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Article ; Online: Association between the controlling nutritional status score and outcomes in ischemic stroke patients with active cancer.

Sakurai, Rei / Gon, Yasufumi / Shimada, Yuki / Okazaki, Shuhei / Todo, Kenichi / Sasaki, Tsutomu / Mochizuki, Hideki

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2024 Volume 120, Page(s) 170–174

Abstract: Background: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear.: Methods: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in ... ...

Abstract	Background: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear. Methods: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in Japan between 2006 and 2016. Patients were followed for 2 years after stroke. The controlling nutritional status (CONUT) score was used to classify undernutrition degree into 4 groups: normal, light, moderate, and severe. Survival rates were compared using the Kaplan-Meier method. Hazard ratio (HR) and 95 % confidence intervals (CIs) for mortality were calculated using Cox regression models. Results: A total of 158 patients (31 % women; median age: 71 years) were analyzed. Of these, 47 % had distant metastasis. The median (interquartile range) National Institute of Health Stroke Scale and CONUT scores were 4 (1-10) and 5 (3-7), respectively. Kaplan-Meier curve indicated that patients with poorer nutritional status had worse outcomes (overall log-rank test, p < 0.001). The univariable Cox regression analysis showed that the HR (95 % CI) for the light, moderate, and severe groups were 1.14 (0.45-2.86), 3.01 (1.27-7.12), and 2.94 (1.10-7.84), respectively. This statistical significance did not persist after adjustment for potential confounders (HR [95 % CI] for the light, moderate, and severe groups were 0.95 [0.36-2.49], 1.56 [0.57-4.28], and 1.34 [0.37-4.92], respectively). Past stroke, distant metastasis, and plasma D-dimer levels on admission were independent predictors of prognosis. Conclusions: This single-center, retrospective study suggests that nutritional status serves as a prognostic indicator for ischemic stroke patients with active cancer. However, the effect is not statistically independent.
MeSH term(s)	Humans ; Female ; Aged ; Male ; Nutritional Status ; Retrospective Studies ; Ischemic Stroke ; Malnutrition ; Prognosis ; Neoplasms ; Stroke
Language	English
Publishing date	2024-01-20
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2024.01.011
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Zs.A 3999: Show issues

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Article ; Online: DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion.

Hamano, Momoko / Nakamura, Toru / Ito, Ryoku / Shimada, Yuki / Iwata, Michio / Takeshita, Jun-Ichi / Eguchi, Ryohei / Yamanishi, Yoshihiro

Bioinformatics (Oxford, England)

2024 Volume 40, Issue 2

Abstract: Motivation: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR- ... ...

Abstract	Motivation: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging. Results: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine. Availability and implementation: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.
MeSH term(s)	Transcription Factors/metabolism ; Transcriptome ; Cellular Reprogramming ; Neurons/metabolism ; Fibroblasts/metabolism
Chemical Substances	Transcription Factors
Language	English
Publishing date	2024-01-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btae048
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Zs.A 2374: Show issues

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Article ; Online: Immature stroma and high infiltration of CD15

Yamada, Yutaka / Yamamoto, Takeo / Tsutsumi, Chikanori / Matsumoto, Takashi / Noguchi, Shoko / Shimada, Yuki / Nakata, Kohei / Ohuchida, Kenoki / Nakamura, Masafumi / Oda, Yoshinao

Cancer science

2024 Volume 115, Issue 3, Page(s) 1001–1013

Abstract: Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along ... ...

Abstract	Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15
MeSH term(s)	Humans ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal ; Neutrophils/metabolism ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Tumor Microenvironment
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.16060
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Article ; Online: Lentinula Edodes Mycelia extract regulates the function of antigen-presenting cells to activate immune cells and prevent tumor-induced deterioration of immune function.

Kajiyama, Shota / Nagatake, Takahiro / Ishikawa, Satoru / Hosomi, Koji / Shimada, Yuki / Matsui, Yasunori / Kunisawa, Jun

BMC complementary medicine and therapies

2023 Volume 23, Issue 1, Page(s) 281

Abstract: Immune cell activation is essential for cancer rejection; however, the tumor microenvironment leads to deterioration of immune function, which enables cancer cells to survive and proliferate. We previously reported that oral ingestion of Lentinula Edodes ...

Abstract	Immune cell activation is essential for cancer rejection; however, the tumor microenvironment leads to deterioration of immune function, which enables cancer cells to survive and proliferate. We previously reported that oral ingestion of Lentinula Edodes Mycelia (L.E.M.) extract enhances the tumor antigen-specific T-cell response and exerts an antitumor effect in a tumor-bearing mouse model. In this study, we focused on antigen-presenting cells (APCs) located upstream of the immune system, induced a T-cell response, then examined the impact of L.E.M. extract on the APCs. L.E.M. extract enhanced the expression of MHC-I, MHC-II, CD86, CD80, and CD40 in bone marrow-derived dendritic cells (DCs) and strongly induced the production of IL-12. L.E.M.-stimulated DCs enhanced IFN-γ production from CD8
MeSH term(s)	Mice ; Animals ; Shiitake Mushrooms ; CD8-Positive T-Lymphocytes ; Antigen-Presenting Cells ; Neoplasms ; Interleukin-12/pharmacology ; Immunity ; Tumor Microenvironment
Chemical Substances	Interleukin-12 (187348-17-0)
Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-023-04106-5
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Article ; Online: Giant left atrial septal pouch stained during trans-septal puncture.

Kuwaki, Hiroshi / Yamashita, Hajime / Shimada, Yuki / Ujino, Keiji

BMJ case reports

2020 Volume 13, Issue 12

MeSH term(s)	Aged ; Atrial Fibrillation/etiology ; Catheter Ablation/adverse effects ; Echocardiography, Transesophageal ; Heart Septal Defects, Atrial/complications ; Heart Septal Defects, Atrial/diagnostic imaging ; Heart Septal Defects, Atrial/pathology ; Humans ; Male ; Punctures/adverse effects
Language	English
Publishing date	2020-12-31
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2020-240128
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Article ; Online: Accuracy of post-publication Financial Conflict of Interest corrections in medical research: A secondary analysis of pharmaceutical company payments to the authors of the CREATE-X trial report in the New England Journal of Medicine.

Ozaki, Akihiko / Saito, Hiroaki / Sawano, Toyoaki / Shimada, Yuki / Tanimoto, Tetsuya

Bioethics

2021 Volume 35, Issue 7, Page(s) 704–713

Abstract: In June 2017, Japanese and Korean authors published the results of the CREATE-X trial in the New England Journal of Medicine (NEJM). After we identified their inadequate disclosures of Financial Conflict of Interests (FCOIs), the authors made a post- ... ...

Abstract	In June 2017, Japanese and Korean authors published the results of the CREATE-X trial in the New England Journal of Medicine (NEJM). After we identified their inadequate disclosures of Financial Conflict of Interests (FCOIs), the authors made a post-publication correction of their FCOIs. The purpose of this study is to evaluate the accuracy of the post-publication corrections by the Japanese authors of the CREATE-X trial. All the Japanese authors of the CREATE-X trial were included in the study. We determined the payments received by these authors in 2016 using publicly available data published by 78 pharmaceutical companies based on the stipulated Japanese transparency guidelines. We retrieved the original and revised versions of the FCOI disclosures as published on the NEJM website, and compared the payments reported by the pharmaceutical companies and the original and revised FCOI disclosures of the authors. Of the 12 authors, nine received payments made by the drug manufacturer involved in the CREATE-X trial. Of these nine, only three (33.3%) originally disclosed their relationships, and another three (33.3%) later disclosed such relationships in the post-publication corrections. Similarly, of the 11 receiving at least one payment from other manufacturers of breast cancer products, none correctly disclosed the payments in the original or the revised disclosure. In the CREATE-X trial, FCOIs with pharmaceutical companies were not properly disclosed by 11 of the 12 Japanese authors, even after the post-publication corrections, which highlights the need to pay more attention to the accuracy of FCOI disclosures in academic publications.
MeSH term(s)	Biomedical Research ; Conflict of Interest ; Disclosure ; Humans ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2021-06-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632984-6
ISSN	1467-8519 ; 0269-9702
ISSN (online)	1467-8519
ISSN	0269-9702
DOI	10.1111/bioe.12854
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Zs.B 2998: Show issues

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Article ; Online: Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma.

Kawata, Jun / Koga, Yutaka / Noguchi, Shoko / Shimada, Yuki / Yamada, Yutaka / Yamamoto, Takeo / Shindo, Koji / Nakamura, Masafumi / Oda, Yoshinao

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2023 Volume 36, Issue 8, Page(s) 100181

Abstract: Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations ... ...

Abstract	Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.
MeSH term(s)	Humans ; Ampulla of Vater/pathology ; Carcinoma/pathology ; Mutation ; Prognosis ; Common Bile Duct Neoplasms/genetics ; Common Bile Duct Neoplasms/pathology
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2023.100181
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Article ; Online: A case of Adult-onset Acute Flaccid Myelitis Accompanied by Rhombencephalitis which First Presented with Prominent Psychiatric Symptoms and Dysautonomia Mimicking Anti-N-methyl-d-aspartate Receptor Encephalitis.

Sumikura, Hiroyuki / Ito, Mai / Sato, Takuma / Hatayama, Naoki / Fujioka, Tomohiro / Nagashima, Nozomi / Shimada, Yuki / Fukasaka, Isao / Shimizu, Mikito / Higashida, Kyoko / Hoshi, Taku / Tanaka, Keiko / Sakaguchi, Manabu

Internal medicine (Tokyo, Japan)

2024

Abstract: A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac ... ...

Abstract	A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac arrest occurred, which required pacemaker placement. She subsequently showed profound flaccid limb paralysis, with magnetic resonance imaging demonstrating focal necrotic lesions localized in the anterior horn of the longitudinal segments of the spinal cord and in the pontine tegmentum. Enteroviruses or autoimmune encephalitis-associated autoantibodies were not detected. We herein report a case of acute flaccid myelitis with profound psychiatric symptoms and dysautonomia, resembling NMDAR encephalitis.
Language	English
Publishing date	2024-04-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.2767-23
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Article ; Online: Response to "Strictness and Transparency in Approval Process of Medical Products: Japanese Situation".

Sawano, Toyoaki / Ozaki, Akihiko / Saito, Hiroaki / Shimada, Yuki / Tanimoto, Tetsuya

Clinical pharmacology and therapeutics

2020 Volume 109, Issue 2, Page(s) 291

MeSH term(s)	Committee Membership ; Drug Approval ; Drug and Narcotic Control ; Government ; Humans ; Japan ; Pharmaceutical Preparations
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2020-08-31
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.1996
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Article ; Online: Pharmaceutical Company Payments to Japanese Government Drug Regulation Committee Members.

Sawano, Toyoaki / Ozaki, Akihiko / Saito, Hiroaki / Shimada, Yuki / Tanimoto, Tetsuya

Clinical pharmacology and therapeutics

2020 Volume 108, Issue 5, Page(s) 1049–1054

Abstract: Little is known about the characteristics and distribution of financial conflicts of interest (FCOIs) in the drug regulation process, both in Japan and globally. This study aimed to identify the characteristics and distribution of pharmaceutical payments ...

Abstract	Little is known about the characteristics and distribution of financial conflicts of interest (FCOIs) in the drug regulation process, both in Japan and globally. This study aimed to identify the characteristics and distribution of pharmaceutical payments to members of Japanese government drug regulation committees, and to assess the accuracy of their FCOI statements. Among members who worked for either of the five committees of the Pharmaceutical Affairs and Food Sanitation Council (PAFSC), which is the advisory committee for pharmaceutical affairs in Japan, from April 1, 2017 to March 31, 2019, the extent of payments in 2016 from 78 major pharmaceutical companies in Japan and the accuracy of the self-reported FCOI disclosures were assessed. Of 108 members, 54 (50%) were medical doctors. The payments to the PAFSC members totaled ¥115,765,006 ($1,064,017), and the mean (SD) payment was ¥1,071,898 ($9,852) (¥2,272,520 ($20,887)). Fifty-one members (47%) received at least one payment from a pharmaceutical company in 2016; 32 members (30%) received more than ¥500,000 ($4,600). Of 8,530 declarations from five councils, 409 (4.8%) of the FCOIs self-reported by the committee members were inaccurate. Of those inaccurate disclosures, 112 of 409 inaccurate disclosures (27.4%) would have prevented the recipients from participating in the drug-approval decision-making processes had they been correctly disclosed. Almost half of drug regulation committee members in Japan received at least one payment from pharmaceutical companies in 2016. Moreover, several FCOIs they reported were inaccurate.
MeSH term(s)	Committee Membership ; Conflict of Interest/economics ; Cross-Sectional Studies ; Drug Approval/economics ; Drug Industry/economics ; Female ; Government Agencies/economics ; Government Regulation ; Humans ; Japan ; Male ; Physicians/economics ; Retrospective Studies ; Time Factors ; Truth Disclosure
Language	English
Publishing date	2020-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.1892
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