardiac Differentiation, Purification, and Cardiac Spheroid Production of Human Induced Pluripotent Stem Cells

Author: Yuika, Morita, Shugo, Tohyama, Jun, Fujita, and Keiichi, Fukuda
Subjects: Organogenesis, Induced Pluripotent Stem Cells, Humans, Cell Differentiation, Myocytes, Cardiac, Regenerative Medicine, Cells, Cultured, Stem Cell Transplantation
Abstract: Human induced pluripotent stem cells (hiPSCs) are one of the most promising cell sources for regenerative medicine. To realize the promise of hiPSCs for cardiac regenerative therapy, three major obstacles must be overcome: the first is the achievement of large-scale production of cardiomyocytes, the second is the successful elimination of non-cardiac cells containing residual pluripotent stem cells (PSCs) to prevent tumor formation, and the third is the achievement of high engraftment efficiency of transplanted cardiomyocytes. In this chapter, we introduce our protocols for cardiac differentiation, purification, and preparation of cardiac spheroids for safe and effective regenerative medicine.
Published: 2021

33. Favorable effects of microneedling on long‐standing androgenetic alopecia in an elderly man: A case report

Author: Jun Fujita
Subjects: Male, medicine.medical_specialty, Erythema, Dermatology, Hair growth, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Elderly persons, medicine, Humans, Family history, Adverse effect, Aged, Scalp, business.industry, Alopecia, Clinical trial, Treatment Outcome, medicine.anatomical_structure, Minoxidil, 030220 oncology & carcinogenesis, medicine.symptom, business, Hair, medicine.drug
Abstract: BACKGROUND Androgenetic alopecia (AGA) is the most common type of alopecia. Currently, various methods have been tried to treat male AGA, but the outcomes are often unsatisfactory, especially for elderly persons. AIMS We report a case of an elderly man with a severe long-standing AGA, which was successfully managed with microneedling and minoxidil. PATIENTS/METHODS The patient was a 70-year-old Japanese man with family history of AGA, showed no abnormality in physical and laboratory examinations, and had received no treatment. We did monotherapy with 5% minoxidil twice daily to the right half of the scalp, while on the left half topical minoxidil was combined with weekly microneedling using an automated microneedling pen. RESULTS After 14 weeks of treatment, negligible hair growth was observed on the monotherapy side. On the combined-therapy side, however, hair growth was obvious and the density of hairs determined under trichoscope was significantly increased compared with the monotherapy side (P < .001). Only transient pain, erythema, and pinpoint bleeding were observed as adverse effects. CONCLUSION Although we need further clinical trials to assess the efficacy and safety and to standardize the method, microneedling combined with topical minoxidil could be a treatment option for severe AGA in elderly patients.
Published: 2020
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34. An effective detachment system for human induced pluripotent stem cells cultured on multilayered cultivation substrates using resonance vibrations

Author: Kenjiro Takemura, Keiichi Fukuda, Shugo Tohyama, Yusuke Terao, Jun Fujita, Yuki Fukuma, and Yuta Kurashina
Subjects: Culture plates, Biophysical methods, Multidisciplinary, Chemistry, lcsh:R, Cell Culture Techniques, lcsh:Medicine, Vibration, Article, Cell biology, Myoblasts, Mice, Induced pluripotent stem cells, Cell Adhesion, Animals, Humans, lcsh:Q, Human Induced Pluripotent Stem Cells, lcsh:Science, Biomedical engineering
Abstract: Clinical application of human induced pluripotent stem cells (hiPSCs) has been hampered by the lack of a practical, scalable culture system. Stacked culture plates (SCPs) have recently attracted attention. However, final cell yields depend on the efficiency of cell detachment, and inefficient cell recovery from SCPs presents a major challenge to their use. We have developed an effective detachment method using resonance vibrations (RVs) of substrates with sweeping driving frequency. By exciting RVs that have 1–3 antinodes with ultra-low-density enzyme spread on each substrate of SCPs, 87.8% of hiPSCs were successfully detached from a 5-layer SCP compared to 30.8% detached by the conventional enzymatic method. hiPSC viability was similar after either method. Moreover, hiPSCs detached by the RV method maintained their undifferentiated state. Additionally, hiPSCs after long-term culture (10 passages) kept excellent detachment efficiency, had the normal karyotypes, and maintained the undifferentiated state and pluripotency. These results indicated that the RV method has definite advantages over the conventional enzymatic method in the scalable culture of hiPSCs using SCPs.
Published: 2019
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35. Enhanced path smoothing based on conjugate gradient descent for firefighting robots in petrochemical complexes

Author: Ryunosuke Hamada, Kazunori Ohno, Naoki Mizuno, Satoshi Tadokoro, Hiroyoshi Kojima, Thomas Westfechtel, Jun Fujita, Hisanori Amano, and Takahiro Suzuki
Subjects: 0209 industrial biotechnology, Computer science, Real-time computing, Firefighting, ComputerApplications_COMPUTERSINOTHERSYSTEMS, Mobile robot, 02 engineering and technology, Computer Science Applications, Human-Computer Interaction, 020901 industrial engineering & automation, Robotic systems, Hardware and Architecture, Control and Systems Engineering, Conjugate gradient method, Path (graph theory), 0202 electrical engineering, electronic engineering, information engineering, Robot, 020201 artificial intelligence & image processing, Motion planning, Software, Smoothing
Abstract: The firefighting robot system (FFRS) comprises several autonomous robots that can be deployed to fire disasters in petrochemical complexes. For autonomous navigation, the path planner should consid...
Published: 2019
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36. Gastric adenocarcinoma of fundic gland type arising from heterotopic gastric glands during a 19-year follow-up period

Author: Akira Suzuki, Junichi Suzuki, Takeshi Uozumi, Mayuko Akimoto, Hideyuki Seki, Susumu Sogabe, Emi Matsuzono, Mitsuru Yanai, Nozomu Sugai, and Jun Fujita
Subjects: Male, Pathology, medicine.medical_specialty, Case Report, Adenocarcinoma, Choristoma, Malignancy, digestive system, 03 medical and health sciences, 0302 clinical medicine, Long-term, Stomach Neoplasms, Gastric glands, Gastroscopy, Gastric adenocarcinoma of fundic gland type, Heterotopic gastric gland, medicine, Carcinoma, Humans, Aged, business.industry, Stomach, Mucins, Gastroenterology, Fundic Gland, Gastric adenocarcinoma of fundic mucosa type, General Medicine, Endoscopic submucosal dissection, medicine.disease, Curvatures of the stomach, digestive system diseases, Gastric chief cell, Foveolar cell, medicine.anatomical_structure, Gastric Mucosa, Duodenal Ulcer, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Biomarkers
Abstract: A 73-year-old man with prior history of duodenal ulcer has been undergoing periodic upper gastrointestinal endoscopy since 1999. In 2017, a 25-mm submucosal tumor-like protrusion was detected in the lesser curvature of the upper stomach; histological examination of the lesion revealed gastric adenocarcinoma of fundic gland type. En bloc resection was achieved using endoscopic submucosal dissection. The patient was histopathologically diagnosed with gastric adenocarcinoma of fundic gland type arising from heterotopic gastric glands. Immunohistochemical staining was positive for MUC5AC, MUC6, pepsinogen I, and proton pump but negative for MUC2 and CD10. Moreover, the patient’s Ki-67 labeling index score was extremely low. The presence of MUC5AC indicated that the tumor differentiated to the foveolar epithelium and fundic glands. Gastric adenocarcinoma of fundic gland type that differentiates to several directions has a higher malignant potential than the disease that differentiates to chief cells. A retrospective review of the patient’s previous endoscopic examination revealed that the submucosal tumor-like protrusion existed since 2000; tumor size increased from 8 mm in 2000 to 25 mm in 2017. The present case is rare in that the carcinoma arose from heterotopic gastric glands. Moreover, the 19-year follow-up revealed that the tumor differentiated to the foveolar epithelium, considered as having high-grade malignancy.
Published: 2019
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37. A remarkable clinical response in advanced gastric cancer treated with trastuzumab plus capecitabine combination chemotherapy: A report of two cases

Author: Shinichi Kinami, Nobuhiko Ueda, Daisuke Kaida, Seiko Miura, Hideto Fujita, Yoritaka Fujii, Yasuto Tomita, Takeo Kosaka, Takashi Miyata, Naohiko Nakamura, and Jun Fujita
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Recurrent gastric cancer, lcsh:Medicine, Case Report, Case Reports, 030204 cardiovascular system & hematology, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Trastuzumab, Internal medicine, medicine, skin and connective tissue diseases, neoplasms, Cisplatin, Chemotherapy, lcsh:R5-920, business.industry, Systemic chemotherapy, capecitabine, gastric cancer, lcsh:R, Combination chemotherapy, General Medicine, Advanced gastric cancer, trastuzumab, 030220 oncology & carcinogenesis, business, lcsh:Medicine (General), medicine.drug
Abstract: Key Clinical Message When trastuzumab + capecitabine and cisplatin chemotherapy could not be conducted continuously because of severe adverse reactions to cisplatin, trastuzumab + capecitabine could be an alternative systemic chemotherapy options for metastatic or recurrent gastric cancer patients.
Published: 2019

38. [Role of Surgical Resection after Chemoradiotherapy in Locally Advanced Pancreatic Cancer]

Author: Nobuhiko, Ueda, Seiko, Miura, Hisashi, Nishiki, Akifumi, Hashimoto, Ryousuke, Kin, Yoritaka, Fujii, Jun, Fujita, Daisuke, Kaida, Yasuto, Tomita, Naohiko, Nakamura, Takashi, Miyata, Hideto, Fujita, and Hiroyuki, Takamura
Subjects: Pancreatic Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, Humans, Neoplasms, Second Primary, Chemoradiotherapy, Pancreas, Neoadjuvant Therapy
Abstract: We investigated 34 cases of preoperative chemoradiotherapy(CRT)for locally advanced pancreatic cancer including resectable pancreatic cancer in our department during the past 11 years. For resectable(R)or borderline resectable(BR)pancreatic cancer, survival curves were generally higher in the CRT plus S-1 group treated after CRT than in the CRT group treated with post-CRT chemotherapy, but there was no statistically significant difference. In non-resected cases, local exacerbation was observed, which was one of the causes of a decline in terminal QOL. From the above, at present, it is desirable to remove R or BR pancreatic cancer after CRT, but the significance of surgery may change in the future due to the improvement of multidisciplinary treatment.
Published: 2021

39. A Method for Cardiac Differentiation, Purification, and Cardiac Spheroid Production of Human Induced Pluripotent Stem Cells

Author: Shugo Tohyama, Keiichi Fukuda, Jun Fujita, and Yuika Morita
Subjects: Transplantation, medicine.anatomical_structure, Cardiac differentiation, Cell, medicine, Spheroid, Human Induced Pluripotent Stem Cells, Biology, Induced pluripotent stem cell, Regenerative medicine, Tumor formation, Cell biology
Abstract: Human induced pluripotent stem cells (hiPSCs) are one of the most promising cell sources for regenerative medicine. To realize the promise of hiPSCs for cardiac regenerative therapy, three major obstacles must be overcome: the first is the achievement of large-scale production of cardiomyocytes, the second is the successful elimination of non-cardiac cells containing residual pluripotent stem cells (PSCs) to prevent tumor formation, and the third is the achievement of high engraftment efficiency of transplanted cardiomyocytes. In this chapter, we introduce our protocols for cardiac differentiation, purification, and preparation of cardiac spheroids for safe and effective regenerative medicine.
Published: 2021
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40. Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells

Author: Sho Tanosaki, Yusuke Soma, Shugo Tohyama, Moon Il Kang, Yuika Morita, Eiji Kobayashi, Kazunori Sasaki, Hidenori Tani, Kotaro Kameda, Otoya Sekine, Keiichi Fukuda, Marina Okada, Yoshikazu Kishino, Hideaki Kanazawa, Kazuaki Nakajima, Taijun Moriwaki, Shota Someya, Jun Fujita, and Tomohiko Umei
Subjects: 0301 basic medicine, Multidisciplinary, Metabolite, 02 engineering and technology, Cell Biology, Biology, 021001 nanoscience & nanotechnology, Stem Cell Research, Regenerative medicine, Article, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Metabolomics, chemistry, Cell culture, Extracellular, Metabolome, lcsh:Q, 0210 nano-technology, Induced pluripotent stem cell, lcsh:Science, Kynurenine
Abstract: Summary Human pluripotent stem cells (hPSCs) have a unique metabolic signature for maintenance of pluripotency, self-renewal, and survival. Although hPSCs could be potentially used in regenerative medicine, the prohibitive cost associated with large-scale cell culture presents a major barrier to the clinical application of hPSC. Moreover, without a fully characterized metabolic signature, hPSC culture conditions are not optimized. Here, we performed detailed amino acid profiling and found that tryptophan (TRP) plays a key role in the proliferation with maintenance of pluripotency. In addition, metabolome analyses revealed that intra- and extracellular kynurenine (KYN) is decreased under TRP-supplemented conditions, whereas N-formylkynurenine (NFK), the upstream metabolite of KYN, is increased thereby contributing to proliferation promotion. Taken together, we demonstrate that TRP is indispensable for survival and proliferation of hPSCs. A deeper understanding of TRP metabolism will enable cost-effective large-scale production of hPSCs, leading to advances in regenerative medicine., Graphical Abstract, Highlights • TRP is the only AA that enables enhanced hPSC proliferation by supplementation • hPSCs proliferate with pluripotency after long-term culture in TRP supplementation • The proliferative properties of hPSCs are independent of AhR signaling • TRP-derived NFK contributes to enhanced hPSC proliferation, Cell Biology; Metabolomics; Stem Cell Research
Published: 2021

41. Purification of cardiomyocytes and neurons derived from human pluripotent stem cells by inhibition of de novo fatty acid synthesis

Author: Sho Tanosaki, Tomohiko Akiyama, Sayaka Kanaami, Jun Fujita, Minoru S.H. Ko, Keiichi Fukuda, and Shugo Tohyama
Subjects: General Immunology and Microbiology, General Neuroscience, General Biochemistry, Genetics and Molecular Biology
Published: 2022
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42. Protocol for enhanced proliferation of human pluripotent stem cells in tryptophan-fortified media

Author: Kotaro Kameda, Shota Someya, Jun Fujita, Keiichi Fukuda, and Shugo Tohyama
Subjects: Pluripotent Stem Cells, General Immunology and Microbiology, General Neuroscience, Cell Culture Techniques, Tryptophan, Humans, General Biochemistry, Genetics and Molecular Biology, Cell Proliferation, Culture Media
Abstract: We describe a protocol for the efficient culture of human pluripotent stem cells (hPSCs) by supplementing conventional culture medium with L-tryptophan (TRP). TRP is an essential amino acid that is widely available at an affordable cost, thereby allowing cost-effective proliferation of hPSCs compared to using a conventional medium alone. Here, we describe the steps for enhanced proliferation of hPSCs from dermal fibroblasts or peripheral blood cells, but the protocol can be applied to any hPSCs. For complete details on the use and execution of this protocol, please refer to Someya et al. (2021).
Published: 2022
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43. Metabolism of human pluripotent stem cells and differentiated cells for regenerative therapy: a focus on cardiomyocytes

Author: Shugo Tohyama, Keiichi Fukuda, Jun Fujita, Sho Tanosaki, and Yoshikazu Kishino
Subjects: 0301 basic medicine, Cardiomyocytes, Somatic cell, Drug discovery, Cellular differentiation, Immunology, Regenerative therapy, Metabolism, Review, Biology, Regenerative medicine, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Pluripotent stem cells, lcsh:Pathology, Immunology and Allergy, Induced pluripotent stem cell, Developmental biology, 030217 neurology & neurosurgery, lcsh:RB1-214
Abstract: Pluripotent stem cells (PSCs) exhibit promising application in regenerative therapy, drug discovery, and disease modeling. While several protocols for differentiating somatic cells from PSCs exist, their use is limited by contamination of residual undifferentiated PSCs and immaturity of differentiated somatic cells.The metabolism of PSCs differs greatly from that of somatic cells, and a distinct feature is required to sustain the distinct properties of PSCs. To date, several studies have reported on the importance of metabolism in PSCs and their derivative cells. Here, we detail advancements in the field, with a focus on cardiac regenerative therapy.
Published: 2020

44. Development of Cardiac Regenerative Medicine Using Human iPS Cell-derived Cardiomyocytes

Author: Jun Fujita
Subjects: 0301 basic medicine, Swine, Cellular differentiation, Induced Pluripotent Stem Cells, Translational research, Economic shortage, Bioinformatics, Regenerative Medicine, Regenerative medicine, 03 medical and health sciences, 0302 clinical medicine, Medicine, Animals, Humans, Myocytes, Cardiac, Induced pluripotent stem cell, business.industry, Myocardium, Cell Differentiation, General Medicine, medicine.disease, Transplantation, 030104 developmental biology, Heart failure, business, 030217 neurology & neurosurgery, Large animal
Abstract: Heart failure is a life-threatening disease prevalent worldwide. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages represent a critical issue. Cardiac regenerative therapy is beneficial, but it is currently unsuitable as a substitute for cardiac transplantation. Human induced pluripotent stem cells (hiPSCs) are excellent sources for the generation of terminally differentiated cells. The preparation of a large number of pure cardiomyocytes (CMs) is the major premise for translational studies. To control the quality of the generated CMs, an efficient differentiation method, purification strategy, and mass-scale culture must be developed. Metabolic purification and large-scale culture systems have been established, and pure hiPSC-derived CMs of clinical grade are now available for translational research. The most critical challenge in cell therapy is the engraftment of transplanted cells. To overcome the low engraftment ratio of single CMs, aggregations of CMs are developed as cardiac spheroids. A cardiac transplantation device with domed tips and lateral holes has been developed for the transplantation of cardiac spheroids. Large animal models are necessary as the next step in the process toward clinical application. The transplant device has successfully been used to inject cardiac spheroids uniformly into myocardial layers in swine, and this approach is progressing toward clinical use. Remaining issues include immunological rejection and arrhythmia, which will require further investigation to establish safe and effective transplantation. This review summarizes the present status and future challenges of cardiac regenerative therapies.
Published: 2020

45. [A Case of Effective Disease Control of Advanced Gastric Cancer with Distant Lymph Node Metastases Following Nivolumab Treatment]

Author: Naohiko, Nakamura, Shinichi, Kinami, Jun, Fujita, Daisuke, Kaida, Yasuto, Tomita, Takashi, Miyata, Hideto, Fujita, Hiroyuki, Takamura, Nobuhiko, Ueda, and Takeo, Kosaka
Subjects: Male, Nivolumab, Gastrectomy, Stomach Neoplasms, Lymphatic Metastasis, Antineoplastic Combined Chemotherapy Protocols, Humans, Lymph Nodes, Cisplatin, Aged
Abstract: A 66-year-old man was diagnosed with advanced gastric cancer(L, Less, Type 2, T4a[SE], N2, M1[LYM], H0, P0, cStage Ⅳ)and received treatment with S-1/cisplatin as first-line chemotherapy. This treatment resulted in partial response(PR) after 3 months, with reduction in the sizes of metastatic lymph nodes surrounding the pancreatic head and paraaortic lesion. However, the sizes of metastatic lymph nodes increased after 7 months of chemotherapy. Ramucirumab/nab-paclitaxel was then administered as second-line chemotherapy, and the diameter of the metastatic lymph nodes subsequently decreased after 4 months of the regimen. However, progressive disease was observed at 7 months, and blood transfusion was required because of bleeding from the primary gastric tumor. Therefore, nivolumab was initiated as third-line chemotherapy 14 months after the first treatment. After nivolumab administration, a 28% reduction in metastatic lymph nodes was achieved within 3 months, together with the regression of the primary gastric tumor and improvement in anemia within 6 months. PR was achieved after 12 months of nivolumab administration, and effective disease control was maintained for 16 months without any adverse reaction to nivolumab.
Published: 2020

46. Pancreatic neuroendocrine tumor featuring growth into the main pancreatic duct and tumor thrombus within the splenic vein: a case report

Author: Takashi Miyata, Takeo Kosaka, Yasuto Tomita, Hisashi Nishiki, Hideto Fujita, Daisuke Kaida, Seiko Miura, Naohiko Nakamura, Hiroyuki Takamura, Akifumi Hashimoto, Shinichi Kinami, Yoritaka Fujii, Nobuhiko Ueda, Ryosuke Kin, and Jun Fujita
Subjects: Pancreatic duct, medicine.medical_specialty, Abdominal pain, AcademicSubjects/MED00910, business.industry, Case Report, intraductal growth, Neuroendocrine tumors, medicine.disease, Jscrep/080, Gastroduodenal artery, medicine.anatomical_structure, splenic vein thrombus, Splenic vein, medicine.artery, medicine, Surgery, Radiology, Thrombus, medicine.symptom, Differential diagnosis, Pancreas, business, neuroendocrine tumor
Abstract: A 48-year-old woman was admitted to our hospital because of upper abdominal pain. Computer tomography showed an enhancing mass in the pancreatic body, dilation of the main pancreatic duct (MPD) and a filling defect within the splenic vein. On the basis of the preoperative diagnosis of pancreatic body cancer, distal pancreatectomy was scheduled. The pancreas was divided along the left edge of the gastroduodenal artery; however, frozen pathological examination of the pancreatic stump was tumor positive, and therefore a total pancreatectomy was performed. The lesion was a white expansive nodular mass that had spread into the MPD and protruded into the splenic vein. A pathological diagnosis of non-functioning neuroendocrine tumor (NET) was made. In general, imaging findings of disruption of the MPD and tumor vein thrombus are characteristics of pancreatic ductal adenocarcinoma, but are uncommon in NET. However, NET should be included in the differential diagnosis for such patients.
Published: 2020

47. Advanced gastric cancer with abdominal wall invasion treated with curative resection after chemotherapy: a case report

Author: Daisuke Kaida, Yasuto Tomita, Hiroyuki Takamura, Hideto Fujita, Nobuhiko Ueda, Takashi Miyata, Shinichi Kinami, Naohiko Nakamura, and Jun Fujita
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Case Report, Abdominal wall, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Gastrectomy, Stomach Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, biology, business.industry, Gastric Obstruction, Abdominal Wall, Transverse colon, Cancer, General Medicine, medicine.disease, Prognosis, Surgery, Oxaliplatin, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Abdominal wall invasion, Resection margin, biology.protein, Medicine, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, Gastric cancer, T4b, medicine.drug
Abstract: Introduction In patients with gastric cancer, 6–27% of patients are diagnosed with T4b disease that invades adjacent organs, and curative resection can improve the prognosis of these patients. Case presentation A 70-year-old Japanese man presented with an abdominal tumor and was diagnosed with advanced gastric cancer (L-Circ type 3 T4b N2 M0 H0 stage IVA, based on the 15th edition of the Japanese Classification of Gastric Carcinoma) with extensive abdominal wall invasion. We performed open gastrojejunal bypass for gastric obstruction and initiated a chemotherapeutic regimen comprising S-1 (120 mg/day) and oxaliplatin (100 mg/m2). Upper gastrointestinal endoscopy performed after the administration of six courses of the S-1 and oxaliplatin regimen revealed a persistent primary lower gastric wall lesion; however, the diameter of the abdominal wall invasion and metastatic lymph nodes was significantly reduced, in addition to decreased serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels. Subsequently, the patient underwent distal gastrectomy with D2 lymphadenectomy combined with transverse colon and abdominal wall resection. We performed radical en bloc resection and achieved a tumor-free resection margin. Simple abdominal wall closure was performed without mesh or musculocutaneous flap placement. Histopathological examination of the resected tumor specimen showed direct invasion of the mesocolon and rectus abdominis muscle. The patient was postoperatively diagnosed with L Gre-Ant type5 T4b (SI: rectus abdominis muscle) N2 PM0 DM0 Stage IIIA R0 Grade 2a gastric cancer based on histopathological findings and received S-1 as adjuvant chemotherapy, 2 months postoperatively. No recurrence was detected 6 months postoperatively. Conclusions We report a case of advanced gastric cancer with extensive abdominal wall invasion that was successfully treated with gastrectomy combined with resection of adjacent organs showing tumor invasion after effective systemic chemotherapy. A therapeutic approach comprising curative surgery combined with perioperative chemotherapy is useful in patients with T4b gastric cancer.
Published: 2020

48. Ontogeny of Mast Cells

Author: Hiroki Nakayama, Akira Kuriu, Yukihiko Kitamura, and Jun Fujita
Subjects: Ontogeny, Mast (botany), Biology, Cell biology
Published: 2020
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49. Laser pass analysis for LiDAR with conical mirrors

Author: Jun FUJITA, Hiroyoshi KOJIMA, Takaaki NARA, Kenta GUNJI, Shotaro KOJIMA, Kazunori OHNO, and Satoshi TADOKORO
Subjects: General Medicine
Published: 2022
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50. Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian cold-inducible proteins

Author: Hiroaki Higashitsuji, Katsuhiko Itoh, Hiroyuki Nishiyama, Jun Fujita, Takanori Fujita, Yu Liu, and Koji Shibasaki
Subjects: 0301 basic medicine, TRPV4, RNA-binding protein, RBM3, Biophysics, TRPM Cation Channels, TRPV Cation Channels, Hypothermia, Biology, Biochemistry, Cell Line, TRPC1, Mice, 03 medical and health sciences, Transient receptor potential channel, 0302 clinical medicine, Western blot, Cold-inducible, TRP channel, TRPM8, medicine, Animals, Channel blocker, Molecular Biology, Ion channel, Mice, Knockout, medicine.diagnostic_test, Cold-Shock Response, Cell Biology, Molecular biology, Cold Temperature, Mice, Inbred C57BL, 030104 developmental biology, Cell culture, Cold Shock Proteins and Peptides, SRSF5, Ion Channel Gating, 030217 neurology & neurosurgery
Abstract: Cold-inducible RNA-binding protein (CIRP), RNA-binding motif protein 3 (RBM3) and serine and arginine rich splicing factor 5 (SRSF5) are RNA-binding proteins that are transcriptionally upregulated in response to moderately low temperatures and a variety of cellular stresses in mammalian cells. Induction of these cold-inducible proteins (CIPs) is dependent on transient receptor potential (TRP) V4 channel protein, but seems independent of its ion channel activity. We herein report that in addition to TRPV4, TRPV3 and TRPM8 are necessary for the induction of CIPs. We established cell lines from the lung of TRPV4-knockout (KO) mouse, and observed induction of CIPs in them by western blot analysis. A TRPV4 antagonist RN1734 suppressed the induction in wild-type mouse cells, but not in TRPV4-KO cells. A TRPV3 channel blocker S408271 and a TRPM8 channel blocker AMTB as well as siRNAs against TRPV3 and TRPM8 suppressed the CIP induction in mouse TRPV4-KO cells and human U-2 OS cells. A TRPV3 channel agonist 2-APB induced CIP expression, but camphor did not. Neither did a TRPM8 channel agonist WS-12. These results suggest that TRPV4, TRPV3 and TRPM8 proteins, but not their ion channel activities are necessary for the induction of CIPs at 32 °C. Identification of proteins that differentially interact with these TRP channels at 37 °C and 32 °C would help elucidate the underlying mechanisms of CIP induction by hypothermia.
Published: 2018
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