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Abstract: A combination of the production of Λ hypernuclei via hadron beams and their precision γ-ray spectroscopy using a Ge detector array, Hyperball/Hyperball2, has played essential roles in studies of hypernuclear structure. After a brief summary of our previous studies for p-shell hypernuclei at KEK-PS and BNL-AGS, we describe our plans of hypernuclear γ-ray spectroscopy experiments at J-PARC, in particular, the first experiment E13 starting in 2012, in which we further study ΛN interaction and measure Λ-spin-flip values using light hypernuclei such as , , , and . [Copyright &y& Elsevier]

The high spin states of 79Kr were studied via the 70Zn(13C, 4n) reaction to search for chiral doublet bands based on the three-quasi-particle configuration, πg9/22 ⊗ νg9/2-1. The 13C beam of 65 MeV was provided by the 930 AVF Cyclotron at CYclotron and RadioIsotope Center (CYRIC) facility at Tohoku University. The triple coincidence γ rays were detected by the Hyperball2 array. The side band structure to the πg9/22 ⊗ νg9/2-1 yrast band has been identified in 79Kr. Spin and parity assignments are made based on the DCO ratio and linear polarization analysis. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of currents on a fringing coral reef, a field survey was conducted, mostly under weak wind conditions in summer, on the east coast of Ishigaki Island, southwest Japan, which is encompassed by well-developed fringing reefs. For the same study period, numerical simulations of the current were also performed using a shallow water turbulent flow model with high accuracy reef bathymetry data, which were estimated from high-resolution imagery obtained from satellite remote sensing. The numerical simulation results showed good agreement with the observed data and revealed that the currents have an appreciable magnitude of tide-averaged velocities, even during neap tides, which are governed mostly by wave set-up effects. The results also indicated that temporal variations in velocity and water surface elevation during a tide cycle in the reef exhibit highly asymmetrical patterns; in spring tides especially, the velocities around channels indicate rapid transitions over a short period from peak ebb flow to peak flood flow. The simulations also indicated that a big channel penetrating deeply into the reef attracts the tide-averaged mean flow, even from distant areas of the reef. [ABSTRACT FROM AUTHOR]

A model for forecasting the amount of CO 2 emissions due to urban commuter travel was developed. The model consisted of three submodels: a commuters' number forecasting model, a fuzzy commute travel mode choice model and a CO 2 emissions estimation. The model was tested using the real data of Osaka, Japan. Using this model, we also forecasted and analysed the effect of policy changes to shift commuters' travel mode from private car to public transport in order to decrease the amount of CO 2 emissions. [ABSTRACT FROM AUTHOR]

Aims: We evaluated the cost-effectiveness of artificial intelligence (AI)-based diabetic retinopathy (DR) screening in Japan. This evaluation compared the simultaneous introduction of AI in nationwide health checkups, namely "specific health check-ups in Japan" (SHC), and diabetes complication management (AI-case) with the current situation where AI is not being introduced (conventional-case) from the healthcare payer's perspective., Methods: A cost-effectiveness analysis was conducted using a new individual-based state transition model. Model parameters, including the incidence and progression of DR, health utility values, and costs of screening and treatment, were based on literature data and expert opinion. The analysis estimated quality-adjusted life years (QALYs), cumulative costs, and incremental cost-effectiveness ratios (ICER)., Results: The ICER comparing the AI-case with conventional-case was estimated to be JPY 1,598,244/QALY (USD 11,375/QALY), which is below the willingness-to-pay threshold of JPY 5 million/QALY (USD 35,584/QALY). Scenario analyses revealed that ICERs for the AI-based DR screening in SHC-only condition was JPY 1,895,226/QALY (USD 13,488/QALY) and JPY 3,960,839/QALY (USD 28,189/QALY) in diabetes management-only condition., Conclusions: The introduction of AI-based DR screening for SHC and diabetes management was cost-effective compared to the current situation in Japan., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RK, RG, HT, YH, and MY received grants from the Ministry of Health, Labor and Welfare, Japan (FA1010, Principal investigator: MY). YA received grants from Daiwa Securities Foundation]., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The Japanese Archipelago consists of a series of isolated yet interconnected islands off the Eurasian continent. The linear topography of the archipelago presents a unique biogeographic context for the dispersal of organisms from the continent. In this study, mitochondrial DNA (mtDNA) and single-nucleotide polymorphism (SNP) variation were employed to elucidate the dispersal history of the Japanese clouded butterfly (Parnassius glacialis) across the Japanese Archipelago, including the northern island (Hokkaido), the main island (Honshu), and Shikoku Island. Network analysis of 1192 bp of mtDNA (cytochrome oxidase I and II) regions revealed 49 haplotypes and three distinct haplotype groups, which correspond geographically to Eastern Japan, Western Japan, and Chugoku-Shikoku. The Chugoku-Shikoku group is the most ancient lineage. Divergence time estimates using whole-genome sequencing of mtDNA suggest that the Japanese lineage diverged from the continental P. glacialis approximately 3.08 million years ago (Ma). Subsequently, the Eastern Japan and Western Japan lineages diverged from the Chugoku-Shikoku lineage around 1.06 Ma, with subsequent divergence of the Eastern and Western Japan lineages at approximately 0.62 Ma. P. glacialis is estimated to have expanded its distribution via a land bridge that once connected China and the Japanese Archipelago. Population structure analysis based on 3067 SNP genotypes revealed five distinct genetic structures within the Japanese Archipelago, indicating geographical differentiation. Through mtDNA and SNP variation analyses, four primary genetic barriers were identified: between Hokkaido and Honshu, between Eastern and Central Japan, within the Kansai region, and in the Chugoku region. The first three barriers correspond to notable geographical features, the Blakiston Line, a line parallel to the Itoigawa-Shizuoka Tectonic Line, and a boundary crossing Lake Biwa. These findings suggest that Japanese P. glacialis diverged from the continental P. glacialis and expanded its range across the Japanese Archipelago via western routes, leading to its current distribution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor that is approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan based on randomized clinical trial data. The aim of the real-world, retrospective Orbit study was to describe long-term clinical outcomes and management in adults (aged ≥ 20 years) with CLL/SLL treated with ibrutinib, either as first-line (1L) treatment or for relapsed or refractory (RR) disease, in routine clinical practice in Japan between July 2018 and December 2020. A total of 246 patients were registered, and the safety and per-protocol sets included 237 and 234 patients, respectively. After a median follow-up of 35.7 months, the 36-month progression-free survival rate was 80.9% in the 1L CLL cohort and 67.2% in the RR CLL cohort, and the 36-month overall survival rates were 90.8% and 83.7%, respectively. Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 adverse events of special interest were atrial fibrillation (2.1%), infections (herpesvirus infection, fungal infection, or Pneumocystis jiroveci pneumonia; 1.7%), bleeding (3.8%), and second primary malignancy (2.5%). These findings confirm the long-term, real-world effectiveness and safety of ibrutinib for the treatment of Japanese patients with newly diagnosed or RR CLL/SLL., Competing Interests: Declarations. Conflict of interest: Yosuke Masamoto has received research funding from Kyowa Kirin Co., Ltd.; has received honoraria for lectures from MSD K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AbbVie GK, Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., Janssen Pharmaceutical K.K., SymBio Pharmaceuticals Ltd., Bristol-Myers Squibb K.K., AstraZeneca K.K., Sanofi K.K., Asahi Kasei Pharma Corporation, Yamasa Corporation, Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., and PharmaEssentia Japan K.K.; has received honoraria for manuscript writing from Janssen Pharmaceutical K.K. and AstraZeneca K.K.; and has participated in data safety monitoring of AbbVie GK and Janssen Pharmaceutical K.K. Go Yamamoto has received honoraria for lectures from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd., Daiichi Sankyo Co., Ltd., Sanofi, Nippon kayaku Co., Ltd., Janssen Pharmaceutical K.K., Novartis Pharma K.K., Bristol-Myers Squibb K.K., Meiji Seika Pharma Co., Ltd., Mundipharma K.K., AstraZeneca K.K., and Genmab K.K. Yoshihiro Kameoka has received research funding and honoraria for lectures from Janssen Pharmaceutical K.K. Shuichi Ota has received honoraria from Novartis Pharma K.K., Takeda Pharmaceutical Co. Ltd., AstraZeneca K.K., AbbVie GK, Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Amgen K.K., and Sanofi K.K. Eri Matsuki has received research funding and honoraria from Janssen Pharmaceutical K.K.; and has received consulting fee from Janssen Asia Pacific. Kazutaka Ozeki has received honoraria for lectures from Janssen Pharmaceutical K.K. Takahiro Kumode has received honoraria for lectures from Janssen Pharmaceutical K.K. and Ono Pharmaceutical Co., Ltd. Hideto Tamura has received honoraria for lectures from Sanofi K.K., Bristol-Myers Squibb K.K., and Ono Pharmaceutical Co., Ltd. Ai Omi is an employee of Janssen Pharmaceutical K.K. Kazuhiro Shibayama and Aki Watanabe are employees of Janssen Pharmaceutical K.K.; and own stocks of Johnson & Johnson. Yasushi Isobe has received consulting fees from LSI Medience Corporation. Kensuke Kojima has received honoraria for lectures from Janssen Pharmaceutical K.K., AstraZeneca K.K., and AbbVie GK.; and has received scholarship from Daiichi Sankyo Co., Ltd. and Eisai Co., Ltd. Jun Takizawa has received consulting fees from Janssen Pharmaceutical K.K., AstraZeneca K.K., and AbbVie GK; has received honoraria from Janssen Pharmaceutical K.K., AstraZeneca K.K., AbbVie GK, Novartis Pharma K.K., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and Nippon Kayaku Co., Ltd.; and his institution has received research grant from Janssen Pharmaceutical K.K., AstraZeneca K.K., AbbVie GK, Novartis Pharma K.K., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly Co., Ltd., and Asahi Kasei Corporation. Hirokazu Nagai has received honoraria from AbbVie GK, AstraZeneca K.K., Genmab K.K., Janssen Pharmaceutical K.K., Eli Lilly Co., Ltd., Takeda Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., MSD, Eisai Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Mundipharma K.K., GlaxoSmithKline K.K., Bristol-Myers Squibb K.K., Nippon Kayaku Co., Ltd., Nippon Shinyaku Co., Ltd., and BeiGene Ltd.; and his institute has received research grant from AbbVie GK, AstraZeneca K.K., BeiGene Ltd., Genmab K.K., HUYABIO international, Janssen Pharmaceutical K.K., Eli Lilly Co., Ltd., Takeda Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., MSD, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Haihe Biopharma, Daiichi Sankyo Co., Ltd, Celgene K.K. Zenyaku Kogyo Co., Ltd., Solasia Pharma K.K., Ono Pharmaceutical Co., Ltd., and Regeneron Pharmaceuticals Inc. Junji Suzumiya has received research grant from Eisai Co., Ltd.; has received consulting fees from Eli Lilly Co., Ltd., Zenyaku Kogyo Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Shinyaku Co., Ltd., and Otsuka Pharmaceutical Co., Ltd.; and has received honoraria for lectures from Janssen Pharmaceutical K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Kyowa Kirin Co., Ltd., Zenyaku Kogyo Co., Ltd., Novartis Pharma K.K., AbbVie Inc., and SymBio Pharmaceuticals Ltd. Sadao Aoki has received honoraria for lectures from Janssen Pharmaceutical K.K., AbbVie GK, AstraZeneca K.K., and Chugai Pharmaceutical Co., Ltd. Tsuyoshi Muta, Shingo Kurahashi, Takanori Toyama, Naoki Takahashi, Nobuyuki Aotsuka, and Takuro Yoshimura have no conflicts of interests to declare., (© 2024. The Author(s).)

Objectives: To determine the association between mothers' persistent maternal depression and their toddlers' behavior., Methods: Online surveys were conducted twice with mothers who gave birth to their first child between March and June 2020. The survey periods were November 2020 and May-June 2022. Measures included baseline characteristics and family environment factors, maternal postpartum depression (Edinburgh Postnatal Depression Scale [EPDS]), maternal lifestyle and mother-reported toddler behaviors, and Internet/media use. Statistical analysis was performed using the χ² test, trend test, and logistic regression., Results: Of the 339 participants, 82 (24.1%) were in the "persistent maternal depression" group with high EPDS scores (≥ 9 points) at both time points, and 178 (52.5%) were in the "no maternal depression" group with low EPDS scores (< 9 points) at both time points. Persistent maternal depression was associated with sleep, eating behavior, physical activity, parenting emotions, and abusive behavior of mothers. Furthermore, persistent maternal depression may be related to undesirable toddler behaviors such as smartphone overuse and hyperactivity-like symptoms., Conclusions for Practice: The persistence of postpartum depression is influenced by factors such as mothers' parenting emotions. Preventing and supporting maternal depression in mothers can foster favorable behaviors in toddlers. In Japan, enhanced individualized, ongoing support for postpartum mothers, tailored in duration and form, could promote both maternal well-being and positive parenting practices., Competing Interests: Declarations. Ethics Approval and Consent to Participate: This study was approved by the Bioethics Review Committee of the Nagoya University Graduate School of Medicine (Approval No. 2020 − 0306, 21–134). Informed consent was obtained from respondents before their participation in the study. Consent for Publication: Not applicable. Conflict of Interest: The authors declare that they have no conflicts of interest., (© 2025. The Author(s).)

Background: A history of hospitalization for heart failure (HHF) before transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement is associated with the prognosis of patients with severe aortic stenosis (AS). However, the impact of prior HHF on clinical outcomes after contemporary TAVI using new-generation transcatheter heart valves (THVs) has not been thoroughly investigated., Methods: Using data from the aLliAnce for exPloring cLinical prospects of AortiC valvE disease (LAPLACE)-TAVI registry, we investigated 2,752 patients who underwent TAVI with new-generation THVs with a median follow-up of 627 days. The primary outcomes were all-cause mortality and heart failure readmission after TAVI., Results: Patients with a history of HHF (n = 809) showed a higher 30-day mortality than patients without prior HHF (n = 1,943). A Kaplan-Meier analysis revealed that the prior HHF group showed a higher incidence of the primary outcome than the non-prior HHF group (27.4% vs. 16.4%, log-rank p = 0.001). In a Cox regression analysis, prior HHF was significantly associated with the risk of the primary outcome, even after adjusting for covariates (hazard ratio, 1.344; 95% confidence interval, 1.103-1.638; p = 0.003). A subanalysis showed that the prior HHF group with ejection fraction (EF) ≥ 50% had a higher risk of the primary outcome than the non-prior HHF group, whereas the prior HHF group with EF < 50% had the worst outcome., Conclusion: A history of prior HHF is associated with worse outcomes in patients with severe AS, both in those with preserved EF and those with reduced EF, even after TAVI using new-generation devices., (© 2024 Wiley Periodicals LLC.)

Background: In patients who experience out-of-hospital cardiac arrest (OHCA), it is important to assess the association of sub-phenotypes identified by latent class analysis (LCA) using pre-hospital prognostic factors and factors measurable immediately after hospital arrival with neurological outcomes at 30 days, which would aid in making treatment decisions., Methods: This study retrospectively analyzed data obtained from the Japanese OHCA registry between June 2014 and December 2019. The registry included a complete set of data on adult patients with OHCA, which was used in the LCA. The association between the sub-phenotypes and 30-day survival with favorable neurological outcomes was investigated. Furthermore, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis using in-hospital data as covariates., Results: A total of, 22,261 adult patients who experienced OHCA were classified into three sub-phenotypes. The factor with the highest discriminative power upon patient's arrival was Glasgow Coma Scale followed by partial pressure of oxygen. Thirty-day survival with favorable neurological outcome as the primary outcome was evident in 66.0% participants in Group 1, 5.2% in Group 2, and 0.5% in Group 3. The 30-day survival rates were 80.6%, 11.8%, and 1.3% in groups 1, 2, and 3, respectively. Logistic regression analysis revealed that the ORs (95% CI) for 30-day survival with favorable neurological outcomes were 137.1 (99.4-192.2) for Group 1 and 4.59 (3.46-6.23) for Group 2 in comparison to Group 3. For 30-day survival, the ORs (95%CI) were 161.7 (124.2-212.1) for Group 1 and 5.78 (4.78-7.04) for Group 2, compared to Group 3., Conclusions: This study identified three sub-phenotypes based on the prognostic factors available immediately after hospital arrival that could predict neurological outcomes and be useful in determining the treatment strategy of patients experiencing OHCA upon their arrival at the hospital., (© 2024. The Author(s).)

Background: Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population., Methods: This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 10 11 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183., Results: There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183., Conclusions: A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults., Trial Registration: NCT number: NCT04354480; Clinical Registry number: CR108768., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs., (© 2024. The Author(s).)

Purpose: To investigate the prevalence and incidence of strabismus in the Japanese population by age group and to estimate the subtype proportions., Design: A nationwide population-based cohort study., Methods: This study investigated the number of cases with previous and new diagnoses of strabismus by age group between 2009 and 2020 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, which includes almost all (≥95%) medical claims data. We calculated the strabismus prevalence and 1-year incidence in 2019 and analyzed the proportion of each strabismus subtype., Results: The strabismus prevalence was 2.154% (2 709 207/125 708 000; 95% CI, 2.152%-2.157%). It showed a bimodal distribution, with a high proportion in school and old ages (especially ≥75 years). Exotropia, esotropia, and cyclovertical strabismus proportions were 67.3%, 26.0%, and 6.7%, respectively. Cyclovertical strabismus was uncommon in patients aged ≤18 years (1.4%) and more common (10.2%) in those aged >18 years. The strabismus incidence in 2019 was 321 per 100 000 person-years (403 093/125 708 000; 95% CI, 320-322). The annual incidence proportion of cyclovertical strabismus as opposed to whole strabismus subtypes in patients aged >18 years (13.1%) was higher than that in those aged ≤18 years (1.4%)., Conclusions: This is the first nationwide population-based cohort study to demonstrate strabismus's overall prevalence and incidence. The high prevalence of cyclovertical strabismus in adults compared with children may suggest that cyclovertical strabismus is a primarily age-related strabismus. The high prevalence of exotropia may indicate a genetic difference between Japanese and other ethnicities., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Real-world studies permit inclusion of a more diverse patient population and provide more information on the effectiveness of treatments used in routine clinical practice. This prospective, multicenter, observational study investigated the effectiveness and safety of ixazomib plus lenalidomide and dexamethasone (IRd) in 295 patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice in Japan. Patients had a median age of 74 years, 80.0% were aged ≥ 65 years, 42.0% had received ≥ 3 lines of prior treatment, and 28.5% were "frail" according to the International Myeloma Working Group frailty score. After a median follow-up of 25.0 months, median progression-free survival (PFS) was 15.3 (95% CI 12.4-19.5) months, while median overall survival was not reached. The overall response rate was 53.9%, and 31.5% of patients had a very good partial response or better. In the subgroup analysis, median PFS was better in patients with 1 versus 2 or ≥ 3 lines of prior treatment (29.0 vs 19.2 or 6.9 months) and paraprotein versus clinical relapse (16.0 vs 7.9 months), but median PFS was not notably affected by frailty score or age group. Dose adjustment was more frequent among patients aged > 75 years, especially early after IRd treatment initiation. Treatment-emergent adverse events (TEAEs) of any grade occurred in 84.4% of patients and 24.7% of patients discontinued treatment due to TEAEs; no new safety concerns were found. These findings suggest that oral IRd triplet regimen is an effective and tolerable treatment option for RRMM patients in real-world settings outside of clinical trials.ClinicalTrials.gov identifier: NCT03433001; Date of registration: 14 February 2018., (© 2023. The Author(s).)

An inter-hospital heart team conference based collaborative follow-up (FU) may facilitate outpatient cardiac rehabilitation (CR) programs, especially in hospitals without an outpatient CR center. Consecutive 145 patients with cardiovascular disease who received inpatient treatment at Yamagata University Hospital were divided into collaborative (n = 76) and same-hospital (n = 69) FU groups. In the collaborative FU group, patients received outpatient care at a university hospital and outpatient CR at different hospitals. In the same-hospital FU group, patients received outpatient care and outpatient CR at the same hospital other than the university hospital. The collaborative FU group held monthly 60-minute inter-hospital heart team conferences with CR specialists. No cardiovascular accidents occurred during the outpatient CR program in either group. Peak oxygen uptake VO 2 , anaerobic threshold, brain natriuretic peptide level, and left ventricular ejection fraction significantly improved in both groups. Kaplan-Meier analysis revealed no significant difference in prognosis between the collaborative and same-hospital FU groups (P = 0.246). Of the patients who had collaborative CR programs, 29 (38.2%) patients (37 consultations) were discussed at an inter-hospital heart team conference. Eighteen (48.6%) consultations were for issues related to continuing outpatient CR programs. Collaborative FU was as useful as same-hospital FU in terms of safety, efficacy, and prognosis in patients with cardiovascular disease. We conclude that regular inter-hospital heart team conferences are useful for facilitating collaboration among outpatient CR programs.

This study aimed to analyze the trends and factors influencing the number of ophthalmic surgeries in Japan using the open data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan published by the Ministry of Health, Labour and Welfare. We calculated the number of cataract, glaucoma, and vitreoretinal surgeries, categorized by sex, age, and surgical type, for the fiscal years (FY) 2014 to 2020. The number of cataract surgeries remained stable at approximately 1.45 million cases from FY 2014 to 2018, increased to nearly 1.6 million cases in FY 2019, and decreased to 1.45 million cases in FY 2020. Among glaucoma surgeries, surgical treatments were increased 1.8 times over 7 years, from 33,000 to 60,000 cases. Laser treatment remained steady at around 55,000 cases from FY 2014 to 2017 and then increased to approximately 60,000 cases. The number of vitreoretinal surgeries was increased 1.2 times from FY 2014 to 2019, from 120,000 to 140,000, and decreased to 130,000 by FY 2020. Trends in ophthalmic surgeries over the past 7 years may be influenced by population aging, minimally invasive surgery, and the coronavirus disease pandemic. These findings have implications on surgical decision-making and resource allocation., (© 2023. The Author(s).)

Purpose: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD)., Design: Prospective observational cohort study., Participants: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society., Methods: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant., Main Outcome Measures: The best-corrected visual acuity (BCVA) 6 months after surgery., Results: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10 -7 ; -0.076, P = 1.6 × 10 -3 , respectively). On the other hand, there were no statistically significant differences for the other comparisons., Conclusions: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: This study evaluated safety, reactogenicity, and immunogenicity of a 2-month homologous booster regimen of Ad26.COV2.S in Japanese adults., Methods: In this multicenter, placebo-controlled, Phase 1 trial, adults (Cohort 1, aged 20-55 years, N = 125; Cohort 2, aged ≥ 65 years, N = 125) were randomized 2:2:1 to receive Ad26.COV2.S 5 × 10 10 viral particles (vp), Ad26.COV2.S 1 × 10 11 vp, or placebo, followed by a homologous booster 56 days later. Safety, reactogenicity, and immunogenicity were assessed., Results: Two hundred participants received Ad26.COV2.S and 50 received placebo. The most frequent solicited local adverse event (AE) was vaccination-site pain, and the most frequent solicited systemic AEs were fatigue, myalgia, and headache. After primary vaccination, neutralizing and binding antibody levels increased through Day 57 (post-prime) in both cohorts. Fourteen days after boosting (Day 71), neutralizing antibody geometric mean titers (GMTs) had almost reached their peak value in Cohort 1 (5 × 10 10 vp: GMT = 1049; 1 × 10 11 vp: GMT = 1470) and peaked in Cohort 2 (504; 651); at Day 85, GMTs had declined minimally in Cohort 2. For both cohorts, binding antibody levels peaked at Day 71 with minimal decline at Day 85., Conclusion: A single dose and homologous Ad26.COV2.S booster increased antibody responses with an acceptable safety profile in Japanese adults (ClinicalTrials.gov Identifier: NCT04509947)., Competing Interests: Declaration of Competing Interest YT is an employee of Janssen Pharmaceutical K.K. KF, HN, KT, and HT are employees of Janssen Pharmaceutical K.K. and are shareholders in Johnson & Johnson. TL is an employee of Janssen Pharmaceuticals, China. MLG and VC are employees of Janssen Pharmaceuticals and shareholders in Johnson & Johnson. TE has no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The aim of this study was to elucidate the epidemiological background of central serous chorioretinopathy (CSC), including its incidence and treatment pattern., Methods: This was a population-based longitudinal cohort study using a nationwide health insurance claims database of the Japan Ministry of Health, Labour and Welfare (MHLW). As Japan employs universal health coverage, the database covers more than 95% of claims issued in Japan. We accessed all data stored in the database with permission from the MHLW. We traced all individuals aged 30 years or older and identified individuals with new onset of CSC between January 2011 and December 2018. CSC cases were categorised by age and sex for each year, and incidence rate was calculated. We also identified major treatments for CSC to elucidate the initial treatment pattern., Results: During the 8-year period, 247 930 incidences of CSC were identified, among which 75.9% were men. The crude incidence rate (per 100 000 person-years) in the general population aged 30 years or older was 34.0 (95% CI 33.9 to 34.2), in men was 54.2 (95% CI 53.9 to 54.4) and in women was 15.7 (95% CI 15.5 to 15.8). The mean age of onset was lower in men than in women (50.5±12.5 years vs 54.7±13.5 years). Most of the patients with newly diagnosed CSC (86.8%) did not receive major treatment., Conclusions: The current study provides the nationwide population-based evidence to clarify the detailed epidemiology of CSC. These results could help to understand the pathogenesis and mechanisms of CSC in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan., Study Design: Best-case-scenario analysis using a Markov model., Methods: The clinical effectiveness and cost-effectiveness of screening for AMD were assessed by calculating the reduction proportion of blindness and the incremental cost-effectiveness ratio (ICER). The Markov model simulation began at screening at the age of 40 years and ended at screening at the age of 90 years. The first-eye and second-eye combined model assumed annual state-transition probabilities in the development and treatment of AMD. Data on prevalence, morbidity, transition probability, utility value, and treatment costs were obtained from previously published reports. Sensitivity analysis was performed to assess the influence of the parameters., Results: In the base-case analysis, screening for AMD every 5 years, beginning at age 40 years and ending at age 74 years (reflecting the screening ages of the current Japanese legal "Specific Health Checkups") showed a decrease of 40.7% in the total number of blind patients. The screening program reduced the number of blind people more than did the additional AREDS/AREDS2 formula supplement intake. However, the ICER of screening versus no screening was ¥9,846,411/QALY, which was beyond what people were willing to pay (WTP) in Japan. Sensitivity analysis revealed that neither OCT nor AI improved the ICER, but the scenario in which the prevalence of smoking decreased by 30% improved the ICER (¥4,655,601/QALY) to the level under the WTP., Conclusions: Ophthalmologic screening for AMD is highly effective in reducing blindness but is not cost-effective, as demonstrated by a Markov model based on real-world evidence from Japan., (© 2021. Japanese Ophthalmological Society.)

Hepatozoon and Hemolivia are members of the haemogregarines and are reported in reptiles and reptile-associated ticks. However, no studies have reported on Hepatozoon and Hemolivia in Japanese reptile-associated ticks. This study aimed to molecularly identify and to characterize Hepatozoon and Hemolivia in Japanese reptile-associated ticks, Amblyomma geoemydae (Cantor, 1847) and Amblyomma nitidum (Hirst & Hirst, 1910). A total of 41 and 75 DNA samples from A. geoemydae and A. nitidum ticks, respectively, were used for screening of Hepatozoon and Hemolivia with polymerase chain reaction targeting 18S rDNA. As a result, Hemolivia and Hepatozoon were detected in two A. geoemydae and one A. nitidum, respectively. The sequences of Hemolivia spp. showed a 99.5% (1,050/1,055 bp) identity with Hemolivia parvula (KR069083), and the Hemolivia spp. were located in the same clade as H. parvula in the phylogenetic tree. The sequences of Hepatozoon sp. showed a 98.4% (1,521/1,545 bp) identity with Hepatozoon colubri (MN723844), and the Hepatozoon sp. was distinct from validated Hepatozoon species in the tree. Our findings highlight the first molecular record of Hemolivia in Japan and present the first detection of Hepatozoon in A. nitidum. Further investigations on these tick-borne protozoa are required to understand their life cycle and pathogenicity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To survey the prevalence and clinical and genetic characteristics of pachydrusen in eyes with central serous chorioretinopathy (CSC) and those of Japanese individuals in the general population., Design: Prospective, observational cohort study., Participants: One thousand thirty-seven Japanese patients were included in this study. Three hundred seven patients (614 eyes) had treatment-naïve CSC without choroidal neovascularization in either eye, whereas 730 individuals (1640 eyes) were Japanese individuals from the general population without explicit ocular diseases., Methods: Pachydrusen were detected using color fundus photography, and subfoveal choroidal thickness was measured using OCT. Genotypic distributions of 3 single nucleotide polymorphisms, ARMS2 A69S, CFH I62V, and CFH Y402H, were evaluated., Main Outcome Measures: Prevalence of pachydrusen and association with choroidal thickness., Results: The prevalence of pachydrusen was significantly higher among CSC patients than among the general population group (40.1% vs. 15.6%; P < 0.001). Individuals with pachydrusen in either group were significantly older than those without pachydrusen (CSC patients: 62.1 years vs. 48.8 years [P < 0.001]; general individuals: 70.3 years vs. 51.9 years [P < 0.001]). No significant difference was found in subfoveal choroidal thickness between those with and without pachydrusen (CSC patients: 370 μm vs. 375 μm; [P = 0.574]; general population: 297 μm vs. 303 μm [P = 0.521]). However, after adjusting for age, gender, and refractive error, subfoveal choroidal thickness was notably thicker in individuals with pachydrusen than that in individuals without pachydrusen in both groups (P = 0.003 and P = 0.013, respectively). No significant difference was found in genotype distributions between CSC patients with pachydrusen and those without it; whereas, the T allele frequency of ARMS2 A69S was higher in general population individuals with pachydrusen than that in general population individuals without pachydrusen (42.2% vs. 33.9%; P < 0.001; OR, 1.86, adjusted for age, gender, and choroidal thickness)., Conclusions: Pachydrusen was observed more frequently in CSC patients compared with individuals from the general population. In both groups, pachydrusen was associated with a thicker choroid, suggesting that pachydrusen should be considered as a significant sign of pachychoroid., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: Pneumococcal and influenza infections can cause serious morbidity and mortality in patients with cardiovascular diseases. The purpose of this study was to investigate the safety and efficacy of simultaneous inoculations of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and trivalent influenza vaccine (TIV) in patients with coronary artery disease (CAD)., Methods: This was a prospective, randomized, single-blind, placebo-controlled study. A total of 40 patients with CAD were randomly assigned to the TIV＋PPSV23 (simultaneous inoculations of TIV and PPSV23) and TIV＋Placebo (inoculations of TIV and placebo) groups. Primary outcomes were the safety of simultaneous vaccinations and the changing of circulating cardiovascular biomarkers before, at 4-, and at 12-weeks after vaccinations., Results: The baseline characteristics between the two groups were identical. The prevalence of injection-site pain, swelling, and reddening were 47%, 37%, and 37% in the TIV＋PPSV23 group, and 10%, 5%, and 0% in the TIV＋Placebo group, respectively. All reactions were self-limited. Body temperature ＞37.0℃ or serious injection-related reaction was not observed. The levels of white blood cells, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, pentraxin-3, and malondialdehide-modified low-density lipoprotein (LDL), were not significantly different between the two groups before and after vaccinations. The levels of anti-oxidized LDL were significantly and step-wisely decreased from baseline, to 4-, and 12-weeks vaccinations in the both groups. No significant changes of other markers were observed in both groups at each time point., Conclusion: Simultaneous inoculations of TIV and PPSV23 were safety in patients with CAD, suggesting that dual vaccinations can be considered even in patients with CAD.

Purpose: To evaluate the efficacy of the claims'-based definition of age-related macular degeneration (AMD) in detecting clinically-diagnosed AMD., Study Design: A validation study using cross-sectional data., Methods: Seven hundred clinically-diagnosed AMD patients and seven hundred non-AMD individuals were randomly selected from patients at the Kyoto University Hospital's ophthalmology outpatient clinic between January 2011 and December 2017. We evaluated the sensitivity, specificity, and positive/negative likelihood ratio of eight different claims'-based definitions of AMD for detecting clinically-diagnosed AMD. These definitions consist of the diagnosis name (AMD) in combination with (1) fluorescent fundus angiography, and/or (2) treatment of AMD, and (3) the exclusion of patients who had a diagnosis of central serous chorioretinopathy (CSC) or myopic choroidal neovascularization., Results: Defining by the diagnosis name AMD in the claims' data showed the highest accuracy (sensitivity 94.9%, specificity 92.6%, accuracy 93.7%). Combining the diagnosis name AMD with fluorescence fundus angiography and/or anti-vascular endothelial growth factor (anti VEGF) treatment increased the specificity at the expense of sensitivity. Notably, the combination with AMD treatment achieved a specificity of 98.3%., Conclusion: The current validation study elucidated the high accuracy of the disease name (AMD) in the claims' data for identifying clinically-diagnosed AMD at a single university hospital. Although drawing wider conclusions may be limited, the results of this study contribute to creating real-world evidence in ophthalmology, based on the National Database of Health Insurance Claims in Japan.

Purpose: To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma., Design: Cross-sectional study., Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016., Methods: All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis., Main Outcome Measures: The association between habitual coffee consumption and IOP among nonglaucoma individuals., Results: Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P < 0.001): the higher the consumption of coffee, the lower the IOP of an individual. The IOP of the group who consumed coffee most frequently (3 times daily or more) was 0.4 mmHg lower (95% confidence interval, 0.2-0.5 mmHg lower) than that of the group that consumed coffee least frequently (less than once daily). However, the logistic regression analysis showed that habitual coffee consumption was not associated significantly with history of glaucoma (P = 0.53)., Conclusions: Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the distribution of ocular biometry and refraction in Japanese adults., Design: Cross-sectional analysis of a prospective cohort study., Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age., Methods: All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized., Main Outcome Measures: Distribution of ocular biometry and refraction., Results: After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and -1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 μm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤-0.5 D) and high myopia (SE, ≤-6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34-59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%])., Conclusions: We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Recently, several tick-borne pathogens were detected in reptile-associated ticks. However, studies on the microorganisms in reptile-associated ticks in Japan are limited. This molecular survey thus aimed to identify and characterize tick-borne pathogens (Rickettsiaceae and Anaplasmataceae) in reptile-associated ticks in Japan. In total, 77 Amblyomma nitidum and 104 Amblyomma geoemydae were collected from wild amphibious sea kraits (Laticauda semifasciata, Laticauda colubrina, and Laticauda laticaudata) and from yellow-margined box turtles (Cuora flavomarginata evelynae), respectively. Conventional polymerase chain reaction was performed using the DNA extracted from the ticks to detect the selected pathogens. Sequencing analysis of four Rickettsia genes (gltA, ompA, ompB, and sca4) led to the identification of a putative novel Rickettsia sp. and Rickettsia aeschlimannii-like rickettsia in A. nitidum and A. geoemydae, respectively. Sequencing analysis of gltA and groEL of Anaplasmataceae revealed that the Ehrlichia spp. in these ticks were novel and related to Candidatus Ehrlichia occidentalis. This is the first study on the microorganisms in A. nitidium and the first record of Rickettsia and Ehrlichia in A. geoemydae. Further studies are required to understand their pathogenicity to humans and animals and their life cycle in the wild., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Aortic aneurysm is an increasingly important public health problem with high morbidity and mortality. It is associated with coronary artery disease (CAD), which is a comorbidity of high incidence that is reported to worsen perioperative complications and long-term clinical outcomes in patients with an aortic aneurysm. Patients with significant coronary artery stenosis may require coronary revascularization and/or optimal medical therapy in the perioperative period of aneurysm surgery. However, the prognostic impact of non-significant coronary artery stenosis not indicated for coronary revascularization on clinical outcomes of patients with aortic aneurysms remains unclear. We performed coronary angiography on 239 consecutive patients with thoracic and abdominal aortic aneurysms before endovascular aortic repair or surgical repair. The patients were divided into the following 3 groups according to the severity of stenosis of major coronary arteries: non-CAD group (with < 25% stenosis), non-significant CAD group (with ≥ 25% but < 75% stenosis), and significant CAD group (with ≥ 75% stenosis). CAD was diagnosed in 133 (56%) patients consisting of 48 (20%) patients with non-significant CAD and 85 (36%) patients with significant CAD. Thirty-nine major adverse cardiovascular and cerebrovascular events (MACCEs) occurred in a median follow-up period of 723 days. Kaplan-Meier analysis revealed that the risk of MACCEs was higher in the significant and non-significant CAD groups than in the non-CAD group. Multivariate Cox proportional hazard regression analysis showed that the risk of MACCEs was equally high in the non-significant CAD and significant CAD groups compared to that in the non-CAD group after adjustment for confounding factors. CAD is significantly associated with poor outcomes in patients with aortic aneurysms, irrespective of the significance of CAD.

The signaling lymphocytic activation molecule family 3 (SLAMF3) is highly expressed on plasma cells from patients with multiple myeloma (MM) and induces high malignant potential by ERK signaling mediated via the interaction with adaptor proteins SHP2 and GRB2. This study focused on the single-nucleotide polymorphism (SNP) of the SLAMF3 gene (rs509749, 1804A>G, M602V) in MM. The SNP G allele was a major type, and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, in patients with MM, which was almost the same as in healthy the control group in the Japanese population. Interestingly, patients with GG genotypes had significantly shorter overall survival times than patients with GA/AA genotypes. Consistent with those results, SLAMF3-overexpressing KMS-34 cells with the G allele (V 602 ) had higher cell proliferation potential and were more resistant to anti-MM agents than those with the A allele (M 602 ). When those cells were subcutaneously inoculated into NOG mice, tumor sizes in mice receiving V 602 cells rapidly increased, and survival was significantly shorter than in mice injected with M 602 cells. Furthermore, SLAMF3 V 602 molecules bound more tightly to SHP2 and GRB2, with increased SHP2 and ERK phosphorylation compared with M 602 cells. The mRNA expression of cell cycle-related genes (CCND1 and CCNE1) and anti-apoptotic genes (BCL2L and p21) was increased in V 602 cells compared with M 602 cells. The results thus suggested that the G allele of SLAMF3 SNP rs509749 may be associated with MM disease progression., Competing Interests: Conflict of interest disclosure The authors declare that they have no conflicts of interest., (Copyright © 2020 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Aims: The latest evidence in the incidence of central retinal artery occlusion (CRAO) is needed to support the development of novel treatments as orphan drugs. However, up-to-date information on the incidence of CRAO in the ageing or aged population is limited. We aimed to investigate the nationwide epidemiological and clinical characteristics of CRAO in Japan, using nationwide health insurance claims data., Methods: We analysed a total of 16 069 762 claims data in the sampling dataset of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which is the nationwide health insurance claims database of 127 million whole Japanese individuals. CRAO was identified using the International Classification of Diseases 10th edition diagnostic code H34.1. The crude incidence rates and age-standardised incidence rates of CRAO, according to the standard age-structure population of the WHO, were calculated., Results: The crude incidence rate of CRAO in Japan was 5.84 (95% CI, 5.71 to 5.97) per 100 000 person-years. With respect to the sex-related incidence, the rate was higher 1.40 times in men than in women (6.85 (95% CI, 6.65 to 7.06) vs 4.88 (95% CI, 4.71 to 5.05), p<0.001). The age-standardised incidence rate was 2.53 (95% CI, 2.29 to 2.76) per 100 000 person-years., Conclusions: The crude incidence rate of CRAO was higher in Japan than in other countries, as reported previously, reflecting the Japanese population structure as a super-aged society. These findings can be helpful for the development of appropriate healthcare policies to address the increasing incidence of CRAO with the ageing population., Competing Interests: Competing interests: HOI reports receiving grants from the Japan Agency for Medical Research and Development during the conduct of the study., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In Japan, approximately 64% of municipal solid waste incineration bottom ash (MSWI BA) is landfilled. Because landfills in Japan are operated without capping, the landfill body is directly exposed to climatic events. Increased frequency of heavy rain is predicted to affect the chemical stabilization of bottom ash (BA) landfill, as rainwater seeps into and interacts with landfill components. This study examined the effect of normal rainfall (15 mm/h) and heavy rainfall (25, 50, and 100 mm/h) events on the leaching behavior of ions (Cl - , Na + , K + , and Ca 2+ ) and total organic carbon (TOC) in BA (<10 mm particle size) using a percolation column test. The results showed the decreased leaching of leachate components after heavy rainfall and increased leaching after normal rainfall. In addition, the pH fluctuated around 11-12 after heavy rainfall but decreased to 7-9 after normal rainfall. The carbonation of the leachate and BA layers appears to be the main factor in lowering the pH value. Changes in the TOC and ion concentrations can be explained by dissolution, dilution, and the contact time of water molecules and BA particles. The data showed that the cumulative TOC and ion release rates were not affected by heavy rain intensities. The release rate of leachate components during normal rainfall was higher than that in heavy rainfall in all the scenarios. Significant correlations were found between the leachate components (TOC, Cl - , Na + , K + , and Ca 2+ concentrations) and rainfall variation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The human leukocyte antigen (HLA) is the strongest genetic risk factor for idiopathic inflammatory myopathy (IIM), and different HLA alleles have been reported to be associated with IIM susceptibility among different ethnic groups. In this study, we have investigated HLA alleles associated with IIM in Japanese patients. Methods: Genotyping of HLA-DRB1 and DPB1 were performed in 252 Japanese IIM patients (166 dermatomyositis [DM] and 86 polymyositis [PM] patients) and the association was analyzed with comparison to controls ( n  = 1026 for DRB1 and n  = 413 for DPB1 ). Results: DRB1*08:03 was associated with IIM ( p  = 1.60 × 10 -5 , p c = .0005, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.52-2.92) and DM ( p  = .0004, p c = .0128, OR 2.06, 95%CI 1.40-3.02). DPB1*05:01 was also associated with IIM ( p  = .0001, p c = .0021, OR 1.96, 95%CI 1.38-2.77) and DM ( p  = .0005, p c = .0075, OR 2.05, 95%CI 1.37-3.08). DRB1*09:01 ( p  = .0012, p c = .0368, OR 0.35, 95% CI 0.18-0.69) and DPB1*04:01 ( p  = .0004, p c = .0057, OR 0.05, 95% CI 0.00-0.85) were protectively associated with PM. Two locus analyses suggested that DRB1*09:01 and DPB1*04:01 were independently associated with PM. Conclusion: Protective associations of HLA were detected in Japanese PM patients.

Kidney dysfunction (KD) is closely associated with poor clinical outcome in patients with heart failure (HF). KD is classified as intrinsic and pre-renal KD. However, the impact of each KD on the clinical outcome in patients with HF has not yet been fully elucidated. We measured the urinary to serum creatinine (UC/SC) ratio, a marker for intrinsic and pre-renal KD, in 1009 consecutive patients with HF at admission. There were 314 cardio-renal events including HF and advanced end-stage renal dysfunction during the median follow-up period of 1154 days. There were 63 (6%) patients with intrinsic KD (UC/SC ratio < 20), 118 (12%) patients with intermediate KD (UC/SC ratio 20-40), 607 (60%) patients with pre-renal KD (UC/SC ratio > 40), and 221 (22%) patients with no KD. Multivariate Cox's proportional hazard regression analysis demonstrated that intrinsic and intermediate KDs were significantly associated with poor clinical outcome. The prediction model for cardio-renal events was significantly improved by the addition of UC/SC ratio to the confounding risk factors. Subgroup analysis in patients with HF with severely reduced glomerular filtration rates showed that the prevalence rates of intrinsic, intermediate, and pre-renal KDs were 23%, 30%, and 47%, respectively. The cardio-renal event rate was the highest in the intrinsic KD group compared with that in the other groups. Intrinsic KD was closely associated with extremely poor clinical outcome in patients with HF. The UC/SC ratio could provide important clinical information for the treatment and management of KD in patients with HF.

Aim: The aim of this study was to investigate epidemiological and clinical aspects of severe postpartum hemorrhage (PPH) in Japan. Methods: We used national health insurance claims from 2011 to 2014 provided by the Ministry of Health, Labour and Welfare. The data included randomly selected claims that covered 10% of all inpatients in October, a so-called sampling dataset (covering 1/120 inpatients per year). We extracted claims for transfused blood, and further narrowed down the claims by names of diseases linked to PPH. As most referral obstetric facilities have adopted the diagnosis procedure combination (DPC)-based payment system while small-scale obstetric facilities have not (non-DPC facilities), the claims were also analyzed separately for DPC and non-DPC facilities. We assessed the incidence and causes of PPH, transfusion volume of red blood cells (RBC) and fresh frozen plasma (FFP), and surgical hemostatic management. Results: The number of PPH cases that required blood transfusion in the sampling dataset was 29, 29, 32, and 36 in 2011, 2012, 2013, and 2014, respectively. The leading cause of PPH was uterine atony followed by placental abruption. Although no specific trends were observed for the volume of transfused RBC (1467 ± 234 ml in 2014), there was a steady increase in the rate of FFP utilization in non-DPC facilities from 37% to 79% over the 4-year sampling period. Intrauterine balloon tamponade emerged in 2014. Conclusion: This nationwide survey indicates that the annual incidence of severe PPH is increasing. Furthermore, FFP has become more prevalent in small-scale obstetric facilities.

In sake brewing, the steamed rice is used in two ways, added to sake-mash (as kake-mai ) and making koji . The rice is an important determinant for the quality of sake, as the metabolites in sake affect its taste/aroma. The sake rice Koshitanrei (KOS) was developed in Niigata Prefecture by genetically crossing two sake rice, Gohyakumangoku and Yamadanishiki . However, the metabolites in sake from KOS have not been analyzed. Here, to investigate the characteristic metabolites in sake from KOS, we performed two types of small-scale sake-fermentation tests changing only the rice used for kake-mai or total rice (both kake-mai and koji ) by these three rice cultivars and examined the effect of KOS on sake metabolites by the metabolome analysis method using UPLC-QTOF-MS. We identified the peaks/metabolites, whose intensity in sake from KOS was higher/lower than those from the other cultivars. The brewing properties of KOS were partially characterized by this analysis.

Background: The purpose of this study was to investigate if the transcatheter aortic valve replacement (TAVR) risk score can independently predict outcomes following TAVR, and to evaluate its predictive performance., Methods and results: This retrospective multicenter study comprised 682 patients with severe aortic stenosis who underwent TAVR. The primary endpoint was all-cause death following TAVR. The clinical model was established using variables identified as independent predictors in the multivariate analysis. Incremental values were assessed after adding atrial fibrillation, body mass index (BMI), and serum albumin to the TAVR risk score in receiver-operating characteristic analysis. The median TAVR risk score was 2.1% with a mean follow-up of 505 days. On Kaplan-Meier analysis, a TAVR risk score >4% had lowest survival rate, whereas TAVR risk score ≤2% had the highest survival rate at 3 years (log-rank P<0.001). The multivariate Cox regression analysis found the TAVR risk score was independently associated with all-cause death, and demonstrated moderate predictive performance for predicting all-cause death at 3 years. However, if each independent predictor is added to the model, it significantly increased discriminatory performance, particularly with BMI and serum albumin level., Conclusions: We demonstrated that the TAVR risk score could independently predict mid-term death following TAVR, and had greater predictive performance for predicting all-cause death at 3 years with BMI and serum albumin level.

Despite many recent advances in medicine, cardiogenic stroke is still a health problem with a high mortality rate. Cardiac biomarkers have been reported to be useful indicators for cardiogenic stroke and subsequent cerebrovascular events. However, there are no data directly comparing the cardiac biomarkers in stroke patients. We measured atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) levels and performed transthoracic and transesophageal echocardiography in 282 stroke patients. There were 108 cases of cardiogenic stroke and 47 cases of major adverse cardiovascular and cerebrovascular events (MACCE) during the follow-up period. Association with left atrial function and left atrial appendage function appeared somewhat stronger for BNP and NT-proBNP than ANP and hsTnT. Multivariate logistic analysis demonstrated that cardiac biomarkers excluding ANP were significantly associated with cardiogenic stroke in stroke patients, multivariate Cox's proportional hazards regression analysis demonstrated that all biomarkers were significantly associated with MACCE after adjustment for confounding risk factors. Receiver operating characteristic curve analysis showed that the C indices of BNP and NT-proBNP for cardiogenic stroke and MACCE were almost equal, but significantly greater than those of ANP and hsTnT. Both BNP and NT-proBNP levels are useful predictors of cardiogenic stroke and subsequent MACCE superior to ANP and hsTnT in stroke patients.

Background: Hemodialysis (HD) patients have heavy calcium deposits in their stenotic coronary arteries and worse post-percutaneous coronary intervention (PCI) prognoses than those who do not undergo HD. Rotational atherectomy (RA) facilitates PCI success in severely calcified lesions. We aimed to identify clinical and procedural characteristics that predict HD patients' long-term prognoses after PCI that included RA in the drug-eluting stent (DES) era., Methods: This study included 302 patients who underwent regular HD from J2T Multicenter Registry database of 1090 consecutive patients who underwent RA to treat de novo calcified lesions at three university hospitals between 2004 and 2015. The primary endpoint was cardiovascular (CV) death., Results: During the 5-year observation period, 59 CV deaths (19.5%) occurred. The CV death group and non-CV death group had comparable profiles except significantly lower left ventricular ejection fraction, higher brain natriuretic peptide (BNP), lower rate of RA burr upsizing, and lower rate of final thrombolysis in myocardial infarction (TIMI) 3 flow achievement in the CV death group. Cox regression analysis revealed that increasing ablation burr size (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.13-0.81), final TIMI 3 flow (HR: 0.07; 95% CI: 0.02-0.28), lower BNP level, and optimal medication were independently associated with better CV mortality in HD patients., Conclusion: In the DES era, oral medications at the time of PCI and stepwise calcium ablation were associated with improved long-term CV mortality in HD patients who are scheduled to undergo RA to treat severely calcified coronary artery stenoses, as therapeutic strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Hypothesis: Japan is an aging society, and the number of nonagenarians with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) is increasing, but their outcomes have not been determined fully., Methods: We prospectively enrolled 767 consecutive patients who underwent TAVI in three Japanese institutions. Clinical characteristics and outcomes of nonagenarians (n = 94) were evaluated and compared with those of patients aged <90 years (n = 673)., Results: Prevalence of New York Heart Association (NYHA) class III/IV was not different between the two groups. Preoperative risk scores were significantly higher in nonagenarians compared with those in non-nonagenarians, whereas the Clinical Frailty Scale was not different. Thirty-day mortality tended to be higher (P = .06) and major vascular complication was significantly higher in nonagenarians than in non-nonagenarians (P < .05), but 3-year mortality was equivalent between the two groups. Even after adjustment for covariates, female sex (hazard ratio, 0.41; 95% confidence interval: 0.25-0.67), body mass index (0.87, 0.80-0.94), and NYHA class III/IV (1.84, 1.06-3.29) were associated with all-cause mortality. Age ≥ 90 years was not associated with all-cause mortality., Conclusions: TAVI could be undertaken safely and effectively in nonagenarians, who had acceptable long-term results compared with those for younger patients, although careful attention should be paid to major vascular complication., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

The aim of this study is to assess the association between smartphone usage and depression in each gender of senior high school students. A cross-sectional study with self-administered questionnaires for 295 high school students, aged 15-19 was conducted in Japan. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Female adolescents used smartphones more hours a day than males. Students who used the smartphones for three hours a day accounted for 44.3% of female students and 22.5% of male students. Female students spent longer hours on online chat, social networking sites (SNS), and Internet browsing. The longer hours they spent for online chat (Odds ratio (OR): 1.74; 95% confidence interval (CI): 1.18-2.56), and SNS (OR: 1.41, 95% CI: 1.04-1.92) were associated with depression. On the other hand, male students spent more hours playing games than female students, and their smartphone use was not correlated with depression. There were gender differences in smartphone usage: female students spent more time on social contacts, whereas males were more likely to use them for entertainment. Therefore, if female students overuse online communication, they may be at a higher risk for depression., (Copyright © 2019. Published by Elsevier B.V.)

Background: Home-visiting nurses are expected to enhance their ability to provide adequate nursing care in a relatively isolated work environment. However, the isolated work environment leads to less opportunity to share patient information. We investigated factors relevant to better patient information sharing among home-visiting nurses, which would contribute to the improved care performance of these nurses., Methods: A cross-sectional study with anonymous self-administered questionnaire was conducted between June 2015 and September 2015 in two districts of Japan. Home-visiting nurses who were working at home health care agencies were recruited. The questionnaires consisted of items on demographic data, job-related variables, communication in the workplace, the current state of patient information sharing, opportunities (or measures) of patient information sharing in the workplace, and job satisfaction. Descriptive analyses were performed on all variables, using the Chi-square test, Fisher's exact test, or Mann-Whitney U-test. Logistic regression analyses were conducted to identify the factors associated with better information sharing, adjusting the years of home-visiting nursing experience as the control variable., Results: Of 762 anonymous self-administered questionnaires were mailed, data from 482 participants who consented to this study and had no missing answer were analyzed. Of the total, 77.2% shared the patients' information. Having a friendly adviser (OR = 2.51, 95% CI = 1.14-5.55, p = 0.023), attending some conferences (OR = 2.32, 95% CI = 1.12-4.82, p = 0.024), joining workshops (OR = 1.89, 95% CI = 1.15-3.10, p = 0.012), and years of home-visiting nursing experience (OR = 1.27, 95% CI = 1.03-1.57, p = 0.025) were significantly associated with sufficient sharing of the information. Nurses sufficiently sharing the information were well satisfied with their job (OR = 5.38, 95% CI =3.19-9.09, p < 0.001) and highly preferred a career in home-visiting nursing care (OR = 5.62, 95% CI =3.41-9.27, p < 0.001)., Conclusions: The results suggested that having opportunities to discuss face-to-face such as at conferences and workshops as well as promoting good relationships among colleagues in the workplace will contribute to better information sharing among home-visiting nurses. Home-visiting nurses with less years of experience need to be supported in order to share the information sufficiently. Additionally, sufficient information sharing was also associated with job satisfaction and preference for home-visiting nursing care, which might lead to job retention for home-visiting nurses.

The aim of this study was to assess the efficacy of a biolimus A9-eluting stent in patients with a right coronary artery (RCA) ostial lesion. Ostial lesions of the RCA have been a limitation of percutaneous coronary intervention even in the drug-eluting stent (DES) era. However, clinical outcomes after the deployment of a second generation DES to an RCA ostial lesion with intravascular ultrasound (IVUS) guidance have not been fully elucidated. From September 2011 to March 2013, 74 patients were enrolled in 17 centers from Japan. RCA ostial lesion was defined as de novo significant stenotic lesion located within 15 mm from ostium. IVUS was used for all cases to confirm the location of ostium and evaluate stent coverage of ostium. Patients with hemodialysis were excluded. The primary endpoint is a major adverse cardiac event (MACE) at 1 year. Forty two percent of patients had multi-vessel disease. Angiographically severe calcification was observed in 26% of the lesions. The mean stent diameter was 3.3 ± 0.3 mm (3.5 mm, 72%, 3.0 mm, 25%, and 2.75 and 2.5 mm, 3%), stent length was 17.5 ± 5.8 mm, and dilatation pressure of stenting was 15.6 ± 4.1 atm. RCA ostium was covered by stent in all lesions in IVUS findings. Post dilatation was performed for 64% of lesions (balloon size 3.7 ± 0.6 mm). MACE rate at 1 year was 5.4% (target lesion revascularization 5.4%, myocardial infarction 1.2%, and no cardiac death). The biolimus A9-eluting stent for RCA ostial lesions with IVUS guidance showed favorable results at 1-year follow-up.

To evaluate the association between vision-related quality of life (QoL), physical inactivity, and locomotor dysfunction in subjects with visual impairment.This cross-sectional study included 215 visually impaired subjects recruited from six ophthalmology departments in Japan. The physical inactivity and locomotor dysfunction associated with their visual impairment was investigated. The physical activity level was assessed using the short form of the International Physical Activity Questionnaire and classified as high, moderate, or low. Locomotor function was evaluated with the Geriatric Locomotive Function Scale. Vision-related QoL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire. Background data, including for age, sex, best-corrected visual acuity for each eye, causative eye diseases, systemic comorbidities, and body mass index, were also collected.The average patient age was 69.6 (range, 20-93 years; standard deviation, 14.5 years) and 118 patients (54.9%) were men. Multivariate analysis showed that vision-related QoL and best-corrected visual acuity in the worse eye were significantly associated with physical inactivity and that vision-related QoL, female sex, age, and presence of systemic comorbidity were significantly associated with locomotor dysfunction. Vision-related quality of life is associated with physical inactivity and locomotor dysfunction.

Background: Rotational atherectomy (RA) is an adjunct tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the long-term clinical outcomes of RA use remain unclear in this drug-eluting stent era., Methods and results: This multi-center registry assessed the characteristics and outcomes of patients treated by RA for calcified coronary lesions between 2004 and 2015. Among 1,090 registered patients, mean age was 70±10 years and 815 (75%) were male. Sixty percent of patients had diabetes mellitus and 27.7% were receiving hemodialysis. The procedure was successful in 96.2%. In-hospital death occurred in 33 patients (3.0%), and 14 patients (1.3%) developed definite/probable stent thrombosis. During the median follow-up period of 3.8 years, the incidence of major adverse cardiac events (MACE), defined as all-cause death, acute coronary syndrome, stent thrombosis, target vessel revascularization and stroke, was 46.7%. On multivariable Cox hazard analysis, hemodialysis (HR, 2.08; 95% CI: 1.53-2.86; P<0.0001) and age (HR, 1.03; 95% CI: 1.01-1.04; P<0.0001) were strong independent predictors of MACE. Conversely, statin treatment was associated with lower incidence of MACE (P=0.035)., Conclusions: This study has provided the largest Japanese dataset for long-term follow-up of RA. Although RA in calcified lesions appears feasible with a high rate of procedural success, a high incidence of MACE was observed.

Multiple myeloma (MM) involves the immune dysregulation not only of B cells but also of NK, T, and dendritic cells. Furthermore, the number of regulatory T and myeloid-derived immunosuppressive cells, which are associated with disease progression, also increases. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide exhibit an antimyeloma effect and improve the immune status. Thus, IMiD-enhanced antibody-dependent cell cytotoxicity increases the cytotoxic activity of monoclonal antibody treatment. Among many antibodies, anti-SLAMF7 elotuzumab and anti-CD38 daratumumab have been approved in Japan, and their targeted antigens are responsible for functions that may influence clinical efficacy. Daratumumab exerts various mechanisms of antitumor activity and enhances T-cell immunity by inhibiting immunosuppressive cells. New monoclonal antibodies, including the anti-CD38 antibody isatuximab and anti-BCMA antibody-drug conjugate, are being developed and are expected to demonstrate clinical efficacy. To improve long-term prognosis and achieve cure for MM, immunotherapies such as IMiD-intensified antibody treatment, which resulted in better response rates and longer survival in refractory/relapsed MM, are essential.

Background: A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin T is recommended by the European Society of Cardiology. However, Asian data are not available., Methods: This prospective cohort study included 413 patients with suspected non-ST elevation myocardial infarction in 3 hospitals in Japan and Taiwan from November 2014 to April 2017. Patients were divided into 3groups-rule-out, observe, and rule-in-according to the algorithm. Major adverse cardiovascular events were evaluated at the 30-dayfollow-up., Results: The algorithm ruled out acute myocardial infarction (AMI) in 171 patients with a negative predictive value and sensitivity of 100% (95% confidential interval [CI], 96.8%-100%) and 100% (95% CI, 88.0%-100%), respectively, in the rule-out group. None of the patients were diagnosed with AMI. Among the 127 patients classified into the rule-in group, 47 were diagnosed as having AMI. The positive predictive value and specificity were 33.1% (95% CI, 25.1%-41.9%) and 66.3% (95% CI, 60.2%-72.0%), respectively. Elective catheter intervention was required in 13 patients (5 in the rule-out group, 8 in the observe group) by the 30-dayfollow-up. The Framingham Risk Score (FRS) identified moderate risk in 5 patients and high risk in 8, while the Global Registry of Acute Coronary Events (GRACE) 2.0 risk score identified low risk in 6 patients and moderate risk in 7., Conclusion: The ESC0-hour/1-hour algorithm could be sufficient in Asian patients. The combination with FRS may be more precise than that with the GRACE 2.0 risk score., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

As Japan becomes a super-aging society, presentation of the best ways to provide medical care for the elderly, and the direction of that care, are important national issues. Elderly people have multi-morbidity with numerous medical conditions and use many medical resources for complex treatment patterns. This increases the likelihood of inappropriate medical practices and an evidence-practice gap. The present study aimed to: derive findings that are applicable to policy from an elucidation of the actual state of medical care for the elderly; establish a foundation for the utilization of National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), and present measures for the utilization of existing databases in parallel with NDB validation.Cross-sectional and retrospective cohort studies were conducted using the NDB built by the Ministry of Health, Labor and Welfare of Japan, private health insurance claims databases, and the Kyoto University Hospital database (including related hospitals). Medical practices (drug prescription, interventional procedures, testing) related to four issues-potential inappropriate medication, cancer therapy, chronic kidney disease treatment, and end-of-life care-will be described. The relationships between these issues and clinical outcomes (death, initiation of dialysis and other adverse events) will be evaluated, if possible.

In high-quality sake brewing, the cerulenin-resistant sake yeast K1801 with high ethyl caproate-producing ability has been used widely; however, K1801 has a defective spindle assembly checkpoint (SAC). To identify the mutation causing this defect, we first searched for sake yeasts with a SAC-defect like K1801 and found that K13 had such a defect. Then, we searched for a common SNP in only K1801 and K13 by examining 15 checkpoint-related genes in 23 sake yeasts, and found 1 mutation, R48P of Cdc55, the PP2A regulatory B subunit that is important for the SAC. Furthermore, we confirmed that the Cdc55-R48P mutation was responsible for the SAC-defect in K1801 by molecular genetic analyses. Morphological analysis indicated that this mutation caused a high cell morphological variation. But this mutation did not affect the excellent brewing properties of K1801. Thus, this mutation is a target for breeding of a new risk-free K1801 with normal checkpoint integrity.

Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2'-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.