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福本 毅大学院医学研究科 医科学専攻准教授
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■ 学位■ 研究キーワード
■ 研究分野
■ 委員歴
研究活動情報
■ 受賞- 2024年 横浜市立大学 医学会賞
- 2023年 日本色素細胞学会研究補助金（久木田淳賞）
- 2022年03月 日本抗加齢医学会 研究奨励賞
- 2021年12月 The 46TH Annual Meeting of the Japanese Society for Investigative Dermatology, 3 minutes presentation Award日本国国内学会・会議・シンポジウム等の賞
- 2021年 日本皮膚科学会 トラベルグラント
- 2020年07月 加齢皮膚医学研究基金 ロート賞日本国出版社・新聞社・財団等の賞
- 2020年 日本色素細胞学会 奨励賞日本国出版社・新聞社・財団等の賞
- 2019年 The 48th most cited author of "Cancer Research" in 2019
- 2016年 神戸大学医学部皮膚科同窓会, 学術賞・研究部門
- 2015年02月 日本研究皮膚科学会 きさらぎ賞日本国出版社・新聞社・財団等の賞
- 2010年 神戸大学医学部皮膚科同窓会, 学術賞・若手部門
- 2007年12月 第37回日本皮膚アレルギー・接触皮膚炎学会総会 学術大会 優秀賞日本国国内学会・会議・シンポジウム等の賞
- Springer Science and Business Media LLC, 2025年04月, Nature Medicine, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2025年04月, International Journal of Clinical Oncology, 英語[査読有り]研究論文（学術雑誌）
- 2025年03月, 皮膚病診療, 47(3) (3), 210 - 214, 日本語母親の多発性黒子が診断の契機となったNoonan syndrome with multiple lentigines（NSML，旧名LEOPARD症候群）の親子例
- 2025年03月, 皮膚病診療, 47(3) (3), 242 - 246, 日本語グルカゴノーマに伴って間擦部に出現した壊死性遊走性紅斑[査読有り]
- Elsevier BV, 2025年03月, The Lancet Respiratory Medicine, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2025年03月, The Lancet Public Health, 英語[査読有り]研究論文（学術雑誌）
- 2025年03月, Skin Cancer, 39(3) (3), 318 - 323, 日本語レチノイド内服と内服PUVA療法の併用療法が奏効した毛包向性菌状息肉症の1例[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2025年02月, The Lancet Public Health, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- 2025年01月, J Dermatol, 英語A case of localized scleroderma with variable response to excimer light therapy[査読有り]
- 2025年01月, Geriatr Gerontol Int., 英語Recent advances in biomarkers for senescence: Bridging basic research to clinic[査読有り]
- Wiley, 2024年12月, The Journal of Dermatology研究論文（学術雑誌）
- Elsevier BV, 2024年12月, The Lancet, 404(10469) (10469), 2314 - 2340[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年12月, The Lancet Infectious Diseases, 国際誌[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年12月, The Lancet, 国際共著している研究論文（学術雑誌）
- Elsevier BV, 2024年12月, Public Health, 237, 212 - 231, 国際共著している研究論文（学術雑誌）
- Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC). Methods: We fed the APCmin/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan. Results: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively. Conclusions: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention.MDPI AG, 2024年11月, Cancers, 16(22) (22), 3846 - 3846, 英語研究論文（学術雑誌）
- Elsevier BV, 2024年11月, The Lancet HIV, 国際共著している研究論文（学術雑誌）
- Elsevier BV, 2024年11月, The Lancet, 国際共著している研究論文（学術雑誌）
- Elsevier BV, 2024年08月, Med, 5(8) (8), 943 - 962.e6, 国際共著している研究論文（学術雑誌）
- Wiley, 2024年07月, The Journal of Dermatology, 英語[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年06月, Journal of Dermatological Science, 英語研究論文（学術雑誌）
- 2024年06月, Front Med (Lausanne), 英語Case report: Usefulness of a picosecond Alexandrite laser therapy on atypical henna-induced Riehl's melanosis inferred from immunohistochemical analyses[査読有り]研究論文（学術雑誌）
- Wiley, 2024年04月, Journal of the European Academy of Dermatology and Venereology, 英語, 国際共著している研究論文（学術雑誌）
- Abstract Background Prurigo nodularis, a chronic inflammatory skin condition, adversely affects the quality of life of affected individuals. Current treatment options for prurigo nodularis in Japan are limited. Objectives To evaluate the optimal dose, efficacy, and safety of long-term treatment with nemolizumab in patients with prurigo nodularis in Japan. Methods In a 16-week, double-blind, phase II/III study, patients aged ≥13 years with prurigo nodularis were randomly assigned (1:1:1) to nemolizumab 30 mg, 60 mg, or placebo groups, with concomitant topical corticosteroids, every 4 weeks. The primary efficacy end point was the percentage change in the weekly mean Peak Pruritus Numerical Rating Scale (PP-NRS) score (range, 0 to 10, with higher scores indicating worse itching) from baseline to week 16. Secondary efficacy end points assessed the impact of treatment on pruritus, prurigo nodularis severity, sleep, and quality of life. Results At week 16, the least-squares mean percentage change from baseline in the PP-NRS score was −61·1% in the nemolizumab 30 mg group (n = 77), −56·0% in the 60 mg group (n = 76), and −18·6% in the placebo group (n = 76). Differences between both nemolizumab groups and placebo were significant; the difference between the 30 mg and placebo groups was −42·5% (95% confidence interval [CI], −51·9 to −33·1; P<0·0001), and between the 60 mg and placebo groups was −37·4% (95% CI, −46·7 to −28·1; P<0·0001). Nemolizumab-treated patients also had greater improvements in the number and severity of prurigo nodules, and in sleep and quality of life compared with the placebo group. Both nemolizumab doses were well tolerated. Conclusions Improvements in prurigo nodularis were greater following nemolizumab treatment, despite continuation of topical corticosteroids in both groups. (Funded by Maruho; jRCT number, 2011200017.)Oxford University Press (OUP), 2024年04月, British Journal of Dermatology, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Abstract Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7–7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2–37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7–2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6–13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8–5.1]; dual-agent: 12.4% [95% CI 8.0–16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4–35.2]; dual-agent: 44.3% [95% CI 31.7–56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0–12.2]; dual-agent: 16.3 months [95% CI 13.5–19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.Springer Science and Business Media LLC, 2024年04月, Scientific Reports, 14(1) (1)[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年04月, The Lancet, 英語, 国際共著している研究論文（学術雑誌）
- Elsevier BV, 2024年04月, Journal of Investigative Dermatology, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年04月, The Lancet, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年04月, The Lancet Neurology, 23(4) (4), 344 - 381, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年03月, The Lancet, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2024年03月, The Lancet, 英語, 国際共著している研究論文（学術雑誌）
- Introduction Solar urticaria (SU), a relatively rare skin inflammatory and photosensitivity disease, is often resistant to standard urticaria treatment. Quality of life (QOL) among SU patients has not been extensively explored. This study was performed to clarify the clinical features and effectiveness of therapies (e.g., hardening therapy) for SU and to determine QOL among SU patients. Methods The authors examined the characteristics, treatments, and QOL statuses of 29 Japanese SU patients using medical records and a questionnaire approach. Results Among 29 patients, H1 antihistamine therapy (H1) was effective in 22 (75.8%) patients. H2 antihistamine therapy (H2) was effective in three of seven (42.9%) patients. Ultraviolet radiation A (UVA) hardening therapy was effective in eight of nine (88.9%) patients. Visible light (VL) hardening therapy was ineffective in three of three patients. In one patient who underwent both UVA and VL hardening therapy, only UVA hardening therapy was effective. In the questionnaire, 18 patients (90%) reported some improvement compared with disease onset (four had complete remission, six had completed treatment although mild symptoms persisted, and eight were receiving treatment with moderate symptoms), whereas two patients reported exacerbation. Patients in complete remission had a mean disease duration of 4 years, whereas patients not in remission had a mean disease duration of 8.8 years. The mean Dermatology Life Quality Index (DLQI) score for the current status was 7.4. There was a correlation between DLQI and symptom/treatment status. However, neither DLQI and action spectra nor DLQI and treatments exhibited significant differences. Discussion The questionnaire revealed current QOL status and long-term prognosis in SU patients. Compared with disease onset, most patients showed improvement when assessed for this study. Both H1 and H2 should be attempted for all SU patients. UVA hardening therapy may be an option for SU patients with an action spectrum that includes UVA.Frontiers Media SA, 2024年02月, Frontiers in Medicine, 11, 英語研究論文（学術雑誌）
- Abstract Cellular senescence occurs in response to endogenous or exogenous stresses and is characterized by stable cell cycle arrest, alterations in nuclear morphology, and secretion of proinflammatory factors, referred to as the senescence-associated secretory phenotype (SASP). An increase of senescent cells is associated with the development of several types of cancer and aging-related diseases. Therefore, senolytic agents that selectively remove senescent cells may offer opportunities for developing new therapeutic strategies against such cancers and aging-related diseases. This review outlines senescence inducers and the general characteristics of senescent cells. We also discuss the involvement of senescent cells in certain cancers and diseases. Finally, we describe a series of senolytic agents and their utilization in therapeutic strategies.Oxford University Press (OUP), 2024年02月, The Journal of Biochemistry, 英語, 国際共著している[査読有り][招待有り]研究論文（学術雑誌）
- Elsevier BV, 2024年02月, Journal of Dermatological Science研究論文（学術雑誌）
- 2024年, 皮膚病診療, 46(10) (10)免疫抑制中に生じたVZV関連の血管炎による片側性難治性下腿潰瘍.
- 2024年, Skin Cancer第38巻3号, p. 211-217, 2024, 日本語基底細胞癌と隣接し診断に苦慮した脂腺腫の１例.[査読有り]
- Elsevier BV, 2024年01月, The Lancet Regional Health - Southeast Asia, 100333 - 100333, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2023年12月, Journal of the American College of Cardiology, 82(25) (25), 2350 - 2473, 国際共著している研究論文（学術雑誌）
- 2023年11月, Medicine (Baltimore), 英語Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2023年10月, The Lancet Rheumatology, 5(10) (10), e594 - e610, 日本語, 国際共著している研究論文（学術雑誌）
- Elsevier BV, 2023年10月, eClinicalMedicine, 64, 102193 - 102193, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Wiley, 2023年09月, The Journal of Dermatology, 英語[査読有り]研究論文（学術雑誌）
- Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.American Medical Association (AMA), 2023年09月, JAMA Oncology, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background Estimating and analyzing trends and patterns of health loss are essential to promote efficient resource allocation and improve Peru’s healthcare system performance. Methods Using estimates from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study (2019), we assessed mortality and disability in Peru from 1990 to 2019. We report demographic and epidemiologic trends in terms of population, life expectancy at birth (LE), mortality, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by the major diseases and risk factors in Peru. Finally, we compared Peru with 16 countries in the Latin American (LA) region. Results The Peruvian population reached 33.9 million inhabitants (49.9% women) in 2019. From 1990 to 2019, LE at birth increased from 69.2 (95% uncertainty interval 67.8–70.3) to 80.3 (77.2–83.2) years. This increase was driven by the decline in under-5 mortality (−80.7%) and mortality from infectious diseases in older age groups (+60 years old). The number of DALYs in 1990 was 9.2 million (8.5–10.1) and reached 7.5 million (6.1–9.0) in 2019. The proportion of DALYs due to non-communicable diseases (NCDs) increased from 38.2% in 1990 to 67.9% in 2019. The all-ages and age-standardized DALYs rates and YLLs rates decreased, but YLDs rates remained constant. In 2019, the leading causes of DALYs were neonatal disorders, lower respiratory infections (LRIs), ischemic heart disease, road injuries, and low back pain. The leading risk factors associated with DALYs in 2019 were undernutrition, high body mass index, high fasting plasma glucose, and air pollution. Before the COVID-19 pandemic, Peru experienced one of the highest LRIs-DALYs rates in the LA region. Conclusion In the last three decades, Peru experienced significant improvements in LE and child survival and an increase in the burden of NCDs and associated disability. The Peruvian healthcare system must be redesigned to respond to this epidemiological transition. The new design should aim to reduce premature deaths and maintain healthy longevity, focusing on effective coverage and treatment of NCDs and reducing and managing the related disability.Frontiers Media SA, 2023年06月, Frontiers in Public Health, 11, 英語[査読有り]研究論文（学術雑誌）
- Varicella zoster virus (VZV) infection may cause large or medium vessel vasculitis, including granulomatous arteritis of the nervous system and central nervous system vasculitis. However, small vessel vasculitis, such as cutaneous leukocytoclastic vasculitis (LCV) associated with localized cutaneous VZV infection, herpes zoster, is uncommon. Herein, we present the case of a 75-year-old man with segmental leukocytoclastic vasculitis associated with herpes zoster on the leg. To the best of our knowledge, there are four cases of segmental leukocytoclastic vasculitis in herpes zoster reported in the English literature; we compared our case with these previous reports. Our review of five patients suggests that most patients were immunosuppressed. We also found that the leg is susceptible to LCV associated with herpes zoster. Anti-viral treatment was effective for LCV as well as herpes zoster. Prior reports have proposed etiologies inducing LCV; for example, immune complexes are mediated by vessel wall damage. In support of this, histopathology in our case showed a C3-positive reaction with the small vessel walls in the dermis in direct immunofluorescence. Although the mechanism of LCV associated with herpes zoster remains unclear, we should consider LCV while diagnosing and treating patients with herpes zoster, especially immunosuppressed patients.PAGEPress Publications, 2023年05月, Dermatology Reports, 英語[査読有り]研究論文（学術雑誌）
- 2023年04月, J Am Coll Surg., 英語Impact of the COVID-19 Pandemic on Cancer Treatment: Nationwide Japanese Registration Until 2021.[査読有り]研究論文（学術雑誌）
- Wiley, 2023年02月, The Journal of Dermatology, 英語研究論文（学術雑誌）
- Wiley, 2023年02月, The Journal of Dermatology, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.Elsevier BV, 2023年01月, The Lancet Global Health, 11(3) (3), e385 - e413, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Lenvatinib, an oral multikinase inhibitor, is a first-line drug for the treatment of unresectable hepatocellular carcinoma. Here, we report a case of a 72-year-old man who presented with severe generalized erythematous rash (GER) approximately four weeks after the commencement of lenvatinib treatment, which he had been receiving for the treatment of unresectable lung metastases stemming from hepatocellular carcinoma. The patient had suffered from ichthyosis since his childhood, which made the diagnosis difficult. He had been diagnosed with dermatomycosis of the skin of whole body and treated by terbinafine tablets and luliconazole cream at another hospital. After remission of GER, lenvatinib was readministered because the patient’s metastatic lung tumor enlarged, which led to a recurrence of erythema with pruritus on the upper part of patient’s body. We confirmed the diagnosis of Lenvatinib-induced generalized GER based on the positive result of the patch test after the informed consent. To the best of our knowledge, this is the first detailed case of lenvatinibinduced GER. Raising physicians’ awareness of this potentially severe adverse effect is of importance because of lenvatinib’s increasing prominence as the drug of choice in cancer therapy.PAGEPress Publications, 2022年12月, Dermatology Reports, 英語[査読有り]研究論文（学術雑誌）
- Dear Editor, Confluent and reticulated papillomatosis (CRP) is a rare skin disorder in young individuals. It is clinically characterized by slightly hyperkeratotic or verrucous grayish-brown papules coalescing to form a reticulated pattern peripherally with confluent plaques centrally. Sites of predilection are the neck, interscapular, intermammary regions, and abdomen. CRP commonly arises during puberty or in early adulthood. Herein, we describe an atypical case of CRP in which the skin lesions developed not only on the abdomen, as a site of predilection, but also on broad areas of the extremities.PAGEPress Publications, 2022年12月, Dermatology Reports, 英語[査読有り]研究論文（学術雑誌）
- Abstract Background Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.Springer Science and Business Media LLC, 2022年12月, BMC Medicine, 20(1) (1), 国際共著している[査読有り]研究論文（学術雑誌）
- Wiley, 2022年12月, FASEB BioAdvances, 5(2) (2), 53 - 61, 英語[査読有り]研究論文（学術雑誌）
- Abstract Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseases, while others had one or two dominant sources of unit-level burden, with no consistent pattern geographically across the entire subcontinent. Using a subnational counterfactual analysis, we show that nearly 300 million DALYs could have been averted since 2000 by raising all units to their national average. Our findings are directly relevant for decision-makers in determining which and targeting where the most appropriate interventions are for increasing child survival.Springer Science and Business Media LLC, 2022年12月, Nature Communications, 13(1) (1), 7457 - 7457, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Wiley, 2022年11月, JEADV Clinical Practice, 国際誌研究論文（学術雑誌）
- Non-pigmenting fixed drug eruption (NPFDE) is a subtype of fixed drug eruption (FDE) in which repeated eruptions occur at the same site. Clinically, NPFDE disappears without pigmentation changes; however, it sometimes causes fever or arthralgia. Its histopathological characteristics reportedly include infiltrations of CD8-positive T cells with a paucity of melanocytes as compared to FDE. We present the first case of severe NPFDE exhibiting general symptoms caused by chondroitin sulfate sodium. The patient was a 44-year-old man. Intravenous injection of chondroitin sulfate sodium caused erythema in the affected area. A histopathological examination of the biopsy tissue revealed infiltration of CD3-positive lymphocytes (both CD4-positive and CD8-positive lymphocytes) into the epidermis, minimal liquefaction degeneration in the basal layer of the epidermis, and few dermal melanophages, which may be responsible for non-pigmentation.Frontiers Media SA, 2022年10月, Frontiers in Medicine, 9[査読有り]研究論文（学術雑誌）
- Koebner phenomenon (KP) is the emergence of new lesions in the uninvolved skin area caused by some sorts of stimulations including mechanical stress, chemical stress, trauma or injury. KP is frequently observed in patients with psoriasis and many triggers for developing KP have been reported. We report a case of a 43-year-old obese male welder developed psoriatic lesions only on areas of repeated burns due to occupation [...]PAGEPress Publications, 2022年10月, Dermatology Reports, 英語[査読有り]研究論文（学術雑誌）
- Wiley, 2022年10月, Journal of Medical Virology[査読有り]研究論文（学術雑誌）
- Wiley, 2022年10月, Respirology[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年10月, The Lancet Global Health, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年10月, The Lancet Global Health, 10(10) (10), e1395 - e1411, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Introduction Chronic inducible urticaria (CIndU) is a subgroup of chronic urticaria induced by a specific stimulus. We evaluated basophil characteristics in patients with CIndU and compared with those in patients with chronic spontaneous urticaria (CSU) and healthy controls (HCs). Methods Blood was collected from patients, and a basophil activation test (BAT) was performed. Basophil responsiveness and surface marker expression in patients with CIndU were compared with those in patients with CSU and HCs. For some patients with CIndU, blood was collected before and after wheals were induced. In these cases, we compared the responsiveness of basophils before and after the appearance of wheals. Result HCs (n=23) and patients with CIndU (n=24) or CSU (n=38) were enrolled in the study. The degree of basophil activation at steady state in patients with CIndU was higher than in HCs. Basophil responsiveness via high-affinity IgE receptor (FcϵRI) stimulation with anti-IgE or anti-FcϵRI antibody in patients with CIndU was equivalent to that in HCs, and higher than that in patients with CSU. No abnormalities in IgE and FcϵRI expressions on the surface of basophils in patients with CIndU were observed. When we induced wheals in some patients with CIndU and performed a BAT before and after the appearance of wheals, no significant changes were found. Conclusion Peripheral blood basophils in CIndU were slightly activated at steady state, but no abnormalities in basophil responsiveness. In future, a higher number of cases should be enrolled to confirm the role of basophils and refine therapeutic targets for CIndU.Frontiers Media SA, 2022年09月, Frontiers in Immunology[査読有り]研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2022年09月, American Journal of Clinical Dermatology[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年08月, The Lancet, 400(10352) (10352), 563 - 591, 国際共著している[査読有り]研究論文（学術雑誌）
- Wiley, 2022年06月, Experimental Dermatology[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年06月, The Lancet Public Health, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年06月, The Lancet, 399(10341) (10341), 2129 - 2154, 国際共著している[査読有り]研究論文（学術雑誌）
- Tawbi et al. (2021) have recently reported that nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses (N1I3) provided durable survival for patients with active melanoma brain metastases without symptoms as first-line regimen. While we believe in the usefulness of the regimen proposed by Tawbi et al. (2021) we sought to investigate whether the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses (N3I1) regimen might lead to better safety profile. To compare the risk of adverse events caused by these two regimes, we have recently conducted a meta-analysis using the data of patients with both melanoma and the other malignancies. N1I3 regimen, compared to N3I1 regimen, more frequently induced any adverse events (N1I3, 96%; N3I1, 85%; P = 0.003), grade III or higher adverse events (N1I3, 64%; N3I1, 36%; P < 0.001; Fig. 1), and serious adverse events (N1I3, 61%; N3I1, 48%; P = 0.004). In terms of organ specific side effects, the N1I3 regimen also caused significantly more hepatic dysfunction, diarrhea, colitis, and pyrexia. We hope that there will be further discussion on the best dosage of the combination therapy.2022年05月, Translational oncology, 22, 101449 - 101449, 英語, 国際誌[査読有り]
- Wiley, 2022年04月, The Journal of Dermatology[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2022年02月, Journal of Dermatological Science[査読有り]研究論文（学術雑誌）
- Ovid Technologies (Wolters Kluwer Health), 2022年01月, Plastic and Reconstructive Surgery - Global Open, 10(1) (1), e4015 - e4015, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Regorafenib is an oral multikinase inhibitor targeting several tyrosine kinase receptors including BRAF and epidermal growth factor receptor (EGFR) and is approved as a third-line treatment for metastatic gastrointestinal stromal tumor (GIST). While acneiform eruptions have been observed in patients receiving other BRAF and EGFR inhibitors, the commonly reported adverse reactions to regorafenib are fatigue and palmar-plantar erythrodysesthesia. Herein, we report, to the best of our knowledge, the first case who presented with a severe acneiform eruption 24 months after beginning regorafenib for the treatment of GIST. A 61-year-old woman developed GIST with multiple liver metastases, and she was treated with imatinib and sunitinib. However, these therapies were discontinued, and regorafenib was administered. Twenty-four months after beginning regorafenib, she developed an acneiform eruption on her back. Histopathologic analysis of a skin biopsy from the back revealed neutrophilic suppurative folliculitis. Therefore, she postponed regorafenib administration for 2 months and was treated with topical application of clindamycin phosphate hydrate, which was effective. Consistent with reported evidence that the presence of acneiform eruption and the efficacy of EGFR inhibitors are positively associated, regorafenib had good anticancer activity in our patient. Ultimately, we found that although regorafenib-associated skin toxicities usually appear within 1 month of treatment, patients potentially can present with delayed-onset acneiform eruptions even 24 months later.PAGEPress Publications, 2022年01月, Dermatology Reports, 14(2) (2)[査読有り]研究論文（学術雑誌）
- SAGE Publications, 2022年01月, Therapeutic Advances in Medical Oncology, 14, 175883592110583 - 175883592110583
Background: No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naïve malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens.Methods: Four major electronic databases were searched; both interventional and observational studies were included. All primary cancer types were permitted. Patients should not have been previously treated with any anti-cancer medications. The frequency of AEs was pooled using a random-model meta-analysis using the generic inverse variance method. Protocol registration: UMIN000044090.Results: Forty articles representing 48 populations with 4,677 patients were included in the study. The pooled frequencies for key indicators were as follows: any AE, 81.3% (95% confidence interval (CI) 77.5-85.1); grade 3 or higher AE, 40.6% (95% CI: 35.7–45.5); serious AE, 32.7% (95% CI: 22.4–43.1); AE leading to discontinuation, 28.3% (95% CI: 23.7–32.8); and treatment-related death, 0.7% (95% CI: 0.4–1.1). AEs with the highest incidence were fatigue (27.9%, 95% CI: 22.6–33.3), followed by diarrhea (26.0%, 95% CI: 21.5–30.5), pruritus (24.6%, 95% CI: 20.3–28.8), rash (24.0% 95% CI: 19.3–28.7), and elevated aspartate aminotransferase (21.2%, 95% CI: 14.9–27.5). Subgroup analyses demonstrated that N3I1, compared to N1I3, less frequently induced any AE (N1I3 95.7%, N3I1 84.5%, p = 0.003), grade 3 or higher AE (N1I3 64.3%, N3I1 35.7%, p < 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, p = 0.004).Conclusions: Approximately 40% of patients had grade 3 or higher AE. The N3I1 regimen was substantiated to trigger fewer any AEs, high grade AEs, and serious AE than the N1I3 regimen.[査読有り]研究論文（学術雑誌） - American Medical Association (AMA), 2021年12月, JAMA Oncology, 国際共著している[査読有り]研究論文（学術雑誌）
- Wiley, 2021年12月, Photodermatology, Photoimmunology & Photomedicine, 英語[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年12月, Journal of Dermatological Science, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年12月, The Lancet Oncology, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年12月, Journal of Investigative Dermatology, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2021年12月, Nature Communications, 12(1) (1)
Abstract CARM1 is often overexpressed in human cancers including in ovarian cancer. However, therapeutic approaches based on CARM1 expression remain to be an unmet need. Cancer cells exploit adaptive responses such as the endoplasmic reticulum (ER) stress response for their survival through activating pathways such as the IRE1α/XBP1s pathway. Here, we report that CARM1-expressing ovarian cancer cells are selectively sensitive to inhibition of the IRE1α/XBP1s pathway. CARM1 regulates XBP1s target gene expression and directly interacts with XBP1s during ER stress response. Inhibition of the IRE1α/XBP1s pathway was effective against ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model. Our data show that pharmacological inhibition of the IRE1α/XBP1s pathway alone or in combination with immune checkpoint blockade represents a therapeutic strategy for CARM1-expressing cancers.[査読有り]研究論文（学術雑誌） - Oxford University Press (OUP), 2021年11月, Clinical and Experimental Dermatology, 47(3) (3), 609 - 611[査読有り]研究論文（学術雑誌）
- Wiley, 2021年10月, The Journal of Dermatology[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年10月, The Lancet, 398(10311) (10311), 1593 - 1618, 国際共著している[査読有り]研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2021年10月, Nature Medicine, 27(10) (10), 1761 - 1782, 英語, 国際共著している
Abstract Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations.[査読有り]研究論文（学術雑誌） - Elsevier BV, 2021年10月, The Lancet HIV, 8(10) (10), e633 - e651, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年10月, The Lancet, 398(10308) (10308), 1317 - 1343, 国際共著している[査読有り]研究論文（学術雑誌）
- American Association for Cancer Research (AACR), 2021年09月, Cancer Research[査読有り]研究論文（学術雑誌）
- Fever due to <i>Helicobacter cinaedi</i> bacteremia under chemotherapy has not been widely recognized among clinicians. We experienced a 72-year-old man with diffuse large B-cell lymphoma, who was complicated with <i>H. cinaedi</i> bacteremia-induced fever under R-CHOP chemotherapy. We summarized 6 cases including ours, suggesting that fever without neutropenia developing around day 6 from starting chemotherapy is a possible symptom caused by <i>H. cinaedi</i> bacteremia. We should discriminate fever due to <i>H. cinaedi</i> bacteremia if fever emerged before myelosuppression in the course of chemotherapy.S. Karger AG, 2021年09月, Case Reports in Oncology, 1315 - 1322[査読有り]研究論文（学術雑誌）
- Cutaneous epidermal cysts are common benign cysts derived from the epidermis or epithelium of hair follicles, and malignancy originating from epidermal cysts is uncommon. When a cutaneous epidermal cyst turns malignant, it is mostly squamous cell carcinoma, and basal cell carcinoma is rare. We present the case of a 58-year-old man with basal cell carcinoma originating from an epidermal cyst on the buttocks. Histopathological analysis with hematoxylin- eosin (H&E) staining showed the presence of the cyst, the wall of which was partially replaced by a malignant tumor. Moreover, the cyst was filled with malignant tumor cells in some areas. The tumor cells were basaloid, and extended through the dermis down to the subcutaneous tissue in a solid pattern. Immunoperoxidase staining for Ber-EP4 was positive. To our knowledge, there are 11 reported cases of BCC originating from epidermal cysts in English, and we reviewed these reports and examined potential trends. We estimate that some longstanding epidermal cysts may have the potential of malignant transformation, and chronic and repeated irritation might trigger malignancy from epidermal cysts. We emphasize that benignlooking cystic lesions showing progressive growth should be examined histopathologically.PAGEPress Publications, 2021年08月, Dermatology Reports, 13(2) (2)[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年08月, Journal of Dermatological Science[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年08月, The Lancet, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2021年08月, The Lancet, 398(10299) (10299), 503 - 521, 国際共著している[査読有り]研究論文（学術雑誌）
- Oxford University Press (OUP), 2021年06月, Rheumatology, 英語, 国際誌
Abstract Objectives No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease (BD).Methods The Japanese government provided us with a dataset of confirmed or suspected BD cases derived from ongoing national registration. ADL were categorized and analyzed into four categories in patients who satisfied the international criteria for BD.Results Data from 2960 patients (men, 38.9%; women, 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising: limited but not assisted, 1058 (35.7%); partially assisted, 116 (3.9%); and fully assisted, 19 (0.6%). Logistic regression analysis showed that chronic ocular lesions (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.46–2.35, p< 0.001), paralysis (OR 2.51, 95% CI 1.58–3.97, p< 0.001), psychosis (OR 3.16, 95% CI 2.02–4.95, p< 0.001), and arthritis (OR 1.69, 95% CI 1.44–1.99, p< 0.001) led to the risk of impaired ADL (not normal ADL). Chronic ocular lesions (OR 3.61, 95% CI 2.27–5.72, p< 0.001), paralysis (OR 3.43, 95% CI 1.87–6.30, p< 0.001), and psychosis (OR 3.60, 95% CI 2.00–6.50, p< 0.001) were related to the requirement of physical assistance (partially or fully assisted), although arthritis (OR 1.39, 95% CI 0.93–2.06, p= 0.108) was not a significant factor in this model.Conclusion Ocular lesion, neurological manifestations, and arthritis affected ADL. Patients with ocular lesion or neurological manifestations more frequently required physical assistance.[査読有り]研究論文（学術雑誌） - Elsevier BV, 2021年06月, The Lancet HIV, 8(6) (6), e363 - e375, 国際共著している[査読有り]研究論文（学術雑誌）
- Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex that catalyses messenger RNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent functions of the methyltransferase complex, the m6A-independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 transcriptionally drives the senescence-associated secretory phenotype (SASP) in an m6A-independent manner. METTL14 is redistributed to the enhancers, whereas METTL3 is localized to the pre-existing NF-κB sites within the promoters of SASP genes during senescence. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL3 and METTL14 are required for both the tumour-promoting and immune-surveillance functions of senescent cells, which are mediated by SASP in vivo in mouse models. In summary, our results report an m6A-independent function of the METTL3 and METTL14 complex in transcriptionally promoting SASP during senescence.2021年04月, Nature cell biology, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 2021年03月, European journal of cancer (Oxford, England : 1990), 147, 140 - 141, 英語, 国際誌[査読有り]
- BACKGROUD: Existing guidelines form no consensus for alopecia areata (AA) treatment due to the absence of a universal standard treatment and arbitrary selection of reference arms in randomized control trials (RCTs). OBJECTIVE: To identify the best treatment and to rank treatments using systematic review and network meta-analysis. METHODS: Data were extracted by the two investigators independently. Odds ratio (OR) of treatment success rate was pooled using the frequentist weighted least squares approach to random-model network meta-analysis. We included RCTs providing data of treatment success rate from PubMed, EMBASE, Web of Science, and manual search. RESULTS: Fifty-four RCTs consisting of 49 treatments and 3149 patients were included. Pentoxifylline plus topical corticosteroids had the highest treatment success rate compared to "no treatment", followed by pentoxifylline alone, topical calcipotriol plus narrowband ultraviolet radiation B phototherapy, topical calcipotriol, intralesional corticosteroids, systemic corticosteroids, minoxidil plus topical corticosteroids, topical bimatoprost, psoralen ultraviolet radiation A phototherapy, and tofacitinib. CONCLUSION: Even with the network meta-analysis, we could not identify the best treatment because of independent loops and wide confidence intervals. Treatment options above may be reasonable strategies, but further comparison is required. This article is protected by copyright. All rights reserved.2021年02月, Dermatologic therapy, e14916, 英語, 国際誌, 国際共著している研究論文（学術雑誌）
- 2021年02月, Allergology international : official journal of the Japanese Society of Allergology, 英語, 国際誌[査読有り]
- Intravenous immunoglobulins (IVIg) are increasingly being used to treat a wide spectrum of dermatological and neurological autoimmune diseases. Although the administration of IVIg does not usually result in severe adverse reactions, side effects of IVIg reportedly occur in 6-13% of patients. Most reported cases were not severe, and IVIg is considered a relatively safe drug. Some reports described a vesicular eczematous eruption caused by IVIg that was cured by applying topical steroid ointments or systemic steroids. Herein, we present, to the best of our knowledge, the first case of severe vesicular eczematous eruption all over the body induced by IVIg that was unresponsive to topical steroid ointment and was subsequently treated with narrow band-ultraviolet B (NB-UVB) therapy successfully. NB-UVB was started at a dose of 400 mJ/cm2 once a week, and swift improvement was observed. The skin rash disappeared in the first 2 months, and the pathogenesis of IVIg-induced eczematous eruption remains unelucidated. No change in eosinophils and complement levels were observed in our case. Given the increase in the widespread use of IVIg, we have shown that NB-UVB therapy is a candidate choice for the treatment of IVIg-induced severe vesicular eczematous eruption.2021年02月, Photodermatology, photoimmunology & photomedicine, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Alterations in components of the SWI/SNF chromatin-remodeling complex occur in ~20% of all human cancers. For example, ARID1A is mutated in up to 62% of clear cell ovarian carcinoma (OCCC), a disease currently lacking effective therapies. Here we show that ARID1A mutation creates a dependence on glutamine metabolism. SWI/SNF represses glutaminase (GLS1) and ARID1A inactivation upregulates GLS1. ARID1A inactivation increases glutamine utilization and metabolism through the tricarboxylic acid cycle to support aspartate synthesis. Indeed, glutaminase inhibitor CB-839 suppresses the growth of ARID1A mutant, but not wildtype, OCCCs in both orthotopic and patient-derived xenografts. In addition, glutaminase inhibitor CB-839 synergizes with immune checkpoint blockade anti-PDL1 antibody in a genetic OCCC mouse model driven by conditional Arid1a inactivation. Our data indicate that pharmacological inhibition of glutaminase alone or in combination with immune checkpoint blockade represents an effective therapeutic strategy for cancers involving alterations in the SWI/SNF complex such as ARID1A mutations.2021年02月, Nature cancer, 2(2) (2), 189 - 200, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- BACKGROUND: Most patients with facial pigmentary disorders have multiple disorders. However, there is no definitive treatment algorithm improving various pigmentary disorders simultaneously. OBJECTIVES: To investigate the clinical efficacy and safety of the combination of the Q-switched alexandrite and the carbon dioxide lasers with ZO SKIN HEALTHⓇ for facial pigmentary disorders. PATIENTS/METHODS: This prospective observational study enrolled 251 patients with at least one facial pigmentary disorder. We assessed treatment efficacy and investigated which disorders were most responsive to combination treatment and the relationship between doctors' skills, outcomes, and dropout rates. RESULTS: There were 246 patients with lentigo senilis, 186 with moles, 79 with melasma, 53 with seborrheic keratosis, 17 with acquired dermal melanocytosis (ADM), and 16 with freckles. Overall, 227 patients completed treatment. Post-treatment outcomes were excellent in 97, good in 113, fair in 17, and poor in 0 patients. Freckles were the most responsive, and ADM was the least responsive. Patient withdrawal and treatment outcomes did not differ significantly based on the doctors' skills. Overall, 3.2% of patients had adverse events. CONCLUSIONS: Our combination algorithm improved several pigmentary disorders of the face simultaneously, regardless of the doctors' proficiency level.2021年02月, Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 74(2) (2), 370 - 376, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Therapy-induced senescence-associated secretory phenotype (SASP) correlates with overcoming resistance to immune checkpoint blockade (ICB). Intrinsic resistance to ICB is a major clinical challenge. For example, ovarian cancer is largely resistant to ICB. Here we show that adoptive transfer of SASP-boosted ex vivo therapy-induced senescent cells sensitizes ovarian tumor to ICB. Topoisomerase 1 (TOP1) inhibitors such as irinotecan enhance cisplatin-induced SASP, which depends on the TOP1 cleavage complex-regulated cGAS pathway. Significantly, intraperitoneal transfer of cisplatin-induced, SASP-boosted senescent cells with irinotecan sensitizes ovarian tumor to anti-PD-1 antibody and improves the survival of tumor-bearing mice in an immunocompetent, syngeneic model. This correlates with the infiltration of transferred senescent cells in the established orthotopic tumors and an increase in the infiltration of activated CD8+ T cells and dendritic cells in the tumor bed. Our findings indicate that adoptive transfer of SASP-boosted therapy-induced senescent cells represents a potential therapeutic strategy to sensitize tumors to ICB.2021年01月, iScience, 24(1) (1), 102016 - 102016, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- The SWI/SNF chromatin remodeler family includes the BAF and PBAF complexes. ARID2, encoding a PBAF complex subunit, is frequently mutated in melanoma independently of BRAF/RAS mutations. Emerging evidence shows that SWI/SNF complexes regulate tumor immunity; for instance, the loss of PBRM1, another PBAF complex subunit, enhances susceptibility to immune checkpoint inhibitors in melanoma. Notably, ARID2 mutations are more frequent in melanoma than PBRM1 mutations. However, the role of ARID2 as a modulator of tumor immunity remains unclear. In this study, we show that ARID2 knockout sensitizes melanoma to immune checkpoint inhibitors. Anti‒PD-L1 treatment restricts tumor growth in mice bearing ARID2-knockout melanoma cells, correlating with an increase in the infiltration of cytotoxic CD8+ T cells. Furthermore, ARID2 deficiency leads to signal transducer and activator of transcription 1 upregulation, which subsequently causes increased expression of T-cell‒attracting chemokines such as CXCL9, CXCL10, and CCL5. These results demonstrate that ARID2 is an immunomodulator and a potential biomarker that indicates immune checkpoint inhibitor effectiveness in patients with melanoma.2020年12月, The Journal of investigative dermatology, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2020年12月, Journal of the American College of Cardiology, 76(25) (25), 2982 - 3021, 国際共著している[査読有り]研究論文（学術雑誌）
- NATURE RESEARCH, 2020年12月, NATURE, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- 日本発汗学会, 2020年11月, 日本発汗学会総会プログラム・抄録集, 28回, 55 - 55, 日本語2008年から2018年にかけて神戸大学皮膚科で経験した特発性後天性全身性無汗症32例の検討
- 2020年11月, Dermatologic therapy, 33(6) (6), e14480, 英語, 国際誌[査読有り]
- 2020年10月, The Australasian journal of dermatology, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Elsevier BV, 2020年10月, The Lancet, 396(10258) (10258), 1250 - 1284, 国際共著している[査読有り]研究論文（学術雑誌）
- Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease.Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden.Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10.8 million (95% uncertainty interval [UI] 9.51-12.1) deaths (19.2% [16.9-21.3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8.71 million (8.12-9.31) deaths (15.4% [14.6-16.2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253-350) DALYs (11.6% [10.3-13.1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0-9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10-24 years, alcohol use for those aged 25-49 years, and high systolic blood pressure for those aged 50-74 years and 75 years and older.Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2020年10月, LANCET, 396(10258) (10258), 1223 - 1249, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries.Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution.Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI.Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2020年10月, LANCET, 396(10258) (10258), 1204 - 1222, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019.Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric.Findings The global TFR decreased from 2.72 (95% uncertainty interval [UI] 2.66-2.79) in 2000 to 2.31 (2.17-2.46) in 2019. Global annual livebirths increased from 134.5 million (131.5-137.8) in 2000 to a peak of 139.6 million (133.0-146.9) in 2016. Global livebirths then declined to 135.3 million (127.2-144.1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2.1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27.1% (95% UI 26.4-27.8) of global livebirths. Global life expectancy at birth increased from 67.2 years (95% UI 66.8-67.6) in 2000 to 73.5 years (72.8-74.3) in 2019. The total number of deaths increased from 50.7 million (49.5-51.9) in 2000 to 56.5 million (53.7-59.2) in 2019. Under-5 deaths declined from 9.6 million (9.1-10.3) in 2000 to 5.0 million (4.3-6.0) in 2019. Global population increased by 25.7%, from 6.2 billion (6.0-6.3) in 2000 to 7.7 billion (7.5-8.0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58.6 years (56.1-60.8) in 2000 to 63.5 years (60.8-66.1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019.Interpretation Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2020年10月, LANCET, 396(10258) (10258), 1160 - 1203, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Five insights from the Global Burden of Disease Study 2019The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.ELSEVIER SCIENCE INC, 2020年10月, LANCET, 396(10258) (10258), 1135 - 1159, 英語, 国際共著している[査読有り]
- BACKGROUND: Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. METHODS: We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. RESULTS: Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). CONCLUSIONS: The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.2020年10月, Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 26(Supp 1) (Supp 1), i36-i45, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- BACKGROUND: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. METHODS: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. RESULTS: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. CONCLUSIONS: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.2020年10月, Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 26(Supp 1) (Supp 1), i12-i26, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- BACKGROUND: As global rates of mortality decrease, rates of non-fatal injury have increased, particularly in low Socio-demographic Index (SDI) nations. We hypothesised this global pattern of non-fatal injury would be demonstrated in regard to bony hand and wrist trauma over the 27-year study period. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 was used to estimate prevalence, age-standardised incidence and years lived with disability for hand trauma in 195 countries from 1990 to 2017. Individual injuries included hand and wrist fractures, thumb amputations and non-thumb digit amputations. RESULTS: The global incidence of hand trauma has only modestly decreased since 1990. In 2017, the age-standardised incidence of hand and wrist fractures was 179 per 100 000 (95% uncertainty interval (UI) 146 to 217), whereas the less common injuries of thumb and non-thumb digit amputation were 24 (95% UI 17 to 34) and 56 (95% UI 43 to 74) per 100 000, respectively. Rates of injury vary greatly by region, and improvements have not been equally distributed. The highest burden of hand trauma is currently reported in high SDI countries. However, low-middle and middle SDI countries have increasing rates of hand trauma by as much at 25%. CONCLUSIONS: Certain regions are noted to have high rates of hand trauma over the study period. Low-middle and middle SDI countries, however, have demonstrated increasing rates of fracture and amputation over the last 27 years. This trend is concerning as access to quality and subspecialised surgical hand care is often limiting in these resource-limited regions.2020年10月, Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 26(Supp 1) (Supp 1), i115-i124, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- BACKGROUND: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. METHODS: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). FINDINGS: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). INTERPRETATION: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.2020年10月, Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 26(Supp 1) (Supp 1), i96-i114, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.2020年10月, Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention, 26(Supp 1) (Supp 1), i125-i153, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- We herein report a unique case of aortic rupture due to co-localization of aortic intimal myofibroblastic sarcoma (IMFS) and urothelial carcinoma (UC). A 76-year-old man who was being followed up after surgery for UC 5 years earlier developed aortic rupture and underwent emergency surgery. Intraoperatively, a tumorous mass on the luminal side of the aortic arch was found near the rupture. A histopathological analysis of the mass revealed aortic IMFS. Furthermore, co-localization of IMFS and UC cells was found near the rupture. The fragility of the aortic wall due to co-localization of IMFS and UC was believed to contribute to the aortic rupture.2020年09月, Internal medicine (Tokyo, Japan), 英語, 国内誌[査読有り]研究論文（学術雑誌）
- Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities.Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs.Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017.Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.ELSEVIER SCI LTD, 2020年09月, LANCET GLOBAL HEALTH, 8(9) (9), E1162 - E1185, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Myeloid-derived suppressor cells (MDSCs) are widely implicated in negative regulation of immune responses in cancer. Inhibition of class I histone deacetylases (HDAC) with entinostat has anti-MDSC activity. However, as single agent, it did not delay tumor growth in EL4 and LLC tumor models. Here, we found that entinostat reduced immune suppressive activity of only one type of MDSC-polymorphonuclear, PMN-MDSC, whereas it had no effect on monocytic M-MDSC or macrophages. M-MDSC had high amount of class II HDAC-HDAC6, which was further increased after the treatment of mice with entinostat. Inhibition of HDAC6 with ricolinostat reduced suppressive activity of M-MDSC, but did not affect PMN-MDSC or delayed tumor growth. However, combination of entinostat and ricolinostat abrogated suppressive activity of both populations of MDSC and substantially delayed tumor progression. Thus, inactivation of MDSC required targeting of both major subsets of these cells via inhibitors of class I and class II HDAC.SPRINGER, 2020年09月, CANCER IMMUNOLOGY IMMUNOTHERAPY, 69(9) (9), 1929 - 1936, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2020年09月, JOURNAL OF DERMATOLOGY, 47(9) (9), E314 - E315, 英語, 国際誌[査読有り]
- SPRINGER LONDON LTD, 2020年09月, LASERS IN MEDICAL SCIENCE, 35(7) (7), 1659 - 1661, 英語, 国際誌[査読有り]
- 2020年08月, Journal of the European Academy of Dermatology and Venereology : JEADV, 英語, 国際誌[査読有り]
- Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17Background Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs.Methods We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2 center dot 5th and 97 center dot 5th percentiles of those 250 draws.Findings While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62 center dot 6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average.Interpretation To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.ELSEVIER SCI LTD, 2020年08月, LANCET GLOBAL HEALTH, 8(8) (8), 1038 - 1060, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- This cohort study reports the trends and variations in skin and subcutaneous diseases, along with malignant melanoma and keratinocyte carcinoma, in the 50 states and the District of Columbia for the past 3 decades.Question Has the burden of skin and subcutaneous diseases varied across the US from 1990 to 2017? Findings This cohort study of patients included in the Global Burden of Disease database from 1990 to 2017 evaluated skin and subcutaneous disease burden across the US, the disability-adjusted life-year rate, incidence, and prevalence of skin disease increased from 1990 to 2017, and disease burden varied by geographic location. The highest age-standardized disability-adjusted life-year rate was found in New York, whereas Wyoming had the lowest rate. Meaning These epidemiological national data on disease burden can guide future research efforts, allocation of resources, prevention strategies, and targeted treatment of skin conditions.Importance Skin and subcutaneous diseases affect the health of millions of individuals in the US. Data are needed that highlight the geographic trends and variations of skin disease burden across the country to guide health care decision-making. Objective To characterize trends and variations in the burden of skin and subcutaneous tissue diseases across the US from 1990 to 2017. Design, Setting, and Participants For this cohort study, data were obtained from the Global Burden of Disease (GBD), a study with an online database that incorporates current and previous epidemiological studies of disease burden, and from GBD 2017, which includes more than 90.000 data sources such as systematic reviews, surveys, population-based disease registries, hospital inpatient and outpatient data, cohort studies, and autopsy data. The GBD separated skin conditions into 15 subcategories according to incidence, prevalence, adequacy of data, and standardized disease definitions. GBD 2017 also estimated the burden from melanoma of the skin and keratinocyte carcinoma. Data analysis for the present study was conducted from September 9, 2019, to March 31, 2020. Main Outcomes and Measures Primary study outcomes included age-standardized disability-adjusted life-years (DALYs), incidence, and prevalence. The data were stratified by US states with the highest and lowest age-standardized DALY rate per 100.000 people, incidence, and prevalence of each skin condition. The percentage change in DALY rates in each state was calculated from 1990 to 2017. Results Overall, age-standardized DALY rates for skin and subcutaneous diseases increased from 1990 (821.6; 95% uncertainty interval [UI], 570.3-1124.9) to 2017 (884.2; 95% UI, 614.0-1207.9) in all 50 states and the District of Columbia. The degree of increase varied according to geographic location, with the largest percentage change of 0.12% (95% UI, 0.09%-0.15%) in New York and the smallest percentage change of 0.04% (95% UI, 0.02%-0.07%) in Colorado, 0.04% (95% UI, 0.01%-0.06%) in Nevada, 0.04% (95% UI, 0.02%-0.07%) in New Mexico, and 0.04% (95% UI, 0.02%-0.07%) in Utah. The age-standardized DALY rate, incidence, and prevalence of specific skin conditions differed among the states. New York had the highest age-standardized DALY rate for skin and subcutaneous disease in 2017 (1097.0 [95% UI, 764.9-1496.1]), whereas Wyoming had the lowest age-standardized DALY rate (672.9 [95% UI, 465.6-922.3]). In all 50 states and the District of Columbia, women had higher age-standardized DALY rates for overall skin and subcutaneous diseases than men (women: 971.20 [95% UI, 676.76-1334.59] vs men: 799.23 [95% UI, 559.62-1091.50]). However, men had higher DALY rates than women for malignant melanoma (men: 80.82 [95% UI, 51.68-123.18] vs women: 42.74 [95% UI, 34.05-70.66]) and keratinocyte carcinomas (men: 37.56 [95% UI, 29.35-49.52] vs women: 14.42 [95% UI, 10.01-20.66]). Conclusions and Relevance Data from the GBD suggest that the burden of skin and subcutaneous disease was large and that DALY rate trends varied across the US; the age-standardized DALY rate for keratinocyte carcinoma appeared greater in men. These findings can be used by states to target interventions and meet the needs of their population.AMER MEDICAL ASSOC, 2020年08月, JAMA DERMATOLOGY, 156(8) (8), 874 - 881, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behcet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan. Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behcet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed. Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women. Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.TAYLOR & FRANCIS LTD, 2020年07月, MODERN RHEUMATOLOGY, 30(4) (4), 708 - 714, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2020年07月, DERMATOLOGIC THERAPY, e13889, 英語, 国際誌[査読有り]
- 2020年06月, European journal of dermatology : EJD, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea.Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates.Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54.0% (95% uncertainty interval [UI] 38.1-65.8), 17.4% (7.7-28.4), and 59.5% (34.2-86.9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage.Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2020年06月, LANCET, 395(10239) (10239), 1779 - 1801, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Objective: Unusual clinical courseBackground: Chronic pancreatitis is a slowly progressive inflammatory disease, affecting patients' quality of life due to chronic pain as well as endocrine and exocrine pancreatic insufficiency. Patients often choose surgery if medical and endoscopic interventions fail. Surgical approaches for chronic pancreatitis can be categorized as follows: resection of the diseased gland, diversion and drainage of the dilated pancreatic duct, or a combination of these approaches. Frey's procedure, which involves resection and drainage by longitudinal pancreaticojejunostomy and coring out of the pancreatic head, is reserved for patients with debilitating pain. Although laparoscopic surgery is gaining popularity in recent years due to its noninvasiveness and cosmetic benefit, few reports describe performing Frey's procedure laparoscopically.Case Report: A 36-year-old Japanese female with chronic pancreatitis complained of back pain and pain in the left upper quadrant abdomen. Plain computed tomography of her abdomen revealed a dilated main pancreatic duct containing diffuse calculi extending to the pancreatic parenchyma. Laboratory findings, including amylase level, were within normal ranges. She was diagnosed with chronic pancreatitis, and subsequently underwent a laparoscopic Frey's procedure. To our knowledge, we are the first to improve operative field visibility by using a Penrose drain to move the stomach from the line of sight. Postoperatively, the patient did well and was discharged 10 days after surgery. She remained symptom-free without medications for 80 months.Conclusions: Due to its noninvasive nature and cosmetic advantages, laparoscopic Frey's procedure may be an attractive therapeutic option for chronic pancreatitis.INT SCIENTIFIC INFORMATION, INC, 2020年06月, AMERICAN JOURNAL OF CASE REPORTS, 21, e924206, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公社)日本皮膚科学会, 2020年05月, 日本皮膚科学会雑誌, 130(5) (5), 1257 - 1257, 日本語当院で経験した特発性後天性全身性無汗症32例の長期予後に関する検討
- NATURE PUBLISHING GROUP, 2020年05月, NATURE MEDICINE, 26(5) (5), 750 - +, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Objectives This paper presents detailed analysis of the global and regional burden of chronic respiratory disease arising from occupational airborne exposures, as estimated in the Global Burden of Disease 2016 study.Methods The burden of chronic obstructive pulmonary disease (COPD) due to occupational exposure to particulate matter, gases and fumes, and secondhand smoke, and the burden of asthma resulting from occupational exposure to asthmagens, was estimated using the population attributable fraction (PAF), calculated using exposure prevalence and relative risks from the literature. PAFs were applied to the number of deaths and disability-adjusted life years (DALYs) for COPD and asthma. Pneumoconioses were estimated directly from cause of death data. Age-standardised rates were based only on persons aged 15 years and above.Results The estimated PAFs (based on DALYs) were 17% (95% uncertainty interval (UI) 14%-20%) for COPD and 10% (95% UI 9%-11%) for asthma. There were estimated to be 519 000 (95% UI 441,000-609,000) deaths from chronic respiratory disease in 2016 due to occupational airborne risk factors (COPD: 460,100 [95% UI 382,000-551,000]; asthma: 37,600 [95% UI 28,400-47,900]; pneumoconioses: 21,500 [95% UI 17,900-25,400]. The equivalent overall burden estimate was 13.6 million (95% UI 11.9-15.5 million); DALYs (COPD: 10.7 [95% UI 9.0-12.5] million; asthma: 2.3 [95% UI 1.9-2.9] million; pneumoconioses: 0.58 [95% UI 0.46-0.67] million). Rates were highest in males; older persons and mainly in Oceania, Asia and sub-S aharan Africa; and decreased from 1990 to 2016.Conclusions Workplace exposures resulting in COPD, asthma and pneumoconiosis continue to be important contributors to the burden of disease in all regions of the world. This should be reducible through improved prevention and control of relevant exposures.BMJ PUBLISHING GROUP, 2020年03月, OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 77(3) (3), 142 - 150, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Objectives This study provides an overview of the influence of occupational risk factors on the global burden of disease as estimated by the occupational component of the Global Burden of Disease (GBD) 2016 study.Methods The GBD 2016 study estimated the burden in terms of deaths and disability-adjusted life years (DALYs) arising from the effects of occupational risk factors (carcinogens; asthmagens; particulate matter, gases and fumes (PMGF); secondhand smoke (SHS); noise; ergonomic risk factors for low back pain; risk factors for injury). A population attributable fraction (PAF) approach was used for most risk factors.Results In 2016, globally, an estimated 1.53 (95% uncertainty interval 1.39-1.68) million deaths and 76.1 (66.3-86.3) million DALYs were attributable to the included occupational risk factors, accounting for 2.8% of deaths and 3.2% of DALYs from all causes. Most deaths were attributable to PMGF, carcinogens (particularly asbestos), injury risk factors and SHS. Most DALYs were attributable to injury risk factors and ergonomic exposures. Men and persons 55 years or older were most affected. PAFs ranged from 26.8% for low back pain from ergonomic risk factors and 19.6% for hearing loss from noise to 3.4% for carcinogens. DALYs per capita were highest in Oceania, Southeast Asia and Central sub-Saharan Africa. On a per capita basis, between 1990 and 2016 there was an overall decrease of about 31% in deaths and 25% in DALYs.Conclusions Occupational exposures continue to cause an important health burden worldwide, justifying the need for ongoing prevention and control initiatives.BMJ PUBLISHING GROUP, 2020年03月, OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 77(3) (3), 133 - 141, 英語[査読有り]研究論文（学術雑誌）
- Objectives This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study.Methods The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs).Results There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens.Conclusions Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.BMJ PUBLISHING GROUP, 2020年03月, OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 77(3) (3), 151 - 159, 英語[査読有り]研究論文（学術雑誌）
- Epithelial ovarian cancer (EOC) is the most lethal of gynecologic malignancies. The standard-of-care treatment for EOC is platinum-based chemotherapy such as cisplatin. Platinum-based chemotherapy induces cellular senescence. Notably, therapy-induced senescence contributes to chemoresistance by inducing cancer stem-like cells (CSC). However, therapeutic approaches targeting senescence-associated CSCs remain to be explored. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT) inhibition suppresses senescence-associated CSCs induced by platinum-based chemotherapy in EOC. Clinically applicable NAMPT inhibitors suppressed the outgrowth of cisplatin-treated EOC cells both in vitro and in vivo. Moreover, a combination of the NAMPT inhibitor FK866 and cisplatin improved the survival of EOCbearing mice. These phenotypes correlated with inhibition of the CSCs signature, which consists of elevated expression of ALDH1A1 and stem-related genes, high aldehyde dehydrogenase activity, and CD133 positivity. Mechanistically, NAMPT regulates EOC CSCs in a paracrine manner through the senescence-associated secretory phenotype. Our results suggest that targeting NAMPT using clinically applicable NAMPT inhibitors, such as FK866, in conjunction with platinum-based chemotherapy represents a promising therapeutic strategy by suppressing therapy-induced senescenceassociated CSCs.Significance: This study highlights the importance of NAMPTmediated NAD(+) biosynthesis in the production of cisplatininduced senescence-associated cancer stem cells, as well as tumor relapse after cisplatin treatment.AMER ASSOC CANCER RESEARCH, 2020年02月, CANCER RESEARCH, 80(4) (4), 890 - 900, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- In response to DNA double-strand breaks, MAD2L2-containing shieldin complex plays a critical role in the choice between homologous recombination (HR) and non-homologous end-joining (NHEJ)-mediated repair. Here we show that EZH2 inhibition upregulates MAD2L2 and sensitizes HR-proficient epithelial ovarian cancer (EOC) to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner. CARM1 promotes MAD2L2 silencing by driving the switch from the SWI/SNF complex to EZH2 through methylating the BAF155 subunit of the SWI/SNF complex on the MAD2L2 promoter. EZH2 inhibition upregulates MAD2L2 to decrease DNA end resection, which increases NHEJ and chromosomal abnormalities, ultimately causing mitotic catastrophe in PARP inhibitor treated HR-proficient cells. Significantly, EZH2 inhibitor sensitizes CARM1-high, but not CARM-low, EOCs to PARP inhibitors in both orthotopic and patient-derived xenografts.CELL PRESS, 2020年02月, CANCER CELL, 37(2) (2), 157 - +, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Cyclic cGMP-AMP synthase (cGAS) is a pattern recognition cytosolic DNA sensor that is essential for cellular senescence. cGAS promotes inflammatory senescence-associated secretory phenotype (SASP) through recognizing cytoplasmic chromatin during senescence. cGAS-mediated inflammation is essential for the antitumor effects of immune checkpoint blockade. However, the mechanism by which cGAS recognizes cytoplasmic chromatin is unknown. Here we show that topoisomerase 1-DNA covalent cleavage complex (TOP1cc) is both necessary and sufficient for cGAS-mediated cytoplasmic chromatin recognition and SASP during senescence. TOP1cc localizes to cytoplasmic chromatin and TOP1 interacts with cGAS to enhance the binding of cGAS to DNA. Retention of TOP1cc to cytoplasmic chromatin depends on its stabilization by the chromatin architecture protein HMGB2. Functionally, the HMGB2-TOP1cc-cGAS axis determines the response of orthotopically transplanted ex vivo therapy-induced senescent cells to immune checkpoint blockade in vivo. Together, these findings establish a HMGB2-TOP1cc-cGAS axis that enables cytoplasmic chromatin recognition and response to immune checkpoint blockade. Here, the authors show that the topoisomerase 1-DNA covalent cleavage complex plays a critical role in mediating cytoplasmic chromatin fragments recognition by cyclic GMP-AMP synthase during senescence. The proposed axis is crucial to promote the inflammatory senescence-associated secretory phenotype and to enable the response to immune checkpoint blockade.NATURE PUBLISHING GROUP, 2020年02月, NATURE COMMUNICATIONS, 11(1) (1), 908 - 908, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Childhood malnutrition is associated with high morbidity and mortality globally(1). Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood(2). Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0-59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards(3-5.) The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization's median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)(7); the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes(8). Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped highspatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrativelevel units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications.NATURE PUBLISHING GROUP, 2020年01月, NATURE, 577(7789) (7789), 231 - +, 英語[査読有り]研究論文（学術雑誌）
- Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.Educational attainment is an important social determinant of maternal, newborn, and child health(1-3). As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting(4-6). The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness(7,8); however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health(9-11). Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries(12-14). By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.NATURE PUBLISHING GROUP, 2020年01月, NATURE, 577(7789) (7789), 235 - +, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Coexistence of bullous pemphigoid (BP) and vitiligo vulgaris (VV) is very rare. We present a unique case of BP associated with VV in a 76-year-old Japanese man, in which BP eruption developed exclusively on preexisting VV regions. The patient was referred to us with a 3-month history of blistering eruption with severe pruritis on the right forearm and left lower limb. In addition, he had been suffering from a widespread depigmented eruption on the trunk and extremities for at least 20 years. Curiously, the blistering eruption developed exclusively on preexisting depigmented eruption. Histopathological and laboratory examinations identified the blistering eruption as BP. The depigmented eruption was diagnosed as VV. BP eruption responded quickly to oral prednisolone therapy, improving within 1 week, and the prednisolone dose was gradually tapered. Within 1 month, BP lesions almost completely resolved. In the present case, BP not only coexisted with VV, but also developed exclusively on preexisting vitiliginous regions. The present case strongly suggests that BP and VV are partly caused by common pathological mechanisms.KARGER, 2020年, CASE REPORTS IN DERMATOLOGY, 12(1) (1), 33 - 36, 英語[査読有り]研究論文（学術雑誌）
- Background: How HLA-A26 modulates Behcet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized. Methods: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available. Results: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146). Conclusion: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.TAYLOR & FRANCIS LTD, 2020年01月, MODERN RHEUMATOLOGY, 1 - 5, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2020年01月, EUROPEAN JOURNAL OF DERMATOLOGY, 30(1) (1), 62 - 63, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980-2017 and forecast these estimates to 2030 for 195 countries and territories.Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package-a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections.Findings Global HIV mortality peaked in 2006 with 1.95 million deaths (95% uncertainty interval 1.87-2.04) and has since decreased to 0.95 million deaths (0.91-1.01) in 2017. New cases of HIV globally peaked in 1999 (3.16 million, 2.79-3.67) and since then have gradually decreased to 1.94 million (1.63-2.29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36.8 million (34.8-39.2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65.7% in Lesotho to 85.7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets.Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.ELSEVIER INC, 2019年12月, LANCET HIV, 6(12) (12), E831 - E859, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Importance Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.Question What is the cancer burden over time at the global and national levels, measured in incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs), and how does it compare with other diseases? Findings Results of this systematic analysis show that in 2017 there were 24.5 million incident cases (16.8 million without nonmelanoma skin cancer), 9.6 million deaths, and 233.5 million DALYs due to cancer; between 2007 and 2017, incident cases increased by 33%, with the lowest increase in the most developed countries, and between 1990 and 2017 neoplasms increased among the top causes of DALYs from the sixth to the second place. Fifty-one percent of cancer cases occurred in countries of high Socio-demographic Index, but only 30% of cancer deaths and 24% of cancer DALYs. Meaning To ensure sustainable global development, increased efforts are needed in cancer prevention and in ensuring universal access to cancer care.This systematic analysis describes cancer burden for 29 cancer groups across 195 countries from 1990 through 2017 to provide data needed for cancer control planning.AMER MEDICAL ASSOC, 2019年12月, JAMA ONCOLOGY, 5(12) (12), 1749 - 1768, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Although many variations of guidelines have been released, there is limited research that compares multiple treatment strategies for basal cell carcinoma (BCC). The aim of this study was to systematically review the studies reporting on multiple treatments for BCC with systematic review and network meta-analyses. Search formulas for databases, such as PubMed, EMBASE, Web of Science Core Collection and Cochrane Central Register of Controlled Trials, were created with the support of Cochrane Japan. The patient-level and tumour-level meta-analyses were performed for both the long-term treatment-failure and treatment-success. Of the 1464 studies identified from the database and hand searches, 14 met our inclusion criteria. These 14 studies included 2524 patients and 1738 tumours. Our study indicated that the incidence of treatment-failure of invasive treatments such as surgery and Mohs micrographic surgery was significantly lower than that of superficial therapies such as cryotherapy, photodynamic therapy, radiotherapy or topical therapies, in the patient-level and the tumour-level analyses, despite histological-type and pretreatment. Relapse of BCC may be a low life-threatening risk, and there are merits of non-surgical treatment. However, the significant difference in the recurrence rate is essential. Our study can provide useful guidance to clinicians in selecting treatment options for BCC.2019年11月, Journal of the European Academy of Dermatology and Venereology : JEADV, 33(11) (11), 2050 - 2057, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- AMER ASSOC CANCER RESEARCH, 2019年11月, CLINICAL CANCER RESEARCH, 25(22) (22), 158 - 158, 英語COMBINATIONAL TARGETING OF HDAC6 AND PD-1/PD-L1 IMMUNE CHECKPOINT IN ARID1A-MUTATED OVARIAN CANCERS[査読有り]
- AMER ASSOC CANCER RESEARCH, 2019年11月, CLINICAL CANCER RESEARCH, 25(22) (22), 204 - 204, 英語THE N6-METHYLATION OF ADENOSINE (M6A) IN FZD10 MRNA CONTRIBUTES TO RESISTANCE TO PARP INHIBITOR[査読有り]
- AMER ASSOC CANCER RESEARCH, 2019年11月, CLINICAL CANCER RESEARCH, 25(22) (22), 226 - 226, 英語CATALYTIC SUBUNITS SWITCH DRIVES RESISTANCE TO EZH2 INHIBITORS IN ARID1A-MUTATED CELLS[査読有り]
- ARID1A, encoding a subunit of the SWI/SNF complex, is the most frequently mutated epigenetic regulator in human cancers and is mutated in more than 50% of ovarian clear cell carcinomas (OCCC), a disease that currently has no effective therapy. Inhibition of histone deacetylase 6 (HDAC6) suppresses the growth of ARID1A-mutated tumors and modulates tumor immune microenvironment. Here, we show that inhibition of HDAC6 synergizes with anti-PD-L1 immune checkpoint blockade in ARID1A-inactivated ovarian cancer. ARID1A directly repressed transcription of CD274, the gene encoding PD-L1. Reduced tumor burden and improved survival were observed in ARID1A(flox/flox)/PIK3CA(H1047R) OCCC mice treated with the HDAC6 inhibitor ACY1215 and anti-PD-L1immune checkpoint blockade as a result of activation and increased presence of IFN gamma-positive CD8 T cells. We confirmed that the combined treatment limited tumor progression in a cytotoxic T-cell-dependent manner, as depletion of CD8(+) T cells abrogated these antitumor effects. Together, these findings indicate that combined HDAC6 inhibition and immune checkpoint blockade represents a potential treatment strategy for ARID1A-mutated cancers.Significance: These findings offer a mechanistic rationale for combining epigenetic modulators and existing immunotherapeutic interventions against a disease that has been so far resistant to checkpoint blockade as a monotherapy.AMER ASSOC CANCER RESEARCH, 2019年11月, CANCER RESEARCH, 79(21) (21), 5482 - 5489, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JAPANESE SOCIETY ALLERGOLOGY, 2019年10月, ALLERGOLOGY INTERNATIONAL, 68(4) (4), 529 - 532, 英語, 国際誌[査読有り]
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.NATURE PUBLISHING GROUP, 2019年10月, NATURE, 574(7778) (7778), 353 - +, 英語, 国際誌, 国際共著している[査読有り]研究論文（学術雑誌）
- Background Accurate childhood cancer burden data are crucial for resource planning and health policy prioritisation. Model-based estimates are necessary because cancer surveillance data are scarce or non-existent in many countries. Although global incidence and mortality estimates are available, there are no previous analyses of the global burden of childhood cancer represented in disability-adjusted life-years (DALYs).Methods Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 methodology, childhood (ages 0-19 years) cancer mortality was estimated by use of vital registration system data, verbal autopsy data, and population-based cancer registry incidence data, which were transformed to mortality estimates through modelled mortality-to-incidence ratios (MIRs). Childhood cancer incidence was estimated using the mortality estimates and corresponding MIRs. Prevalence estimates were calculated by using MIR to model survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated by multiplying age-specific cancer deaths by the difference between the age of death and a reference life expectancy. DALYs were calculated as the sum of YLLs and YLDs. Final point estimates are reported with 95% uncertainty intervals.Findings Globally, in 2017, there were 11.5 million (95% uncertainty interval 10.6-12.3) DALYs due to childhood cancer, 97.3% (97.3-97.3) of which were attributable to YLLs and 2.7% (2.7-2.7) of which were attributable to YLDs. Childhood cancer was the sixth leading cause of total cancer burden globally and the ninth leading cause of childhood disease burden globally. 82.2% (82.1-82.2) of global childhood cancer DALYs occurred in low, low-middle, or middle Socio-demographic Index locations, whereas 50.3% (50.3-50.3) of adult cancer DALYs occurred in these same locations. Cancers that are uncategorised in the current GBD framework comprised 26.5% (26.5-26.5) of global childhood cancer DALYs.Interpretation The GBD 2017 results call attention to the substantial burden of childhood cancer globally, which disproportionately affects populations in resource-limited settings. The use of DALY-based estimates is crucial in demonstrating that childhood cancer burden represents an important global cancer and child health concern. (C) 2019 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2019年09月, LANCET ONCOLOGY, 20(9) (9), 1211 - 1225, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. Colony formation capability of single cells in G2/M, but not G1 phase, is significantly reduced by ARID1A inactivation. This correlates with an increase in apoptosis and a reduction in tumor growth. Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.NATURE PUBLISHING GROUP, 2019年09月, NATURE COMMUNICATIONS, 10(1) (1), 4067 - 4067, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2019年09月, EUROPEAN JOURNAL OF DERMATOLOGY, 29(5) (5), 561 - 562, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2019年08月, AUSTRALASIAN JOURNAL OF DERMATOLOGY, 60(3) (3), E240 - E242, 英語, 国際誌[査読有り]
- Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behcet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.TAYLOR & FRANCIS LTD, 2019年07月, MODERN RHEUMATOLOGY, 29(4) (4), 640 - 646, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries.Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health.Findings Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $ 1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55% [5.18-5.95]), mainly due to growth in government health spending, and in lower-middle-income countries (3.71% [3.10-4.34]), mainly from DAH. Health spending globally reached $ 8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $ 10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$ 5252 (5184-5319) in high-income countries, $ 491 (461-524) in upper-middle-income countries, $ 81 (74-89) in lower-middle-income countries, and $ 40 (38-43) in low-income countries. In 2016, 0.4% (0.3-0.4) of health spending globally was in low-income countries, despite these countries comprising 10.0% of the global population. In 2018, the largest proportion of DAH targeted HIV/AIDS ($ 9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($ 644.7 million in 2018). Globally, health spending is projected to increase to $ 15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $ 21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments' increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending.Interpretation Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets.ELSEVIER SCIENCE INC, 2019年06月, LANCET, 393(10187) (10187), 2233 - 2260, 英語, 国際共著している[査読有り]
- Despite the high initial response rates to PARP inhibitors (PARPi) in BRCA-mutated epithelial ovarian cancers (EOC), PARPi resistance remains a major challenge. Chemical modifications of RNAs have emerged as a new layer of epigenetic gene regulation. N6-methyladenosine (m6A) is the most abundant chemical modification of mRNA, yet the role of m6A modification in PARPi resistance has not previously been explored. Here, we show that m6A modification of FZD10 mRNA contributes to PARPi resistance by upregulating the Wnt/b-catenin pathway in BRCA-mutated EOC cells. Global m6A profile revealed a significant increase inm6Amodification in FZD10 mRNA, which correlated with increased FZD10 mRNA stability and an upregulation of the Wnt/b-catenin pathway. Depletion of FZD10 or inhibition of the Wnt/b-catenin sensitizes resistant cells to PARPi. Mechanistically, downregulation of m6A demethylases FTO and ALKBH5 was suffi-cient to increase FZD10 mRNA m6A modification and reduce PARPi sensitivity, which correlated with an increase in homologous recombination activity. Moreover, combined inhibition of PARP and Wnt/b-catenin showed synergistic suppression of PARPi-resistant cells in vitro and in vivo in a xenograft EOC mousemodel. Overall, our results showthatm6A contributes to PARPi resistance in BRCA-deficient EOC cells by upregulating the Wnt/b-catenin pathway via stabilization of FZD10. They also suggest that inhibition of the Wnt/b-catenin pathway represents a potential strategy to overcome PARPi resistance. Significance: These findings elucidate a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficientEOCcells via upregulation of Wnt/b-catenin pathway.AMER ASSOC CANCER RESEARCH, 2019年06月, CANCER RESEARCH, 79(11) (11), 2812 - 2820, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9.0 million [8.8-9.4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42.2% [38.6-46.1]), migraine (16.3% [11.7-20.8]), Alzheimer's and other dementias (10.4% [9.0-124]), and meningitis (7.9% [6.6-10.4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1.12 [1.05-1.20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0.7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88.8% (86.5-90.9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22.3% [11.8-35.1] of DALYs are risk attributable) and idiopathic epilepsy (14.1% [10.8-17.5] of DALYs are risk attributable).Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Copyright (C) The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2019年05月, LANCET NEUROLOGY, 18(5) (5), 459 - 480, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Congenital entropion is an ocular condition involving malpositioning of the eyelid, which can result in ocular pain, conjunctival epiphora, or photophobia. Noninvasive treatment is effective in some cases; however, surgical treatment is indicated when keratitis and ocular irritating symptoms occur. There is no consensus regarding the most appropriate surgical technique. Moreover, some patients complain of changes in their appearance or unwanted incision scars after surgery. In particular, individuals with certain types of Asian heritage exhibit a lower eyelid morphology that differs from that of white individuals, caused by orbital fat locational difference. Subciliary muscle bulges cause swelling in the lower eyelid called Namidabuluro and are considered to create a youthful and beautiful appearance in Asians. Accordingly, some Asian individuals tend to be sensitive about changes to the appearance of the lower eyelid. To our knowledge, no report has yet described changes to Namidabukuro during congenital entropion repair in Asians. We describe a novel surgical technique for congenital entropion repair with the creation of cosmetically natural Namidabuluro in an East Asian cohort. The study included 8 lower eyelids of 4 Japanese female patients. Scarring was not noticeable in any of the 4 cases. Eversion of the cilia and the creation of cosmetically natural Namidabuluro were accomplished in all cases. There has been no case of recurrence yet. The novel surgical technique we developed enables not only the treatment of congenital entropion but also the creation of cosmetically acceptable Namidabuluro, resulting in increased patient satisfaction.LIPPINCOTT WILLIAMS & WILKINS, 2019年04月, PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN, 7(4) (4), e2122, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Objectives: This study aimed to identify patients with high-probability of ocular involvement of Behcet's disease (BD). Methods: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. Results: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. Conclusion: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.TAYLOR & FRANCIS LTD, 2019年03月, MODERN RHEUMATOLOGY, 29(2) (2), 357 - 362, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2019年03月, EUROPEAN JOURNAL OF DERMATOLOGY, 29(2) (2), 224 - 225, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD(+) metabolism influences both tissue ageing and cancer. However, the role of NAD(+) metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD(+) salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest. NAMPT expression is regulated by high mobility group A (HMGA) proteins during senescence. The HMGA-NAMPT-NAD(+) signalling axis promotes the proinflammatory SASP by enhancing glycolysis and mitochondrial respiration. HMGA proteins and NAMPT promote the proinflammatory SASP through NAD(+)-mediated suppression of AMPK kinase, which suppresses the p53-mediated inhibition of p38 MAPK to enhance NF-kappa B activity. We conclude that NAD(+) metabolism governs the proinflammatory SASP. Given the tumour-promoting effects of the proinflammatory SASP, our results suggest that anti-ageing dietary NAD(+) augmentation should be administered with precision.NATURE PUBLISHING GROUP, 2019年03月, NATURE CELL BIOLOGY, 21(3) (3), 397 - +, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- © Published by the BMJ Publishing Group Limited. Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.2019年01月, BMJ (Online), 364[査読有り]研究論文（学術雑誌）
- Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury.Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility.Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions.Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2019年01月, LANCET NEUROLOGY, 18(1) (1), 56 - 87, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2019年01月, EUROPEAN JOURNAL OF DERMATOLOGY, 29(1) (1), 87 - 88, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Acute meningitis has a high case-fatality rate and survivors can have severe lifelong disability. We aimed to provide a comprehensive assessment of the levels and trends of global meningitis burden that could help to guide introduction, continuation, and ongoing development of vaccines and treatment programmes.Methods The Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study estimated meningitis burden due to one of four types of cause: pneumococcal, meningococcal, Haemophilus influenzae type b, and a residual category of other causes. Cause-specific mortality estimates were generated via cause of death ensemble modelling of vital registration and verbal autopsy data that were subject to standardised data processing algorithms. Deaths were multiplied by the GBD standard life expectancy at age of death to estimate years of life lost, the mortality component of disability-adjusted life-years (DALYs). A systematic analysis of relevant publications and hospital and daims data was used to estimate meningitis incidence via a Bayesian meta-regression tool. Meningitis deaths and cases were split between causes with meta-regressions of aetiological proportions of mortality and incidence, respectively. Probabilities of long-term impairment by cause of meningitis were applied to survivors and used to estimate years of life lived with disability (YLDs). We assessed the relationship between burden metrics and Socio-demographic Index (SDI), a composite measure of development based on fertility, income, and education.Findings Global meningitis deaths decreased by 21.0% from 1990 to 2016, from 403 012 (95% uncertainty interval [UI] 319426-458 514) to 318 400 (265 218-408 705). Incident cases globally increased from 2.50 million (95% UI 2.19-2.91) in 1990 to 2.82 million (2.46-3.31) in 2016. Meningitis mortality and incidence were dosely related to SDI. The highest mortality rates and incidence rates were found in the peri-Sahelian countries that comprise the African meningitis belt, with six of the ten countries with the largest number of cases and deaths being located within this region. Haemophilus influenzae type b was the most common cause of incident meningitis in 1990, at 780 070 cases (95% UI 613 585-978 219) globally, but decreased the most (-494%) to become the least common cause in 2016, with 397 297 cases (291076-533 662). Meningococcus was the leading cause of meningitis mortality in 1990 (192833 deaths [95% UI 153 358-221 503] globally), whereas other meningitis was the leading cause for both deaths (136 423 [112 682-178 022]) and incident cases (1.25 million [1.06-1.49]) in 2016. Pneumococcus caused the largest number of YLDs (634458 [444 787-839 749]) in 2016, owing to its more severe long-term effects on survivors. Globally in 2016, 1.48 million (1.04-1.96) YLDs were due to meningitis compared with 21.87 million (18.20-28.28) DALYs, indicating that the contribution of mortality to meningitis burden is far greater than the contribution of disabling outcomes.Interpretation Meningitis burden remains high and progress lags substantially behind that of other vaccine-preventable diseases. Particular attention should be given to developing vaccines with broader coverage against the causes of meningitis, making these vaccines affordable in the most affected countries, improving vaccine uptake, improving access to low-cost diagnostics and therapeutics, and improving support for disabled survivors. Substantial uncertainty remains around pathogenic causes and risk factors for meningitis. Ongoing, active cause-specific surveillance of meningitis is crucial to continue and to improve monitoring of meningitis burdens and trends throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年12月, LANCET NEUROLOGY, 17(12) (12), 1061 - 1082, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- WILEY, 2018年12月, JOURNAL OF DERMATOLOGY, 45(12) (12), E337 - E339, 英語, 国際誌[査読有り]
- Ovarian cancer remains the most lethal gynecologic malignancy in the developed world. Despite the unprecedented progress in understanding the genetics of ovarian cancer, cures remain elusive due to a lack of insight into the mechanisms that can be targeted to develop new therapies. SWI/SNF chromatin remodeling complexes are genetically altered in approximately 20% of all human cancers. SWI/SNF alterations vary in different histologic subtypes of ovarian cancer, with ARID1A mutation occurring in approximately 50% of ovarian clear cell carcinomas. Given the complexity and prevalence of SWI/SNF alterations, ovarian cancer represents a paradigm for investigating the molecular basis and exploring therapeutic strategies for SWI/SNF alterations. This review discusses the recent progress in understanding SWI/SNF alterations in ovarian cancer and specifically focuses on: (i) ARID1A mutation in endometriosis-associated clear cell and endometrioid histologic subtypes of ovarian cancer; (ii) SMARCA4 mutation in small cell carcinoma of the ovary, hypercalcemic type; and (iii) amplification/upregulation of CARM1, a regulator of BAF155, in high-grade serous ovarian cancer. Understanding the molecular underpinning of SWI/SNF alterations in different histologic subtypes of ovarian cancer will provide mechanistic insight into how these alterations contribute to ovarian cancer. Finally, the review discusses how these newly gained insights can be leveraged to develop urgently needed therapeutic strategies in a personalized manner. (C) 2018 AACR.AMER ASSOC CANCER RESEARCH, 2018年12月, MOLECULAR CANCER RESEARCH, 16(12) (12), 1819 - 1825, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally.Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systetns, sample registration systetns, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950.Findings Globally, 18.7% (95% uncertainty interval 18.4-19.0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58.8% (58.2-59.3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48.1 years (46.5-49.6) to 70.5 years (70.1-70.8) for men and from 52.9 years (51.7-54.0) to 75.6 years (75.3-75.9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49.1 years (46.5-51.7) for men in the Central African Republic to 87.6 years (86.9-88.1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216.0 deaths (196.3-238.1) per 1000 livebirths in 1950 to 38.9 deaths (35.6-42.83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5.4 million (5.2-5.6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult tnales, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development.Interpretation This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, wotnen, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing. Copyright C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1684 - 1735, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.Methods We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting.Findings Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 39% (95% uncertainty interval [UI] 3.1-4. 6) from 1990 to 2017; however, the all-age YLD rate increased by 7.2% (6.0-8.4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7.9% (6 6-9. 2) for males and 6.5% (5.4-7.7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-hatin and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]).Interpretation Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1789 - 1858, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years.Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Sociodemographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males.Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7.4 years (95% uncertainty interval 74-7.8), from 65.6 years (65.3-65- 8) in 1990 to 73.0 years (72.7-73.3) in 2017. The increase in years of life varied from 5.1 years (5.0-5.3) in high SDI countries to 12.0 years (11.3-12.8) in low SDI countries. Of the additional years of life expected at birth, 26.3% (20.1-33.1) were expected to be spent in poor health in high SDI countries compared with 11.7% (8.8-15.1) in low-middle SDI countries. HALE at birth increased by 6.3 years (5.9-6.7), from 57.0 years (54.6-59.1) in 1990 to 63.3 years (60.5-65.7) in 2017. The increase varied from 3.8 years (3.4-4.1) in high SDI countries to 10.5 years (9.8-11.2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1.0 year (0.4-1.7) in Saint Vincent and the Grenadines (62.4 years [59.9-64.7] in 1990 to 63.5 years [60.9-65.8] in 2017) to 23.7 years (21.9-25.6) in Eritrea (30.7 years [28.9-32.2] in 1990 to 54.4 years [51.5-57.1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1.4 years (0.6-2.3) in Algeria to 11.9 years (10.9-12.9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75.8 years [72.4-78.7]) and males (72.6 years [69 " 8-75.0]) and the lowest estimates were in Central African Republic (47.0 years [43.7-50.2] for females and 42.8 years [40.1-45.6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41.3% (38.8-43.5) for communicable diseases and by 49"8% (47.9-51.6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40.1% (36.8-43.0), although age-standardised DALY rates decreased by 18.1% (16.0-20.2).Interpretation With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low S DI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1859 - 1922, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of "leaving no one behind", it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health -related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment.Methods We measured progress on 41 health-related S DG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2.5th percentile and 100 as the 97.5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator.Findings The global median health-related SDG index in 2017 was 59.4 (IQR 35.4-67.3), ranging from a low of 11.6 (95% uncertainty interval 9.6-14.0) to a high of 84.9 (83.1-86.7). SDG index values in countries assessed at the subnational level varied substantially particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attaimnent by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030.Interpretation The GBD study offers a unique, robust platform for monitoring the health -related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health -related SDG indicators, NCDs, NCD-related risks, and violence -related indicators will require a concerted shift away from what might have driven past gains curative interventions in the case of NCDs towards multisectoral, prevention -oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the S DGs. What is clear is that our actions or inaction today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.Copyright (C) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 2091 - 2138, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods.Methods We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10-54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10-14 years and 50-54 years was estimated from data on fertility in women aged 15-19 years and 45-49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-cotnponent method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories.Findings From 1950 to 2017, TFRs decreased by 49.4% (95% uncertainty interval [UI] 46.4-52.0). The TFR decreased from 4.7 livebirths (4.5-4.9) to 2.4 livebirths (2.2-2.5), and the ASFR of mothers aged 10-19 years decreased from 37 livebirths (34-40) to 22 livebirths (19-24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83.8 million people per year since 1985. The global population increased by 197-2% (193.3-200.8) since 1950, from 2.6 billion (2.5-2.6) to 7.6 billion (7.4-7.9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2.0%; this rate then remained nearly constant until 1970 and then decreased to 1.1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2.5% in 1963 to O7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2.7%. The global average age increased from 26.6 years in 1950 to 32.1 years in 2017, and the proportion of the population that is of working age (age 15-64 years) increased from 59.9% to 65.3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1.0 livebirths (95% UI 0. 9-1.2) in Cyprus to a high of 7.1 livebirths (6.8-7.4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0.08 livebirths (0.07-0.09) in South Korea to 2.4 livebirths (2.2-2.6) in Niger, and the TFR over age 30 years (I F030; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0.3 livebirths (0.3-0-4) in Puerto Rico to a high of 3.1 livebirths (3.0-3.2) in Niger. TF030 was higher than TFU25 in 145 countries and territories in 2017.33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2.0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger.Interpretation Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1995 - 2051, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017.Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised.Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases.Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1736 - 1788, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations.Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low.Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.ELSEVIER SCIENCE INC, 2018年11月, LANCET, 392(10159) (10159), 1923 - 1994, 英語, 国際共著している[査読有り]研究論文（学術雑誌）
- WILEY, 2018年11月, JOURNAL OF DERMATOLOGY, 45(11) (11), E322 - E324, 英語, 国際誌[査読有り]
- WILEY, 2018年11月, JOURNAL OF DERMATOLOGY, 45(11) (11), E297 - E298, 英語, 国際誌[査読有り]
- Inactivation of the subunits of SWI/SNF complex such as ARID1A is synthetically lethal with inhibition of EZH2 activity. However, mechanisms of de novo resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated cells. SMARCA4 loss upregulates anti-apoptotic genes in the EZH2 inhibitor-resistant cells. EZH2 inhibitor-resistant ARID1A-mutated cells are hypersensitive to BCL2 inhibitors such as ABT263. ABT263 is sufficient to overcome resistance to an EZH2 inhibitor. In addition, ABT263 synergizes with an EZH2 inhibitor in vivo in ARID1A-inactivated ovarian tumor mouse models. Together, these data establish that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 underlies the acquired resistance to EZH2 inhibitors. They suggest BCL2 inhibition alone or in combination with EZH2 inhibition represents urgently needed therapeutic strategy for ARID1A-mutated cancers.NATURE PUBLISHING GROUP, 2018年10月, NATURE COMMUNICATIONS, 9(1) (1), 4116 - 4116, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2018年06月, JOURNAL OF DERMATOLOGY, 45(6) (6), E152 - E153, 英語, 国際誌[査読有り]
- 2018年04月, Journal of the European Academy of Dermatology and Venereology : JEADV, 32(4) (4), e147-e149, 英語, 国際誌[査読有り]
- JAPANESE SOCIETY ALLERGOLOGY, 2018年04月, ALLERGOLOGY INTERNATIONAL, 67(2) (2), 295 - 297, 英語, 国際誌[査読有り]
- Hyaluronic acid (HA) is present in the connective tissues of the skin and decreases with age. HA fillers are popular as facial rejuvenation treatments. They are generally considered safe; however, complications, such as cutaneous necrosis and blindness due to vascular embolism, sometimes occur. Because vascular embolisms are likely associated with the deep placement of HA fillers, a strategy that involves injection into superficial regions (the conventional method) is commonly used to reduce risks. However, deep injections to achieve revolumization are becoming common, even in high-risk areas for intravascular infusion. We aimed to study the usefulness of the ultrasonography-guided cannula method for preventing intravascular infusion of HA fillers. An HA filler was injected into the region just under the dermis on the left side of the face of a 38-year-old man using the conventional method, and another HA filler was injected into the periosteum on the right side using the ultrasonography-guided cannula method. The skin blood flow on both sides was compared using laser speckle flowgraphy (LSFG). The ultrasonography-guided method was successful in detecting the cannula and the blood vessel, and the HA filler was safely injected into a deep region. Using LSFG, a difference in skin blood flow between the 2 methods was detected. The ultrasonography-guided cannula method was effective in aiding the safe injection of an HA filler in a deep high-risk area and maintained skin blood flow. LSFG may be adopted to evaluate skin blood flow after HA filler injections.LIPPINCOTT WILLIAMS & WILKINS, 2018年04月, PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN, 6(4) (4), e1776, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2018年03月, EUROPEAN JOURNAL OF DERMATOLOGY, 28(2) (2), 275 - 277, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner. HDAC2 functions as a corepressor of EZH2 to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse models. This correlated with a significant improvement of survival of mice bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers.CELL PRESS, 2018年03月, CELL REPORTS, 22(13) (13), 3393 - 3400, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2018年01月, JOURNAL OF DERMATOLOGY, 45(1) (1), E1 - E2, 英語, 国際誌[査読有り]
- JOHN LIBBEY EUROTEXT LTD, 2018年01月, EUROPEAN JOURNAL OF DERMATOLOGY, 28(1) (1), 115 - 116, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- TAYLOR & FRANCIS LTD, 2018年, EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT, 3(4) (4), 233 - 236, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2017年12月, JOURNAL OF DERMATOLOGY, 44(12) (12), e350 - e352, 英語, 国際誌[査読有り]
- Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.WILEY, 2017年11月, JOURNAL OF DERMATOLOGY, 44(11) (11), 1268 - 1275, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2017年11月, JOURNAL OF DERMATOLOGY, 44(11) (11), E272 - E273, 英語, 国際誌[査読有り]
- JOHN LIBBEY EUROTEXT LTD, 2017年11月, EUROPEAN JOURNAL OF DERMATOLOGY, 27(6) (6), 660 - 661, 英語, 国際誌[査読有り]
- We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of alpha-SMA+, CD34- myofibroblasts and alpha-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-beta were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-beta released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution.WILEY, 2017年11月, JOURNAL OF DERMATOLOGY, 44(11) (11), 1303 - 1308, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2017年11月, EUROPEAN JOURNAL OF DERMATOLOGY, 27(6) (6), 652 - 654, 英語, 国際誌[査読有り]
- JOHN LIBBEY EUROTEXT LTD, 2017年09月, EUROPEAN JOURNAL OF DERMATOLOGY, 27(5) (5), 535 - 536, 英語, 国際誌[査読有り]
- Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity-associated AN in a 12-year-old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity-associated AN are discussed. In addition, reports of concomitant CRP and obesity-associated AN are reviewed. CRP and obesity-associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity-associated AN. Together with the observation that skin lesions of CRP and obesity-associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.WILEY, 2017年08月, JOURNAL OF DERMATOLOGY, 44(8) (8), 954 - 958, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Unilateral lichen planus (LP) is a rare clinical variant of LP. The etiology of unilateral LP has not been clarified, although various causes have been reported because of the characteristic distribution. We focused on the contribution of metal allergy and sweating in the development of unilateral LP in this case. To confirm the presence of metal allergy, patch tests with metal allergens were performed. To investigate the cause of the unilateral distribution in unilateral LP, the function of sweating and sweat leaking in the dermis was assessed by a thermoregulatory sweat test and immunohistochemical staining of dermcidin. The patch tests with SnCl2, H2PtCl6, ZnCl2 and MnCl2 were positive. The thermoregulatory sweat test using the starch-iodine method (Minor test) with sweating provoked by heat stimulation revealed hypohidrosis of the affected area, whereas no skin lesions were observed on the dorsal hand and wrist where sweating was normal. Histopathological examination showed keratin plugging of the acrosyringium and lymphocytic infiltrations in the papillary and subpapillary dermis around the intraepidermal and intradermal eccrine duct in the affected area. The immunohistochemical staining of dermcidin confirmed sweat leakage in the subpapillary dermis in the affected area. The symptoms refractory to the topical steroids were markedly improved after removal of the dental metals. The coexistence of metal allergy and sweat leakage in the hypohidrotic area may be involved in the development of unilateral LP.WILEY, 2017年08月, JOURNAL OF DERMATOLOGY, 44(8) (8), 963 - 966, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Solitary venous malformation (VM) of the skin, previously known as cavernous hemangioma, is frequently observed in the dermatological field, but multiple acquired VM are rare. We present a case of multiple VM of the skin associated with multiple cerebral cavernous malformations (CCM) in a 70-year-old Japanese woman. In addition, we summarize seven reported similar cases, including the present case. That some reports have described concomitant VM of the skin and CCM, together with the present case, suggests a tight relationship or a common pathogenetic pathway between these two diseases.WILEY, 2017年07月, JOURNAL OF DERMATOLOGY, 44(7) (7), 813 - 817, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- WILEY, 2017年05月, JOURNAL OF DERMATOLOGY, 44(5) (5), e105 - e106, 英語, 国際誌[査読有り]
- WILEY, 2017年03月, GENES TO CELLS, 22(3) (3), 328 - 328, 英語[査読有り]
- JOHN LIBBEY EUROTEXT LTD, 2017年03月, EUROPEAN JOURNAL OF DERMATOLOGY, 27(2) (2), 177 - 178, 英語, 国際誌[査読有り]
- JOHN LIBBEY EUROTEXT LTD, 2017年01月, EUROPEAN JOURNAL OF DERMATOLOGY, 27(1) (1), 85 - 86, 英語, 国際誌[査読有り]
- Acquired dermal melanocytosis (ADM) classically occurs on the face. However, extrafacial ADM including palmar ADM has been reported on rare occasions. We present the first report of ADM confined to the palm without ADM lesions in other regions in a 30-year-old Japanese woman. The patient presented with several interspersed macules up to 1 cm in diameter with poorly defined margins, containing faint slate-gray spots 1-2 mm in diameter, on the left palm near the first and second fingers and on the palmar side of the first finger near the metacarpophalangeal joint. These slate-gray spots were prominent on and around palmar creases and on wrinkles on the metacarpophalangeal joint. The patient was right hand-dominant. Histopathological examination revealed scattered spindle-shaped cells with melanin granules and melanophages in the upper to middle dermis. Pigment-bearing spindle-shaped cells were demonstrated to be dermal melanocytes because of positive staining for Melan-A after melanin removal. We review the published work for ADM on the hands.WILEY-BLACKWELL, 2016年06月, JOURNAL OF DERMATOLOGY, 43(6) (6), 701 - 705, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2016年05月, EUROPEAN JOURNAL OF DERMATOLOGY, 26(3) (3), 321 - 322, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2016年03月, EUROPEAN JOURNAL OF DERMATOLOGY, 26(2) (2), 204 - 205, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Ultraviolet (UV) B is a major factor in melanomagenesis. This fact is linked to the resistance of melanocytes to UVB-induced apoptosis. In this study, we characterized the involvement of Mcl-1L in the regulation of UVB-induced apoptosis in melanocytes and in melanoma cells. In melanocytes, apoptosis was not evident at 24h after UVB irradiation. The Mcl-1L expression increased after UVB irradiation, and the high Mcl-1L expression continued for at least 24h. This UVB-dependent increase in Mcl-1L was mediated by the MEK-ERK-pS-STAT3 (STAT3 phosphorylated at Ser727) pathway. The Ser727 phosphorylation facilitated nuclear localization of STAT3. In melanoma cells, the expression levels of Mcl-1L varied depending on the cell line. WM39 melanoma cells expressed high levels of Mcl-1L via the MEK-ERK-pS-STAT3 pathway and were resistant to UVB-induced apoptosis without up-regulation of Mcl-1L. In melanocytes and in WM39 cells, transfection with Mcl-1 siRNA promoted UVB-induced apoptosis. Immunohistochemical studies showed that melanoma cells in insitu lesions expressed high amounts of Mcl-1L. These results indicate that the high expression of Mcl-1L mediated by the MEK-ERK-pS-STAT3 pathway protects melanocytes and melanoma cells from UVB-induced apoptosis.WILEY, 2016年02月, GENES TO CELLS, 21(2) (2), 185 - 199, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- JOHN LIBBEY EUROTEXT LTD, 2014年01月, EUROPEAN JOURNAL OF DERMATOLOGY, 24(1) (1), 112 - 113, 英語[査読有り]
- 47歳,男性.22年前より潰瘍性大腸炎(ulcerative colitis:UC)にて加療中であった.右下腿に犬咬傷を受傷し,同部が有痛性で周囲が堤防状に隆起する7×6.5cm大の潰瘍となった.辺縁部からの病理組織所見では,真皮から皮下組織にかけて好中球を主体とした炎症細胞浸潤を認め,UCを合併した壊疽性膿皮症(pyoderma gangrenosum:PG)と診断した.プレドニゾロン40mg/日内服にて著明に改善し,約3ヵ月後に潰瘍は瘢痕治癒した.症状は安定していたが約1年後にUCが急速に悪化し,頭部,後頸部,胸部,上肢に紅暈を伴う有痛性膿疱が多発した.病理組織検査で角層下膿疱,毛包を中心とした好中球の浸潤が認められ,細菌培養は陰性であり膿疱型PGと診断した.皮疹は約3週間で消退したがUCはコントロール不良であり,多量の下血とともに呼吸器感染症を発症し死の転帰をたどった.膿疱型PGはまれであり,今後症例の蓄積が期待される.(著者抄録)(株)医学書院, 2014年01月, 臨床皮膚科, 68(1) (1), 80 - 84, 日本語
- 63歳,男性.2010年1月心窩部痛が出現し,精査の結果,T4N1M1 Stage IVbの肝癌,Child-Pugh分類Bと診断された.同年5月,右上腕の腫瘤に気付いた.同年11月中旬当科初診時には,径4cmの紫紅色結節を認め,腫瘍全摘術を施行した.病理組織学的所見は,真皮浅層から皮下組織にかけて,高度に異型のある細胞よりなる充実性の腫瘍塊を認め,一部管状構造を構成していた.腫瘍細胞はサイトケラチンAE1/3およびビメンチン陽性で,α-フェトプロテインおよびhepatocyte paraffin 1は陰性であった.全身検索の結果,肝癌以外の悪性腫瘍は見出せず,肝癌の皮膚転移と診断した.また,同年11月下旬より歯肉転移も出現し,同年12月中旬から放射線療法を開始したが,放射線療法開始3日後に永眠した.肝癌皮膚転移の本邦報告28例を検討した.単発例で上腕に転移が出現した例はこれまで報告がない.(著者抄録)(株)医学書院, 2013年04月, 臨床皮膚科, 67(4) (4), 362 - 366, 日本語
- WILEY-BLACKWELL, 2012年11月, JOURNAL OF DERMATOLOGY, 39(11) (11), 960 - 962, 英語, 国際誌[査読有り]
- 症例は63歳、男性。主訴は心窩部痛。精査にて門脈・下大静脈腫瘍栓、多発肺転移を伴う進行肝細胞癌と診断された。緩和治療を治療方針として十全大補湯の内服を開始。診断から9ヵ月後、肝機能の改善と原発巣の著明な退縮と転移巣の縮小、腫瘍マーカーの低下を認めた。その後、腫瘍の再増大と多臓器転移を認め永眠されたが、肝細胞癌に対する十全大補湯の抗腫瘍効果が示唆された貴重な症例であった。(著者抄録)(株)協和企画, 2012年10月, 漢方医学, 36(4) (4), 303 - 307, 日本語
- (一社)日本皮膚悪性腫瘍学会, 2011年06月, 日本皮膚悪性腫瘍学会学術大会プログラム・抄録集, 27回, 135 - 135, 日本語上腕に紫紅色結節を呈した転移性皮膚腫瘍の1例
- 日本皮膚科学会-大阪地方会・京滋地方会, 2011年04月, 皮膚の科学, 10(2) (2), 189 - 189, 日本語上腕に紫紅色結節を呈した転移性皮膚腫瘍の1例
- 2004年2月から2007年4月の当院での運動神経障害を伴った帯状疱疹男性6例,女性1例につき検討した.27〜85歳,平均67.8歳.基礎疾患は悪性腫瘍が4例,高脂血症,糖尿病が各々2例,高血圧,喘息,脳動脈瘤が各々1例.部位は顔面領域が3例,上下肢領域が4例(上肢3例,下肢1例).運動神経障害の予後に対する,罹患部位,抗ウイルス薬の開始時期,ステロイド全身投与の影響を検討した.顔面領域帯状疱疹に比し上下肢領域病変例では発症後の抗ウイルス薬投与開始が遅い症例が多く,一方,ステロイド全身投与を併用している症例が少なかった.上下肢領域例の運動神経障害は顔面領域例に比し難治の傾向があった.上記の治療法の差異が関与している可能性が考えられる.可及的早期の抗ウイルス薬投与が最も運動神経障害の予後を良くすると考えられた.しかし,ステロイド全身投与の有用性については今回の7例の検討では不明であった.(著者抄録)(株)医学書院, 2011年02月, 臨床皮膚科, 65(2) (2), 112 - 119, 日本語
- Baker's asthmaが先行し,小麦依存性運動誘発アナフィラキシー(WDEIA)を発症した47歳女性.誘発試験にて小麦とアスピリンと運動負荷を組み合わせたときのみアレルギー症状誘発とともに血中グリアジン濃度の上昇を認め,ω-5グリアジン特異的IgE抗体が陽性であったことから,ω-5グリアジンが主要抗原のWDEIAと診断した.Baker's asthmaの既往があるため,不溶性のみならず可溶性抗原についても免疫ブロットを施行した.小麦不溶性蛋白では,ω-5グリアジンのみならず,β-,γ-グリアジンと考えられるバンドが検出された.可溶性蛋白では有意なバンドは検出されなかった.以上より自験例ではグリアジンがWDEIAのみならず,baker's asthmaの原因抗原であると考えられた.(著者抄録)(一社)日本アレルギー学会, 2010年05月, アレルギー, 59(5) (5), 552 - 557, 日本語
- [Analysis of causative allergen of the patient with baker's asthma and wheat-dependent exercise-induced anaphylaxis (WDEIA)].A 47 years-old woman suffering from baker's asthma for several years developed anaphylaxis when she was walking hard after taking wheat. On the provocation test, neither wheat alone nor exercise alone induced any symptoms. The combination of exercise, wheat and aspirin induced urticaria and marked elevation of blood gliadin levels. According to the high titer of omega-5 gliadin specific IgE in her serum and the result of challenge test, we diagnosed wheat-dependent exercise-induced anaphylaxis (WDEIA). By means of western blotting of soluble and insoluble wheat proteins, we detected several bands which were supposed to be beta-, gamma- and omega-5 gliadin by their relative molecular mass. Wheat gliadins might be causative allergen of both baker's asthma and WDEIA in our case.2010年05月, Arerugi = [Allergy], 59(5) (5), 552 - 7, 日本語, 国内誌[査読有り]研究論文（学術雑誌）
- 【背景・目的】小麦依存性運動誘発アナフィラキシー(Food-dependent exercise-induced anaphylaxis:WDEIA)誘発における運動やアスピリン摂取は,血中グリアジンを上昇させる.消化性潰瘍治療薬の1種でありプロスタグランディンE1(PGE1)誘導体であるミソプロストールは,アスピリンにより低下する消化管粘膜のPGを補充し,腸管粘膜を保護する.WDEIA患者におけるアスピリン誘発に対するPGE1製剤の抑制効果を評価する.【対象・方法】小麦摂取後運動時のショックの現病歴,血液検査や皮膚テストよりWDEIAが疑われた2例を対象とした.小麦摂取と運動やアスピリンを組み合わせて膨疹の誘発や血中グリアジンの経時的変化をみる負荷試験を施行し,PGE1製剤前投与による抑制効果をみた.【結果】2例とも運動負荷のみでは変化なく,アスピリン前投与を加えることで血中グリアジン上昇と膨疹の誘発をみた.2例ともアスピリンと共にPGE1製剤の前投与にて,血中グリアジンの上昇と膨疹誘発は抑制された.【結論】PGE1製剤はアスピリンによるWDEIA誘発において,アレルゲン吸収を抑制し,症状誘発を防止できる可能性がある.(著者抄録)(一社)日本アレルギー学会, 2009年10月, アレルギー, 58(10) (10), 1418 - 1425, 日本語
- [The inhibition effect of a synthetic analogue of prostaglandin E1 to the provocation by aspirin in the patients of WDEIA].BACKGROUND: Exercise or aspirin intake enhances symptoms by increasing blood gliadin levels in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). Misoprostol, a synthetic analogue of prostaglandin E1 (PGE1) compensates prostagrandins of which synthesis is inhibited by aspirin and protect the gastrointestinal mucosa. We projected to examine the effect of misoprostol in suppression the allergic symptom and elevation of blood gliadin levels in WDEIA induced by aspirin. PATIENTS AND METHODS: Two patients with a history of recurrent anaphylaxis associated with wheat ingestion accompanied with exercise, positive specific IgE and/or skin test were enrolled in the provocation test. On the provocation test of WDEIA, wheat ingestion, exercise, aspirin intake were combined on various ways. During the test, the patients' symptom and serum gliadins levels were monitored. RESULTS: Although wheat with exercise did not induce any symptoms, addition of aspirin induced urticaria and elevation of blood gliadin levels in both cases. In case 1, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by exercise, wheat and aspirin intake. In case 2, premedication of misoprostol suppressed the urticaria and elevation of blood gliadin levels which were induced by wheat and aspirin intake. CONCLUSION: These findings suggest that a synthetic analogue of PGE1 may suppresses the absorption of the allergen levels and outbreak the allergic symptom induced by aspirin in the patients with WDEIA.2009年10月, Arerugi = [Allergy], 58(10) (10), 1418 - 25, 日本語, 国内誌[査読有り]研究論文（学術雑誌）
- (株)学研メディカル秀潤社, 2009年08月, Visual Dermatology, 8(9) (9), 918 - 920, 日本語【皮膚と食物アレルギー】小麦と蕁麻疹 小麦依存性運動誘発アナフィラキシーとbaker's asthma合併例における小麦中の原因抗原の検討
- WILEY, 2009年05月, INTERNATIONAL JOURNAL OF DERMATOLOGY, 48(5) (5), 522 - 524, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 市販サプリメントに含まれる葉酸によるアナフィラキシーの1症例42歳女性。以前妊娠時に葉酸内服の既往あり。市販サプリメントを初回摂取2時間後より蕁麻疹と呼吸困難が出現した。プリックテストにてサプリメントとその成分である葉酸が強陽性であった。葉酸代謝拮抗剤のメソトレキサートもプリックテスト陽性で、交差反応と考えた。食物中の葉酸には無反応であったが、これは代謝・吸収の違いによると考えた。妊娠時には葉酸の積極的摂取が推奨されているが、本例は妊娠中に摂取した葉酸で感作されたと思われた。葉酸によるアレルギーは稀であるが、全身症状をきたすことが多く注意する必要がある。(著者抄録)(株)北隆館, 2009年02月, アレルギーの臨床, 29(2) (2), 173 - 177, 日本語
- モモアレルギー10例について病歴聴取や皮膚テストとともにモモ主要抗原Pru p 1(Bet v1ホモログ)、Pru p 3(lipid transfer protein)、Pru p 4(プロフィリン)特異IgE(ImmunoCAP)の測定とモモのイムノブロットにより原因抗原を検討した。その結果2群に分類された。モモ摂取でショックを起こした3例は、Pru p 1、Pru p 3、Pru p 4のImmunoCAPはすべて陰性。イムノブロットでもPru p 1やPru p 4に相当する17kDa、14kDaのバンドは陰性、1例でPru p 3と考えられる9 kDaのバンドを検出したが、他に20kDaや28kDaのバンドが検出された。多種の果物のOASも合併していたモモOAS7例は多くの症例でPru p 1、Pru p 4特異IgE(ImmunoCAP)陽性で、イムノブロットでもPru p 1、Pru p 4に相当する17kDa、14kDaのバンドを検出した。後者の多くはハンノキからの交叉反応が主と推測された。わが国でもこの2群間には感作経路や反応抗原の差異があるが、ヨーロッパに比してPru p 3の陽性率が低い可能性があると考えた。(著者抄録)(一社)日本皮膚アレルギー・接触皮膚炎学会, 2009年01月, Journal of Environmental Dermatology and Cutaneous Allergology, 3(1) (1), 23 - 31, 日本語
- モモアレルギー5症例における臨床的特徴と原因抗原の検討モモアレルギー5例について病歴聴取や皮膚テストとともにモモ主要抗原Pru p1(Bet v1ホモログ)、Pru p3(lipid transfer protein)、Pru p4(Bet v2ホモログプロフィリン)特異IgEをImmunoCAPで測定し、モモのイムノブロットも施行して原因抗原を検討した。その結果2群に分類された。モモ摂取によりショックを起こした3例では、Pru p1、Pru p3、Pru p4のImmunoCAPは全て陰性であった。イムノブロットでもPru p1やPru p4に相当する17kDa,14kDaのバンドは陰性、1例のみにPru p3と考えられる9kDAのバンドを検出したが、他に20kDaや28kDaなどのバンドが検出された。多種の果物のOASも合併していたモモOAS2例ではImmunoCAP、イムノブロットともにPru p1、Pru p4特異IgEや、Pru p1、Prup4に相当する17kDa,14kDaのバンドを検出した。後者の多くはハンノキ花粉症を有し、ハンノキからの交差反応が主であると推測された。本邦でもモモショック例と多種の果物OAS合併例では感作経路や反応抗原が異なると考えられたが、ヨーロッパとは異なる可能性がある。(著者抄録)(株)北隆館, 2008年12月, アレルギーの臨床, 28(13) (13), 1167 - 1173, 日本語
- (一社)日本皮膚アレルギー・接触皮膚炎学会, 2008年10月, Journal of Environmental Dermatology and Cutaneous Allergology, 2(4) (4), 336 - 336, 日本語
- (一社)日本皮膚アレルギー・接触皮膚炎学会, 2008年10月, Journal of Environmental Dermatology and Cutaneous Allergology, 2(4) (4), 336 - 336, 日本語
- (一社)日本アレルギー学会, 2008年10月, アレルギー, 57(9-10) (9-10), 1485 - 1485, 日本語
- 症例は、74歳男性。2004年12月に右大腿に紅斑を自覚し、結節を伴うようになった。2005年6月に皮膚生検を行い、芽球様異型リンパ球の広範な皮膚への浸潤を認めた。この細胞は、免疫組織学的特殊染色ではCD4,CD56,CD123,TdTが陽性、cCD3,CD45RO,CD20,CD79a,TIA,LFA-1が陰性であった。遺伝子検査では、T細胞レセプター、免疫グロブリンH鎖の遺伝子再構成がなく、またEBウイルスのterminal repeatが認められないことよりCD4+/CD56+hematodermic neoplasmと診断した。CHOP療法6クールにて一旦完全に緩解を認めたが、5ヵ月後に、両大腿の皮膚とその所属リンパ節に再発を認めた。皮膚病変は外科的に切除した。その1ヵ月後には所属リンパ節への腫瘍細胞の浸潤、次に髄膜浸潤を認め、いずれも電子線照射を施行した。しかし、その後末梢血中への腫瘍細胞の白血化を認め、2006年10月に多臓器不全・脳幹部出血にて永眠した。(著者抄録)(一社)日本皮膚悪性腫瘍学会, 2008年06月, Skin Cancer, 23(1) (1), 66 - 71, 日本語
- (一社)日本アレルギー学会, 2008年04月, アレルギー, 57(3-4) (3-4), 431 - 431, 日本語
- (公社)日本皮膚科学会, 2008年03月, 日本皮膚科学会雑誌, 118(4) (4), 810 - 810, 日本語小麦依存性運動誘発アナフィラキシーにおけるインタールとサイトテックの有効性
- 分担執筆, 血管外漏出, 2024年がん化学療法ファーストタッチ・血管外漏出
- 分担執筆, 薬剤性皮膚障害, じほう, 2024年がん化学療法ファーストタッチ・薬剤性皮膚障害
- 分担執筆, メディカルレビュー社, 2024年治りにくい皮膚疾患・どうする？
- 分担執筆, 日本老年学会, 2024年老化分子バイオマーカーと老化制御の基礎医学展望/高齢者および高齢社会に関する検討ワーキンググループ報告書
- 分担執筆, 全日本病院出版会, 2024年Derma. 今こそ極める蕁麻疹. 蕁麻疹診療で行われる検査
- 分担執筆, 南江堂, 2024年最新の臨床WEB. 皮膚疾患. 悪性黒色腫
- 分担執筆, 南江堂, 2024年最新の臨床WEB. 皮膚疾患. 血管肉腫
- 分担執筆, 南江堂, 2024年最新の臨床WEB. 皮膚疾患. 悪性リンパ腫
- 分担執筆, 円形脱毛症の治療（局所療法）, 科学評論社, 2024年皮膚科 Dermatology
- 分担執筆, 物理性蕁麻疹の診断と治療, 科学評論社, 2023年皮膚科 Dermatology
- 分担執筆, 皮膚科におけるepigenetics, 科学評論社, 2022年皮膚科 Dermatology
- 分担執筆, 刺激誘発型の蕁麻疹⑥水蕁麻疹, 秀潤社, 2021年目で見る皮膚科学 Visual Dermatology
- 分担執筆, 外来化学療法における対策 横浜市立大学附属病院における抗がん剤漏出対応, メディカル・サイエンス・インターナショナル, 2021年LiSA徹底分析シリーズ
- 11th World Congress of Melanoma and 21st EADO Congress, 2025年04月, 英語Clinical and histopathological characteristics and prognosis of 6790 patients with malignant melanoma in Japan口頭発表（一般）
- 第16回日本IgG4関連疾患学会学術集会・シンポジウム, 2025年03月, 日本語IgG4関連疾患の皮膚症状を再考する[招待有り]シンポジウム・ワークショップパネル（指名）
- 第507回日本皮膚科学会大阪地方会, 2025年02月, 日本語RASA1バリアントによるcapillary malformation-arteriovenous malformationの一例口頭発表（一般）
- 第15回日本皮膚科心身医学会・スイーツセミナー, 2025年01月, 日本語JAK-STAT制御がもたらすアトピー性皮膚炎治療の新展開口頭発表（一般）
- 第46回水疱症研究会, 2025年01月, 日本語尋常性乾癬に合併した水疱性類天疱瘡にグセルクマブが奏功した1例口頭発表（一般）
- 第46回水疱症研究会, 2025年01月, 日本語粘膜類天疱瘡との鑑別を要した抗BP180抗体陽性の口腔内扁平苔癬の一例口頭発表（一般）
- 神戸大学研究基盤センター若手フロンティア研究会2024, 2024年12月, 日本語イチゴアレルゲンFra a 1.01機能欠損体の解析口頭発表（一般）
- 第54回日本皮膚免疫アレルギー学会学術大会・ランチョンセミナー, 2024年12月, 日本語アトピー性皮膚炎におけるサイバインコの治療メカニズムと臨床応用[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第506回日本皮膚科学会大阪地方会, 2024年12月, 日本語Proliferative fasciitisの一例口頭発表（一般）
- The 49 th Annual Meeting of the Japanese Society for Investigative Dermatology, 2024年12月, 英語Establishment of Porokeratosis Model Cells by Gene Editing Using the CRISPR Cas9 System口頭発表（一般）
- The 49 th Annual Meeting of the Japanese Society for Investigative Dermatology, 2024年12月, 英語Three cases of non-hereditary solitary porokeratosis of Mibelli exhibiting lesion-specific biallelic somatic defects in FDFT1ポスター発表
- 第408回日本皮膚科学会宮城地方会学術大会・スイーツセミナー, 2024年11月, 日本語アトピー性皮膚炎治療におけるIL-13阻害の意義を考える[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第118回日本皮膚科学会群馬地方会・ランチョンセミナー, 2024年11月, 日本語アトピー性皮膚炎の新たな治療アプローチ〜サイバインコの基礎から臨床例まで〜[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第88回日本皮膚科学会東京支部学術大会・ランチョンセミナー, 2024年11月, 日本語病態から考える乾癬治療の選択公開講演，セミナー，チュートリアル，講習，講義等
- 園芸学会令和6年度秋季大会, 2024年11月, 日本語イチゴアレルゲンFra a 1.01機能欠損変異体の作出口頭発表（一般）
- 神戸大学高等学術研究院・卓越教員シンポジウム, 2024年10月難治性がんに対する治療戦略の創出に向けたPhysician-Scientistの挑戦シンポジウム・ワークショップパネル（指名）
- 第6回阪和皮膚疾患研究会, 2024年10月, 日本語皮膚バリアからみたアトピー性皮膚炎の長期管理公開講演，セミナー，チュートリアル，講習，講義等
- 第75回日本皮膚科学会中部支部学術大会, 2024年10月, 日本語尋常性乾癬に合併した水疱性類天疱瘡にグセルクマブが奏功した1例口頭発表（一般）
- 第75回日本皮膚科学会中部支部学術大会, 2024年10月, 日本語当院における臍部子宮内膜症の２例口頭発表（一般）
- 第75回日本皮膚科学会中部支部学術大会, 2024年10月, 日本語アトピー性皮膚炎の病態におけるサイバインコの作用機序と実臨床での使いどころ公開講演，セミナー，チュートリアル，講習，講義等
- 第505回日本皮膚科学会大阪地方会, 2024年10月両下腿に多毛を伴う再発性の結節性紅斑様皮疹を呈した1例口頭発表（一般）
- 日本皮膚科学会愛媛地方会第79回学術大会・スイーツセミナー, 2024年10月IL-13の役割から再考するアトピー性皮膚炎公開講演，セミナー，チュートリアル，講習，講義等
- 第76回日本皮膚科学会西部支部学術大会, 2024年09月巨大な皮下結節を呈し質量解析とゲノムシーケシングにて菌種を同定し得た播種性クリプトコッカス症の1例口頭発表（一般）
- 第76回日本皮膚科学会西部支部学術大会, 2024年09月抗BP180抗体陽性を示した難治性口腔内扁平苔癬にシクロスポリン含嗽療法が著効した一例口頭発表（一般）
- 第76回日本皮膚科学会西部支部学術大会・ランチョンセミナー, 2024年09月アトピー性皮膚炎治療におけるIL-13阻害の意義を考える[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第42回日本美容皮膚科学会総会・学術大会教育講演, 2024年08月, 日本語作用機序から再考する美白剤[招待有り]口頭発表（招待・特別）
- 第117回近畿皮膚科集談会（第504回大阪地方会・486回京滋地方会）, 2024年07月, 日本語Digital papillary adenocarcinomaの一例口頭発表（一般）
- 第40回日本小児臨床アレルギー学会・教育セミナー, 2024年07月, 日本語皮膚科医からみたアトピー性皮膚炎診療と病診連携の重要性[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第48回日本小児皮膚科学会学術大会, 2024年07月, 日本語COL7A1のp.Gly1563Argヘテロ接合性バリアントが病原性と考えられたtransient bullous dermolysis of the newbornの１例口頭発表（一般）
- 14th Meeting of the German – Japanese Society of Dermatology., 2024年06月, 英語Potential of IL-23 inhibitors and New Therapeutic Strategies in Palmoplantar pustulosis公開講演，セミナー，チュートリアル，講習，講義等
- 第50回皮膚かたち研究学会学術大会, 2024年06月, 日本語MVDに生じた体細胞変異が染色体組換えによりホモ接合性となり発症した線状汗孔角化症と考えた1例口頭発表（一般）
- 第123回日本皮膚科学会総会ランチョンセミナー, 2024年06月皮膚科医からみた発汗障害～多汗症・無汗症の診断から治療まで～[招待有り]
- 第123回日本皮膚科学会総会, 2024年06月四肢にアミロイド苔癬を伴った難治性のアトピー性皮膚炎にNemolizumabが奏功した１例口頭発表（一般）
- 第123回日本皮膚科学会総会, 2024年06月耳介低位と母親の顔の多発性黒子から診断に至ったNoonan syndrome with multiple lentiginesの親子例口頭発表（一般）
- 第123回日本皮膚科学会総会, 2024年06月イブルチニブが奏功した皮膚硬化型慢性移植片対宿主病の一例口頭発表（一般）
- 第123回日本皮膚科学会総会, 2024年06月免疫抑制中に生じたVZV関連血管炎による片側性難治性下腿潰瘍の1例口頭発表（一般）
- 第123回日本皮膚科学会総会ランチョンセミナー, 2024年06月皮膚バリア機能に着目したアトピー性皮膚炎の病態と治療戦略[招待有り]
- 第74回日本東洋医学会学術総会・ミニシンポジウム, 2024年06月皮膚科における生物学的製剤使用の現況〜神戸大学医学部附属病院・炎症性皮膚疾患専門外来の取組も含めて〜[招待有り]
- 第503回日本皮膚科学会大阪地方会, 2024年05月診断に苦慮したNK/T細胞リンパ腫・鼻型の1例口頭発表（一般）
- 第54回日本職業・環境アレルギー学会・シンポジウム, 2024年05月アトピー性皮膚炎のバリア機能に対するIL-4/13抑制の関与と抑制の意義〜Dupilumabの有効性を踏まえて〜[招待有り]シンポジウム・ワークショップパネル（指名）
- 第40回日本皮膚悪性腫瘍学会学術大会, 2024年05月治療法の選択に苦慮したSolitaly fibrous tumorの1例口頭発表（一般）
- 第40回日本皮膚悪性腫瘍学会学術大会, 2024年05月菌状息肉症の経過中に発生した皮膚原発CD30陽性T細胞リンパ増殖性疾患の１例口頭発表（一般）
- 塩入桃子、吉岡愛育、福本毅、久保亮治、花房宏昭, 2024年03月, 日本語KRT5のL12ドメインに新規2アミノ酸欠失バリアントを認めた単純型表皮水疱症の1例口頭発表（一般）
- 第502回日本皮膚科学会大阪地方会, 2024年03月, 日本語MVKにヘテロ接合性の病的バリアントと皮疹部表皮特異的なloss of heterozygosityを同定したporokeratosis ptychotropicaの1例口頭発表（一般）
- 第10回皮膚リンパ腫検討会, 2024年02月, 日本語診断に苦慮したNK/T細胞リンパ腫の一例口頭発表（一般）
- 第501回日本皮膚科学会大阪地方会, 2024年02月, 日本語剣創状強皮症にエキシマライトが奏効した１例口頭発表（一般）
- 第45回水疱症研究会, 2024年01月, 日本語DPP-4阻害薬との関連が疑われた結節性類天疱瘡における経時的な抗体の推移口頭発表（一般）
- 第53回日本皮膚免疫アレルギー学会学術大会, 2023年12月, 日本語そう痒の強いアミロイド苔癬を伴ったアトピー性皮膚炎にNemolizumabが奏効した１例口頭発表（一般）
- 第500回日本皮膚科学会大阪地方会, 2023年12月, 日本語右下腿に生じた皮膚原発孤立性形質細胞腫の1例口頭発表（一般）
- 第500回日本皮膚科学会大阪地方会, 2023年12月, 日本語DPP-4阻害薬との関連が疑われた結節性類天疱瘡の一例口頭発表（一般）
- 日本皮膚科学会大阪地方会 第500回記念地方会スイーツセミナー, 2023年12月, 日本語免疫原性を考えた乾癬診療における薬剤選択[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- The 10th Hokkaido University Institute for Genetic Medicine Symposium., 2023年12月Chemo-senolytic therapeutic potential against angiosarcoma.
- 第10回大倉山カンファレンス, 2023年11月, 日本語DPP-4阻害薬が発症に関与したと疑われる結節性類天疱瘡の一例口頭発表（一般）
- 第74回日本皮膚科学会中部支部学術大会, 2023年10月, 日本語易感染宿主に生じたMorganella morganiiによる壊死性筋膜炎の1例口頭発表（一般）
- 第74回日本皮膚科学会中部支部学術大会, 2023年10月, 日本語タクロリムス軟膏外用療法が奏効した多発Angiolymphoid Hyperplasia with Eosinophiliaの1例口頭発表（一般）
- 第74回日本皮膚科学会中部支部学術大会 ランチョンセミナー, 2023年10月, 日本語原発性局所多汗症診療ガイドラインが改訂された多汗症から無汗症までを含めた発汗障害の診療を考える[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第72回日本アレルギー学会学術大会 イブニングセミナー, 2023年10月, 日本語皮膚科医が考えるアトピー性皮膚炎の病態とオルミエントの役割[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- The 9th Hokkaido University Cross-Departmental Symposium., 2023年10月Chemo-senolytic therapeutic potential against angiosarcoma.
- 第19回日本血管腫血管奇形学会, 2023年09月, 日本語MAP3K3に病原性多型をモザイクで認めたVerrucous venous malformation口頭発表（一般）
- 第5回 日本白斑学会学術大会, 2023年09月, 日本語老化メラノサイトでのホメオスタシスの変化[招待有り]口頭発表（招待・特別）
- 高等学術研究院 卓越教員シンポジウム, 2023年08月, 日本語老化に起因する発がんの機序解明[招待有り]ポスター発表
- 第39回日本皮膚悪性腫瘍学会学術大会, 2023年08月, 日本語基底細胞癌を合併し診断に苦慮した脂腺腫の1例口頭発表（一般）
- 第39回日本皮膚悪性腫瘍学会学術大会, 2023年08月, 日本語Imatinibが奏功したKITp.Asn655Lys変異を伴う粘膜悪性黒色腫の一例口頭発表（一般）
- 第116回近畿皮膚科集談会, 2023年07月, 日本語グルカゴノーマに対するランレオチド酢酸塩が奏功した壊死性遊走性紅斑の一例口頭発表（一般）
- 第49回皮膚かたち研究学会学術大会, 2023年07月, 日本語鳥肌様の外観を呈した folliculotropic mycosis fungoidesの1例口頭発表（一般）
- 第47日本小児皮膚科学会学術大会, 2023年07月, 日本語Verrucous venous malformationの1例口頭発表（一般）
- 第7回神戸皮膚炎症疾患研究会, 2023年07月, 日本語グルカゴノーマに対するランレオチド酢酸塩が奏功した壊死性遊走性紅斑の一例口頭発表（一般）
- 第45回日本光医学・光生物学会, 2023年06月, 日本語5-ALA内服中に発症した環状弾性線維融解性巨細胞肉芽腫の一例口頭発表（一般）
- 第45回日本光医学・光生物学会, 2023年06月, 日本語DNA修復機構欠損マウスでUVB照射により形成された皮膚腫瘍の網羅的遺伝子変異解析
- 第39回日本臨床皮膚科医会総会・学術大会, 2023年06月, 日本語大学病院での発汗障害診療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第122回日本皮膚科学会総会, 2023年06月, 日本語母乳中に自己抗原反応性IgAが認められたNeonatal linear IgA bullous dermatosisの1例口頭発表（一般）
- 第122回日本皮膚科学会総会, 2023年06月, 日本語露光部に有棘細胞癌を多発し色素性乾皮症を疑われたボリコナゾール長期内服例ポスター発表
- 第122回日本皮膚科学会総会, 2023年06月, 日本語反復性の熱傷が誘因と考えられた乾癬の１例ポスター発表
- Plenary, 25th International Pigment Cell Conference, 2023年05月, 英語Seeds for new therapeutic strategies of malignant melanoma[招待有り]口頭発表（招待・特別）
- 日本皮膚科学会第497回大阪地方会, 2023年05月, 日本語毛包性ムチン沈着症を伴い鳥肌様の特異な臨床像を示した毛包向性菌状息肉症の1例口頭発表（一般）
- The International Societies for Investigative Dermatology 2023, 2023年05月, 英語Construction of the Atopic Dermatitis Sweat Function Registry (ADSF Registry) for sweating disturbance in atopic dermatitis evaluated by automatic assessment for skin microstructure and sweatingポスター発表
- The International Societies for Investigative Dermatology 2023, 2023年05月, 英語Effect of CXCL1-neutralizing antibodies on UV-induced skin tumors in mice deficient in DNA repair systemsポスター発表
- 日本皮膚科学会第496回大阪地方会, 2023年03月, 日本語頭部に生じ皮下膿瘍を形成した壊疽性膿皮症の１例口頭発表（一般）
- 第495回大阪地方会総会・スポンサードセミナー, 2023年02月, 日本語中等症アトピー性皮膚炎に対するオルミエントの役割[招待有り]
- 第44回水疱症研究会, 2023年01月, 日本語母乳由来のIgAが原因と考えられたNeonatal linear IgA bullous dermatosisの1例口頭発表（一般）
- 第52回日本皮膚免疫アレルギー学会, 2022年12月, 日本語蕁麻疹診療における問診票を用いたスクリーニングの有用性の検討 -問診票を用いてどこまで蕁麻疹の病型を絞り込めるか-
- 第47回日本研究皮膚科学会学術大会, 2022年12月, 英語The landscape of genetic alterations of UVB-induced skin tumors in DNA repair-deficient mice口頭発表（一般）
- 第47回日本研究皮膚科学会学術大会, 2022年12月, 英語Detailed serological examinations to examine the pathogenesis of a pemphigus case with oral erosions and pemphigus foliaceus skin lesions口頭発表（一般）
- The 9th Lunch Meeting of Institute for Genetic Medicine in 2022, 2022年12月Exploring potential therapeutics for angiosarcoma by targeting senescent cells.
- 第86回 日本皮膚科学会東京支部学術大会, 2022年11月, 日本語全身性疼痛の管理に難渋したアドレナリン蕁麻疹の一例口頭発表（一般）
- 第86回 日本皮膚科学会東京支部学術大会, 2022年11月, 日本語デュピルマブ投与後に悪化した顔面紅斑にタクロリムス軟膏が有効であったアトピー性皮膚炎の１例口頭発表（一般）
- 第31回日本色素細胞学会学術大会, 2022年11月, 日本語カルボシアニン色素を用いたメラニントランスファーにおけるエンドサイトーシス/ファゴサイトーシスの動的可視化
- 第74回 日本皮膚科学会西部支部学術大会, 2022年10月, 日本語アルファカルシドールが被疑薬と考えられた急性汎発性発疹性膿疱症の１例口頭発表（一般）
- 第7回関西若手皮膚科医の集い, 2022年10月, 日本語日光蕁麻疹患者血清中の内因性光抗原の検出のための好塩基球活性化試験の樹立
- 第7回関西若手皮膚科医の集い, 2022年10月, 日本語Neonatal linear IgA bullous dermatosisの1例
- 第71回日本アレルギー学会学術大会, 2022年10月, 日本語水蕁麻疹の3例
- The 51st ESDR annual meeting, 2022年09月, 英語Steady-state activation and suppressed responsiveness of basophils from patients with atopic. dermatitis
- 第22回日本抗加齢医学会総会（褒章制度受賞者講演）, 2022年06月, 日本語iPS細胞を用い細胞老化に着目した色素性乾皮症における光老化の機序解明[招待有り]
- 第121回日本皮膚科学会総会, 2022年06月, 英語A case of non-pigmenting fixed drug eruption caused by chondroitin sulfate sodium
- 第121回日本皮膚科学会総会 基礎医学研究費（資生堂寄付）, 2022年06月, 日本語iPS細胞を用い細胞老化に着目した色素性乾皮症の病態解明[招待有り]口頭発表（招待・特別）
- 第490回日本皮膚科学会大阪地方会, 2022年03月, 日本語抗ラミニンα３抗体を同定し抗ラミニン332型粘膜類天疱瘡と診断した1例口頭発表（一般）
- 北播磨Type２炎症3領域講演会, 2022年02月, 日本語⽪膚科医からみたデュピルマブの アトピー性⽪膚炎に対する効果[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 2021 GA2LEN UCARE Urticaria Conference, 2021年12月, 英語, 国際会議Color of wheals in cholinergic urticaria: Red or whiteポスター発表
- 2021 GA2LEN UCARE Urticaria Conference, 2021年12月, 英語, 国際会議Solar urticaria: prognosis and DLQI change among 29 Japanese patients口頭発表（一般）
- 第46回日本研究皮膚科学会学術大会, 2021年12月, 英語Cautions for the discrepancy between CLEIA and ELISA and the presence of non-pathogenic antibodies are needed in pemphigus managementポスター発表
- 第46回日本研究皮膚科学会学術大会, 2021年12月, 英語Epigenetic regulation in melanocytes differentiated from induced pruripotent stem cells originated from xeroderma pigmentosum口頭発表（一般）
- 第46回日本研究皮膚科学会学術大会, 2021年12月, 英語, 国際共著しているNUMB inhibits melanoma migration, invasion, and metastasisポスター発表
- 第46回日本研究皮膚科学会学術大会, 2021年12月, 英語The presence of multiple epitopes within BP180 molecule in a case of dipeptidyl peptidase-4 inhibitor-related bullous pemphigoidポスター発表
- 第51回日本皮膚免疫アレルギー学会総会学術大会, 2021年11月, 日本語神戸大学における特発性アナフィラキシー11例の検討口頭発表（一般）
- 第72回 日本皮膚科学会中部支部学術大会, 2021年11月, 日本語ビベグロンの関与が疑われた紫斑型薬疹の1例口頭発表（一般）
- 第72回 日本皮膚科学会中部支部学術大会, 2021年11月, 日本語ベキサロテン内服と全身皮膚電子線照射療法の併用が奏効したCD4陰性CD8陰性皮膚T細胞リンパ腫の1例口頭発表（一般）
- ISSCR/JSRM International Symposium The International Society for Stem Cell Research (ISSCR) and the Japanese Society for Regenerative Medicine (JSRM), 2021年10月, 英語, 国際会議USEFULNESS OF MELANOCYTES DIFFERENTIATED FROM INDUCED PLURIPOTENT STEM CELLS FOR RESERCH ON PATHOLOGY OF XERODERMA PIGMENTOSUMポスター発表
- 第30回日本色素細胞学会学術大会（日本色素細胞学会 奨励賞）, 2021年10月, 日本語色素細胞を軸とした色素性乾皮症の病態解明[招待有り]口頭発表（招待・特別）
- 第30回日本色素細胞学会学術大会, 2021年10月, 日本語色素性乾皮症A群由来iPS細胞より分化したメラノサイトを用いた網羅的遺伝子発現解析口頭発表（一般）
- 第487回大阪地方会, 2021年10月, 日本語24か月間の投与後に発症したRegorafenibによるざ瘡様皮疹と考えられた1例口頭発表（一般）
- The 50th European Society for Dermatological Research Annual Meeting, 2021年09月, 英語, 国際会議Comprehensive analyses on melanocytes differentiated from induced pruripotent stem cells originated from xeroderma pigmentosum complementation group Aポスター発表
- The 50th European Society for Dermatological Research Annual Meeting, 2021年09月, 英語, 国際会議, 国際共著しているThe role of NUMB in melanomaポスター発表
- 第14回加齢皮膚医学研究基金ロート賞受賞講演, 2021年08月小胞体ストレス応答を介する薬剤耐性のエピゲノム制御に着目した悪性黒色腫の個別化治療[招待有り]口頭発表（招待・特別）
- 第8回汗と皮膚疾患の研究会, 2021年08月神戸大学皮膚科で経験した特発性後天性全身性無汗症32例のまとめ口頭発表（招待・特別）
- 第37回日本皮膚悪性腫瘍学会学術大会, 2021年07月上腕部に生じたPrimary cutanouse adenocysic carcinomaの１例口頭発表（一般）
- 第120回日本皮膚科学会総会, 英語Intravenous immunoglobulin-induced eczema treated with narrow band-ultraviolet B therapy口頭発表（一般）
- 第486回日本皮膚科学会大阪地方会, 2021年05月, 日本語ケブネル現象を呈した猪苓湯誘発顆粒状C3皮膚症の１例口頭発表（一般）
- 第484回日本皮膚科学会大阪地方会, 2021年03月, 日本語色素性乾皮症の現況口頭発表（一般）
- 第469回日本皮膚科学会北陸地方会（望月隆先生退官記念地方会）, 2021年02月, 日本語局所温熱療法と抗真菌剤外用の併用療法が奏功した皮膚アルテルナリア症の１例口頭発表（一般）
- 第2回関西皮膚リンパ腫症例検討会, 2021年02月, 日本語ベキサロテン内服と全身皮膚電子線照射療法の併用が奏功したCD４/CD８ double-negative T-cell lymphomaの１例口頭発表（一般）
- 第42回水疱症研究会, 2021年01月上顎癌の既往があり190kDaペリプラキンと210kDaエンボプラキンに反応を示した抗180型粘膜類天疱瘡の１例口頭発表（一般）
- 第481回大阪地方会, 2020年12月633nmの可視光線が原因であった光線蕁麻疹の1例口頭発表（一般）
- 第28回日本発汗学会総会, 2020年11月2008年から2018年にかけて神戸大学皮膚科で経験した特発性後天性全身性無汗症32例の検討口頭発表（一般）
- 第6回白斑・白皮症研究会, 2020年10月水圧式ナイフを用いた吸引水疱蓋表皮移植術（SBT）による白斑治療口頭発表（一般）
- 第71回日本皮膚科学会中部支部学術大会, 2020年10月チアマゾールとの関連が考えられたcutaneous leukocytoclastic vasculitisの１例ポスター発表
- 第71回日本皮膚科学会中部支部学術大会, 2020年10月神戸大学における円形脱毛症に対するステロイドパルス療法２１例についての検討口頭発表（一般）
- 第113回近畿皮膚科集談会, 2020年07月放射線治療の照射領域とその周辺領域に複数の基底細胞癌を発症した1例口頭発表（一般）
- 第119回日本皮膚科学会総会, 2020年06月当院で経験した特発性後天性全身性無汗症32例の長期予後に関する検討口頭発表（一般）
- 第119回日本皮膚科学会総会, 2020年06月Cutaneous Granulomas in a Patient with Mucosa-associated Lymphoid Tissue Lymphomaポスター発表
- The 24th International Pigment Cell Conference, 2020年, 国際会議, 国際共著しているAT-rich interactive domain 2 regulates therapeutic antitumor immunity in melanomaその他
- 88th Plastic Surgery The Meeting 2019, American Society of Plastic Surgeons, 2019年09月, 国際会議Algorithm of treatments for pigmentary disorders of the face: A prospective observational study in Asian patientsポスター発表
- 第41回日本美容外科学会総会, 2018年10月超音波ガイド下ヒアルロン酸注入法と注入後のLSFGによる皮膚血流評価の経験口頭発表（一般）
- 第36回日本頭蓋顎顔面外科学会学術集会, 2018年10月整容性を考慮した下眼瞼内反症手術の経験口頭発表（一般）
- 12th Biennial Ovarian Cancer Research Symposium, 2018年09月, 国際会議Combination targeting of HDAC6 and PD-1/PD-L1 immune checkpoint in ARID1A-mutated ovarian cancersポスター発表
- 12th Biennial Ovarian Cancer Research Symposium, 2018年09月, 国際会議SWI/SNF catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cellsポスター発表
- 12th Biennial Ovarian Cancer Research Symposium, 2018年09月, 国際会議The N6-methylation of adenosine (m6A) in FZD10 mRNA contributes to resistance to PARP inhibitorポスター発表
- 2nd International Keloid Symposium, 2018年06月, 国際会議Bilateral annular breast keloids that developed as a paraneoplastic phenomenon and showed unique immunohistochemical findings in an elderly woman associated with bilateral breast cancersポスター発表
- 日本研究皮膚科学会 第42回年次学術大会・総会, 2017年12月TPA-induced growth arrest of malignant melanoma is mediated by tyrosine phosphatases, SH-PTP2 and TC-PTP.口頭発表（一般）
- ConBio2017, 2017年12月Functional characterization of phosphatases in TPA-induced growth inhibition of metastatic melanoma.ポスター発表
- 2017 International Pigment Cell Conference, 2017年08月, 国際会議Tyrosine phosphatase, TC-PTP and SH-PTP2 mediate dephosphorylation of STAT3 in TPA-induced growth inhibition of melanoma.ポスター発表
- 第34回日本皮膚悪性腫瘍学会学術大会, 2017年06月, 日本語インフリキマブ投与が著効した免疫チェックポイント阻害剤による高度大腸炎の１例
- 2017 SID Annual Meeting, 2017年04月, 国際会議A novel serum metabolomics-based approach for skin cancersポスター発表
- 第458回 日本皮膚科学会 大阪地方会, 2016年12月運動により有痛性鳥肌様皮疹が誘発された後天性特発性限局性無汗症の1例～アダパレンゲルの著効例～口頭発表（一般）
- 第115回兵庫県皮膚科医会, 2016年11月, 日本語アダパレンゲルが著効した後天性特発性限局性無汗症の1例
- 第457回 日本皮膚科学会 大阪地方会, 2016年10月MALTリンパ腫が合併した抗セントロメア抗体と抗RNAポリメラーゼⅢ抗体が共に陽性を示した全身性強皮症の一例口頭発表（一般）
- 第109回近畿皮膚科集談会, 2016年10月NivolumabからVemurafenibに切り替えて長期生存した多発転移を伴う悪性黒色腫の１例口頭発表（一般）
- 神戸大学医学部皮膚科同窓会学術賞・研究部門 受賞講演, 2016年06月MEK-ERK-phospho-STAT3 (Ser727)経路により誘導されるMcl-1L高発現は、メラノサイトとメラノーマ細胞においてUVBによるアポトーシスを抑制する[招待有り]口頭発表（招待・特別）
- 第115回日本皮膚科学会総会, 2016年06月ブドウ膜炎を合併した皮膚Rosai-Dorfman 病の1例と同様既報告例の検討ポスター発表
- 大阪地方会, 2016年05月歯科金属除去と金属除去食により治癒に至った扁平苔癬の一例口頭発表（一般）
- 日本研究皮膚科学会 第40回年次学術大会・総会, 2015年12月きさらぎ賞受賞講演[招待有り]口頭発表（招待・特別）
- 第35回日本サルコイドーシス／肉芽腫性疾患学会総会, 2015年11月皮膚Rosai-Dorfman diseaseの1例口頭発表（一般）
- 第35回日本サルコイドーシス／肉芽腫性疾患学会総会, 2015年11月妊娠線条を避けて生じた 環状弾性線維融解性巨細胞肉芽腫の1例口頭発表（一般）
- 第10回神戸大学医学部医学科ホームカミングデイ, 2015年10月High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) signaling pathway protects melanocytes from UVB-induced apoptosis: a mechanism essential for melanomagenesisポスター発表
- 第2回関西若手皮膚科医の集い, 2015年10月MEK-ERK-STAT3経路で制御されるMcl-1Lによる色素細胞の アポトーシス抑制とメラノーマ発症口頭発表（一般）
- The 45th Annual European Society for Dermatological Research Meeting, 2015年09月, 国際会議High expression of Mcl-1L via the MEK-ERK-STAT3 signaling pathway protects melanocytes from UVB-induced apoptosis: a mechanism essential for melanomagenesis[招待有り]口頭発表（招待・特別）
- 第114回日本皮膚科学会総会, 2015年05月慢性骨髄単球性白血病（CMML-1）の進行と同調して増悪したびまん性扁平黄色腫の1例ポスター発表
- The Conference in GRU Cancer Center Basic Science Laboratories, 2015年05月, 国際会議High expression of Mcl-1 mediated by MEK–ERK1/2–STAT3 signaling pathway protects melanocytes and melanoma cells against ultraviolet B-induced apoptosis.[招待有り]口頭発表（招待・特別）
- The 74th Society for Investigative Dermatology Annual Meeting, 2015年05月, 国際会議High expression of Mcl-1 mediated by MEK–ERK1/2–STAT3 signaling pathway protects melanocytes and melanoma cells against ultraviolet B-induced apoptosisポスター発表
- 第448回日本皮膚科学会大阪地方会, 2015年03月色素細胞のultraviolet B(UVB)誘導性アポトーシスにおけるMcl-1の役割とメラノーマ発症口頭発表（一般）
- The 22th International Pigment Cell Conference, 2014年09月, 国際会議Ultraviolet B-induced up-regulation of Mcl-1L is mediated by the MEK–ERK1/2 signaling pathway with STAT3 phosphorylated at Ser727 as a transcription factor and protects melanocytes from apoptosis口頭発表（一般）
- 第111回 日本皮膚科学会総会, 2012年06月ランダム皮膚生検にて診断し得た血管内リンパ腫の1例口頭発表（一般）
- 第19 回東播磨皮膚科研究会, 2012年03月ランダム皮膚生検にて診断しえた血管内リンパ腫Intravascular large B-cell lymphoma(IVLBCL)口頭発表（一般）
- 第27回日本皮膚悪性腫瘍学会学術大会, 2011年06月上腕に紫紅色結節を呈した転移性皮膚腫瘍の1例口頭発表（一般）
- 第425回日本皮膚科学会大阪地方会, 2011年05月木村病の1例口頭発表（一般）
- 第423回日本皮膚科学会大阪地方会, 2011年02月上腕に紫紅色結節を呈した転移性皮膚腫瘍の1例口頭発表（一般）
- The3rd Kobe Biologics Academy in Dermatology, 2011年01月独立行政法人国立病院機構神戸医療センターにおける生物学的製剤（抗ヒトTNFαモノクローナル抗体インフリキシマブ：レミケードⓇ）が著効した１例口頭発表（招待・特別）
- 神戸大学医学部皮膚科同窓会学術賞・若手部門 論文賞受賞公演, 2010年06月モモアレルギー原因抗原の検討口頭発表（招待・特別）
- 第21回日本アレルギー学会春季臨床大会, 2009年06月, 日本語コリン性蕁麻疹14例の臨床的特徴と自己汗減作療法の問題点について
- 第21回日本アレルギー学会春季臨床大会（岐阜）, 2009年06月ソバアレルギーで発症した短期間に魚類や甲殻類にもアレルギーーを示すようになった成人例における抗原解析口頭発表（一般）
- 第108回日本皮膚科学会総会, 2009年04月アンピシリンによる薬疹との鑑別を要した分娩を機に膿疱化した乾癬の１例口頭発表（一般）
- 第38回日本皮膚アレルギー接触皮膚炎学会, 2008年11月, 日本語亜硫酸水素Naのパッチテスト陽性もその内服負荷が陰性であった亜硫酸Naの含有静注製剤 による紅皮症型薬疹
- 第58回日本アレルギー学会秋季学術大会, 2008年11月亜硫酸水素Naのパッチテスト陽性もその内服負荷が陰性であった亜硫酸Naの含有静注製剤による紅皮症型薬疹ポスター発表
- 第59回日本皮膚科学会中部, 2008年10月抗サイログロブリン抗体の抗SSA抗体高値を伴い片側性に眼瞼下垂と眼瞼腫脹を呈した症例口頭発表（一般）
- 第101回近畿皮膚科集談会, 2008年07月C型肝炎に対するペグイントロン＋リバビリン療法で生じた多形紅斑の1例口頭発表（一般）
- 第20回日本アレルギー会春季臨床大会, 2008年06月モモ単独ショック３例と多種の果物にも反応するモモ口腔アレルギー症候群７例との原因抗原の比較口頭発表（一般）
- 第30回兵庫県臨床アレルギー研究会, 2008年05月モモアレルギーの１０例口頭発表（一般）
- 第107回日本皮膚科学会総会, 2008年04月皮膚筋炎の自験２３例における内臓癌合併の有無による臨床像予後についての比較口頭発表（一般）
- 第406回日本皮膚科学会大阪地方会, 2008年03月マンシン孤虫症の１例口頭発表（一般）
- 第31回皮膚脈管膠原病研究会, 2008年01月皮膚筋炎の自験２３例における内臓癌合併の有無による臨床像予後についての比較口頭発表（一般）
- 第37回日本皮膚アレルギー接触皮膚炎学会総会学術大会, 2007年12月モモ単独ショック３例と多種の果物にも反応するモモ口腔アレルギー症候群７例との原因抗原の比較
- 第57回日本アレルギー学会秋季学術大会（横浜）, 2007年11月モモ単独のアレルギーと多種の果物アレルギー合併例との比較口頭発表（一般）
- 第58回日本皮膚科中部支部学術大会（京都）, 2007年10月高齢者に生じたT-cell/Histiocyto-Rich B cell lymphoma口頭発表（一般）
- 第58回日本皮膚科中部支部学術大会（京都）, 2007年10月運動神経障害を伴った帯状疱疹の８例口頭発表（一般）
- 第12回日本ラテックスアレルギー研究会（広島）, 2007年07月モモアレルギーの３例口頭発表（一般）
- 第23回日本皮膚悪性腫瘍学会学術大会（新潟, 2007年05月白血化し死の転帰をたどったCD４+/CD５６+hematodenmic neoplasma（Blastic NK-cell lymphoma）の1例口頭発表（一般）
- アトピー性皮膚炎治療研究会
- 日本乾癬学会
- 日本人類遺伝学会
- 日本基礎老化学会
- 日本抗加齢医学会
- 日本皮膚免疫アレルギー学会
- 日本白斑学会
- 白斑白皮症研究会
- 加齢皮膚医学研究会
- 汗と皮膚疾患の研究会
- 日本発汗学会
- 日本研究皮膚科学会
- 日本色素細胞学会
- 日本美容皮膚科学会
- 日本皮膚悪性腫瘍学会
- 日本アレルギー学会
- 日本皮膚科学会
- 科学研究費助成事業（科研費）, 国際共同研究加速基金（海外連携研究）, 2024年 - 2029年03月, 研究分担者超高線量率X線による革新的がん治療法のメカニズム解明
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2024年04月 - 2027年03月一次繊毛のエピゲノム制御に着目した悪性黒色腫のBRAF阻害剤耐性獲得機序の解明
- 日本学術振興会, 科学研究費助成事業, 基盤研究(B), 公益財団法人佐々木研究所, 2023年04月 - 2027年03月, 研究分担者正常組織における変異クローンの空間的増殖を誘導する遺伝・環境要因相互作用の解明
- 北海道大学 遺伝子病制御研究所 感染癌とその関連現象に関わる染色体ゲノム構造の解明, 2025年04月 - 2026年03月, 研究代表者色素細胞の老化制御機構に関与するゲノム構造の解明・継続
- 国立研究開発法人日本医療研究開発機構（AMED） 次世代がん医療加速化研究, 2024年05月 - 2026年03月, 研究代表者iPS細胞を用いた老化関連皮膚がんの革新的治療戦略の開発
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2023年04月 - 2026年03月, 研究分担者エピゲノムによる細胞老化制御から読み解くメラノサイトの恒常性破綻と発がん機構
- 日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 2023年04月 - 2026年03月, 研究分担者汗孔角化症の病態解明を通じた細胞競合／クローン拡大機構の理解と新規治療法開発
- 文部科学省, 研究費助成事業「新学術領域研究（研究領域提案型）『学術研究支援基盤形成』」先進ゲノム支援, 2024年04月 - 2025年03月, 研究代表者＊科学研究費助成事業課題
- 北海道大学 遺伝子病制御研究所 感染癌とその関連現象に関わる染色体ゲノム構造の解明, 2024年04月 - 2025年03月, 研究代表者色素細胞の老化制御機構に関与するゲノム構造の解明・継続
- 国立研究開発法人日本医療研究開発機構（AMED）, 橋渡し研究プログラム大阪大学シーズAH, 橋渡し研究プログラム大阪大学シーズAH支援, 2024年04月 - 2025年03月, 研究代表者色素性乾皮症患者由来iPS細胞を用いた抗光老化剤の開発
- 国立研究開発法人日本医療研究開発機構（AMED）革新的先端研究開発支援事業, 健康・医療の向上に向けた早期ライフステージにおける生命現象の解明（PRIME）, 2021年10月 - 2025年03月, 研究分担者若年期体細胞モザイクの発生要因・拡大原理の解明とその制御による新規治療基盤の創出
- 厚生労働省, 厚生労働科学研究費（ 難治性疾患政策研究事業）, 2023年 - 2025年, その他神経皮膚症候群および色素性乾皮症・ポルフィリン症の学際的診療体制に基づく 医療最適化と患者 QOL 向上のための研究 ２３ＦＣ １０３７
- 文部科学省, 研究費助成事業「新学術領域研究（研究領域提案型）『学術研究支援基盤形成』」先進ゲノム支援, 2023年04月 - 2024年03月, 研究代表者＊科学研究費助成事業課題
- 北海道大学 遺伝子病制御研究所, 感染癌とその関連現象に関わる染色体ゲノム構造の解明, 2023年04月 - 2024年03月, 研究代表者色素細胞の老化制御機構に関与するゲノム構造の解明・継続
- 国立研究開発法人日本医療研究開発機構（AMED）, 橋渡し研究プログラム大阪大学シーズA支援, 2023年04月 - 2024年03月, 研究代表者色素性乾皮症患者由来iPS細胞を用いた抗光老化剤の開発
- 日本色素細胞学会, 2022年度 日本色素細胞学会研究補助金, 2023年04月 - 2024年03月, 研究代表者色素細胞に着目した色素性乾皮症の病態解明研究
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2022年04月 - 2024年03月, 研究代表者低分子代謝のエピゲノム制御に着目したメラノーマの病態解明と新規治療標的の探索
- 神戸大学学術研究推進機構先端的異分野共創研究推進室・先端的異分野共創研究プロジェクト, 2024年, 研究分担者ゲノム編集による低アレルゲン化食品の開発
- 科学研究費助成事業 基盤研究(C), 科学研究費助成事業, 基盤研究(C), 神戸大学, 2024年 - 2027年03月, 研究分担者多発血管腫に着目した皮膚血管内皮「セカンドヒット病」の探索と新規原因遺伝子の同定
- 公益財団法人ひょうご科学技術協会 学術研究助成金, 2024年, 研究代表者がんにおける一次繊毛の動的挙動の解明と薬剤耐性
- 日本白斑学会, 2022年度 ポーラ化成工業（株）白斑研究助成金, 2022年11月 - 2023年10月老化特異的な3次元ゲノム構造がメラノサイトのホメオスタシス制御に与える影響
- 北海道大学 遺伝子病制御研究所, 感染癌とその関連現象に関わる染色体ゲノム構造の解明, 2022年04月 - 2023年03月色素細胞の老化制御機構に関与するゲノム構造の解明・継続
- 日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 2020年04月 - 2023年03月汗孔角化症の病態メカニズム解明を通じたヒト細胞競合の理解汗孔角化症とは、メバロン酸経路に関わる代謝酵素をコードする遺伝子の欠損により皮疹が生じる疾患である。汗孔角化症患者の2症例において、正常部と病変部のそれぞれから組織を採取し、初代培養ケラチノサイトを樹立した。いずれの細胞も、血清存在下では同じ増殖を示した。ところが無血清培地においては、正常皮膚由来のケラチノサイトは血清存在下と同様に増殖したのに対し、病変部皮膚由来のケラチノサイトは死滅した。無血清培地にコレステロールを添加したところ、病変部由来のケラチノサイトも正常に増殖したことから、患者病変部表皮の細胞ではメバロン酸経路が機能していないためにコレステロールの生合成ができず、正常に増殖できないことが考えられた。これら2種類の細胞間で生じる細胞競合現象を解析するために、2種類の細胞を単独培養した時には生じず、2種類の細胞を混合して培養した場合に生じる現象を探索する。2種類の細胞を適切な比率で混合し、正常細胞が変異細胞に取り込まれる条件と、逆に変異細胞が正常細胞に取り囲まれる培養条件においてmRNA発現を網羅的に比較した。変異細胞においては、コレステロール生合成経路の酵素のmRNA発現が上昇していた。2種類の細胞を混合培養した時に上昇すると予想される、細胞競合／細胞増殖に関わるシグナルについて検索中である。また、汗孔角化症の疾患モデルマウスを作成するため、汗孔角化症の原因遺伝子であるMVDとMVKについてfloxマウスを作成した。今後、K14-creERTマウスおよび組み換えが生じた場合に細胞が発する蛍光が変化するmT-mGマウスとの掛け合わせにより、適切な確立でcre-loxP組み換えが起こり、汗孔角化症の皮膚症状がタモキシフェン投与により誘導されるかを探索する。
- 文部科学省科学研究費助成事業「新学術領域研究『学術研究支援基盤形成』」先進ゲノム解析研究推進プラットフォーム, 先進ゲノム支援, 2022年 - 2023年＊科学研究費助成事業課題
- 兵庫県, アグリビジネス創出支援事業, 2022年 - 2023年丹波黒大豆の高ポリフェノール含有に着目した簡易摂取型食品の開発
- 公益財団法人金原一郎医学医療振興財団 第38回基礎医学医療研究助成金, 2023年, 研究代表者色素性乾皮症特異的iPS細胞から分化させる色素細胞を用いた光老化のメカニズムの解明
- 第55回(2023年度)内藤記念科学奨励金・研究助成, 2023年, 研究代表者疾患特異的iPS細胞から分化させる色素細胞を用いた色素性乾皮症の病態メカニズムの解明
- 神戸大学, 神戸大学イノベーションファンドプログラム（ＧＡＰファンドプログラム）, 2023年, 研究分担者コラーゲン分解酵素MMP-1の発現を抑制することによりシワだけでなく、「たるみ」も予防する神戸大学発のスキンケア商品の開発
- 北海道大学 遺伝子病制御研究所, 感染癌とその関連現象に関わる染色体ゲノム構造の解明, 2021年04月 - 2022年03月, 研究代表者色素細胞の老化制御機構に関与するゲノム構造の解明
- 国立研究開発法人日本医療研究開発機構（AMED）, 難治性疾患実用化研究事業, 2020年04月 - 2022年03月, 研究分担者色素性乾皮症に対する新規治療法の開発
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2020年04月 - 2022年03月エピゲノム制御による小胞体ストレス応答を介する薬剤耐性獲得に着目した新規がん治療クロマチンリモデリングを調整するSWI/SNF複合体のAT-rich interactive domain-containing protein 2（ARID2）は、メラノーマで変異率が高い。今までARID2の変異が、メラノーマのがん化進展に与える影響は不明であった。本研究では、ARID2のメラノーマの増殖能や浸潤能への制御を解明した。さらに、SWI/SNF複合体が腫瘍免疫を調節することが報告されており、本研究でも、ARID2がメラノーマ細胞の免疫チェックポイント阻害剤への反応に影響を与えることを示した。
- 厚生労働省, 厚生労働科学研究費補助金（難治性疾患政策研究事業）, 2021年 - 2022年『神経皮膚症候群のレジストリによる悉皆的調査研究』(神経皮膚症候群に関する診療科横断的な診療体制の確立)
- 兵庫県, アグリビジネス創出支援事業, 2021年 - 2022年, 研究分担者丹波黒大豆の高ポリフェノール含有に着目した簡易摂取型食品の開発
- 文部科学省科学研究費助成事業「新学術領域研究『学術研究支援基盤形成』」先進ゲノム解析研究推進プラットフォーム, 先進ゲノム支援, 2021年 - 2022年, 研究代表者＊科学研究費助成事業課題
- 木下基礎科学研究基金助成事業, 2022年, 研究代表者iPS細胞を用いて樹立した複数細胞による疾患特異的３次元皮膚による病態解明
- 国立研究開発法人日本医療研究開発機構（AMED）難治性疾患等実用化研究事業, 希少難治性疾患に対する画期的な医薬品の実用化に関する研究分野／医薬品の治験（医薬品ステップ２), 2022年, 研究分担者サンバーン増強型の色素性乾皮症を対象とした既存薬による新規治療の効果と安全性を評価する医師主導治験
- シグナル伝達医学研究展開センター, 若手共同研究プロジェクト, 2020年04月 - 2021年03月, 研究分担者Hippo-YAP経路によるメラノサイトの制御機構
- 日本皮膚科学会, 日本皮膚科学会基礎医学研究費, 2021年 - 2021年, 研究代表者iPS細胞を用い細胞老化に着目した色素性乾皮症の病態解明
- 公益財団法人コスメトロジー研究振興財団, 2021年度コスメトロジー研究助成, 2021年, 研究代表者iPS細胞を用いた色素細胞の老化機序の解明
- 公益財団法人SGH財団, 第33回SGHがん研究助成, 2021年, 研究代表者がん代謝のエピゲノム制御から解明するメラノーマの病態
- 武田科学振興財団, 2021年度医学系研究助成（がん領域・臨床）, 2021年, 研究代表者がん代謝のエピゲノム制御に着目した新規治療戦略の開発
- 神戸大学研究推進部研究推進課研究助成グループ, 2021年, 研究代表者令和４年度科学研究費早期支援プログラム
- 令和３年度公益財団法人蓬庵社特別研究助成, 2021年, 研究代表者Hippo-YAP経路によるメラノサイトの老化制御のがん化進展における役割の解明とその新規作用点を標的とする独創的治療戦略の開発
- 第33回中冨健康科学振興財団研究助成, 2020年, 研究代表者Hippo-YAP経路によるメラノサイトの老化制御機構とその破綻が起こす病態
- 公益財団法人冲中記念成人病研究所, 研究助成, 2020年, 研究代表者エピゲノムによる小胞体ストレス制御に着目した新規がん治療の確立
- 講師, 2021年 - 現在常識を覆す、膜の力 ヒトにも膜がある！？「STEAMライブラリー - 未来の教室」
- 講師, 宝塚市医師会学術講演会, 2025年04月26日神戸大学で行う発汗障害診療～多汗症・無汗症の診断から治療まで～
- 講師, 皮膚疾患セミナーin岡山, 2025年04月18日病院内連携と地域連携で支えられている発汗障害診療
- 講師, 兵庫県アレルギー疾患対策事業・アレルギー疾患医療従事者等研修会, 2025年02月23日皮膚アレルギー疾患（アトピー性皮膚炎）
- 講師, 2024年12月19日PDE4阻害剤の作用機序と乾癬治療における臨床応用
- 講師, 2024年12月04日アトピー性皮膚炎に対する疾病負荷と目指すべき治療ゴールを再考する
- 講師, 2024年11月09日アトピー性皮膚炎のゴールは長期寛解維持 ～デュピルマブと医療連携～
- 講師, 2024年10月25日PsD概念を踏まえた乾癬治療戦略〜生物学的製剤の使い分けを含めて〜
- 講師, 第326 回 兵庫小児アレルギー研究会, 2024年10月10日アトピー性 皮膚炎に関連 するサイトカインの働き、皮膚バリア機能について
- 講師, 神戸市兵庫区医師会学術講演会, 2024年09月20日アトピー性皮膚炎と掌蹠膿疱症の診断ポイントと最新治療法について
- 講師, 関西医療薬学研究会, 2024年09月08日炎症性皮膚疾患（乾癬・アトピー性皮膚炎）に対する新規治療戦略
- 講師, 第144回兵庫県皮膚科医会学術講演会・特別講演, 2024年09月07日まるっと乾癬診療〜非薬物療法からバイオ治療まで〜
- 講師, 2024年07月27日乾癬治療の過去と未来～これから変わる乾癬治療のストラテジー
- 講師, 2024年07月13日若手皮膚科医と考えるバリアとキャリア
- 講師, 2024年02月24日皮膚科医からみたかんせんとアトピー性皮膚炎の治療トレンドと注意点
- 講師, 2024年02月15日IL-31から多角的に考えるアトピー性皮膚炎の病態
- 講師, 2024年01月13日乾癬の病態におけるIL-17の役割から考える薬剤選択
- 講師, 2023年12月09日皮膚科医の立場から多角的に捉えるアトピー性皮膚炎の病態
- 講師, 2023年11月09日大きく変化したアトピー性皮膚炎と多汗症の治療戦略
- 講師, 2023年10月19日掌蹠膿疱症の病態から考える治療戦略
- 講師, 2023年07月23日大学病院が行う発汗障害診療〜多汗症を中心に〜
- 講師, 2023年05月20日皮膚科医が行う発汗障害診療〜多汗症を中心に〜
- 講師, 2023年05月17日ここまできた多汗症治療
- 講師, 2023年02月26日⽪膚科医からみたデュピルマブの アトピー性⽪膚炎に対する効果
- 講師, 尼崎臨床皮膚科勉強会, 2023年02月16日神戸大学医学部附属病院皮膚科で行っている多汗症治療や患者指導の工夫
- 講師, 2023年01月25日ここまできた乾癬・アトピー治療〜診断から薬剤選択まで〜
- 講師, 神戸市学校薬剤師会研修会WEB講演会, 2022年11月26日神戸大学医学部附属病院で診療している発汗障害
- 講師, 「第31回皮膚の日」市民公開講座, 2022年11月12日大学病院で診療している発汗障害〜多汗症から無汗症まで〜
- 講師, 掌蹠膿疱症 神戸皮膚科・歯科連携講演会, 2022年11月11日医療連携から考える掌蹠膿疱症の病態と治療
- 講師, 2021年08月26日多汗症の病態解明と治療
- 講師, 2016年08月23日神戸市養護教諭研究会幼稚園部 夏季全体研修会 幼稚園で遭遇する子供の皮膚疾患
- 講師, 2010年06月皮膚癌をみつけよう
- 講師, 2010年02月平成21年度（4月～12月）当院皮膚科での手術症例