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Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022. Recently, the European Society of Cardiology (ESC) published the guidelines for the management of acute coronary syndrome in 2023. Major new updates in the 2023 ESC guideline include: (1) intravascular imaging should be considered to guide PCI (Class IIa); (2) timing of complete revascularization; (3) antiplatelet therapy in patient with high-bleeding risk. Reflecting rapid advances in the field, the Task Force on Primary PCI of the CVIT group has now proposed an updated expert consensus document for the management of ACS focusing on procedural aspects of primary PCI in 2024 version., (© 2024. The Author(s).)

Percutaneous coronary intervention for left main coronary artery disease (LM-PCI) represents a high-risk yet life-saving procedure that has evolved significantly over the years. This review outlines the current state-of-the-art practices for LM-PCI in Japan in detail, emphasizing the integration of coronary physiology and intracoronary imaging alongside with evidence-based standardized technique using latest drug-eluting stents. These advancements enable precise lesion assessment, stent sizing, and optimal deployment, thereby enhancing procedural safety and efficacy. Despite discrepancies between current guidelines favoring coronary artery bypass grafting and real-world practice trends towards increased LM-PCI adoption, particularly in elderly populations with multiple comorbidities, careful patient selection and procedural planning are critical. Future perspectives include further refining LM-PCI through conducting randomized controlled trials integrating advanced techniques and addressing the issue of ostial left circumflex lesions and nationwide standardization of medical care for LM disease., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Introduction: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity., Aim: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273)., Methods: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT)., Results: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed., Conclusion: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear., Method: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels., Results: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke., Conclusions: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Telemedicine is a growing segment of the healthcare industry. As telemedicine gains prominence in Japan, the importance of telemedicine patient satisfaction research will also grow. This study examines whether Japanese patients are equally impacted by the same latent dimensions discovered in the multi-dimensional service satisfaction model used by a United States (U.S.) study., Methods: The subjects (n = 110) were patients who received telemedicine service between January and December 2023 at Juntendo University Hospital, Tokyo, Japan. Patient satisfaction perceptions were collected using a questionnaire composed of Likert scale items. Overall patient satisfaction served as the dependent variable, and patient perceptions of various aspects of the service were the independent variables. LASSO regression analysis was used to test the impact of the independent variables on overall patient satisfaction along with cluster analysis to examine the satisfaction ratings based upon patient characteristics., Results: Japanese patient perceptions of telemedicine health benefits were the most impactful driver of overall satisfaction. Cluster analysis indicated that males were generally more satisfied than females. The least satisfied patients were predominately female and those experiencing telemedicine for the first time. Patients receiving service from a specialist physician were least satisfied with the telemedicine financial costs., Discussion: Patient satisfaction levels were found to be highly impacted by perceptions of the health benefits received and the non-financial costs of service. These benefits could be highlighted by Japanese telemedicine providers to increase utilization of telemedicine services. Patient satisfaction was also found to be influenced by patient-centered care (ie, the "soft skills" of providers) to a lesser degree. Therefore, Japanese telemedicine providers may benefit from developing patient-centered communication skills., Conclusion: The model used provides nuanced understandings of telemedicine patient satisfaction, which highlights where targeted improvements in Japanese telemedicine patient satisfaction are likely to be most impactful., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Rapid sand filters (RSFs) are employed in a drinking water treatment to remove undesirable elements such as suspended solids and dissolved metal ions. At a closed uranium (U) mine site, two sets of tandemly linked paired RSF systems (RSF1-RSF2 and RSF1-RSF3) were utilized to remove iron and manganese from mine water. In this study, a 16S rRNA-based amplicon sequencing survey was conducted to investigate the core microbes within the RSF system treating the mine water. In RSF1, two operational taxonomic units (OTUs) related to methanotrophic bacteria, Methylobacter tundripaludum (relative abundance: 18.1%) and Methylovulum psychrotolerans (11.5%), were the most and second most dominant species, respectively, alongside iron-oxidizing bacteria. The presence of these OUTs in RSF1 can be attributed to the microbial community in the inlet mine water, as the three most abundant OTUs in the mine water also dominated RSF1. Conversely, in both RSF2 and RSF3, Nevskia sp., previously isolated from the Ytterby mine manganese oxide producing ecosystem, became dominant, although known manganese-oxidizing bacterial OTUs were not detected. In contrast, a unique OTU related to Rhodanobacter sp. was the third most abundant (8.0%) in RSF1, possibly due to selective pressure from the radionuclide-contaminated environment during RSF operation, as this genus is known to be abundant at nuclear legacy waste sites. Understanding the key bacterial taxa in RSF system for mine water treatment could enhance the effectiveness of RSF processes in treating mine water from closed U mines.

Because of its superior safety profile and improved outcomes, trans-radial percutaneous coronary intervention (TRI) has become the preferred access in percutaneous coronary intervention (PCI) of native coronary disease. This study investigated the impact of TRI on in-hospital outcomes after PCI for coronary artery bypass graft vessels (GV-PCI). We analyzed patients who underwent GV-PCI in 2019-2022 from the Japanese nationwide registry. Patients were categorized into the TRI and trans-femoral PCI (TFI) groups. We assessed the association between TRI and in-hospital outcomes. The primary outcome was a composite of in-hospital death and major bleeding. In this study, 2,295 patients were analyzed.. The primary outcomes occurred in 29 patients (1.3%), including 17 deaths (0.7%). Major bleeding occurred in 12 patients (0.5%), and access site bleeding in 7 patients (0.3%). The TRI group (n = 1,521) showed lower crude rates of the primary outcome (0.9% vs 1.9%, p = 0.039), major bleeding (0.3% vs 1.0%, p = 0.027), and access site bleeding (0.1% vs 0.6%, p = 0.047) compared with the TFI group (n = 774). Univariable logistic regression demonstrated a significant association of TRI with reduced primary outcome (odd ratio [OR] 0.47, 95% confidence interval [CI] 0.22 to 0.98), major bleeding (OR 0.25, 95% CI 0.07 to 0.80), and access site bleeding (OR 0.20, 95% CI 0.03 to 0.94). In the multivariable analysis, TRI was still significantly associated with a decrease in major bleeding events (OR 0.29, 95% CI 0.07 to 0.93). In conclusion, the use of TRI was associated with a reduction in bleeding events when referenced to TFI in the context of GV-PCI., Competing Interests: Declaration of competing interest Dr. Kohsaka reports a relationship with Bristol-Myers Squibb, Pfizer, Novartis, and AstraZeneca that includes: funding grants and speaking and lecture fees. Dr. Ishii reports a relationship with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Kowa, Novartis, Nippon Boehringer Ingelheim, Otsuka Pharma, Pfizer, Mochida Pharma, and Tanabe Mitsubishi that includes: speaking and lecture fees. Dr. Amano reports a relationship with Astellas Pharma, AstraZeneca, Bayer, Daiichi Sankyo, and Bristol-Myers Squibb that includes: speaking and lecture fees. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives We aimed to assess the unmet medical needs of young adult patients with juvenile idiopathic arthritis by evaluating real-world treatment data. Methods We analyzed data on juvenile idiopathic arthritis in the 20-29 age group from the National Database of Designated Incurable Diseases of Japan, which records severe cases or those requiring high-cost medical care registered between April 2018 and March 2020. Results Overall, 322 patients with juvenile idiopathic arthritis transitioning to adulthood were included. A high frequency of methotrexate use was observed among all juvenile idiopathic arthritis subtypes. The frequency of methotrexate use at registration was significantly higher in patients with rheumatoid factor-positive polyarthritis and those with oligoarthritis or polyarthritis than in those with systemic arthritis. The historical use percentage of any biological disease-modifying antirheumatic drug was ≥85% for all juvenile idiopathic arthritis subtypes. The proportion of patients with ≥2 biological disease-modifying antirheumatic drug prescriptions was significantly higher in patients with rheumatoid factor-positive polyarthritis than in those with systemic arthritis. Conclusions High-cost drugs were necessary for many patients with juvenile idiopathic arthritis transitioning to young adulthood and registered in the database. Further studies on the medical interventions and support for these patients are needed., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate the status of the global standardization of, and prefectural differences in, systematic lupus erythematosus (SLE) treatments in Japan., Methods: The Japanese National Database of Health Insurance Claims and Specific Health Checkups (NDB Japan) was used. A patient with SLE was defined as having a disease with ICD10 code M321 or M329 between April 2019 and March 2020, for which oral corticosteroids (OCS), immunosuppressive agents or biologic agents were prescribed at least once during a given month. SLE treatments were evaluated by treatment center type and prefecture., Results: In total, 74,277 patients met the definition of SLE. The SLE prevalence was 60 per 100,000 (range: 47 - 102 per 100,000 by prefecture). Nationwide, 79.4% of the patients (range: 52.1% - 93.3% by prefecture) visited a specialized treatment center (STC); 37.4% (range: 26.4% - 51.3% by prefecture) received only OCS, with fewer of these patients visiting a STC than a non-STC (34.8% and 49.7%, p<0.001); and 21.4% (range: 10.7% - 35.0%) received HCQ, with more of these patients visiting a STC than a non-STC (23.0% and 13.5%; p<0.001)., Conclusions: NDB Japan demonstrated delayed global standardization of, and prefectural disparity in, SLE treatments in Japan., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Gender disparity remains a significant global concern in interventional cardiology, and there is a lack of extensive research examining the outcomes of percutaneous coronary interventions (PCIs) performed by female interventionalists., Objectives: The aim of this study was to examine the practice patterns and outcomes of PCIs conducted by female interventionalists in Japan., Methods: This retrospective observational study analyzed data from the Japanese Percutaneous Coronary Intervention registry between January 2019 and December 2021. The primary endpoint was in-hospital mortality and the secondary endpoint was the success rate of PCIs., Results: A total of 447 female operators (7.3% of all operators) performed 35,211 PCIs (5.3%) during the study period. Female doctors treated a higher percentage of patients with ST-segment elevation myocardial infarction compared with their male counterparts (20.2% vs 17.7%; P  = 0.001), whereas male doctors were more likely to perform PCIs for left main disease (4.9% vs 5.9%; P  < 0.001) and lesions treated with rotational atherectomy (3.5% vs 4.9%; P  < 0.001). The success rate of PCIs was higher for female interventionalists (97.8% vs 97.2%; P  < 0.001). After conducting a risk-adjusted analysis, we found no significant difference in in-hospital mortality (adjusted OR: 0.896; 95% CI: 0.78-1.03; P  = 0.12), or procedural complications associated with the operator's gender., Conclusions: Overall, female operators exhibited outcomes similar to their male counterparts in terms of adjusted procedural outcomes, and higher crude success rate in certain subgroups. These findings emphasize gender disparities and stress the need to increase gender diversity in interventional cardiology., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Cryopyrin-associated periotic syndrome (CAPS) is a rare autoinflammatory disease caused by genetic variants in innate immunity genes. Autoinflammatory diseases, including CAPS, mediate proinflammatory cytokines such as interleukin (IL)-1 and IL-18 and result in severe systemic inflammation. A gain-of-function mutation in the NLR family pyrin domain-containing 3 (NLRP3) gene, which encodes the protein cryopyrin, was identified to be responsible for CAPS in 2001, and since then several additional pathogenic mutations have been found. Moreover, other phenotypes have been identified based on severity and symptomatology, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease/chronic neurologic cutaneous articular syndrome. Prompt diagnosis of CAPS remains challenging, however, due to unspecific, extensive clinical signs, and delayed diagnosis and treatment targeting IL-1 lead to multiorgan damage. Another factor complicating diagnosis is the existence of somatic mosaic mutations in the NLRP3 gene in some cases, resulting in symptoms and clinical courses that are atypical. The frequency of somatic mosaic mutations in CAPS was estimated to be 19% in a systematic review. Psoriasis is a chronic inflammatory skin disease that affects ∼3% of the global population. Although no reports have shown complication between CAPS and psoriasis, these diseases have several similarities and potential relationships, for instance activation of T helper 17 cells in the dermis and increased NLRP3 gene expression in psoriatic skin compared with normal skin. Here, we report a case of CAPS due to a somatic mosaic mutation with recurrent circinate erythematous psoriasis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Type I interferons (IFN-Is) play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Double-filtration plasmapheresis (DFPP) is a treatment option for SLE; however, its effect on IFN-Is remains unclear. Therefore, we investigated the effects of DFPP on IFN-Is. Plasma from patients with SLE ( n  = 11) who regularly underwent DFPP was analysed using a cell-based reporter system to detect the bioavailability and inducing activity of IFN-I. The concentration of plasma dsDNA was measured, and western blotting analysis was used to assess the phosphorylation of the STING pathway. A higher IFN-I bioavailability and inducing activity were observed in patients compared to healthy controls, and both parameters decreased after DFPP. The reduction in IFN-I-inducing activity was particularly prominent in patients with high disease activity. Notably, this reduction was not observed in STING-knockout reporter cells. Additionally, plasma dsDNA levels decreased after DFPP treatment, suggesting that inhibition of the STING pathway was responsible for the observed decrease in activity. Western blotting analysis revealed suppression of STING pathway phosphorylation after DFPP. DFPP reduced IFN-I bioavailability and the inducing activity of plasma. This reduction is likely attributable to the inhibition of the STING pathway through the elimination of dsDNA.

Soil cover is a prevailing method used at mine sites to ensure the safety of hazardous materials and restore ecological functions when the base materials are unfavorable for plant growth. The former open-pit Ningyo-toge Mine was backfilled with overburden and neutralized smelting residues and covered with soil in 1987. After 36 years, the vegetation remained dominated by the perennial herb Miscanthus sinensis, and woody plant establishment did not progress successfully. This study investigated the factors that inhibited woody plant establishment at the site. The soil profile survey revealed that the soil cover formed Bg horizons (pseudogley soil) with cloudy mottling, representative of poorly drained soil. In the Bg horizon, woody plant roots of Pinus densiflora and Weigela hortensis exhibited growth inhibition. Elemental analysis revealed that in the Bg horizon the roots of P. densiflora and W. hortensis accumulated high Fe concentrations exceeding 10,000 mg/kg DW at critical levels. Our results suggested that woody plant roots in the Bg horizon may have suffered from chronic oxygen deficiency accompanied by excessive Fe stress in the soil cover. Topsoil water content (<50 mm) and microtopographic features were not critical factors disrupting woody plant establishment because some individuals were growing in areas with high soil water content, exceeding 60%. Considering that woody plant roots were developed primarily in the shallow A horizon, A horizon formation by M. sinensis is a key step in initiating woody plant establishment by improving the soil structure and physiochemical characteristics of the soil cover, such as carbon content, exchangeable nutrients, and air-filled porosity. For successful mine pollution control and vegetation recovery, implementing an appropriate topsoil system, such as native forest soil, loosely graded and minor infiltration layer above the overburden would be necessary., 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 Elsevier Ltd. All rights reserved.)

Introduction: The femoral head contralateral to the collapsed femoral head requiring total hip arthroplasty (THA) often manifests in the precollapse stage of osteonecrosis of the femoral head (ONFH). It is not yet demonstrated how autologous concentrated bone marrow injection may prevent collapse of the femoral head concurrent with contralateral THA. The primary objective is to evaluate the efficacy of autologous concentrated bone marrow injection for the contralateral, non-collapsed, femoral head in patients with bilateral ONFH, with the ipsilateral collapsed femoral head undergoing THA., Methods and Analysis: This is a multicentre, prospective, non-randomised, historical-data controlled study. We will recruit patients with ONFH who are scheduled for THA and possess a non-collapsed contralateral femoral head. Autologous bone marrow will be collected using a point-of-care device. After concentration, the bone marrow will be injected into the non-collapsed femoral head following the completion of THA in the contralateral hip. The primary outcome is the percentage of femoral head collapse evaluated by an independent data monitoring committee using plain X-rays in two directions 2 years after autologous concentrated bone marrow injection. Postinjection safety, adverse events, pain and hip function will also be assessed. The patients will be evaluated preoperatively, and at 6 months, 1 year and 2 years postoperatively., Ethics and Dissemination: This protocol has been approved by the Certified Committee for Regenerative Medicine of Tokyo Medical and Dental University and Japan's Ministry of Healthy, Labour and Welfare and will be performed as a class III regenerative medicine protocol, in accordance with Japan's Act on the Safety of Regenerative Medicine. The results of this study will be submitted to a peer-review journal for publication. The results of this study are expected to provide evidence to support the inclusion of autologous concentrated bone marrow injections in the non-collapsed femoral head in Japan's national insurance coverage., Trial Registration Number: jRCTc032200229., Competing Interests: Competing interests: The following are potential competing interests: YH and TB have received honoraria for lectures about hip arthroplasty from Zimmer Biomet Japan. TB and MI received a scholarship grant from Zimmer Biomet Japan, which was not used for this study. MI was a representative of endowed departments from several industries, including Zimmer Biomet from April 2021. MI was not involved in data management, monitoring or the statistical analysis. TB has been a member (non-paid) of endowed departments from several industries, including Zimmer Biomet since September 2021., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Radioactivity of Ra isotopes in natural waters is of serious concern. Control of 226 Ra concentrations in tailings ponds, which store waste from U ore extraction processes, is an important issue in mill tailings management. In this study, we tested microbially formed Mn(IV) oxide as an adsorbent for removal of Ra in water treatment. Biogenic Mn(IV) oxide (BMO) was prepared using a Mn(II)-oxidizing fungus, Coprinopsis urticicola strain Mn-2. First, adsorption experiments of Sr and Ba, as surrogates for Ra, onto BMO were conducted in aqueous NaCl solution at pH 7. Distribution coefficients for Ba and Sr were estimated to be ∼10 6.5 and ∼10 4.3  mL/g, respectively. EXAFS analysis indicated that both Sr and Ba adsorbed in inner-sphere complexes on BMO, suggesting that Ra would adsorb in a similar way. From these findings, we expected that BMO would work effectively in removal of Ra from water. Then, BMO was applied to remove Ra from mine water collected from a U mill tailings pond. Just 7.6 mg of BMO removed >98% of the 226 Ra from 3 L of mine water, corresponding to a distribution coefficient of 10 7.4  mL/g for Ra at pH ∼7. The obtained value was convincingly high for practical application of BMO in water treatment. At the same time, the high distribution coefficient indicates that Mn(IV) oxide can be an important carrier and host phase of Ra in the environment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kazuya Tanaka reports financial support was provided by the Kurita Water and Environment Foundation. If there are other authors, they 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 Elsevier Ltd. All rights reserved.)

In recent years, with the trend of open science, there have been many efforts to share research data on the internet. To promote research data sharing, data curation is essential to make the data interpretable and reusable. In research fields such as life sciences, earth sciences, and social sciences, tasks and procedures have been already developed to implement efficient data curation to meet the needs and customs of individual research fields. However, not only data sharing within research fields but also interdisciplinary data sharing is required to promote open science. For this purpose, knowledge of data curation across the research fields is surveyed, analyzed, and organized as an ontology in this paper. As the survey, existing vocabularies and procedures are collected and compared as well as interviews with the data curators in research institutes in different fields are conducted to clarify commonalities and differences in data curation across the research fields. It turned out that the granularity of tasks and procedures that constitute the building blocks of data curation is not formalized. Without a method to overcome this gap, it will be challenging to promote interdisciplinary reuse of research data. Based on the analysis above, the ontology for the data curation process is proposed to describe data curation processes in different fields universally. It is described by OWL and shown as valid and consistent from the logical viewpoint. The ontology successfully represents data curation activities as the processes in the different fields acquired by the interviews. It is also helpful to identify the functions of the systems to support the data curation process. This study contributes to building a knowledge framework for an interdisciplinary understanding of data curation activities in different fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Minamiyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Enhanced interferon α (IFNα) production has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We previously reported IFNα production by monocytes upon activation of the stimulator of IFN genes (STING) pathway was enhanced in patients with SLE. We investigated the mechanism of enhanced IFNα production in SLE monocytes. Monocytes enriched from the peripheral blood of SLE patients and healthy controls (HC) were stimulated with 2'3'-cyclic GAMP (2'3'-cGAMP), a ligand of STING. IFNα positive/negative cells were FACS-sorted for RNA-sequencing analysis. Gene expression in untreated and 2'3'-cGAMP-stimulated SLE and HC monocytes was quantified by real-time PCR. The effect of GATA binding protein 4 (GATA4) on IFNα production was investigated by overexpressing GATA4 in monocytic U937 cells by vector transfection. Chromatin immunoprecipitation was performed to identify GATA4 binding target genes in U937 cells stimulated with 2'3'-cGAMP. Differentially expressed gene analysis of cGAS-STING stimulated SLE and HC monocytes revealed the enrichment of gene sets related to cellular senescence in SLE. CDKN2A, a marker gene of cellular senescence, was upregulated in SLE monocytes at steady state, and its expression was further enhanced upon STING stimulation. GATA4 expression was upregulated in IFNα-positive SLE monocytes. Overexpression of GATA4 enhanced IFNα production in U937 cells. GATA4 bound to the enhancer region of IFIT family genes and promoted the expressions of IFIT1, IFIT2, and IFIT3, which promote type I IFN induction. SLE monocytes with accelerated cellular senescence produced high levels of IFNα related to GATA4 expression upon activation of the cGAS-STING pathway., Competing Interests: NT received grants from Astellas, Asahi Kasei Pharma, AbbVie, Ayumi, Chugai, Eisai, Nippon Boehringer Ingelheim, Taisho and Tanabe Mitsubishi, and speaker’s fees from AbbVie, Asahi Kasei Pharma, AstraZeneca, Bristol Myers Squibb, Chugai, Eli Lilly Japan, GlaxoSmithKline, Novartis, and Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuga, Chiba, Murayama, Hosomi, Nakagawa, Yahagi, Noto, Kusaoi, Kawano, Yamaji, Tamura and Miyake.)

Background: Quality indicators (QIs) have been developed to improve and standardize care quality in percutaneous coronary intervention (PCI). In Japan, consecutive PCI procedures are registered in a nationwide database (the Japanese Percutaneous Coronary Intervention registry), which introduces a benchmarking system for comparing individual institutional performance against the national average., Objectives: The aim of this study was to assess the impact of the benchmarking system implementation on QI improvement at the hospital level., Methods: A total of 734,264 PCIs were conducted at 1,194 institutions between January 2019 and December 2021. In January 2018, a web-based benchmarking system encompassing 7 QIs for PCI at the institutional level, including door-to-balloon time and rate of transradial intervention, was introduced. The process by which institutions tracked their QIs was centrally monitored., Results: During the 3-year study period, the benchmarking system was reviewed at least once at 742 institutions (62.1%) (median 4 times; Q1-Q3: 2-7 times). The institutions that reviewed their records had higher PCI volumes. Among these institutions, although door-to-balloon time was not directly associated, the proportion of transradial intervention increased by 2.3% in the system review group during the initial year compared with 0.7% in their counterparts. However, in the subsequent year, the association between system reviews and QI improvement was attenuated., Conclusions: The implementation of a benchmarking system, reviewed by participating institutions in Japan, was partially associated with improved QIs during the first year; however, this improvement was attenuated in the subsequent year, highlighting the need for further efforts to develop effective and sustainable interventions to enhance care quality in PCI., Competing Interests: This study was supported by a grant from the Chiba Foundation for Health Promotion and Disease Prevention and the Health and Labor Sciences Research Grants (21FA1015). Dr Inohara is an employee of Eli Lilly Japan. Dr Kohsaka has received investigator-initiated grants from Novartis and AstraZeneca; and has received lecture fees from Bristol Myers Squibb. Dr Kumamaru has received consultation fee from EPS Corporation; has received speaker fee from Chugai Pharmaceutical; and is affiliated with the Department of Health Quality Assessment at the University of Tokyo, a social collaboration department supported by the National Clinical Database, Johnson & Johnson, Nipro Corporation, and Intuitive Surgical Sàrl. Dr Ishii has received lecture fees from AstraZeneca, Bayer Pharmaceutical, Boehringer Ingelheim Japan, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharpe & Dohme, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis Japan, and Pfizer Japan. Dr Amano has received lecture fees from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Recent studies have showed that asymptomatic cerebral infarction (ACI) developed in a reasonable number of patients after cardiac catheterization. However, no study has investigated the long-term prognostic impact of ACI after cardiac catheterization. We investigated whether ACI after cardiac catheterization affects long-term mortality and subsequent cardiovascular events.We retrospectively enrolled patients who underwent cardiac catheterization before cardiac surgery and cerebral diffusion-weighted magnetic resonance imaging (DWI). The incidence and clinical features of ACI were investigated. The long-term prognosis, including all-cause mortality and subsequent major cardiovascular events (MACE; all-cause mortality, stroke, acute myocardial infarction, fatal arrhythmia, and hospitalized heart failure), was also assessed.A total of 203 patients were enrolled. Of these, 10.3% had ACI diagnosed by DWI. There were no differences in baseline characteristics between patients with and without ACI, except more frequent history of symptomatic stroke in patients with ACI. In the Kaplan-Meier analysis during a median follow-up of 1009 days, the patients with ACI showed worse mortality and a slightly higher occurrence of MACE compared with those without ACI (P = 0.01 and P = 0.08, respectively). In addition, ACI was a prognostic marker independent of age, surgery type, and history of stroke.ACI after cardiac catheterization frequently developed and was also associated with long-term prognosis. It may be an independent prognostic marker in high-risk patients who underwent subsequent cardiac surgery.

In response to the coronavirus disease 2019 pandemic, the coronavirus disease 2019 vaccine was rapidly developed and the effectiveness of the vaccine has been established. However, various adverse effects have been reported, including the development of autoimmune diseases. We report a case of new-onset polyarteritis nodosa in a 32-year-old male following the coronavirus disease 2019 vaccination. The patient developed limb pain, fever, pulmonary embolism, multiple subcutaneous nodules, and haematomas. Skin biopsy revealed necrotising inflammation accompanied by fibrinoid necrosis and high inflammatory cell infiltration in the walls of medium to small arteries. The symptoms resolved following corticosteroid treatment. Although it is difficult to prove a relationship between the vaccine and polyarteritis nodosa, similar cases have been reported and further reports and analyses are therefore necessary., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

The European League Against Rheumatism and the American College of Rheumatology have stated that the halo sign on vascular ultrasonography (v-US) is relevant in diagnosing giant cell arteritis (GCA) and is equivalent to temporal artery biopsy. However, there are only a few reports about transitions in v-US findings after glucocorticoid (GC) therapy. We report the transitions in the v-US findings in a case of GCA after GC therapy. The patient had rapidly progressive symptoms, and there were concerns about blindness. After GC therapy, we first observed improvement in headache and visual impairment symptoms within 1 week, followed by rapid improvement in laboratory findings within 2 weeks. Subsequently, there were improvements in v-US findings after more than 2 months. In conclusion, these findings showed a dissociation between improvements in clinical symptoms and v-US findings of the temporal artery. Additionally, this case suggests that regular examination of v-US findings is useful in evaluating GCA with evident vascular wall thickness before GC therapy., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Temporal trends in the management of acute coronary syndrome complicated with cardiogenic shock after the revision of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella require further investigation, because their impact remains uncertain., Methods and Results: Using the Japanese Percutaneous Coronary Intervention (J-PCI) registry database from 2019 to 2021, we identified 12 171 patients undergoing percutaneous coronary intervention for acute coronary syndrome complicated with cardiogenic shock under mechanical circulatory support. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella, and (3) venoarterial extracorporeal membrane oxygenation (VA-ECMO); the VA-ECMO group was further stratified into (3a) VA-ECMO alone, (3b) VA-ECMO in combination with IABP, and (3c) VA-ECMO in combination with Impella. The quarterly prevalence and outcomes were reported. The use of IABP alone decreased significantly from 63.5% in the first quarter of 2019 to 58.3% in the fourth quarter of 2021 ( P for trend=0.01). Among 4245 patients requiring VA-ECMO, the use of VA-ECMO in combination with IABP decreased significantly from 78.7% to 67.3%, whereas the use of VA-ECMO in combination with Impella increased significantly from 4.2% to 17.0% ( P for trend <0.001 for both). After adjusting for the confounders, the risk difference in the fourth quarter of 2021 relative to the first quarter of 2019 for in-hospital mortality was not significant (adjusted odds ratio, 0.84 [95% CI, 0.69-1.01])., Conclusions: Our study revealed substantial changes in the use of different mechanical circulatory support modalities in acute coronary syndrome complicated with cardiogenic shock, but they did not significantly improve the outcomes.

Background: There is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS)., Methods: Among 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score., Results: The median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality., Conclusions: The risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2 months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6 years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1 year, 12.4% at 3 years, 17.4% at 5 years, and 21.4% at 7 years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6 years of follow-up. Statin discontinuation was associated with subsequent mortality., Competing Interests: Declaration of Competing Interest Dr. Morimoto reports lecturer's fees from Bayer, Daiichi Sankyo, Japan Lifeline, Kyocera, Mitsubishi Tanabe, Novartis, and Toray and manuscript fees from Bristol-Myers Squibb and Kowa and served advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Sanofi. Dr. Shiomi reports personal fees from Abbott Vascular, Boston Scientific, and Daiichi Sankyo. Dr. Ehara reports personal fees from Abbott vascular Japan, Bayer, Boehringer Ingelheim (Bristol), Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifescience, Medtronic, Pfizer (New York, NY, United States), Takeda, and Terumo. Dr. Kimura reports personal fees from Abbott Vascular, Abiomed, Astellas, Astellas Amgen BioPharma, AstraZeneca, Bayer, Boston Scientific, Boehringer Ingelheim-Myers Squibb, Chugai Pharmaceutical, Edwards Lifescience, EISAI, Daiichi Sankyo, Interscience, Japan Society for the Promotion of Science, Kowa, Kowa Pharmaceutical, Lifescience, Medical Review, MSD, MSD Life Science Foundation, Mitsubishi Tanabe Pharma, Novartis Pharma, Ono Pharmaceutical, OrbusNeich, Otsuka Pharmaceutical, Pharmaceuticals and Medical Devices Agency, Philips, Public Health Research Foundation, Sanofi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Terumo, Toray, and Tsumura. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Transradial intervention (TRI) for percutaneous coronary intervention (PCI) is used to reduce periprocedural complications. However, its effectiveness and safety for patients on dialysis are not well established. We aimed to investigate the association of TRI with in-hospital complications in dialysis patients undergoing PCI., Methods and Results: We included 44 462 patients on dialysis who underwent PCI using Japanese nationwide PCI registry data (2019-21) regardless of acute or chronic coronary syndrome. Patients were categorized based on access site: TRI, transfemoral intervention (TFI). Periprocedural access site bleeding complication requiring transfusion was the primary outcome and in-hospital death, and other periprocedural complications were the secondary outcomes. Matched weighted analysis was performed for TRI and TFI. Here, 8267 (18.6%) underwent TRI, and 36 195 (81.4%) underwent TFI. Patients who received TRI were older and had lower rates of comorbidities than those who received TFI. Access site bleeding rate and in-hospital death were significantly lower in the TRI group (0.1% vs. 0.7%, P < 0.001; 1.8% vs. 3.2%, P < 0.001, respectively). After adjustment, TRI was associated with a lower risk of access site bleeding (odds ratio [OR] [95% confidence interval (CI)]: 0.19 [0.099-0.38]; P < 0.001) and in-hospital death (OR [95% CI]: 0.79 [0.65-0.96]; P = 0.02). Other periprocedural complications between TRI and TFI were not significantly different., Conclusion: In patients undergoing dialysis and PCI, TRI had a lower risk of access site bleeding and in-hospital death than TFI. This suggests that TRI may be safer for this patient population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background The prevalence of traditional atherosclerotic risk factors (TARFs) and their association with clinical profiles or mortality in percutaneous coronary intervention remain unclear. Methods and Results The study analyzed 559 452 patients who underwent initial percutaneous coronary intervention between 2012 and 2019 in Japan. TARFs were defined as male sex, hypertension, dyslipidemia, diabetes, smoking, and chronic kidney disease. We calculated the relative importance according to R 2 and machine learning models to assess the impact of TARFs on clinical profile and in-hospital mortality. The relative contribution (RC) of each TARF was defined as the average percentage of the relative importance calculated from these models. The age-specific prevalence of TARFs, except for chronic kidney disease, formed an inverted U-shape with significantly different peaks and percentages. In the logistic regression model and relative risk model, smoking was most strongly associated with acute myocardial infarction (adjusted odds ratio [OR], 1.62 [95% CI, 1.60-1.64]; RC, 47.1%) and premature coronary artery disease (adjusted unstandardized beta coefficient, 2.68 [95% CI, 2.65-2.71], RC, 42.2%). Diabetes was most strongly associated with multivessel disease (adjusted unstandardized beta coefficient, 0.068 [95% CI, 0.066-0.070], RC, 59.4%). The absence of dyslipidemia was most strongly associated with presentation of cardiogenic shock (adjusted OR, 0.62 [95% CI, 0.61-0.64], RC, 34.2%) and in-hospital mortality (adjusted OR, 0.44 [95% CI, 0.41-0.46], RC, 39.8%). These specific associations were consistently observed regardless of adjustment or stratification by age. Conclusions Our analysis showed a significant variation in the age-specific prevalence of TARFs. Further, their contribution to clinical profiles and mortality also varied widely.

To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study was conducted to determine autoantibodies associated with lupus nephritis (LN), especially those useful in diagnosing proliferative and membranous nephritis., Methods: A total of 106 patients with LN and 63 patients with systemic lupus erythematosus but no nephritis were enrolled; then, 55 patients were selected from the LN group and were divided into two groups: proliferative nephritis patients (n = 36) and membranous nephritis patients (n = 19). The autoantibody profiles of patients' sera were evaluated using the EUROLINE ANA Profile 3 (IgG) kit., Results: A higher positivity rate of anti-double-stranded DNA antibody and anti-histone antibody was seen in LN patients compared to nonrenal systemic lupus erythematosus patients. In comparing between proliferative and membranous nephritis, the positivity of anti-nucleosome antibody was higher in proliferative nephritis, although it was not statistically significant. However, anti-nucleosome antibody-positive patients with LN had a higher prevalence of haematuria and pyuria, which are strong indications of proliferative nephritis. Also, a significantly higher positivity rate of anti-RNP70 antibody was seen in membranous nephritis compared to proliferative nephritis., Conclusions: Our results showed that anti-nucleosome and anti-RNP70 antibodies may be predictive nonhistological factors for discriminating between proliferative and membranous LN., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is a paucity of data on the effect of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with standard PCI or coronary artery bypass grafting (CABG) in patients with multivessel disease., Methods and results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI including the left anterior descending coronary artery using IVUS aiming to meet the prespecified criteria for optimal stent expansion. We conducted propensity score matching analyses between the OPTIVUS group and historical PCI or CABG control groups from the CREDO-Kyoto registry cohort-3 (1,565 and 899 patients) fulfilling the inclusion criteria for this study. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. In the propensity score-matched cohort (OPTIVUS vs. historical PCI control: 926 patients in each group; OPTIVUS vs. historical CABG control: 436 patients in each group), the cumulative 1-year incidence of the primary endpoint was significantly lower in the OPTIVUS group than in the historical PCI control group (10.4% vs. 23.3%; log-rank P<0.001) or the historical CABG control group (11.8% vs. 16.5%; log-rank P=0.02)., Conclusions: IVUS-guided PCI targeting the OPTIVUS criteria combined with contemporary clinical practice was associated with superior clinical outcomes at 1 year compared with not only the historical PCI control, but also the historical CABG control.

Background: The optimal revascularization strategy in patients with multivessel disease and intermediate SYNTAX score (SS) has not been fully elucidated. This study aimed to investigate the clinical outcomes of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) stratified by SS., Methods: This was a substudy of the OPTIVUS-Complex PCI study Multivessel Cohort, which aimed to meet the prespecified criteria for optimal stent expansion after IVUS-guided PCI. A total of 1,005 patients were divided into 3 groups according to SS: low, ≤22; intermediate, 23 to 32; and high, ≥33. The primary end points were major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of death, myocardial infarction, stroke, or coronary revascularization., Results: The cumulative 1-year incidence of the primary end point was significantly higher in patients with high SS than in those with intermediate or low SS (25.0%, 10.9%, and 9.5%, respectively; p = 0.003). This difference was mainly caused by the incidence of coronary revascularization. In the multivariable Cox proportional hazards models, the excess risk of patients with high versus low SS remained significant for the primary end point (hazard ratio 3.19, 95% confidence interval 1.65 to 6.16, p <0.001), whereas the excess risk of patients with intermediate versus low SS was no longer significant (hazard ratio 1.20, 95% confidence interval 0.72 to 2.01, p = 0.46)., Conclusions: After IVUS-guided multivessel PCI, patients with intermediate SS had a similar 1-year risk of MACCE to that of patients with low SS, whereas patients with high SS had a higher 1-year risk of MACCE than those with low SS., Competing Interests: Declaration of Competing Interest Dr. Hibi reports funding grants from Abbott; lecturer fees from Abbott Medical, Daiichi Sankyo, and Medtronic; research grants from the Research Institute for Production Development and Japan Medical Device Corporation; and scholarship funds from Abbott Medical and Nipro. Dr. Morimoto reports lecturer fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; manuscript fees from Bristol-Myers Squibb and Kowa; and participation on the advisory boards of Novartis and Teijin. Dr. Tanabe reports honoraria from Abbott Medical, Boston Scientific, Japan Lifeline, Medtronic, OrbusNeich, and Terumo. Dr. Kimura reports research grants from Abbott Medical and Boston Scientific; honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; and participation on the advisory boards of Abbott Medical, Boston Scientific, and Sanofi. The remaining authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease associated with an increased risk of developing hepatocellular carcinoma; at present, no efficient therapeutic strategy has been established. Herein, we examined the efficacy of PRI-724, a potent inhibitor of CBP/β-catenin signaling, for treating NASH-related liver fibrosis and disorder and characterized its mechanism. Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-fed mice exhibited NASH-induced liver fibrosis that is characterized by steatosis, lobular inflammation, hepatocellular injury and collagen fibrils. To examine the therapeutic effect, CDAHFD-fed mice were administered PRI-724. Serum levels of ALT and pro-fibrotic molecule, i.e. Mac-2 bp, alpha smooth muscle actin, type I and type III collagens, decreased significantly. mRNA levels of the matrix metalloproteinases Mmp8 and Mmp9 in the liver were significantly increased, and increases in the abundance of MMP9-producing neutrophils and macrophages were observed. Marco + Mmp9 + Cd68 + Kupffer cells were only observed in the livers of mice treated with PRI-724, and Mmp9 expression in Marco + Cd68 + Kupffer cells increased 4.3-fold. Moreover, hepatic expression of the lipid metabolism regulator, pyruvate dehydrogenase kinase 4 and liver lipid droplets also decreased significantly. PRI-724-treated NASH mice not only recovered from NASH-related liver fibrosis through the effect of PRI-724 down-regulating the expression of pro-fibrotic genes and up-regulating the expression of anti-fibrotic genes, but they also recovered from NASH-induced liver disorder. PRI-724, a selective CBP/β-catenin inhibitor, thus shows a potent therapeutic effect for NASH-related liver fibrosis and for decreasing adipose tissue in the liver., Competing Interests: Declaration of Competing Interest We all authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In-hospital mortality following percutaneous coronary intervention (PCI) varies across institutions with different annual PCI volumes. The failure to rescue (FTR) rate, defined as the mortality rate following PCI-related complications, may account for the volume-outcome relationship. The Japanese Nationwide PCI Registry, a consecutive, nationally mandated registry between 2019 and 2020, was queried. The FTR rate is defined as 'the number of patients who died following PCI-related complications' divided by 'the number of patients who experienced at least one PCI-related complication.' Multivariate analysis was used to calculate the risk-adjusted odds ratio (aOR) of the FTR rates among hospitals stratified into tertiles as low (≤ 236/year), medium (237-405/year), and high (≥ 406/year). A total of 465,716 PCIs and 1007 institutions were included. A volume-outcome relationship was observed for in-hospital mortality, and the medium-volume (aOR 0.90, 95% confidence interval [CI] 0.85-0.96), as well as high-volume (aOR 0.84, 95% CI 0.79-0.89) hospitals, had significantly lower in-hospital mortality than low-volume hospitals. Complication rates were lower at high-volume centers (1.9%, 2.2%, and 2.6% for high-, medium-, and low-volume centers, respectively; p < 0.001). The overall FTR rate was 19.0%. The FTR rates for the low-, medium-, and high-volume hospitals were 19.3%, 17.7%, and 20.6%, respectively. The medium-volume hospitals had a lower FTR rate (aOR 0.82, 95% [CI] 0.68-0.99), whereas the FTR rate was similar at the high-volume hospitals compared with that of the low-volume hospitals (aOR 1.02, 95% CI 0.83-1.26). In-hospital mortality was low after PCI in high-volume hospitals. However, the FTR rate in high-volume hospitals was not necessarily lower than that in low-volume hospitals. The FTR rate did not account for the volume-outcome relationship in PCI., (© 2023. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

The typical seasonally dry forests in Southeast Asia are the mixed deciduous forest (MDF), dry dipterocarp (deciduous) forest (DDF), and dry evergreen forest (DEF). We obtained 21 physiological traits in the top/sunlit leaves of 107, 65 and 51 tree species in MDF, DEF and DDF, respectively. Approximately 70%, 95% and 95% of canopy tree species which consist of MDF, DEF and DDF are sampled, respectively. Light-saturated photosynthetic rates (A sat ) exhibit a positive correlation with foliar nitrogen (N) and phosphorus (P) on leaf mass and area bases across tree species. Decreased leaf mass-based P reduces the positive slope of the mass-based N and A sat relationship across species and habitats. The differences in nutrient and water use and leaf habits are well matched to the variation in soil properties among the forest types, highlighting the reliability of this comprehensive database for revealing the mechanism of niche segregation based on edaphic factors., (© 2023. Springer Nature Limited.)

Exposure to particulate matter less than 2.5 µm in diameter (PM 2.5 ) is a cause of concern in cities and major emission regions of northern India. An intensive field campaign involving the states of Punjab, Haryana and Delhi national capital region (NCR) was conducted in 2022 using 29 Compact and Useful PM 2.5 Instrument with Gas sensors (CUPI-Gs). Continuous observations show that the PM 2.5 in the region increased gradually from < 60 µg m -3 in 6-10 October to up to 500 µg m -3 on 5-9 November, which subsequently decreased to about 100 µg m -3 in 20-30 November. Two distinct plumes of PM 2.5 over 500 µg m -3 are tracked from crop residue burning in Punjab to Delhi NCR on 2-3 November and 10-11 November with delays of 1 and 3 days, respectively. Experimental campaign demonstrates the advantages of source region observations to link agricultural waste burning and air pollution at local to regional scales., (© 2023. Springer Nature Limited.)

In complement activation system, although the classical pathway has shown to play a critical role for the pathogenesis of SLE, the role of lectin pathway has remained unknown in the pathogenesis of SLE. As Mannose-binding lectin-associated serine proteases (MASPs) are associated with activation of the lectin pathway, we conducted this study to clarify MASPs associations in the pathogenesis of SLE. We evaluated the serum level of MASPs (MASP-1 and MASP-2) in total 68 SLE patients consisting of 15 patients with biopsy-confirmed membranous lupus nephritis (M-LN), 35 patients with biopsy-confirmed proliferative lupus nephritis (P-LN), and 18 SLE patients without LN (non-LN). Our data showed that the serum levels of MASPs were reduced in both P-LN and non-LN although those of M-LN were not reduced. Our data show that the lectin pathway mediated by MASPs plays a critical role for the pathogenesis of SLE except for M-LN., Competing Interests: 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., (© 2023 The Authors.)

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 ( Gp2 ) - , SRY-box transcription factor 8 ( Sox8 ) - , or Spi-B transcription factor ( Spib )-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2 , Ccl20 , and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity., Competing Interests: Author TM is employed by the company Toko Yakuhin Kogyo Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Toyama, Honda, Iwabuchi, Hashimoto, Yamaji, Tokunaga, Matsumoto, Kawaji, Miyazaki, Kikkawa and Kohara.)

Objectives: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis., Methods: This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis., Results: The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis., Conclusion: The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

RNA activation (RNAa) is a burgeoning area of research in which double-stranded RNAs (dsRNAs) or small activating RNAs mediate the upregulation of specific genes by targeting the promoter sequence and/or AU-rich elements in the 3'- untranslated region (3'-UTR) of mRNA molecules. So far, studies on the phenomenon have been limited to mammals, plants, bacteria, Caenorhabditis elegans, and recently, Aedes aegypti. However, it is yet to be applied in other arthropods, including ticks, despite the ubiquitous presence of argonaute 2 protein, which is an indispensable requirement for the formation of RNA-induced transcriptional activation complex to enable a dsRNA-mediated gene activation. In this study, we demonstrated for the first time the possible presence of RNAa phenomenon in the tick vector, Haemaphysalis longicornis (Asian longhorned tick). We targeted the 3'-UTR of a novel endochitinase-like gene (HlemCHT) identified previously in H. longicornis eggs for dsRNA-mediated gene activation. Our results showed an increased gene expression in eggs of H. longicornis endochitinase-dsRNA-injected (dsHlemCHT) ticks on day-13 post-oviposition. Furthermore, we observed that eggs of dsHlemCHT ticks exhibited relatively early egg development and hatching, suggesting a dsRNA-mediated activation of the HlemCHT gene in the eggs. This is the first attempt to provide evidence of RNAa in ticks. Although further studies are required to elucidate the detailed mechanism by which RNAa occurs in ticks, the outcome of this study provides new opportunities for the use of RNAa as a gene overexpression tool in future studies on tick biology, to reduce the global burden of ticks and tick-borne diseases., (© 2023. The Author(s).)

Background: Delirium is common in critically ill patients. Haloperidol has long been used for the treatment of delirium. Dexmedetomidine has recently been used to treat delirium among intubated critically ill patients. However, the efficacy of dexmedetomidine for delirium in non-intubated critically ill patients remains unknown. We hypothesize that dexmedetomidine is superior to haloperidol for sedation of patients with hyperactive delirium, and would reduce the prevalence of delirium among non-intubated patients after administration. We will conduct a randomized controlled trial to compare dexmedetomidine and haloperidol for the treatment of nocturnal hyperactive delirium in non-intubated patients in high dependency units (HDUs)., Methods: This is an open-label, parallel-group, randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for nocturnal hyperactive delirium in non-intubated patients at two HDUs of a tertiary hospital. We will recruit consecutive non-intubated patients who are admitted to the HDU from the emergency room, and allocate them in a 1:1 ratio to the dexmedetomidine or haloperidol group in advance. The allocated investigational drug will be administered only when participants develop hyperactive delirium (Richmond Agitation-Sedation Scale [RASS] score ≥1 and a positive score on the Confusion Assessment Method for the ICU between 19:00 and 6:00 the next day) during the night at an HDU. Dexmedetomidine is administered continuously, while haloperidol is administered intermittently. The primary outcome is the proportion of participants who achieve the targeted sedation level (RASS score of between -3 and 0) 2h after the administration of the investigational drug. Secondary outcomes include the sedation level and prevalence of delirium on the day following the administration of the investigational drugs, and safety. We plan to enroll 100 participants who develop nocturnal hyperactive delirium and receive one of the two investigational drugs., Discussion: This is the first randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for sedation of non-intubated critically ill patients with hyperactive delirium in HDUs. The results of this study may confirm whether dexmedetomidine could be another option to sedate patients with hyperactive delirium., Trial Registration: Japan Registry of Clinical Trials, jRCT1051220015, registered on 21 April 2022., (© 2023. The Author(s).)

At a sedimentary site in an old mine site, Miscanthus sinensis formed patches, where Pinus densiflora seedlings could grow better compared with those outside the patches, indicating that M. sinensis would improve P. densiflora seedling establishment. The purpose of this study was to understand the mechanisms by which M. sinensis facilitates the survival of P. densiflora seedlings by considering the soil properties, heavy metal tolerance, and root endophytes in P. densiflora seedlings at the sedimentary site. The sedimentary site, which is a bare ground, contained high concentrations of Fe, indicating that plants should be exposed to Fe and high soil temperature stresses. Measurement of soil temperature revealed that M. sinensis suppressed sharp increases and alternation of soil temperature, resulting in reducing high soil temperature stress in P. densiflora seedlings. To adapt to the Fe stress environment, P. densiflora outside and inside the patches produced Fe detoxicants, including catechin, condensed tannin, and malic acid. Ceratobasidium bicorne and Aquapteridospora sp. were commonly isolated from P. densiflora seedlings outside and inside the patches as root endophytes, which might enhance Fe tolerance in the seedlings. Aquapteridospora sp., which is considered as a dark-septate endophyte (DSE), was also isolated from the roots of M. sinensis, suggesting that M. sinensis might play a source of a root endophyte to P. densiflora seedlings. Ceratobasidium bicorne could be classified into root endophytes showing symbiosis and weak pathogenicity to host plants. Therefore, high soil temperature stress would weaken P. densiflora seedlings, causing root endophytic C. bicorne to appear pathogenic. We suggested that P. densiflora could adapt to the Fe stress environment via producing Fe detoxicants, and M. sinensis would facilitate the establishment of P. densiflora seedlings in the sedimentary site by providing a DSE, Aquapteridospora sp., and maintaining symbiosis of C. bicorne from high soil temperature stress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Haruma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several stent expansion criteria derived from the intravascular ultrasound (IVUS) evaluation have been proposed to predict future clinical outcomes, but optimal stent expansion criteria as a guide during percutaneous coronary intervention (PCI) are still controversial. There are no studies evaluating the utility of stent expansion criteria along with the clinical and procedural factors in predicting target lesion revascularization (TLR) after contemporary IVUS-guided PCI., Methods: OPTIVUS-Complex PCI study (Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention) multivessel cohort was a prospective multicenter study enrolling 961 patients undergoing multivessel PCI including left anterior descending coronary artery using IVUS with an intention to meet the prespecified criteria for optimal stent expansion. We compared several stent expansion criteria (minimum stent area [MSA], MSA/distal or average reference lumen area, MSA/distal or average reference vessel area, OPTIVUS criteria, IVUS-XPL [Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions] criteria, and modified MUSIC [Multicenter Ultrasound Stenting in Coronaries Study] criteria) as well as clinical, angiographic, and procedural characteristics between lesions with and without TLR., Results: Among 1957 lesions, the cumulative 1-year incidence of lesion-based TLR was 1.6% (30 lesions). Hemodialysis, treatment of proximal left anterior descending coronary artery lesions, calcified lesions, small proximal reference lumen area, and small MSA had univariate associations with TLR, while all of the stent expansion criteria except for MSA were not associated with TLR. The independent risk factors of TLR were calcified lesions (hazard ratio, 2.34 [95% CI, 1.03-5.32]; P =0.04) and small proximal reference lumen area (Tertile 1: hazard ratio, 7.01 [95% CI, 1.45-33.93]; P =0.02; and Tertile 2: hazard ratio, 5.40 [95% CI, 1.17-24.90]; P =0.03)., Conclusions: In contemporary IVUS-guided PCI practice, the 1-year incidence of TLR was very low. MSA, but not other stent expansion criteria, had univariate association with TLR. Independent risk factors of TLR were calcified lesions and small proximal reference lumen area, although the findings should be interpreted with caution due to small number of TLR events, limited lesion complexity, and short duration of follow-up., Competing Interests: Disclosures Dr Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; article fees from Bristol-Myers Squibb and Kowa; advisory board for Novartis and Teijin. Dr Tanabe reports honoraria from Abbott Medical, Boston Scientific, Japan Lifeline, Medtronic, Orbusneich, and Terumo. Dr Kimura reports research grant from Abbott Medical and Boston Scientific; honoraria from Abbott Medical, Boston Scientific, Daiichi Sankyo, Sanofi, and Terumo; participation on advisory board from Abbott Medical, Boston Scientific, and Sanofi. The other authors report no conflicts.

Background: The REAL-CAD trial, reported in 2017, demonstrated a significant reduction in cardiovascular events with high-intensity statins in patients with chronic coronary syndrome. However, data are scarce on the use of high-intensity statins in Japanese patients with acute coronary syndrome (ACS)., Methods and results: In STOPDAPT-2 ACS, which exclusively enrolled ACS patients between March 2018 and June 2020, 1,321 (44.2%) patients received high-intensity statins at discharge, whereas of the remaining 1,667 patients, 96.0% were treated with low-dose statins. High-intensity statins were defined as the maximum approved doses of strong statins in Japan. The incidence of the cardiovascular composite endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke) was significantly lower in patients with than without high-intensity statins (1.44% vs. 2.69% [log-rank P=0.025]; adjusted hazard ratio [aHR] 0.48, 95% confidence interval [CI] 0.24-0.94, P=0.03) and the effect was evident beyond 60 days after the index percutaneous coronary intervention (log-rank P=0.01; aHR 0.38, 95% CI 0.17-0.86, P=0.02). As for the bleeding endpoint, there was no significant difference between the 2 groups (0.99% vs. 0.73% [log-rank P=0.43]; aHR 0.96, 95% CI 0.35-2.60, P=0.93)., Conclusions: The prevalence of high-intensity statins has increased substantially in Japan. The use of the higher doses of statins in ACS patients recommended in the guidelines was associated with a significantly lower risk of the primary cardiovascular composite endpoint compared with lower-dose statins.