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1. National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study

Author

Satoshi Suzuki, Kenji Yamamoto, Hiroaki Tanaka, Hiroshi Ozawa, Yuji Okamoto, Tatsuya Abe, Hidenori Suzuki, Akiko Kada, Shigeki Nishino, Nobuyuki Sakai, Kunihiro Nishimura, Tomoyoshi Oikawa, Takanari Kitazono, Hiroshi Tanaka, Daisuke Onozuka, Akihito Hagihara, Hiroshi Ooyama, Akira Watanabe, Shinichi Yoshimura, Toru Iwama, Hiroki Sato, Satoshi Ushikoshi, Kiyohiro Houkin, Nobuhiro Mikuni, Naoyuki Nakao, Michio Nakamura, Nanako Tamiya, Naofumi Isono, Koji Iihara, Yutaka Yamaguchi, Kuniaki Ogasawara, Osamu Onodera, Yusaku Nakamura, Naoki Hayashi, Akira Takada, Masayuki Ezura, Akio Hyodo, Shigeru Miyachi, Susumu Miyamoto, Yuji Matsumaru, Ichiro Nakahara, Tomoaki Terada, Kazunari Yoshida, Ai Kurogi, Ataru Nishimura, Yoshiaki Shiokawa, Koichi Arimura, Kaoru Kurisu, Fusao Ikawa, Kenji Ohata, Kyoichi Nomura, Nobuhito Saito, Hiroaki Fujiwara, Susumu Suzuki, Masanori Isobe, Soshiro Ogata, Takeshi Matsuoka, Junichiro Satomi, Takashi Matsumoto, Hiroyuki Nakase, Yasunari Niimi, Manabu Kinoshita, Mamoru Murakami, Masaaki Uno, Junichi Iida, Takashi Matsuoka, Tatsuya Sasaki, Shinichi Wakabayashi, Hiroki Toda, Hideki Sakai, Hajime Ohta, Osamu Yamamura, Hideyuki Ohnishi, Hiroko Oyama, Junichi Ono, Izumi Nagata, Hiroharu Kataoka, Ryota Kurogi, Hajime Arai, Atsuo Yoshino, Tsuyoshi Ohta, Hiroshi Sugimori, Hidehiro Hirabayashi, Hiroyuki Masaoka, Satoshi Yamamoto, Hideki Murakami, Kazuhiko Nozaki, Hiroyuki Matsumoto, Yuichiro Tanaka, Takahisa Mori, Keizo Yasui, Akira Takahashi, Ichiro Suzuki, Sachio Suzuki, TAKASHI YOSHIDA, Masanori Morimoto, Tetsuya Ueba, Hiromu Hadeishi, Masaki Chin, Michihiro Kohno, Hitoshi Fukuda, Toru Nishi, Kazunari Koga, Toshihiko Wakabayashi, Hiroki Ohkuma, Kazuhiro Hongo, Hiroshi Nakane, Kazumi Nitta, Satoshi Utsuki, Toshihiko Iuchi, Nice Ren, Hidefuku Gi, Kensuke Kawai, Masayuki Ishihara, Eiji Kohmura, Yoshihiro Nishiura, Kazutaka Yatsushiro, Kensaku Yoshida, Atsushi Tominaga, Masayuki Sumida, Hidenori Yoshida, Atsushi Sato, Takashi Inoue, Hiroaki Shimizu, Eiichiro Kamatsuka, Makoto Ichinose, Naoya Takeda, Tsuyoshi Inoue, Hidekazu Takahashi, Satoshi Kuroda, Toshiaki Osato, Nobutaka Horie, Isao Date, Yoichiro Hashimoto, Haruhiko Hoshino, Takafumi Shimogawa, Koji Yoshimoto, Teiji Tominaga, Isao Sasaki, Kazuo Kitazawa, Minoru Saitoh, Hitoshi Saito, Minoru Asahi, Makoto Goda, Atsuhito Takemura, Masaaki Shibukawa, Isao Fuwa, Saburo Watanabe, Seiko Kataoka, Koji Takasaki, Kouji Shiga, Kensuke Hayashida, Ryunosuke Uranishi, Chiaki Ito, Kenji Wakui, Takashi Saegusa, Isao Kitahara, Yasushi Ejima, Satoru Hayashi, Kazuyoshi Hattori, Shinji Okita, Toshikazu Ichihashi, Tsugumichi Ichioka, Shinichi Shirakami, Teruo Kimura, Tomonori Kobayashi, Kanehisa Kohno, Kazunori Yamanaka, Akira Morooka, Nozomi Mori, Hideo Kunimine, Masahiro Satoh, Syougo Imae, Hirochiyo Wada, Masanori Kabuto, Katsuyuki Hirakawa, Isao Inoue, Kiyoshi Kazekawa, Masani Nonaka, Kouzou Fukuyama, Shigenari Kin, Kiyoshi Saito, Yoichi Watanabe, Tadashi Arisawa, Kou Takahashi, Tetsuya Tanigawara, Junki Ito, Kei Hisada, Makoto Takeda, Jun Niwa, Mikio Nishiya, Shuji Hayashi, Ichiro Fujishima, Teiji Nakayama, Yoshihiko Watanabe, Koichirou Matsukado, Takamichi Yuguchi, Tadahisa Shono, Hiroyuki Nishimura, Jyunya Hayashi, Keisuke Migita, Kazuhiro Yokoyama, Hirotoshi Ohtaka, Takata Hisashi, Takamitsu Uchizawa, Naoki Shinohara, Mitsunobu Kaijima, Junkoh Yamamoto, Yoshio Sakagami, Hideo Aihara, Takayuki Sakaki, Keishi Fujita, Sumio Kobayashi, Nobuaki Momozaki, Masahito Hara, Akazi Kazunori, Fumitaka Miya, Hisato Minamide, Shinichiro Kurokawa, Syuichi Ishikawa, Naohisa Miura, Shinya Noda, Shoji Mashiyama, Shinji Amano, Takayuki Sugawara, Yukihiko Shimizu, Keiichi Saito, Kazuyuki Miura, Akinori Yabuta, Tatumi Yamanome, Hiroshi Seto, Makoto Hasebe, Hikaru Mizobuchi, Junkoh Sasaki, Shin Tsuruoka, Keiichi Nishimaki, Katsumi Takizawa, Hitoshi Tsugu, Nozomi Suzuki, Takeshi Kohno, Shu Hasegawa, Ken Asakura, Masaki Miyatake, Hiromu Konno, Katsunobu Takenaka, Akira Ikeda, Keizou Yamamoto, Keigo Matsumoto, Satoshi Inoha, Masaki Morisige, Kunihiko Harada, Hirofumi Hiyama, Yasuaki Takeda, Taturou Mori, Takekazu Akiyama, Osamu Okuda, Kazuaki Awamori, Naoki Shirasaki, Kimihiro Yoshino, Atsushi Shindo, Kazuho Hirahara, Shunichi Tanaka, Teruaki Kawano, Kazunori Arita, Hiroaki Sawaura, Yoichi Uozumi, Masahiko Tanaka, Shunsuke Shiraga, Shuji Sato, Mitsutoshi Nakada, Kimihisa Kinoshita, Nakazawa Kazutomo, Yasuhiro Fujimoto, Kunikazu Yoshimura, Masaaki Iwase, Shinichi Yagi, Atsushi Tsuchiya, Junichi Harashina, Sadao Kaneko, Naoto Kuwayama, Junya Hayashi, Masayuki Sasou, Sotaro Higashi, Masakazu Kitahara, Sumio Suda, Amami Kato, Satoshi Magarisawa, Kenji Hashimoto, Hirotoshi Hamaguchi, Tomohiko Satou, Masaru Idei, Haruhisa Tsukamoto, Toshihiro Kumabe, Naoaki Sato, Yasuyuki Toba, Takashi Tominaga, Haruo Yamashita, Toyoaki Shinohara, Kazuyoshi Watanabe, Hidenori Endo, Kenjirou Hujiwara, Toshinori Hasegawa, Hisashi Nitta, Kuroyanagi Takayuki, Nobuhiko Mizutani, Akira Tsunoda, Fumio Suzuki, Tetsuya Morimoto, Takuya Kawai, Mitsuyuki Fujitsuka, Hiromasa Tsuiki, Junichi Kuratsu, Hidemichi Sasayama, Shigehiro Ohmori, Seiko Hasegawa, Kazuhiro Kikuchi, Motohiro Morioka, Masayuki Yokota, Nozomu Murai, Yasumasa Yamamoto, Nobuhito Mori, Minoru Kidooka, Hiroshi Tenjin, Yoshihiro Iwamoto, Hitonori Takaba, Sei Haga, Yoshinori Arai, Toshiyuki Tsukada, Hirohide Karasudani, Masakazu Suga, Kawamoto Yukihiko, Naoto Izumi, Youtarou Takeuchi, Motohiro Arai, Shinji Okumura, Hisashi Tanaka, Yasushi Shibata, Tetsuya Masaoka, Masahiko Kasai, Hitoshi Miyake, Osamu Hamasaki, Misao Nishikawa, Naohiko Kubo, Yosimasa Kinosita, Hiroyuki Kaidu, Tarou Komuro, Hiroaki Shigeta, Yoshikazu Kusano, Shigekazu Takeuchi, Takayuki Matsuo, Yoshiharu Tokunaga, Norimoto Nakahara, Nobukazu Hashimoto, Mitsuhito Mase, Junpei Yoshimoto, Jin Momoji, Kenji Kamiyama, Koji Oka, Hiromichi Koga, Kazuya Morimoto, Tsutomu Kadekaru, Naoki Tokumitsu, Yasuyuki Nagai, Hirokazu Tanno, Takato Kagawa, Masaaki Saiki, Kotaro Ogihara, Junichi Imamura, Katsuhiro Yamashita, Akira Nakamizo, Yoshinari Nakamura, Ei-Ichirou Urasaki, Noriyuki Suzaki, Chiaki Takahashi, Youichirou Namba, Kazuo Hashikawa, Tomonori Yamada, Kazuyuki Kuwayama, Keiichi Sakai, Katsuhiro Kuroda, Hideyuki Kurihara, Masayuki Miyazono, Kosuke Miyahara, Hideaki Takahashi, Akihiko Saito, Igarashi Michitoku, Mitsuo Kouno, Shiro Kobayashi, Shunichi Yoneda, Hiroshi Kusunoki, Hiroji Miyake, Toshio Yokoe, Tatsuya Nakamura, Takayuki Kubodera, Mitsuhiko Hokari, Yasunari Otawara, Cheho Park, Hidemitu Nakagawa, Souichi Obara, Haruki Takahashi, Masafumi Ohtaki, Atsuya Okubo, Katsuhiko Hayashi, Masahisa Kawakami, Yu Takeda, Akihiko Kaga, Ryoichi Hayashi, Koji Tokunaga, Hiroyuki Nakashima, Yasuyuki Miyoshi, Atusi Kimoto, Toshimitsu Uchihara, Tomoaki Nagamine, Masahiro Noha, Hiromichi Sadashima, Toshihiko Kinjo, Osamu Tao, Masayuki Nakajima, Akira Isoshima, Kouichi Kuramoto, Shigeru Daido, Yoshiyasu Iwai, Toshihiko Kuroiwa, Akatsuki Wakayama, Kohsuke Yamashita, Yasunobu Gotou, Kouich Iwatsuki, Yoshida Masahiro, Nobuaki Kobayasi, Yoshimasa Niiya, Syouji Mabuchi, Motohiro Takayama, Kazuo Yamamoto, Junta Moroi, Masato Sugitani, Akio Ookura, Naoko Fujimura, Osamu Nishizaki, Sumio Isimaru, Hiroshi Wanihuchi, Nobukuni Murakami, Hiroto Murata, Naoki Kitagawa, Katsuhiko Kono, Michiya Kubo, Masashi Nakatsukasa, Makoto Inaba, Hidetoshi Ooigawa, Atsuhiro Kojima, Takamitsu Fujimaki, Osamu Fukuda, Yoshikazu Nakajima, Kazuyuki Kouno, Takaaki Yoshida, Reizou Kanemaru, Yohei Kudoh, Toshitaka Nakamura, Masayoshi Takigami, Shogo Nishi, Rokuya Tanikawa, Seisaburo Sakamoto, Makio Kaminogo, Seiichiro Hoshi, Yoshinari Okumura, Shinichi Okabe, Haruhiko Sato, Shiro Miyata, Kotaro Tsumura, Hiroshi Karibe, Noriaki Watabe, Ryuji Nakamura, Norifumi Shimoeda, Tsutomu Hitotsumatsu, Tomoaki Kameda, Hiroshi Ishiguchi, Atsuo Shinoda, Masanobu Hokama, Akinori Yamamura, Takeshi Kondoh, Kenichi Murao, Takafumi Wataya, Seiji Fukazawa, Shinsuke Muraoka, Hirosuke Fujisawa, Tsuneo Shishido, Mayumi Mori, Arai Hiroaki, Shinjitsu Nishimura, Zenichiro Watanabe, Susumu Nakashima, Kazuhito Nakamura, Yukinari Kakizawa, Hiroki Takano, Norihito Shirakawa, Masahiro Kagawa, Eiichiro Mabuchi, Kazusige Maeno, Takayuki Koizumi, Warou Taki, Yusuke Nakagaki, Kazuyuki Tane, Hiromichi Ooishi, Katsuyuki Asaoka, Yoshinori Akiyama, Tadao Kawamura, Atumi Takenobu, Takehisa Tuji, Masami Shimoda, Mitsunori Matsumae, Shinji Noda, Koiti Moroki, Hirofumi Oka, Masahito Agawa, Hajimu Miyake, Masateru Katayama, Shinichi Numazawa, Taketoshi Maehara, Hiroyuki Jimbo, Satoshi Ihara, Koji Matuoka, Oikawa Akihiro, Takahiro Oota, Makoto Noguchi, Takakazu Kawamata, Youichi Hashimoto, Keiichirou Onitsuka, Masahiko Kitano, Jae-Hyun Son, Toru Masuoka, Naoki Koketsu, Keiichi Akatsuka, Masamichi Kurosaki, Miyamori Tadao, Hiroaki Hondo, Kazumasa Yamatani, Hirofumi Oyama, Junji Koyama, Ogura Koichiro, Shinji Yamamoto, Hitoshi Tabata, Kazuya Uemura, Kazuhiko Sato, Hideyuki Yoshida, Takafumi Nishizaki, Hiroshi Egami, Hideo Takeshima, Shogo Ishiuchi, Akira Matsumura, Hiroyuki Kinouchi, Susumu Mekaru, Mikihiko Takeshita, Hitoshi Ozawa, Kiichiro Zenke, Takeshi Matsuyama, Toshikazu Kuwata, Teruyuki Habu, Tomoyoshi Okumura, Seiya Takehara, Rei Kondo, Takashi Kumagai, Keiten So, Sunao Takemura, Sonoda Yukihiko, Manabu Urakawa, Yasuhiro Hamada, Michiyasu Suzuki, Mikito Uchida, Hidehito Koizumi, Masaru Yamada, Takashi Tsuruno, Gen Ishida, Ryouichi Masuda, Makoto Kimura, Shinichirou Ishihara, Masashi Morikawa, Hidetoshi Murata, Katsumi Sakata, Motohiro Nomura, Akihiro Nemoto, Sumio Endou, Nobuo Hirota, Kennji Itou, Hiroaki Minami, and Yoshihumi Teramoto

Subjects
Medicine
Abstract

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Published
2023
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2. Cortical and Internal Watershed Infarcts Might Be Key Signs for Predicting Neurological Deterioration in Patients with Internal Carotid Artery Occlusion with Mild Symptoms

Author

Yuki Amano, Hiroyasu Sano, Ayataka Fujimoto, Hiroaki Kenmochi, Haruhiko Sato, and Soichi Akamine

Subjects
large vessel occlusion, watershed infarction, mild symptom, lenticulostriate arteries, internal carotid artery occlusion, cardioembolism, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Treatment for acute ischemic stroke due to large vessel occlusion (LVO) with mild symptoms is under discussion. Although most patients have good outcomes, some patients deteriorate and have unfavorable results. Imaging findings that predict the prognosis of LVO with mild symptoms are needed to identify patients who require treatment. In this study, we focused on watershed infarctions (WSIs), because this clinical phenomenon quite sensitively reflects changes in cerebral blood flow. The purpose of this study was to assess positive rates of WSI on MRI findings in patients with internal carotid artery (ICA) occlusion, and compare WSI-positive rates between patients divided according to their clinical course. Methods: We retrospectively collected data of 1,531 patients who presented with acute ischemic stroke between June 2006 and July 2019. Among them, we chose symptomatic ICA occlusion patients with a past history of atrial fibrillation who were treated conservatively. We divided these patients into two groups, those with maintenance or improvement in their NIHSS score after hospitalization, and those whose NIHSS score worsened. We compared WSI-positive rates between these two groups. Results: Thirty-seven of the 1,531 patients were included in this study. Of them, total NIHSS score was maintained or improved in 8 patients (group A), 3 of whom (37.5%) had internal watershed infarctions (IWIs). In group B, consisting of patients whose NIHSS score worsened by >2 at 7 days from symptom onset, 24 (82.8%) had IWIs. Group A thus had statistically lower IWI positivity rates than group B (p = 0.02). Three patients (37.5%) in group A had cortical watershed infarctions (CWIs), while 27 patients in group B (93.1%) had CWIs. Group A thus had a significantly lower CWI positivity rate than group B (p = 0.002). Conclusion: In patients with mildly symptomatic ICA occlusion, CWIs and IWIs might be key signs for predicting neurological deterioration after hospitalization.

Published
2020
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3. Association Between Physical Function and Neighborhood Environment in Healthy, Older Adults: An Exploratory Study Using Regression Tree Analysis

Author

Masataka Ando RPT, MA, Naoto Kamide RPT, CSW, PhD, Yoshitaka Shiba RPT, PhD, Miki Sakamoto RPT, PhD, Haruhiko Sato RPT, PhD, Takeshi Murakami ST, PhD, and Shuichiro Watanabe MD, PhD

Subjects
Geriatrics, RC952-954.6
Abstract

The aim of this study was to perform an exploratory investigation of the individual characteristics of older adults that affect the relationships between physical function and neighborhood environment. A total of 624 community-dwelling older adults living independently, aged ≥65 years, participated in this cross-sectional study. Physical function was assessed by muscle strength (grip strength and knee extension strength) and physical performance (5-m walking time and Timed Up and Go Test). The neighborhood environment was assessed using the International Physical Activity Questionnaire Environmental Module. The individual characteristics that affect the association between both were analyzed using multiple regression analysis and Classification and Regression tree (CaRT) analysis. In both older men and women, multiple regression analysis showed that neighborhood environment was significantly associated with physical function. On the other hand, on CaRT analyses, older men ≤80 years of age without low back pain and depressive symptoms and perceived good access to recreational facilities had the shortest 5-m walking time. However, CaRT analyses found no relationship between physical function and neighborhood environment in older women. The relationships between physical function and neighborhood environment may be altered by sex, age, and physical and mental health conditions.

Published
2021
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4. Fall-related efficacy is a useful and independent index to detect fall risk in Japanese community-dwelling older people: a 1-year longitudinal study

Author

Naoto Kamide, Yoshitaka Shiba, Miki Sakamoto, Haruhiko Sato, and Akie Kawamura

Subjects
Accidental falls, Aged, Fall-related efficacy, Japanese, Physical performance, Geriatrics, RC952-954.6
Abstract

Abstract Background Fall-related efficacy has been found to be associated with both falls and fall risk factors such as physical performance. The aim of the present study was to clarify whether fall-related efficacy is, independent of physical performance and other potential risk factors, associated with future falls in community-dwelling older people. Methods The study participants were 237 Japanese older people aged 65 years and over who were living independently in their community. Fall-related efficacy and physical performance were assessed at baseline using the short version of the Falls Efficacy Scale-International (short FES-I) and 5-m walking time, the Timed Up and Go Test, the 5 Times Sit to Stand Test, and grip strength. Physical performance was then again assessed at 1-year follow-up. The number of falls was obtained every 6 months for 1 year after the baseline survey. Instrumental activities of daily living (IADL), depression, fall history, current medications, medical history, and pain were also investigated as potential confounding factors that have possible associations with falls. The associations between the short FES-I, physical performance, and number of falls were analyzed using Poisson regression analysis adjusted for physical performance and potential confounding factors. Results The mean age of the participants (75.9% women) was 71.1 ± 4.6 years, and 92.8% could perform IADL independently. The total numbers of falls and fallers during the 1-year follow-up period were 70 and 42, respectively. On Poisson regression analysis adjusted for walking time and potential confounding factors, independent of physical performance, the short FES-I was found to be significantly associated with number of falls (relative risk = 1.09, p

Published
2019
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5. Characteristics Associated with Early Worsening of Retinopathy in Patients with Type 2 Diabetes Diagnosed with Retinopathy at Their First Visit: A Retrospective Observational Study

Author

Sayaka Wakabayashi Sugawa, Yoko Yoshida, Yusuke Hikima, Haruhiko Sato, Akira Shimada, Mitsuhiko Noda, and Akifumi Kushiyama

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Aims/Introduction. To investigate whether the occurrence of early worsening of diabetic retinopathy in patients with type 2 diabetes diagnosed with simple or preproliferative diabetic retinopathy at their first visit differed according to HbA1c reduction and/or treatment intensification. Materials and Methods. Our study design was a retrospective observational study. Subjects with type 2 diabetes diagnosed with either simple or preproliferative diabetic retinopathy by ophthalmologists at their first visit and followed up for 6–18 months thereafter were included and divided into worsening and nonworsening groups. Thereafter, baseline characteristics and changes in HbA1c and therapy over a year were investigated. Results. Among the 88 subjects with simple diabetic retinopathy, 16% improved to no retinopathy, 65% retained their simple diabetic retinopathy, 18% worsened to preproliferative diabetic retinopathy, and 1% worsened to proliferative diabetic retinopathy. Among the 47 subjects with preproliferative diabetic retinopathy, 9% improved to simple diabetic retinopathy, 72% retained their preproliferative diabetic retinopathy, and 19% worsened to proliferative diabetic retinopathy. Patients with simple diabetic retinopathy had an odds ratio of 1.44 for worsening retinopathy with a 1% increase in baseline HbA1c. Meanwhile, the odds ratios for worsening retinopathy with a 1% decrease in HbA1c from baseline at 3, 6, and 12 months were 1.34, 1.31, and 1.38, respectively. Among patients with simple diabetic retinopathy, significantly more new interventions were introduced in the worsening group than in the nonworsening group. Conclusions. Increased baseline HbA1c, a substantial decrease in HbA1c, and intensified therapy were identified as risk factors for early worsening of diabetic retinopathy in patients with simple diabetic retinopathy at the first visit. Patients should therefore be intimately followed for retinopathy after their first visit.

Published
2021
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6. A Cross-Sectional Study on the Association between Body Mass Index and Frailty According to Sex in Elderly Patients with Disabilities from an Elderly Day-Care Center

Author

Tsuyoshi Asai, Masanori Wakida, Ryo Kubota, Yoshihiro Fukumoto, Haruhiko Sato, Jiro Nakano, and Kimitaka Hase

Subjects
body mass index, elderly, frailty, physically disabled, sex, Geriatrics, RC952-954.6
Abstract

The association between body mass index (BMI) and frailty in elderly patients with disabilities is unclear. We aimed to investigate the association between BMI and frailty in the elderly with disabilities according to sex. This cross-sectional study included 280 elderly patients with disabilities from an elderly daycare center. BMI classification for the Asian population was used to categorize the patients into four groups: underweight, normal, overweight, and obese. Frailty score was based on the phenotypic definition of frailty and consisted of five criteria derived from the revised Japanese version of the Cardiovascular Health Study. Those who had three or more criteria were considered frail. Logistic regression models were constructed to investigate the associations between frailty and BMI in each group (males and females). In females, being underweight was significantly associated with frailty after adjusting for confounders (age and Mini-Mental State Examination score); after adding medical history as a confounder, the aforementioned association was not significant. In males, BMI was not significantly associated with frailty. The association between BMI and frailty differed according to sex among the elderly with disabilities. This finding provides important information regarding frailty risk to workers in daycare facilities.

Published
2021
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7. Clarifying the structure of serious head and spine injury in youth Rugby Union players.

Author

Koh Sasaki, Haruhiko Sato, Akihiko Nakamura, Takumi Yamamoto, Ichiro Watanabe, Takashi Katsuta, and Ichiro Kono

Subjects
Medicine, Science
Abstract

This study aimed to clarify the cause of rugby head and spinal cord injuries through a network centrality analysis of 14-year (2004-2018) longitudinal data in Japan. The study hypothesis is that understanding the causal relationship among the occurrence of serious injuries, the quality of player experience and play situation as a network structure could be possible to obtain practical knowledge on injury prevention. In this study, bipartite graphs are used to make it easier to understand the situation of players and injuries. This would also help to elucidate more characteristic subgroup. A network bipartite graph and subgroup (cluster) analyses were performed to clarify the injured players' experience and the cause of injury. We used the algorithm of R program, IGRAPH, clustering edge betweenness. For subgroup extraction, the modularity Q value was used to determine which step to cut. The Japanese rugby population was 93,873 (2014-2018 average), and 27% were high school students. The data showed that careful attention would be particularly needed for groups of inexperienced Japanese high school players. Our study suggests that we should consider introducing rules that prohibit "head-on collisions" in youth rugby.

Published
2020
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8. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism

Author

Tatsuya Tamura, Hiroshi Noda, Eri Joyashiki, Maiko Hoshino, Tomoyuki Watanabe, Masahiko Kinosaki, Yoshikazu Nishimura, Tohru Esaki, Kotaro Ogawa, Taiji Miyake, Shinichi Arai, Masaru Shimizu, Hidetomo Kitamura, Haruhiko Sato, and Yoshiki Kawabe

Subjects
Science
Abstract

Hypoparathyroidism and osteoporosis can be treated with parathyroid hormone, but frequent injections are required. Here the authors develop a small-molecule agonist for the parathyroid hormone type I receptor that can be administered orally, and demonstrate its efficacy in rats.

Published
2016
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10. The Influence of Age on the Outcomes of Traumatic Brain Injury: Findings from a Japanese Nationwide Survey (J-ASPECT Study-Traumatic Brain Injury)

Author

Takigami, Masayoshi, Kamiyama, Kenji, Houkin, Kiyohiro, Nishi, Shougo, Yoshimoto, Tetsuyuki, Kaneko, Sadao, Oka, Koji, Ooyama, Hiroshi, Kamada, Kyousuke, Makino, Kenichi, Tokumitsu, Naoki, Sako, Kazuhiro, Suzuki, Susumu, Suzuki, Nozomi, Izumi, Naoto, Nitta, Kazumi, Ootaki, Masahumi, Isobe, Masanori, Nishiya, Mikio, Yamazaki, Takaaki, Mabuchi, Syouji, Ogasawara, Kuniaki, Kubo, Naohiko, Shimizu, Yukihiko, Saito, Keiichi, Yamanome, Tatumi, Yoshino, Atsuo, Fujitsuka, Mitsuyuki, Takami, Masaaki, Ohtaka, Hirotoshi, Hirano, Teruyuki, Shiokawa, Yosiaki, Okada, Takaharu, Suzuki, Ichiro, Kohno, Michihiro, Haraoka, Jou, Arai, Yoshinori, Kawamura, Noriyoshi, Isoshima, Akira, Yasue, Masaharu, Takayoshi Kobayashi, Mitsuhiko Hokari, Kawai, Kensuke, Maehara, Taketoshi, Arai, Hajime, Noguchi, Makoto, Hoshino, Haruhiko, Hiyama, Hirofumi, Yoshida, Kensaku, Utsugi, Osamu, Takeda, Yasuaki, Tamaki, Kouichi, Karasudani, Hirohide, Urabe, Takao, Kobayashi, Shiro, Nakamura, Michio, Koguchi, Yorio, Ono, Junichi, Suda, Sumio, Hadeishi, Hiromu, Fukutake, Toshio, Wakui, Kenji, Tanno, Hirokazu, Ishige, Naoki, Ohasi, Takashi, Sakai, Hideki, Nishimura, Yasuaki, Watanabe, Takayuki, Matsumoto, Takashi, Koketsu, Naoki, Hirose, Yuichi, Doyu, Manabu, Hasegawa, Toshinori, Kuwayama, Naoto, Terao, Shinichi, Mizutani, Nobuhiko, Suzaki, Noriyuki, Okuda, Satoshi, Yasui, Keizo, Seki, Yukio, Hasegawa, Yasuhiro, Ikeda, Akira, Takeuchi, Youtarou, Ohara, Sigeki, Araki, Yoshio, Wakabayashi, Toshihiko, Tanaka, Hisashi, Yoshimoto, Junpei, Sugiura, Makoto, Koichiro, Ogura, Kobayashi, Nozomu, Yamada, Tomonori, Kato, Amami, Toshiho, Ohtsuki, Wakayama, Akatsuki, Takahashi, Jun, Kataoka, Hiroharu, Yoshimine, Toshiki, Nakajima, Yoshikazu, Gi, Hidehuku, Uranishi, Ryunosuke, Nakamura, Yusaku, Yamanaka, Kazunori, Ohmori, Kazumi, Matsumoto, Hiroyuki, Oiwa, Yoshitugu, Uemura, Yosihiko, Fujiwara, Hiroaki, Iwai, Yoshiyasu, Morikawa, Masashi, Tane, Kazuyuki, Hashikawa, Kazuo, Fujinaka, Toshiyuki, Yoneda, Shunichi, Yamashita, Kohsuke, Kitano, Masahiko, Tominaga, Shinsuke, Nakamura, Kazuhito, Kono, Katsuhiko, Ohata, Kenji, Taniguchi, Hirokatsu, Hazama, Takanori, Kuroiwa, Toshihiko, Tamura, Yoji, Maeno, Kazusige, Arai, Motohiro, Iwase, Masaaki, Hashimoto, Kenji, Yamada, Keisuke, Turuno, Takashi, Ichinose, Tsutomu, Kurokawa, Shinichiro, Matsuyama, Takeshi, Fujita, Toshiaki, Yuguchi, Takamichi, Teramoto, Yoshihumi, Kakita, Hiroto, Matsuo, Takayuki, Izumo, Tsuyoshi, Ryu, Nobutoshi, Naoki Kitagawa, Wataru Haraguchi, Kaminogo, Makio, Sakamoto, Seisaburo, Tokunaga, Yosiharu, Urasaki, Ei-Ichirou, Kuratsu, Junichi, Takada, Akira, Terasaki, Tadashi, Hisami Oosima, Isao Fuwa, Yamashiro, Shigeo, Hiromasa Tsuiki, Makoto Yoshikawa, Koga, Kazunari, Egami, Hiroshi, Kawamura, Tadao, Mitsuo, Kunihiko, Masaki Morisige, Takamitu Hikawa, Takeda, Yuu, Yamaguchi, Yutaka, Shunro Uchinokura, Shiro Miyata, Goya, Tomokazu, Takeshima, Hideo, Yatsushiro, Kazutaka, Ohta, Hajime, Nagadou, Tatsui, Hirahara, Kazuho, Obara, Souichi, Seto, Hiroshi, Moroki, Koiti, Arita, Kazunori, Ishiuchi, Shogo, Uchihara, Toshimitsu, Mekaru, Susumu, Nagamine, Tomoaki, Jin Momoji, Naoki Tomiyama, Atusi Kimoto, Kouzi Idomari, Kadekaru, Tsutomu, Syamoto, Hirosi, Sasaki, Osamu, Minagawa, Makoto, Takahashi, Hideaki, Hiroyuki Arai, Kiyoshi Onda, Takeuchi, Shigekazu, Abe, Hiroshi, Fukuda, Osamu, Kouno, Mitsuo, Tamura, Tetsuro, Michiya Kubo, Yukio Horie, Hondo, Hiroaki, Takada, Hisashi, Masuoka, Toru, Shirasaki, Naoki, Nitta, Hisashi, Yasuo Katsuki, Makoto Kimura, Hisato Minamide, Yutaka Hayashi, Munemoto, Shigeru, Ikeda, Kiyonobu, Yutaka Hayashi, Mitsutoshi Nakada, Sato, Syuji, Hatano, Taketo, Yamamura, Osamu, Kabuto, Masanori, Jyunya Hayashi, Takahiro Sakuma, Kinouchi, Hiroyuki, Koizumi, Hidehito, Imae, Syougo, Fujita, Manabu, Suga, Masakazu, Kanehisa Kohno, Shinji Iwata, Zenke, Kiichiro, Fujisawa, Mutsuo, Mizobuchi, Hikaru, Hayashi, Satoru, Morimoto, Masanori, Ueba, Tetsuya, Nishimura, Hiroyuki, Ikawa, Naoki, Matsumoto, Yuzo, Kannuki, Seiji, Kagawa, Masahiro, Hayashi, Naoki, Atsushi Shindo, Takashi Tamiya, Yoshino, Kimihiro, Masaoka, Tetsuya, Nakahara, Ichiro, Satoshi Suzuki, Akira Nakamizo, Okamoto, Yuji, Takahashi, Haruki, Iihara, Koji, Hirakawa, Katsuyuki, Nagata, Shinji, Ookura, Akio, Yoshiro Kaneko, Hidenori Yoshida, Nakane, Hiroshi, Inoue, Isao, Hitotsumatsu, Tsutomu, Kouichi Kuramoto, Terukazu Kuramoto, Hiromichi Ooishi, Yoshihisa Matumoto, Masani Nonaka, Tooru Inoue, Morioka, Motohiro, Shuji Sakata, Hiroshi Sugimori, Takashima, Hiroshi, Ishihara, Shin-Ichiro, Suzuyama, Kenji, Miyazono, Masayuki, Itaro Hattori, Masafumi Morimoto, Ozaki, Satoshi, Hirota, Nobuo, Yasuhiko Mochimatsu, Yasunori Takemoto, Takagi, Makoto, Kenji Nakayama, Isao Yamamoto, Hiroshi Tanaka, Yoshinori Uchida, Sakata, Katsumi, Nobutaka, Kawahara, Nomura, Motohiro, Ozawa, Hitoshi, Tsumura, Kotaro, Michiyuki Maruyama, Makoto Inaba, Mori, Tatsuro, Mori, Takahisa, Sugitani, Masato, Tanaka, Yuichiro, Yamada, Masaru, Matsumae, Mitsunori, Onitsuka, Keiichirou, Tatsuya Takahashi, Kosuke Miyahara, Endou, Sumio, Takahashi, Hidekazu, Kaidu, Hiroyuki, Chikashi Maruki, Akira Tsunoda, Fujimaki, Takamitsu, Ooigawa, Hidetoshi, Masatsugu Uchida, Masahiko Tanaka, Kouiti Katoh, Hiroshi Wanihuti, Hyodo, Akio, Asakura, Ken, Nakajima, Shigeyoshi, Kanzawa, Takao, Kurihara, Hideyuki, Ohmori, Sigehiro, Hiroshi Kusunoki, Mitsugi Yoshinao, Magarisawa, Satoshi, Okabe, Shinichi, Kujiraoka, Yuuji, Tsuruoka, Shin, Takeshita, Mikihiko, Akira Matsumura, Tetsuya Yamamoto, Uemura, Kazuya, Tabata, Hitoshi, Sonobe, Makoto, Ryoji Yoshida, Masashi Nakatsukasa, Shimoeda, Norifumi, Kunimine, Hideo, Ishihara, Masayuki, Murai, Nozomu, Murakami, Nobukuni, Kidooka, Minoru, Iwamoto, Yoshihiro, Tenjin, Hiroshi, Masahiko Takamasu, Kouji Shiga, Mori, Nobuhito, Kose, Shigeru, Kohmura, Eiji, Matsumoto, Keigo, Sakaki, Takayuki, Miyake, Hiroji, Mabuchi, Eiichiro, Yokota, Masayuki, Yosihiro Kuga, Hideyuki Ohnishi, Kimura, Mitsuru, Masaaki Saiki, Osamu Narumi, Nakajima, Norio, Asahi, Minoru, Koyama, Junji, Noda, Shinya, Iida, Junichi, Fujita, Toyohisa, Nakase, Hiroyuki, Toru Hoshida, Hidehiro Hirabayashi, Fujimoto, Takayoshi, Nakao, Naoyuki, Tanaka, Yoshiyuki, Ozaki, Fuminori, Nakamura, Yoshinari, Miki, Kazuhito, Watanabe, Takashi, Hasegawa, Seiko, Konno, Hiromu, Takemura, Atsuhito, Okubo, Atsuya, Saito, Hitoshi, Taizen Nakase, Tatsuya Ishikawa, Toshio Sasajima, Hiroaki Shimizu, Sasou, Masayuki, Watanabe, Yoichi, Kiyoshi Saito, Taku Sato, Masahiro Satoh, Satoshi Taira, Koizumi, Takayuki, Shoji Mashiyama, Yasuhiro Suzuki, Oikawa, Tomoyoshi, Sonoda, Yukihiko, Shinjiro Saito, Rei Kondo, Shinoda, Atsuo, Kamatsuka, Eiichiro, So, Keiten, Kinjo, Toshihiko, Kennji Itou, Tooru Sasaki, Hiroaki Shimizu, Hidenori Endo, Karibe, Hirosi, Takahashi, Kou, Nakajima, Masayuki, Watanabe, Kazuyoshi, Takayama, Motohiro, Komuro, Taro, Fumio Suzuki, Hisao Hirai, Suzuki, Hidenori, Murata, Hiroto, Miya, Fumitaka, Kanamaru, Kenji, Tamura, Akira, Harada, Kiyoshi, Fukazawa, Seiji, Takehara, Seiya, Watanabe, Yoshihiko, Nakayama, Teiji, Hiroshi Nagura, Haruhiko Sato, Chiharu Tanoi, Shinji Amano, Kuroda, Katsuhiro, Morooka, Satoru, Masashi Kitagawa, Takafumi Wataya, Koide, Kazuo, Tanigawara, Tetsuya, Iwama, Toru, Ito, Junki, Noda, Shinji, Kouno, Kazuyuki, Kitazawa, Kazuo, Toshiki Takemae, Yoshikazu Kusano, Hokama, Masanobu, Yoshihisa Nishiyama, Hiroki Sato, Seguchi, Tatsuya, Yoshihiko Inui, Sumio Kobayashi, Oohigashi, Youji, Muraoka, Shinsuke, Miyatake, Masaki, Nakagawa Shinichi, Kensuke Hayashida, Inoue, Atsushi, Sakai, Keiichi, Yamaguchi, Shuhei, Fusao Ikawa, Tatsuya Mizoue, Hideki Irie, Gen Ishida, Kagawa, Takato, Namba, Yoichiro, Nakashima, Hiroyuki, Koji Abe, Isao Date, Uno, Masaaki, Sen Yamagata, Masaki Chin, Soitiro Takao, Hidemiti Sasayama, Kouji Muneda, Hideyuki Yoshida, Watanebe, Akira, Katou, Syouichi, Hamada, Yasuhiro, Suzuki, Michiyasu, Nishizaki, Takafumi, Yamashita, Katsuhiro, Ryuji Nakamura, Takaharu Nakamura, Wakabayashi, Shinichi, Okazaki, Takahito, Kurisu, Kaoru, Matsumoto, Masayasu, Katsuzo Kiya, Atsushi Tominaga, Syuichi Oki, Masaaki Shibukawa, Nakahara, Toshinori, Okita, Shinji, Torii, Tuyosi, Kenjirou Fujiwara, Minoru Nakagawa, Syuuhei Nishimura, Takashi Matsuoka, Naoyuki Isobe, Osamu Hamasaki, Shinji Nagahiro, Junichiro Satomi, Agawa, Masahito, Oka, Hirofumi, Yoshimura, Kunikazu, Kato, Tsutomu, Satoshi Minoshima, Nobuaki Kobayasi, Mikuni, Nobuhiro, Tanikawa, Rokuya, Sasaki, Jyunkou, Otawara, Yasunari, Tominaga, Teiji, Sasaki, Tatsuya, Takemura, Sunao, Kawakami, Masahisa, Ihara, Satoshi, Shibata, Yasushi, Saegusa, Takashi, Iuchi, Toshihiko, Ito, Chiaki, Okuda, Osamu, Yoshida, Kazunari, Masateru Katayama, Sadao Suga, Akihiro, Oikawa, Miura, Naohisa, Ota, Takahiro, Kumabe, Toshihiro, Suzuki, Sachio, Kumagai, Takashi, Nishimaki, Keiichi, Hongo, Kazuhiro, Shigeta, Hiroaki, Hattori, Kazuyoshi, Uozumi, Yoichi, Nakahara, Norimoto, Hashimoto, Nobukazu, Shu Imai, Shinichi Shirakami, Okumura, Yoshinari, Kazuhiro Yokoyama, Ryo Tamaki, Miyamoto, Susumu, Yamamoto, Kazuo, Ichioka, Tsugumichi, Inoue, Tsuyoshi, Kinoshita, Manabu, Saitoh, Minoru, Aihara, Hideo, Miyake, Hajimu, Tukasa Nishiura, Kotaro Ogihara, Nishino, Shigeki, Miyoshi, Yasuyuki, Arisawa, Tadashi, Shoji Tsuchimoto, Shigeru Daido, Kinoshita, Kimihisa, Keisuke Migita, Kiyoshi Yuki, Akatsuka, Keiichi, Fujisawa, Hirosuke, Shono, Tadahisa, Tsugu, Hitoshi, Hayashi, Shuji, Toshio Matsushima, Tatsuya Abe, Nakashima, Susumu, Tuji, Takehisa, Kaga, Akihiko, Kanemaru, Reizou, Takasaki, Koji, Imamura, Junichi, Noha, Masahiro, Watanabe, Saburo, Sakai, Nobuyuki, Hiroaki Minami, Yasuhisa Yoshida, Okumura, Tomoyoshi, Nishimura, Shinjitsu, Numazawa, Shinichi, Masanori Tsutsumi, Kiyoshi Kazekawa, Fukuyama, Kouzou, Fujimoto, Yasuhiro, Yamagami, Keitaro, Kurogi, Ryota, Kurogi, Ai, Nishimura, Kunihiro, Onozuka, Daisuke, Ren, Nice, Kada, Akiko, Nishimura, Ataru, Arimura, Koichi, Ido, Keisuke, Mizoguchi, Masahiro, Sakamoto, Tetsuya, Kayama, Takamasa, and Hagihara, Akihito

Published
2019
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17. Use of the reliable change index to evaluate the effect of a multicomponent exercise program on physical functions

Author

Haruhiko Sato, Masanori Wakida, Ryo Kubota, Takayuki Kuwabara, Kimihiko Mori, Tsuyoshi Asai, Yoshihiro Fukumoto, Jiro Nakano, and Kimitaka Hase

Subjects
Aging, Humans, Muscle Strength, Walking, Geriatrics and Gerontology, Postural Balance, Gait, Aged, Exercise Therapy
Abstract

Using the reliable change index (RCI), we aimed to examine the effect of a multicomponent exercise program on the individual level.Overall, 270 adults (mean age, 78 years) completed a multicomponent physical exercise program (strength, aerobic, gait, and balance) for 40 min, 1-2 times per week, continued up to 1 year at a daycare center. Effectiveness was assessed using grip, ankle, knee, and hip strength; Timed UpGo (TUG); Berg Balance Scale (BBS); gait speed; and 6-min walking distance. These were measured at baseline and every 3 months thereafter. We calculated the RCI using the data between two-time points (baseline and at 3, 6, 9, or 12 months) in each participant and then calculated the mean RCI value across the participants. A paired t-test was also employed to evaluate the effect of the intervention as an average-based statistics.The highest mean RCI values were on ankle plantar-flexion strength, followed by gait speed, hip abduction strength, BBS, knee extensor strength, 6-min walk distance, grip strength, and finally TUG. Paired t-test also revealed significant improvement with moderate effect sizes for ankle plantar-flexion strength (0.504), gait speed (0.413), hip abduction strength (0.374), BBS (0.334), knee extensor strength (0.264), and 6-min walk distance (0.248). Significant but small effect size was seen on TUG (0.183).The RCI is a convenient method of comparing the effect between different assessments, especially at an individual level. This index can be applied to the use of personal feedback.

Published
2022
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26. Data from YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification

Author

Toshiyuki Mio, Nobuya Ishii, Haruhiko Sato, Hiroshi Koyano, Hirosato Ebiike, Kiyomoto Ogasawara, Kiyoaki Sakata, Toshihiko Fujii, Yukako Tachibana, Yasuko Satoh, Masami Hasegawa, Hiromi Tanimura, Nukinori Akiyama, Kana Horiguchi-Takei, Takakazu Mizuno, Yoshito Nakanishi, and Natsuki Hamanaka

Abstract

Targeting genetic alterations of oncogenes by molecular-targeted agents (MTA) is an effective approach for treating cancer. However, there are still no clinical MTA options for many cancers, including esophageal cancer. We used a short hairpin RNA library to screen for a new oncogene in the esophageal cancer cell line KYSE70 and identified YES proto-oncogene 1 (YES1) as having a significant impact on tumor growth. An analysis of clinical samples showed that YES1 gene amplification existed not only in esophageal cancer but also in lung, head and neck, bladder, and other cancers, indicating that YES1 would be an attractive target for a cancer drug. Because there is no effective YES1 inhibitor so far, we generated a YES1 kinase inhibitor, CH6953755. YES1 kinase inhibition by CH6953755 led to antitumor activity against YES1-amplified cancers in vitro and in vivo. Yes-associated protein 1 (YAP1) played a role downstream of YES1 and contributed to the growth of YES1-amplified cancers. YES1 regulated YAP1 transcription activity by controlling its nuclear translocation and serine phosphorylation. These findings indicate that the regulation of YAP1 by YES1 plays an important role in YES1-amplified cancers and that CH6953755 has therapeutic potential in such cancers.Significance:These findings identify the SRC family kinase YES1 as a targetable oncogene in esophageal cancer and describe a new inhibitor for YES1 that has potential for clinical utility.See related commentary by Rai, p. 5702

Published
2023
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27. Supplementary Table S4 from YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification

Author

Toshiyuki Mio, Nobuya Ishii, Haruhiko Sato, Hiroshi Koyano, Hirosato Ebiike, Kiyomoto Ogasawara, Kiyoaki Sakata, Toshihiko Fujii, Yukako Tachibana, Yasuko Satoh, Masami Hasegawa, Hiromi Tanimura, Nukinori Akiyama, Kana Horiguchi-Takei, Takakazu Mizuno, Yoshito Nakanishi, and Natsuki Hamanaka

Abstract

Anti-proliferative activity against KYSE70 expressing mock, YES1-WT and SRC-WT

Published
2023
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29. Supplementary FigureS1, S2, S3, S4, S5, S6, S7, S8, S9 from YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification

Author

Toshiyuki Mio, Nobuya Ishii, Haruhiko Sato, Hiroshi Koyano, Hirosato Ebiike, Kiyomoto Ogasawara, Kiyoaki Sakata, Toshihiko Fujii, Yukako Tachibana, Yasuko Satoh, Masami Hasegawa, Hiromi Tanimura, Nukinori Akiyama, Kana Horiguchi-Takei, Takakazu Mizuno, Yoshito Nakanishi, and Natsuki Hamanaka

Abstract

Supplementary Figure S1. YES1 gene is amplified and YES1 expression is related to poor prognosis in esophageal cancer and lung cancer in clinical. Supplementary Figure S2. YES1 gene amplification including the upregulation of YES1 expression. Supplementary Figure S3. Cell growth inhibition profile of various molecular targeted agents. Supplementary Figure S4. Antiproliferative activity of dasatinib against cancer cell lines expressing YES1-WT or YES1-GK. Supplementary Figure S5. The contribution of SFK other than YES1 in YES1-amplified cancer cell lines. Supplementary Figure S6. The antitumor activity of dasatinib against YES1-amplified xenograft tumor. Supplementary Figure S7. Dasatinib inhibited YAP1 downstream signal via YES1 kinase inhibition against YES1-amplified cancer cell. Supplementary Figure S8. YAP1 and DAPI staining in treatment with CH6953755. Supplementary Figure S9. YAP1 localization change in xenograft tumor tissue by CH6953755 treatment.

Published
2023
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44. A Case of Acute Embolism of the Accessory Middle Cerebral Artery Treated Using ADAPT Thrombectomy without Lesion Passing

Author

Satoru Kida, Hiroaki Kenmochi, Souichi Akamine, Haruhiko Sato, Tomoya Arakawa, Hisaya Hiramatsu, and Hiroyasu Sano

Subjects
medicine.medical_specialty, business.industry, Case Report, medicine.disease, Lesion, Embolism, thrombectomy, medicine.artery, Middle cerebral artery, cardiovascular system, accessory middle cerebral artery, medicine, Radiology, ADAPT, medicine.symptom, business
Abstract

An accessory middle cerebral artery (AMCA) is a variant vessel that branches from the anterior cerebral artery (ACA) and runs through the Sylvian fissure along the middle cerebral artery (MCA). We report a case of acute embolic occlusion of the AMCA that was treated with thrombectomy using direct aspiration first pass technique (ADAPT). An 88-year-old woman with a history of atrial fibrillation, loss of consciousness, and right hemiparesis was referred to our hospital. Diffusion-weighted magnetic resonance imaging (MRI) showed high signal intensity in the left frontal lobe, insular cortex, and deep white matter, and magnetic resonance angiography (MRA) demonstrated left internal carotid artery (ICA) occlusion. Mechanical thrombectomy using the ADAPT technique was performed with complete recanalization. Final angiography revealed left ACA and AMCA because of the thrombus located at the origin of the left ACA and AMCA. In the case of an acute ischemic stroke associated with AMCA, it is difficult to understand and recognize the anatomy of the vessel before thrombectomy. Therefore, the ADAPT technique, which can treat acute embolic occlusion without lesion passing, is recommended due to its safety. If there is a mismatch between the perfusion area of the occluded artery and the ischemic area or the neurological findings before thrombectomy, it is extremely important to keep in mind the presence of vessel variation in the MCA.

Published
2021
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46. Longitudinal effects of physical exercise on health-related outcomes based on frailty status in community-dwelling older adults

Author

Masanori Wakida, Tsuyoshi Asai, Ryo Kubota, Takayuki Kuwabara, Yoshihiro Fukumoto, Haruhiko Sato, Jiro Nakano, Kimihiko Mori, Tome Ikezoe, and Kimitaka Hase

Subjects
Frailty, Frail Elderly, Humans, General Medicine, Independent Living, Exercise, Geriatric Assessment, Aged, Exercise Therapy
Abstract

To clarify the difference in the longitudinal effects of physical exercise on health-related outcomes according to the baseline frailty status (frail or non-frail) in community-dwelling older adults.Participants included 177 adults aged ≥65 years who carried out multicomponent physical exercises (strength, aerobic, gait and balance) for 40 min, one to three times per week, for 1 year at a day-care center. Bodyweight, comfortable walking speed, 6-min walking distance and Mini-Mental State Examination were measured at baseline and every 3 months. For longitudinal trend, we analyzed the change in scores from baseline for each outcome using the linear mixed effects model. Fixed effects included "group" (frail or non-frail), "time" (4 time points every 3 months, from 3 to 12 months) and "interaction between group and time."The effect sizes from baseline showed almost all positive values for each outcome. The linear mixed effects model showed significant effects on "interaction between group and time" in changes in bodyweight (P = 0.033), "group" in changes in walking speed (P = 0.013) and "time" in changes in the Mini-Mental State Examination (P 0.001). Bodyweight showed a decreasing trend in the non-frail group after 3 months, unlike in the frail group. For walking speed, moderate effect sizes (d = 0.67-0.74) were sustained over time in the frail group, as did lesser effect sizes (d = 0.26-0.40) in the non-frail group.Exercise-based multicomponent interventions were effective for both groups. The longitudinal effects on walking speed and bodyweight were greater in the frail group. Geriatr Gerontol Int 2022; 22: 213-218.

Published
2021

47. Lead Optimization and Avoidance of Reactive Metabolite Leading to PCO371, a Potent, Selective, and Orally Available Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist

Author

Yoshiaki Watanabe, Haruhiko Sato, Hidetomo Kitamura, Tomoya Kotake, Yoshikazu Nishimura, Masaru Shimizu, Takashi Emura, Kotaro Ogawa, Toru Esaki, Toshito Nakagawa, Akemi Mizutani, Yoshiyuki Furuta, Shinichi Arai, Hiroshi Noda, Masateru Ohta, Tatsuya Tamura, and Yoshiaki Isshiki

Subjects
Agonist, Hypoparathyroidism, Swine, medicine.drug_class, Administration, Oral, Parathyroid hormone, Pharmacology, Imidazolidines, Rats, Sprague-Dawley, chemistry.chemical_compound, Oral administration, Drug Discovery, medicine, Animals, Humans, Spiro Compounds, Receptor, Receptor, Parathyroid Hormone, Type 1, Sulfonyl, chemistry.chemical_classification, Rats, chemistry, Hormone receptor, Microsome, LLC-PK1 Cells, Molecular Medicine, Female, Lead compound
Abstract

We have previously shown that the oral administration of the small molecule hPTHR1 agonist PCO371 and its lead compound, 1 (CH5447240) results in PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. However, 1 was converted to a reactive metabolite in a human liver microsome assay. In this article, we report on the modification path that led to an enhancement of PTHR1 agonistic activity and reduction in the formation of a reactive metabolite to result in a potent, selective, and orally active PTHR1 agonist 1-(3,5-dimethyl-4-(2-((4-oxo-2-(4-(trifluoromethoxy)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-8-yl)sulfonyl)ethyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione (PCO371, 16c). This compound is currently being evaluated in a phase 1 clinical study for the treatment of hypoparathyroidism.

Published
2020
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48. YES1 Is a Targetable Oncogene in Cancers Harboring YES1 Gene Amplification

Author

Kiyomoto Ogasawara, Natsuki Hamanaka, Nukinori Akiyama, Takakazu Mizuno, Toshiyuki Mio, Toshihiko Fujii, Hirosato Ebiike, Kiyoaki Sakata, Hiroshi Koyano, Hiromi Tanimura, Masami Hasegawa, Nobuya Ishii, Kana Horiguchi-Takei, Yukako Tachibana, Haruhiko Sato, Yoshito Nakanishi, and Yasuko Satoh

Subjects
0301 basic medicine, YAP1, Cancer Research, YES1, Oncogene, Kinase, business.industry, Esophageal cancer, medicine.disease, Small hairpin RNA, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Cancer research, medicine, Src family kinase, business, Proto-oncogene tyrosine-protein kinase Src
Abstract

Targeting genetic alterations of oncogenes by molecular-targeted agents (MTA) is an effective approach for treating cancer. However, there are still no clinical MTA options for many cancers, including esophageal cancer. We used a short hairpin RNA library to screen for a new oncogene in the esophageal cancer cell line KYSE70 and identified YES proto-oncogene 1 (YES1) as having a significant impact on tumor growth. An analysis of clinical samples showed that YES1 gene amplification existed not only in esophageal cancer but also in lung, head and neck, bladder, and other cancers, indicating that YES1 would be an attractive target for a cancer drug. Because there is no effective YES1 inhibitor so far, we generated a YES1 kinase inhibitor, CH6953755. YES1 kinase inhibition by CH6953755 led to antitumor activity against YES1-amplified cancers in vitro and in vivo. Yes-associated protein 1 (YAP1) played a role downstream of YES1 and contributed to the growth of YES1-amplified cancers. YES1 regulated YAP1 transcription activity by controlling its nuclear translocation and serine phosphorylation. These findings indicate that the regulation of YAP1 by YES1 plays an important role in YES1-amplified cancers and that CH6953755 has therapeutic potential in such cancers. Significance: These findings identify the SRC family kinase YES1 as a targetable oncogene in esophageal cancer and describe a new inhibitor for YES1 that has potential for clinical utility. See related commentary by Rai, p. 5702

Published
2019
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49. Setting pressure can change the size and shape of MRI artifacts caused by adjustable shunt valves: a study of the 4 newest models

Author

Haruhiko Sato, Tokutaro Tanaka, Teiji Nakayama, Yuki Amano, Daiki Uchida, Naoto Ando, Takayuki Masui, Tetsuro Sameshima, and Hirokazu Nakatogawa

Subjects
Scanner, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, equipment and supplies, Temporal scalp, 03 medical and health sciences, 0302 clinical medicine, Body axis, 030220 oncology & carcinogenesis, Healthy volunteers, Magnetic components, Medicine, business, 030217 neurology & neurosurgery, Shunt valve, Shunt (electrical), Biomedical engineering
Abstract

OBJECTIVEAdjustable shunt valves that have been developed for the management of hydrocephalus all rely on intrinsically magnetic components, and artifacts with these valves on MRI are thus inevitable. The authors have previously reported that the shapes of shunt artifacts differ under different valve pressures with the proGAV 2.0 valve. In the present study the authors compared the size and shape of artifacts at different pressure settings with 4 new-model shunt valves.METHODSThe authors attached 4 new models of MRI-resistant shunt valve to the temporal scalp of a healthy volunteer: the proGAV 2.0; Codman Certas Plus; Polaris; and Strata MR. They set 3 different scales of pressures for each valve, depending on magnet orientation to the body axis. Artifacts were evaluated and compared among all valves on a 3.0-T GE scanner and 2 valves were also evaluated on a Philips scanner and a Siemens scanner. In-plane artifact sizes were evaluated as the maximum distance of the artifact from the expected scalp.RESULTSThe sizes and shapes of artifacts changed depending on valve pressure for all valves on the 3 different MRI scanners. Artifacts were less prominent on spin echo sequences than on gradient echo sequences. For diffusion-weighted imaging and time-of-flight MR angiography, the authors matched image numbers within the same sequence and compared appearances of artifacts. For all valves, the number of images affected by artifacts and the image number showing the largest artifact differed among valve settings.CONCLUSIONSArtifacts of all adjustable shunt valves showed gross changes corresponding to pressure setting. Not only the maximum distance of artifacts but also the shape changed significantly. The authors suggest that changing pressure settings offers one of the easiest ways to minimize artifacts on MRI.

Published
2019
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50. Relationship between static balance and gait parameters in preschool children

Author

Haruhiko Sato, Yuko Nomura, and Kanami Kamide

Subjects
Male, Child, Preschool, Rehabilitation, Biophysics, Humans, Orthopedics and Sports Medicine, Female, Gait, Postural Balance
Abstract

Postural sway while standing reflects the degree of sensory integration function. The relationship between static balance and gait parameters in preschool children is essential for understanding which component of gait function is linked to the sensory integration function.We aimed to clarify the relationship between static balance and gait in children, aged 2-6 years, with typical development METHODS: A total of 105 children (48 girls, 57 boys) participated in this study. Static balance parameters were computed using positions at the center of pressure (COP) while standing (COP length, velocity, and sway area). Spatiotemporal parameters during gait were analyzed for stride length, step width, stance time, cadence, coefficient of variation (CV) of step length, and CV of stance time as gait variability. Pearson correlation coefficients were estimated to explore the relationship between age and static balance or gait parameters. Partial correlation analysis controlling for age was also performed to examine the relationship between static balance and gait parameters.A moderate association between age and static balance parameters and between age and gait parameters was found. Partial correlation analysis revealed that the variability parameters of gait were associated with the static balance parameters. No relationship was found between both spatial and temporal gait parameters and static balance parameters.Among the gait parameters that are considered to develop in early childhood, gait variability was associated with COP sway while standing, whereas stride length with increasing age was independent of any static balance parameters. Of the spatial, temporal, and variability parameters of gait, only gait variability maybe associated with the development of sensory integration function.

Published
2021

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