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Article ; Online: Parkinson' s disease complicated after 12 years from the onset of multiple sclerosis.

Shindo, Kazumasa / Morishima, Yuto / Hata, Takanori / Nakajima, Sho / Ueno, Yuji

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2023 Volume 45, Issue 4, Page(s) 1775–1778

MeSH term(s)	Humans ; Parkinson Disease/complications ; Multiple Sclerosis/complications
Language	English
Publishing date	2023-11-16
Publishing country	Italy
Document type	Letter
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-023-07201-0
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Article ; Online: 224-Gbit/s 4-PAM operation of a high-modulation-bandwidth high-output-power Hi-FIT AXEL transmitter.

Kanazawa, Shigeru / Shindo, Takahiko / Chen, Mingchen / Nakanishi, Yasuhiko / Nakamura, Hirotaka / Matsuzaki, Hideaki

Optics letters

2022 Volume 47, Issue 12, Page(s) 3019–3022

Abstract: ... integrated distributed feedback (EADFB) laser (AXEL) for 200-Gbit/s/λ application. The Hi-FIT makes ... than 66 GHz. We obtained clear 224-Gbit/s 4-level pulse amplitude modulation (4-PAM) eye diagrams ...

Abstract	We fabricated an optical transmitter with high frequency and integrated design based on the flip-chip interconnection technique (Hi-FIT) and assisted extended reach electroadsorption modulator integrated distributed feedback (EADFB) laser (AXEL) for 200-Gbit/s/λ application. The Hi-FIT makes it possible to increase modulation bandwidth thanks to wire-free interconnection and peaking control techniques while the AXEL can increase the optical modulation output power thanks to an integrated semiconductor optical amplifier (SOA). The fabricated Hi-FIT AXEL transmitter has a 3-dB bandwidth of more than 66 GHz. We obtained clear 224-Gbit/s 4-level pulse amplitude modulation (4-PAM) eye diagrams with a chip-output optical modulation amplitude (OMA) of more than +7.9 dBm at distributed feedback (DFB) laser and SOA currents of 70 and 30 mA, respectively.
Language	English
Publishing date	2022-06-16
Publishing country	United States
Document type	Journal Article
ISSN	1539-4794
ISSN (online)	1539-4794
DOI	10.1364/OL.457568
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Article ; Online: Clinical outcomes of second‑line chemotherapy after gemcitabine and cisplatin plus S‑1 treatment for patients with advanced biliary tract cancer in the KHBO1401‑3A study.

Shindo, Yoshitaro / Nagano, Hiroaki / Kanai, Masashi / Kobayashi, Shogo / Wada, Hiroshi / Sakai, Daisuke / Eguchi, Hidetoshi / Baba, Hideo / Kamachi, Hirofumi / Takayama, Tadatoshi / Ueno, Masaki / Takahashi, Masahiro / Nakagami, Yuki / Yoshimura, Kenichi / Hatano, Etsuro / Ioka, Tatsuya

Oncology reports

2023 Volume 49, Issue 2

Abstract: ... of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S‑1 (GCS), GCS has become a standard chemotherapy ... chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S‑1 (GS) (n=4) and S‑1 (n=18). The 6‑ and 12 ...

Abstract	Since the completion of the KHBO1401 study, which evaluated the efficacy of the combination of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S‑1 (GCS), GCS has become a standard chemotherapy for patients with advanced biliary tract cancer (BTC). However, there are currently no data revealing second‑line therapy options after GCS. The present study aimed to evaluate the survival outcomes of patients receiving second‑line chemotherapy for advanced BTC, refractory or intolerant to GCS, using data from the KHBO1401 study. Patients who received a second‑line treatment after GCS chemotherapy between July 2014 and February 2016 were retrospectively studied. Overall survival (OS) was calculated from the day of GCS treatment failure or the first day of second‑line chemotherapy to the final follow‑up date or until death from any cause. Among 83 patients refractory or intolerant to GCS chemotherapy, 51 (61%) received second‑line chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S‑1 (GS) (n=4) and S‑1 (n=18). The 6‑ and 12‑month OS rates were 66.7 and 44.4%, respectively, following second‑line chemotherapy, and 6.3 and 3.1%, respectively, in the best supportive care group (P<0.0001). In addition, the 12‑ and 24‑month OS rates were 59.3 and 36.2%, respectively, in the multidrug chemotherapy group, and 26.9 and 9.0%, respectively, in the single‑agent chemotherapy group (P=0.0191). These results suggested that second‑line combination chemotherapy is a viable treatment option for patients with advanced BTC that is refractory or intolerant to first‑line GCS therapy.
MeSH term(s)	Humans ; Gemcitabine ; Cisplatin ; Deoxycytidine ; Retrospective Studies ; Biliary Tract Neoplasms/drug therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bile Duct Neoplasms/drug therapy ; Treatment Outcome
Chemical Substances	Gemcitabine ; Cisplatin (Q20Q21Q62J) ; Deoxycytidine (0W860991D6)
Language	English
Publishing date	2023-01-12
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2023.8478
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Zs.A 4213: Show issues

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Article: Deep sequencing analysis of serum hepatitis B virus-RNA during nucleot(s)ide analogue therapy.

Hepatology research : the official journal of the Japan Society of Hepatology

2021 Volume 51, Issue 1, Page(s) 39–50

Abstract: ... particle production is inhibited by nucleot(s)ide analogues (NAs). However, the dynamics of the HBV ...

Abstract	Aim: Recently, serum hepatitis B virus (HBV)-RNA has been reported to be detectable even when HBV particle production is inhibited by nucleot(s)ide analogues (NAs). However, the dynamics of the HBV-RNA sequence compared with those of HBV-DNA during the emergence of antiviral resistance are yet to be elucidated. Methods: First, we quantified serum HBV-RNA in 181 infected patients, and its relationships with clinical characteristics as well as HBV markers were investigated. Next, we undertook simultaneous deep sequencing of HBV-RNA/HBV-DNA and their dynamics among four patients receiving NA therapy who were experiencing viral breakthrough. Results: Serum HBV-RNA was detected in 25% (31/123) of cases among patients with HBV without NAs, and the detection rate was significantly high in hepatitis B e antigen-positive cases with high viral activity. In patients with chronic hepatitis, hepatitis B core-related antigen was significantly correlated with serum HBV-RNA irrespective of NA use. In the analysis of the four patients experiencing viral breakthrough, no NA resistance mutation was detected in the serum HBV-RNA immediately before the breakthrough. However, NA-resistant sequences appeared at the rates of 0%, 3%, 14%, and 100%, and the NA-resistant HBV-RNA sequence rate was correlated with the peak HBV-DNA titer multiplied by the HBV-DNA detection duration during the breakthrough (R Conclusion: Serum HBV-RNA could reflect the transcriptional activity of covalently closed circular DNA and hepatitis B core-related antigen. The dynamics of HBV-RNA could help understanding of the turnover process of HBV covalently closed circular DNA in the liver.
Language	English
Publishing date	2021-01-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1387041-5
ISSN	1386-6346 ; 0928-4346
ISSN	1386-6346 ; 0928-4346
DOI	10.1111/hepr.13574
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Zs.A 3826: Show issues

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Article ; Online: Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401- MITSUBA).

Journal of hepato-biliary-pancreatic sciences

2022 Volume 30, Issue 1, Page(s) 102–110

Abstract: ... adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve ...

Abstract	Background: Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials have been able to demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC. Methods: We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. The GCS regimen comprised gemcitabine (1000 mg/m Results: Between July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms. Conclusions: GCS is the first regimen which demonstrated survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.
MeSH term(s)	Humans ; Gemcitabine ; Cisplatin ; Biliary Tract Neoplasms/drug therapy ; Deoxycytidine/therapeutic use ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome
Chemical Substances	Gemcitabine ; Cisplatin (Q20Q21Q62J) ; Deoxycytidine (0W860991D6)
Language	English
Publishing date	2022-08-09
Publishing country	Japan
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article
ZDB-ID	2536236-7
ISSN	1868-6982 ; 1868-6974
ISSN (online)	1868-6982
ISSN	1868-6974
DOI	10.1002/jhbp.1219
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Zs.A 4024: Show issues

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Article ; Online: Quasifree Neutron Knockout Reaction Reveals a Small s-Orbital Component in the Borromean Nucleus ^{17}B.

Yang, Z H / Kubota, Y / Corsi, A / Yoshida, K / Sun, X-X / Li, J G / Kimura, M / Michel, N / Ogata, K / Yuan, C X / Yuan, Q / Authelet, G / Baba, H / Caesar, C / Calvet, D / Delbart, A / Dozono, M / Feng, J / Flavigny, F /

Gheller, J-M / Gibelin, J / Giganon, A / Gillibert, A / Hasegawa, K / Isobe, T / Kanaya, Y / Kawakami, S / Kim, D / Kiyokawa, Y / Kobayashi, M / Kobayashi, N / Kobayashi, T / Kondo, Y / Korkulu, Z / Koyama, S / Lapoux, V / Maeda, Y / Marqués, F M / Motobayashi, T / Miyazaki, T / Nakamura, T / Nakatsuka, N / Nishio, Y / Obertelli, A / Ohkura, A / Orr, N A / Ota, S / Otsu, H / Ozaki, T / Panin, V / Paschalis, S / Pollacco, E C / Reichert, S / Roussé, J-Y / Saito, A T / Sakaguchi, S / Sako, M / Santamaria, C / Sasano, M / Sato, H / Shikata, M / Shimizu, Y / Shindo, Y / Stuhl, L / Sumikama, T / Sun, Y L / Tabata, M / Togano, Y / Tsubota, J / Xu, F R / Yasuda, J / Yoneda, K / Zenihiro, J / Zhou, S-G / Zuo, W / Uesaka, T

Physical review letters

2021 Volume 126, Issue 8, Page(s) 82501

Abstract: ... a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital ... component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p ...

Abstract	A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.
Language	English
Publishing date	2021-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.126.082501
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Article ; Online: Cisplatin Plus Capecitabine After Adjuvant S-1 in Metastatic Gastric Cancer: A Phase II T-CORE1102 Trial.

Yoshioka, Takashi / Takahashi, Masanobu / Sakamoto, Yasuhiro / Okita, Akira / Fukui, Tadahisa / Murakawa, Yasuko / Shindo, Yoshiaki / Imai, Hiroo / Ohori, Hisatsugu / Shirota, Hidekazu / Chiba, Natsuko / Sasahara, Yuriko Ito / Nomura, Takashi / Fukushima, Norimasa / Yamaguchi, Takuhiro / Shimodaira, Hideki / Ishioka, Chikashi

Anticancer research

2022 Volume 42, Issue 4, Page(s) 2009–2015

Abstract: ... in patients with advanced gastric cancer refractory to adjuvant S-1.: Patients and methods: This single-arm ... that was refractory to S-1 were enrolled. Patients received 80 mg/m: Results: In total, 21 patients were ...

Abstract	Background/aim: This phase II study assessed the efficacy of capecitabine plus cisplatin in patients with advanced gastric cancer refractory to adjuvant S-1. Patients and methods: This single-arm, open-label, multicenter, phase II study was conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE) in Japan. Patients aged ≥20 years with advanced HER2-negative gastric cancer that was refractory to S-1 were enrolled. Patients received 80 mg/m Results: In total, 21 patients were enrolled from seven hospitals. The median patient age was 63 years. Nineteen patients received the protocol treatment. Median PFS was 3.7 months [90% confidence interval (CI)=2.7-5.6 months], which did not reach the predefined threshold of 4.0 months. ORR was 5.9% (95%CI=0.0-17.1%). Median OS was 11.9 months (95% CI 6.3-19.4 months). Febrile neutropenia was observed in 5.3% of patients. The most frequently observed grade 3 non-hematologic toxicities were nausea (15.8%) and hyponatremia (15.8%). Conclusion: The addition of a fluoropyrimidine to a platinum agent after adjuvant therapy is not suitable for gastric cancer.
MeSH term(s)	Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Capecitabine ; Cisplatin ; Humans ; Middle Aged ; Splenic Neoplasms/drug therapy ; Stomach Neoplasms/pathology ; Young Adult
Chemical Substances	Capecitabine (6804DJ8Z9U) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-03-28
Publishing country	Greece
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15680
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Zs.A 1642: Show issues

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Article: [A Case of Advanced Gastric Cancer with Multiple Liver Metastases Treated with Curative Conversion Therapy after S-1 plus CDDP].

Shindo, Yukito / Fukuda, Shinichiro / Kataoka, Ryoko / Kuwamoto, Nobutsuna / Takaishi, Hitomi / Miura, Yasuaki / Hirayama, Ryoichi / Otsuka, Ryo / Saito, Shuji / Fujita, Rikiya

Gan to kagaku ryoho. Cancer & chemotherapy

2018 Volume 45, Issue 3, Page(s) 480–482

Abstract: ... N3, M1, HEP, cStage IV, and the patient received chemotherapy with S-1 plus CDDP(SP). After 10 ...

Abstract	A57 -year-old man was diagnosed with advanced gastric cancer(adenocarcinoma[tub2/por1])with multiple(S3, S4, S5, S6, S8)liver and para-aortic lymph node metastases. The tumor was classified as cT4a, N3, M1, HEP, cStage IV, and the patient received chemotherapy with S-1 plus CDDP(SP). After 10 courses of SP, a CT scan revealed that the primary tumor and the metastases disappeared. The patient presented with cCR and underwent distal gastrectomy, D2 lymph node dissection, partial hepatic resection, and cholecystectomy. The histological diagnosis was classified as ypT0N0M0,(ypStage 0), pCR, and pathological Grade 3.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/administration & dosage ; Digestive System Surgical Procedures ; Drug Combinations ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/secondary ; Male ; Middle Aged ; Neoadjuvant Therapy ; Oxonic Acid/administration & dosage ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/pathology ; Stomach Neoplasms/surgery ; Tegafur/administration & dosage
Chemical Substances	Drug Combinations ; S 1 (combination) (150863-82-4) ; Tegafur (1548R74NSZ) ; Oxonic Acid (5VT6420TIG) ; Cisplatin (Q20Q21Q62J)
Language	Japanese
Publishing date	2018-03
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	604842-0
ISSN	0385-0684
ISSN	0385-0684
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Zs.B 2573: Show issues

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Article ; Online: Study protocol of the HGCSG1803: a phase II multicentre, non-randomised, single-arm, prospective trial of combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) as first-line treatment for metastatic or relapsed pancreatic cancer.

BMJ open

2022 Volume 12, Issue 5, Page(s) e048833

Abstract: ... regimen with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. In the phase ...

Abstract	Introduction: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has become one of the standard treatments for metastatic pancreatic cancer. However, the use of FOLFIRINOX requires prolonged infusion. Therefore, we planned to develop a new combination chemotherapy regimen with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. In the phase Ⅰ study that was conducted previously, the safety and recommended dose of OX-IRIS were assessed. In this study, we will evaluate the efficacy and safety of OX-IRIS. Methods and analysis: The HGCSG1803 study started as a multicentre, non-randomised, single-arm, prospective, phase II study in December 2019. Eligible subjects were patients with untreated metastatic or relapsed pancreatic cancer. OX-IRIS is administered as follows: 30 min infusion of antiemetic; 2-hour infusion of oxaliplatin (65 mg/m Ethics and dissemination: All the procedures will be conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1964 and its later versions. All the patients will receive written information about the trial and will provide informed consent before enrolment. This trial was approved by the Hokkaido University Certified Review Board (approval No: 018-037). Trial registration number: jRCTs011190008.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Humans ; Irinotecan/therapeutic use ; Multicenter Studies as Topic ; Oxaliplatin ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Prospective Studies ; Pancreatic Neoplasms
Chemical Substances	Oxaliplatin (04ZR38536J) ; Irinotecan (7673326042)
Language	English
Publishing date	2022-05-09
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-048833
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Article ; Online: Repurposing bromocriptine for Aβ metabolism in Alzheimer’s disease (REBRAnD) study

Hidekazu Tomimoto / Takayuki Kondo / Yoshihide Sunada / Hidehiro Ishikawa / Akihiro Shindo / Yuishin Izumi / Haruhiko Banno / Satoshi Morita / Koji Fujita / Ryosuke Takahashi / Haruhisa Inoue / Takakuni Maki / Toshifumi Watanabe / Kenji Ishii / Manabu Ikeda / Taro Okunomiya / Yoko Amino / Kayoko Endo / Akiyoshi Nakakura /

Akemi Kinoshita / Harue Tada / Ken Yasuda / Yosuke Taruno / Takashi Suehiro / Kohji Mori / Kazutomi Kanemaru / Kazue Shigenobu / Yumiko Kutoku / Shinobu Kawakatsu / Shunji Shiota / Osamu Uchikawa

BMJ Open, Vol 11, Iss

randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer’s disease with presenilin 1 (PSEN1) mutations

2021 Volume 6

Abstract: Introduction Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic ...

Abstract	Introduction Alzheimer’s disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD.Methods and analysis This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.Ethics and dissemination The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process.Trial registration number jRCT2041200008, NCT04413344.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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