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Article: [Innovation of novel anti-hypertensive drug(s) that inhibit adrenal aldosterone synthase gene (CYP11B2) expression].

Sugawara, Akira

Nihon yakurigaku zasshi. Folia pharmacologica Japonica

2020 Volume 155, Issue 5, Page(s) 319–322

Abstract: In Japan, hypertensive patients are speculated to be 40 million, and 30 million among them are poor controlled. Moreover, 20% of them are estimated as "resistant hypertension" those are above their target blood pressure even in the simultaneous use of ... ...

Abstract	In Japan, hypertensive patients are speculated to be 40 million, and 30 million among them are poor controlled. Moreover, 20% of them are estimated as "resistant hypertension" those are above their target blood pressure even in the simultaneous use of three different classes anti-hypertensive drugs. Recently, aldosterone is recognized as one of the main causes of the etiology of "resistant hypertension." Therefore, it is important to discover novel drugs that inhibit the synthesis and secretion of aldosterone. We recently generated a stable H295R cell line expressing aldosterone synthase gene (CYP11B2) promoter (-1521~+2)/luciferase cDNA chimeric reporter construct. We thereafter established a high-throughput screening (HTS) system for the discovery of novel anti-hypertensive drugs that inhibit angiotensin II-induced CYP11B2 expression using the cell line. After confirmation of its validation (Z' score > 0.5), we performed HTS using Core Library (9,600 chemical compounds) and Validated Compound Library (1,979 chemical compounds) obtained from Drug Discovery Initiative (The University of Tokyo), and Tohoku University Chemical Library (5,562 chemical compounds), respectively. We obtained several hit compounds from each library, and focused on one compound (bortezomib) obtained from Validated Compound Library. The compound did not affect cell viability by WST-1 assay, and was demonstrated to lower blood pressure of Tsukuba Hypertensive Mice, significantly. The compound may therefore be a potential candidate of novel anti-hypertensive drugs in the future.
MeSH term(s)	Aldosterone ; Angiotensin II ; Animals ; Antihypertensive Agents/pharmacology ; Cytochrome P-450 CYP11B2/genetics ; Humans ; Japan ; Mice
Chemical Substances	Antihypertensive Agents ; Angiotensin II (11128-99-7) ; Aldosterone (4964P6T9RB) ; Cytochrome P-450 CYP11B2 (EC 1.14.15.4)
Language	Japanese
Publishing date	2020-09-28
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1097532-9
ISSN	1347-8397 ; 0015-5691
ISSN (online)	1347-8397
ISSN	0015-5691
DOI	10.1254/fpj.19105
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Article ; Online: Orofacial symptoms suggestive of malignant lesions and the role of imaging: literature review and case presentation.

Sugawara, Chieko / Takahashi, Akira

Oral radiology

2023 Volume 39, Issue 4, Page(s) 599–613

Abstract: Among the patients seeking dental treatment, some may present with symptoms that cannot be resolved by dental treatment alone. Patients with orofacial symptoms associated with malignant diseases, which require medical treatment, often visit dental ... ...

Abstract	Among the patients seeking dental treatment, some may present with symptoms that cannot be resolved by dental treatment alone. Patients with orofacial symptoms associated with malignant diseases, which require medical treatment, often visit dental clinics for their initial consultation. Delays in making a definitive diagnosis worsen the patient's prognosis. Therefore, dental clinicians should also be aware of the signs and symptoms associated with malignant diseases. The chief complaints of these patients include numb chin syndrome (NCS), painless swelling of the palate and neck, trismus and temporomandibular disorders, and an enlarged tongue. This article aimed to review these orofacial symptoms and related diseases and describe representative cases of these diseases to obtain a definitive diagnosis via imaging. Panoramic radiograph is widely used in general dentistry, and this article reaffirmed the importance of panoramic radiograph anatomical landmarks in diagnosing the cases presented in this paper.
MeSH term(s)	Humans ; Syndrome ; Prognosis ; Diagnosis, Differential ; Tomography, X-Ray Computed
Language	English
Publishing date	2023-07-25
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	639456-5
ISSN	1613-9674 ; 0911-6028
ISSN (online)	1613-9674
ISSN	0911-6028
DOI	10.1007/s11282-023-00701-x
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Article ; Online: Rethinking Japan's Health System Sustainability Under the Planetary Health Framework.

Shimabukuro, Akira / Minamitani, Kenta / Sugawara, Joji

Health systems and reform

2023 Volume 9, Issue 1, Page(s) 2268360

MeSH term(s)	Humans ; Japan ; Government Programs
Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Editorial
ZDB-ID	2820935-7
ISSN	2328-8620 ; 2328-8620
ISSN (online)	2328-8620
ISSN	2328-8620
DOI	10.1080/23288604.2023.2268360
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Article ; Online: Association between personality and the risk of ischemic heart disease mortality before and after the Great East Japan Earthquake: Data from the Miyagi Cohort Study.

Sugawara, Yumi / Kanemura, Seiki / Fukao, Akira / Tsuji, Ichiro

Journal of psychiatric research

2023 Volume 161, Page(s) 84–90

Abstract: Background: The purpose of the present study was to investigate the association between personality and the risk of IHD mortality among Great East Japan Earthquake (GEJE) survivors, and to investigate whether personality traits affected the increase in ... ...

Abstract	Background: The purpose of the present study was to investigate the association between personality and the risk of IHD mortality among Great East Japan Earthquake (GEJE) survivors, and to investigate whether personality traits affected the increase in IHD mortality observed after the GEJE. Methods: We analyzed data for 29,065 men and women in the Miyagi Cohort Study who were 40-64 years old at baseline. We divided the participants into quartiles based on scores for each of the four personality subscales (extraversion, neuroticism, psychoticism, and lie), using the Japanese version of the Eysenck Personality Questionnaire-Revised Short Form. We divided the eight years before and after the GEJE event (11 March 2011) into two period, and examined the relationship between personality traits and the risk of IHD mortality. Cox proportional hazards analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of IHD mortality according to each personality subscale category. Results: In the four years before the GEJE, neuroticism was significantly associated with an increased risk of IHD mortality. Compared with the lowest category for neuroticism, the multivariate-adjusted HR (95% CI) for IHD mortality in the highest category was 2.19 (1.03-4.67) (p-trend = 0.12). In contrast, no statistically significant association between neuroticism and IHD mortality was observed in the four years after the GEJE. Conclusion: This finding suggests that the observed increase in IHD mortality after the GEJE can be attributed to risk factors other than personality.
MeSH term(s)	Male ; Humans ; Female ; Adult ; Middle Aged ; Cohort Studies ; Earthquakes ; Japan/epidemiology ; Prospective Studies ; Personality ; Myocardial Ischemia
Language	English
Publishing date	2023-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3148-3
ISSN	1879-1379 ; 0022-3956
ISSN (online)	1879-1379
ISSN	0022-3956
DOI	10.1016/j.jpsychires.2023.02.024
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Book ; Online: Evaluating the Rationale Understanding of Critical Reasoning in Logical Reading Comprehension

Kawabata, Akira / Sugawara, Saku

2023

Abstract: To precisely evaluate a language model's capability for logical reading comprehension, we present a dataset for testing the understanding of the rationale behind critical reasoning. For questions taken from an existing multiplechoice logical reading ... ...

Abstract	To precisely evaluate a language model's capability for logical reading comprehension, we present a dataset for testing the understanding of the rationale behind critical reasoning. For questions taken from an existing multiplechoice logical reading comprehension dataset, we crowdsource rationale texts that explain why we should select or eliminate answer options, resulting in 3,003 multiple-choice subquestions that are associated with 943 main questions. Experiments on our dataset show that recent large language models (e.g., InstructGPT) struggle to answer the subquestions even if they are able to answer the main questions correctly. We find that the models perform particularly poorly in answering subquestions written for the incorrect options of the main questions, implying that the models have a limited capability for explaining why incorrect alternatives should be eliminated. These results suggest that our dataset encourages further investigation into the critical reasoning ability of language models while focusing on the elimination process of relevant alternatives. Comment: Accepted to EMNLP 2023
Keywords	Computer Science - Computation and Language
Subject code	160
Publishing date	2023-11-30
Publishing country	us
Document type	Book ; Online
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Article ; Online: Primary aldosteronism and obstructive sleep apnea: the strong ties between them.

Sugawara, Akira / Shimada, Hiroki / Otsubo, Yuri / Kouketsu, Takumi / Yokoyama, Atsushi

Hypertension research : official journal of the Japanese Society of Hypertension

2023 Volume 46, Issue 7, Page(s) 1712–1713

MeSH term(s)	Humans ; Prevalence ; Hypertension/physiopathology ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/physiopathology ; Hyperaldosteronism/complications
Language	English
Publishing date	2023-05-09
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1175297-x
ISSN	1348-4214 ; 0916-9636
ISSN (online)	1348-4214
ISSN	0916-9636
DOI	10.1038/s41440-023-01303-0
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Article ; Online: A new species of the genus

Maekawa, Nitaro / Sugawara, Ryo / Nakano, Ryo / Shino, Ryotaro / Sotome, Kozue / Nakagiri, Akira / Oba, Yuichi

Mycoscience

2023 Volume 64, Issue 4, Page(s) 109–115

Abstract: Aleurodiscus ... ...

Abstract	Aleurodiscus sagittisporus
Language	English
Publishing date	2023-07-31
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1285813-4
ISSN	1618-2545 ; 1340-3540
ISSN (online)	1618-2545
ISSN	1340-3540
DOI	10.47371/mycosci.2023.06.001
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Article ; Online: Sleep duration and the risk of endometrial cancer incidence among Japanese women: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

Sugawara, Yumi / Lu, Yukai / Kanemura, Seiki / Fukao, Akira / Tsuji, Ichiro

Cancer epidemiology

2023 Volume 86, Page(s) 102427

Abstract: Objective: Endometrial cancer has been increasing worldwide, and is one of the most common female hormone-related cancers. The purpose of this study was to examine the association between sleep duration and risk of endometrial cancer among Japanese ... ...

Abstract	Objective: Endometrial cancer has been increasing worldwide, and is one of the most common female hormone-related cancers. The purpose of this study was to examine the association between sleep duration and risk of endometrial cancer among Japanese women. Methods: We conducted a pooled analysis of two prospective studies conducted among residents of Miyagi Prefecture in rural northern Japan. A total of 36,537 women aged 40-79 years participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994. The participants responded to a self-administered questionnaire that including sleep duration. Sleep duration was assessed at the baseline using a self-administered questionnaire. The participants entered the mean integer number representing the hours of sleep taken per day during the previous year. We divided the participants into three groups (≤6 h, 7-8 h, or ≥9 h). Cox proportional hazards regression analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for endometrial cancer incidence. Results: During 745,993 person-years of follow-up, we identified 146 incident cases of endometrial cancer. Compared with women who slept 7-8 h per day, the multivariate HR (95%CI) for endometrial cancer incidence was 1.07 (0.72-1.60) for those who slept 6 h or less, and 1.05 (0.57-1.93) for those who slept 9 h or longer (p-trend=0.57). Conclusion: In analysis of two population -based prospective cohort studies conducted among Japanese women, we found no significant associations between sleep duration and the incidence of endometrial cancer.
MeSH term(s)	Female ; Humans ; Cohort Studies ; East Asian People ; Endometrial Neoplasms/epidemiology ; Incidence ; Japan/epidemiology ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Sleep Duration ; Adult ; Middle Aged ; Aged
Language	English
Publishing date	2023-07-20
Publishing country	Netherlands
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2508729-0
ISSN	1877-783X ; 1877-7821
ISSN (online)	1877-783X
ISSN	1877-7821
DOI	10.1016/j.canep.2023.102427
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Article ; Online: The physiological and pathophysiological roles of carbohydrate response element binding protein in the kidney.

Yokoyama, Atsushi / Suzuki, Susumu / Okamoto, Koji / Sugawara, Akira

Endocrine journal

2022 Volume 69, Issue 6, Page(s) 605–612

Abstract: Glucose is not only the energy fuel for most cells, but also the signaling molecule which affects gene expression via carbohydrate response element binding protein (ChREBP), a Mondo family transcription factor. In response to high glucose conditions, ... ...

Abstract	Glucose is not only the energy fuel for most cells, but also the signaling molecule which affects gene expression via carbohydrate response element binding protein (ChREBP), a Mondo family transcription factor. In response to high glucose conditions, ChREBP regulates glycolytic and lipogenic genes by binding to carbohydrate response elements (ChoRE) in the regulatory region of its target genes, thus elucidating the role of ChREBP for converting excessively ingested carbohydrates to fatty acids as an energy storage in lipogenic tissues such as the liver and adipose tissue. While the pathophysiological roles of ChREBP for fatty liver and obesity in these tissues are well known, much of the physiological and pathophysiological roles of ChREBP in other tissues such as the kidney remains unclear despite its high levels of expression in them. This review will thus highlight the roles of ChREBP in the kidney and briefly introduce the latest research results that have been reported so far.
MeSH term(s)	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Glucose/metabolism ; Kidney/metabolism ; Liver/metabolism ; Response Elements ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Transcription Factors ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-04-26
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1151918-6
ISSN	1348-4540 ; 0918-8959
ISSN (online)	1348-4540
ISSN	0918-8959
DOI	10.1507/endocrj.EJ22-0083
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Article ; Online: Factors associated with incidence of acute kidney injury: a Japanese regional population-based cohort study, the Shizuoka study.

Dote, Hisashi / Nakatani, Eiji / Mori, Kiyoshi / Sugawara, Akira

Clinical and experimental nephrology

2022 Volume 27, Issue 4, Page(s) 321–328

Abstract: Background: Acute kidney injury (AKI) is a globally critical issue. Most studies about AKI have been conducted in limited settings on perioperative or critically ill patients. As a result, there is little information about the epidemiology and risk ... ...

Abstract	Background: Acute kidney injury (AKI) is a globally critical issue. Most studies about AKI have been conducted in limited settings on perioperative or critically ill patients. As a result, there is little information about the epidemiology and risk factors of AKI in the general population. Methods: We conducted a population-based cohort study using the Shizuoka Kokuho Database. We included subjects with records of health checkup results. The observation period for each participant was defined as from the date of insurance enrollment or April 2012, whichever occurred later, until the date of insurance withdrawal or September 2020, whichever was later. Primary outcome was AKI associated with admission based on the ICD-10 code. We described the incidence of AKI and performed a multivariate analysis using potential risk factors selected from comorbidities, medications, and health checkup results. Results: Of 627,814 subjects, 8044 were diagnosed with AKI (incidence 251 per 100,000 person-years). The AKI group was older, with more males. Most comorbidities and prescribed medications were more common in the AKI group. As novel factors, statins (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.80-0.89) and physical activity habits (HR 0.79, 95% CI 0.75-0.83) were associated with reduced incidence of AKI. Other variables associated with AKI were approximately consistent with those from previous studies. Conclusions: The factors associated with AKI and the incidence of AKI in the general Japanese population are indicated. This study generates the hypothesis that statins and physical activity habits are novel protective factors for AKI.
MeSH term(s)	Male ; Humans ; Incidence ; Cohort Studies ; Retrospective Studies ; East Asian People ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Risk Factors ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/epidemiology ; Acute Kidney Injury/etiology
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2022-12-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-022-02310-0
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