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Maintaining concentration on demanding cognitive tasks, such as vigilance (VG) and working memory (WM) tasks, is crucial for successful task completion. Previous research suggests that internal concentration maintenance fluctuates, potentially declining to sub-optimal states, which can influence trial-by-trial performance in these tasks. However, the timescale of such alertness maintenance, as indicated by slow changes in pupil diameter, has not been thoroughly investigated. This study explored whether "pupil trends"-which selectively signal sub-optimal tonic alertness maintenance at various timescales-negatively correlate with trial-by-trial performance in VG and WM tasks. Using the Psychomotor Vigilance Task (VG) and the Visual-Spatial 2-back Task (WM), we found that human pupil trends lasting over 10 seconds were significantly higher in trials with longer reaction times, indicating poorer performance, compared to shorter reaction time trials, which indicated better performance. The Attention Network Test further validated that these slow trends reflect sub-optimal states related to (tonic) alertness maintenance rather than sub-optimal performance specific to VG and WM tasks, which is more associated with (phasic) responses to instantaneous interference. These findings highlight the potential role of detecting and compensating for non-optimal states in VG and WM performance, significantly beyond the 10-second timescale. Additionally, the findings suggest the possibility of estimating human concentration during various visual tasks, even when rapid pupil changes occur due to luminance fluctuations. Significance Statement Using biomarkers to estimate human concentration levels can adaptively enhance performance in daily activities. Theoretically, the pupil diameter, which measurably fluctuates over several seconds, could mirror real-time concentration in demanding tasks like vigilance (VG) and working memory (WM). Although capable of accurately estimating concentration in the presence of rapid luminance changes, empirical evidence linking these pupil measures at the slow timescales to trial-by-trial VG and WM task performance is lacking. This study demonstrates that the 10-second pupil trend accurately reflects these tasks' performance, underscoring its potential for daily concentration assessment., (Copyright © 2024 Yamashita et al.)

Endoscopic surgery, including endoscopic endonasal transsphenoidal surgery (ETSS), requires special psychomotor skills from surgeons. The learning curve in the acquisition of psychomotor skills varies among individuals, and studies about laparoscopy indicate that the difference can be predicted using spatial ability tests. We examined the association between the results of such tests and the learning curve in ETSS to determine the need for a personalized curriculum for ETSS skill training. A total of 30 fifth-year medical students from Kindai University School of Medicine (17 men, 13 women; mean age, 26 years) without ETSS experience completed the spatial orientation test (SOT) for the measurement of spatial visualization ability. They performed the dural incision task (DIT) twice on an ETSS training model for surgical psychomotor skill evaluation. The SOT scores (angle errors) exhibited substantial individual differences in spatial visualization ability, whereas the DIT scores significantly improved in the second trial (Wilcoxon signed-rank test, P = 0.0035). However, no significant difference was observed in the DIT scores between the smaller error and larger error groups of the SOT. The results indicated that two DIT trials were sufficient to acquire psychomotor skills for the DIT as the endoscope was almost fixed and learning only one viewpoint and line of sight combination was adequate. In conclusion, a personalized ETSS training program based on the trainee's spatial ability is not necessary for the DIT. Further research is warranted to determine the effect of spatial ability on more complex tasks, such as suturing in cranial base repair.

Background: Some patients with postoperative hip fractures (HF) experience persistent severe pain. In this longitudinal study, we examined the characteristics of patients with persistent pain after HF surgery, and the factors influencing pain intensity., Methods: We conducted an 8-week prospective study in patients with postsurgical HF. Verbal rating scale (VRS), and multifaceted outcomes, including pressure pain threshold (PPT) (affected site and biceps), were evaluated at 2, 4, and 8 weeks postoperatively. Patients were divided into mild (VRS ≤1) and severe (VRS ≥2) groups according to pain intensity at 8 weeks postoperatively. Statistical analyses were performed using two-way ANOVA and decision-tree analysis., Results: VRS, PPT at the affected site and biceps, and physical activity (PA) time were significantly lower in the severe group than in the mild group 2 weeks postoperatively. VRS, PPT at the affected site, pain catastrophizing (PCS)-13, and the Tampa Scale for Kineshiophobia (TSK)-11 did not show significant improvements in the severe group. Decision tree analysis revealed that the VRS and PCS-13 at 4 weeks, PA time at 2 weeks, and TSK-11 change between 4 weeks and 2 weeks were factors influencing severe pain intensity at 8 weeks after HF surgery., Conclusion: Persistent severe pain after HF surgery was characterised by high peripheral and central sensitisation, pain catastrophizing, and reduced PA at 2 weeks after HF surgery. In addition, early pain intensity, pain catastrophizing, and PA may be hierarchically influential factors for persistent pain 8 weeks after HF surgery., 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.)

Background: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course., Methods: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed., Results: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p < 0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48-4.89, p = 0.001) and 4.25 (95% confidence interval, 1.98-9.10, p < 0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer., Conclusions: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment., Competing Interests: Disclosure statement Tsujino I. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka, Takeyama, and the Medical System Network outside the submitted work. Hosokawa K. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer outside the submitted work. Taniguchi Y. reported grants from Janssen Pharmaceutical and Nippon Shinyaku and personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Inami T. reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin outside the submitted work. Yamashita J. reports a grant from Abbott Vascular Japan and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin outside the submitted work. Ogino H. reports consulting fees from Terumo, Japan Lifeline, and Century Medical, outside the submitted work. Ikeda N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Bristol-Myers Squibb outside the submitted work. Yaoita N. reports personal fees from Bayer Yakuhin and Konica Minolta outside the submitted work. Shimokawahara H. reports a grant from Bayer Yakuhin and personal fees from Actelion Pharmaceuticals Japan, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Tanabe N. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku outside the submitted work. Kubota K. reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku outside the submitted work. Ogihara Y. reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Daiichi Sankyo and grants from Bayer Yakuhin and Daiichi Sankyo outside the submitted work. Kawakami T. reports personal fees from Kaneka Medix, Abbott Medical Japan., and ACIST Japan outside the submitted work. Tamura Y. reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical outside the submitted work. Abe K. reports a grant from Konica Minolta and Daiichi Sankyo outside the submitted work. Nakamura J., Masaki K., Funakoshi K., Adachi S., Hatano M, Shigeta A., Horimoto K., Dohi Y., and Tatsumi K. report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry., Methods and Results: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN., Conclusions: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Porphyrins have emerged as highly effective photosensitizers in the field of photodynamic therapy (PDT) because of their high singlet oxygen generation efficiency. However, most porphyrin derivatives do not have adequate water solubility and cell membrane permeability suitable for use in PDT. In addition, they frequently suffer from low durability under photoirradiation. Here, we propose rotaxane-type photosensitizers, in which a porphyrin axle is irreversibly encapsulated within cyclodextrins (CDs), to overcome the drawbacks of porphyrins for PDT. The rotaxane-type photosensitizers were synthesized in high yields by employing a cooperative capture strategy. The CD derivatives worked as a transparent shell to impart a porphyrin axle not only with water solubility but also with photostability. These rotaxanes showed higher cell membrane permeability and photoinduced cytotoxic abilities than talaporfin sodium, presently used as a clinical photosensitizer. The rotaxane-based photosensitizer could have potential for being ideal PDT drugs.

Susceptibility of human cells to cold stress restricts the use of therapeutic hypothermia and long-term preservation of organs at low temperatures. In contrast, cells of mammalian hibernators possess remarkable cold resistance, but little is known about the molecular mechanisms underlying this phenomenon. In this study, we conducted a gain-of-function screening of genes that confer cold resistance to cold-vulnerable human cells using a cDNA library constructed from the Syrian hamster, a mammalian hibernator, and identified Gpx4 as a potent suppressor of cold-induced cell death. Additionally, genetic deletion of or pharmacological inhibition of Gpx4 revealed that Gpx4 is necessary for suppressing lipid peroxidation specifically under cold in hamster cell lines. Genetic disruption of other ferroptosis-suppressing pathways, namely biopterin synthesis and mitochondrial or plasma membrane CoQ reduction pathways, also accelerated cold-induced cell death under Gpx4 dysfunction. Collectively, ferroptosis-suppressing pathways protect the cells of a mammalian hibernator from cold-induced cell death and the augmentation of these pathways renders cold resistance to cells of non-hibernators, including humans., (© 2024. The Author(s).)

Tiopronin is a key drug used to treat cystinuria. A 41-year-old Japanese woman with cystinuria presented with eyelid edema and weight gain after the administration of tiopronin. Her serum albumin was 1.8 g/dL and her urinary protein level was 5.5 g/gCre. After cessation of tiopronin, she achieved remission of nephrotic syndrome (NS). Secondary NS due to tiopronin was evident based on the clinical course and laboratory values. A kidney biopsy showed membranous nephropathy (MN), and an immunofluorescence analysis revealed strong deposition of immunoglobulin G4 (IgG4). However, a previous case report of tiopronin-induced MN showed staining for IgG1 and IgG3. This case report suggests a novel etiology for tiopronin-induced MN.

Background: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI., Methods: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups., Results: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000)., Conclusions: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE., Competing Interests: Declaration of competing interest Dr. Yasuda reports remuneration for lectures from Takeda, Daiichi Sankyo, and Bristol-Myers Squibb and trust research/joint research funds from Takeda and Daiichi Sankyo; Dr. Takayama reports lecture fees from Daiichi Sankyo; and Dr. Ogawa reports lecture fees and research grants from Abbot Medical Japan, Bayer, Daiichi Sankyo, Eisai, Kowa, Takeda Pharmaceutical, and Teijin. Other authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Injuries to the posterolateral compartment (PLC) of the knee require special attention, as incorrect diagnosis and treatment may lead to considerable morbidity. However, no gold standard treatment has been established for PLC injuries., Methods: 38 patients with concomitant (posterior cruciate ligament (PCL) and PLC injuries were divided into two groups according to surgical treatment of the proximal popliteal tendon injury. They were treated with anatomic popliteal tendon, lateral collateral ligament (LCL), and popliteofibular ligament (PFL) reconstruction (group 1; n  = 19) and were treated with popliteal tendon tenodesis, LCL, and PFL reconstruction (group 2; n  = 19). The Lysholm score, dial test, and lateral compartment opening on varus stress X-ray were used as outcome measurements evaluated before surgery and at 6, 12, and 24 months of follow-up., Results: Overall, there was a progressive improvement in the Lysholm score and the lateral opening on varus stress radiography during the evaluated periods for both groups ( p  < 0.001). Patients from group 2 recorded better Lysholm scores than those from group 1 at 12- and 24-month follow-up ( p  = 0.02). Dial test was negative in all patients after 6, 12, and 24 months., Conclusion: Patients with popliteal tendon tenodesis were found to have better Lysholm scores than patients with reconstruction after 12 and 24 months of follow-up. There was no difference in the lateral joint opening evaluated by stress radiography between groups. These results show that tenodesis could be a viable treatment option for lateral femoral condyle popliteal disruptions in the context of PLC and PCL combined injuries, and should be considered in the surgical planning process., Competing Interests: Conflicts of interestAll authors declare no conflicts of interest or potential disclosures., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission., Methods and Results: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m 2 , a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004)., Conclusions: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear., Objectives: This study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan., Methods: Among 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated., Results: The BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P  = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m 2 ; P  = 0.030)., Conclusions: BPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784)., Competing Interests: This study is supported by the Japan Agency for Medical Research and Development (grant numbers JP20ek0109371, JP19lk0201102, JP22lk0201125, and JP19lk1601003), JSPS KAKENHI (grant number JP20286266), and grant from Konica Minolta based on a contract. The funding body had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr Hosokawa has received grants from Konica Minolta; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Janssen Pharmaceutical, Pfizer, and Konica Minolta, outside the submitted work. Dr Taniguchi has received grants from Nippon Shinyaku and Janssen Pharmaceutical; and personal fees from Nippon Shinyaku, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Inami has received personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Yamashita has received a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Ogino has received consulting fees from Terumo, Japan Lifeline, and Century Medical; and personal fees from Bayer Yakuhin, Daiichi-Sankyo, Pfizer, and Nippon Shinyaku, outside the submitted work. Dr Tsujino has received personal fees from Nippon Shinyaku and Janssen Pharmaceutical; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, Mochida Pharmaceutical, Kaneka Medix, Takeyama, and Medical System Network, outside the submitted work. Dr Hatano has received personal fees from Bayer Yakuhin and Janssen Pharmaceutical, outside the submitted work. Dr Yaoita has received personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Ikeda has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi -Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Shimokawahara has received a grant from Bayer Yakuhin; and personal fees from Bayer Yakuhin and Nippon Shinyaku, outside the submitted work. Dr Tanabe has received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku, outside the submitted work. Dr Kubota has received personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ogihara has received grants from Bayer Yakuhin; and personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Bristol Myers Squibb, outside the submitted work. Dr Kawakami has received personal fees from Kaneka Medix and Abbott Medical Japan, and consulting fees from ACIST Japan, outside the submitted work. Dr Tamura has received grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi-Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Abe has received a grant from Konica Minolta and Daiichi-Sankyo, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objective: Although benign, ameloblastoma is a locally aggressive lesion in some patients and the development of additional treatments is needed. Verteporfin (VP) is a photosensitizer exhibiting considerable photocytotoxicity in various tumor cells. We aimed to investigate the effects of verteporfin photodynamic therapy (VP PDT) on ameloblastoma., Methods: Eighteen patients who underwent surgery for ameloblastoma were randomly selected. We performed an immunohistochemical assessment to investigate the expression of low-density lipoprotein receptor (LDLR) and Yes-associated protein (YAP), targets of VP, in human ameloblastoma tissues and cultured human ameloblastoma cell line (HAM1). The effect of VP PDT on cell proliferation and apoptosis in HAM1 was analyzed., Results: The expression of LDLR and YAP were detected in human ameloblastoma tissues and HAM1. LDLR expression was significantly higher in patients who had previously undergone surgery than in patients who were receiving it for the first time. The cytotoxic effect of the combination of low-concentration VP administration and laser irradiation was comparable to high-concentration VP administration with and without laser irradiation. The addition of laser irradiation to VP administration significantly accelerated apoptotic bleb formation compared with VP administration alone., Conclusion: VP PDT has the potential to become an additional treatment for large-sized ameloblastoma., (© 2023 Wiley Periodicals LLC.)

The 16th GCC Closed Forum was held in Orlando, FL, USA, on 23 June 2023. Representatives from international bioanalytical Contract Research Organizations were in attendance in order to discuss scientific and regulatory issues specific to bioanalysis. The issues discussed at the meeting included: IS response, flow cytometry, changes to the bioanalytical industry, NGS assays, biomarker assay for tissues, dPCR validation, immunogenicity harmonization and ICH M10 implementation. Conclusions and consensus from discussions of these topics are included in this article.

Background: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI)., Methods and results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71)., Conclusions: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Accumulating evidence suggests that various cellular stresses interfere with the end processing of mRNA synthesis and lead to the production of abnormally long transcripts, known as readthrough transcripts (RTTs), which extend beyond the termination sites. Small mammalian hibernators repeatedly enter a state referred to as deep torpor (DT), where the metabolic rate, respiration rate, and core body temperature become extremely low, which produces various types of cellular stresses and therefore induces RTTs. However, the types of stresses and processes around the DT that cause RTTs are unclear. In the present study, we showed that RTTs are produced from different gene loci in the livers of Syrian hamsters under DT and summer-like conditions. Moreover, in vitro analysis using hamster primary hepatocytes revealed that DT-specific RTTs are induced by a slow decline in temperature, as seen in body temperature in the entrance phase of DT, but not by rapid cold treatment or hypoxia. In addition, it was observed that RTTs were not elongated under a significantly cold temperature (4 °C). These results indicate that DT-specific RTTs are produced during the entrance phase of torpor by a slow decrease in body temperature., 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 Inc. All rights reserved.)

We developed a simulation model of human oral microbiota using Bio Palette oral medium (BPOM) containing 0.02% glucose and lower bacterial nitrogen sources, derived from saliva and dental plaque. By decreasing the concentration of Gifu anaerobic medium (GAM) from 30 to 10 g L -1 , we observed increased ratios of target pathogenic genera, Porphyromonas and Fusobacterium from 0.5% and 1.7% to 1.2% and 3.5%, respectively, in the biofilm on hydroxyapatite (HA) discs. BPOM exhibited the higher ratios of Porphyromonas and Fusobacterium, and amplicon sequence variant number on HA, compared with GAM, modified GAM and basal medium mucin. Mixing glycerol stocks of BPOM culture solutions from four human subjects resulted in comparable ratios of these bacteria to the original saliva. In this simulation model, sitafloxacin showed higher inhibitory effects on P. gingivalis than minocycline hydrochloride at a low dosage of 0.1 μg mL -1 . Probiotics such as Streptococcus salivarius and Limosilactobacillus fermentum also showed significant decreases in Porphyromonas and Fusobacterium ratios on HA, respectively. Overall, the study suggests that BPOM with low carbon and nutrients could be a versatile platform for assessing the efficacy of antibiotics and live biotherapeutics in treating oral diseases caused by Porphyromonas and Fusobacterium., (© 2024 The Authors. Environmental Microbiology Reports published by Applied Microbiology International and John Wiley & Sons Ltd.)

Competing Interests: Disclosures Dr Hosokawa reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer, outside the submitted work. Dr Taniguchi reports grants from Janssen Pharmaceutical and Nippon Shinyaku; and personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ikeda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, and Bristol-Myers Squibb, outside the submitted work. Dr Inami reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Murohara reports a grant and personal fees from Daiichi Sankyo, outside the submitted work. Dr Hatano reports a grant from Japan Agency for Medical Research and Development and personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Tamura reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Yamashita reports a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Tsujino reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, and Mochida Pharmaceutical, outside the submitted work. Dr Yaoita reports personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Minatsuki reports a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Todaka reports a grant from Mochida Pharmaceutical; and personal fee from Bayer Yakuhin, outside the submitted work. Dr Fukuda reports grants from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, outside the submitted work. Dr Tsutsui reports grants from Mitsubishi Tanabe Pharma, IQVIA Services Japan, MEDINET, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, NEC, and Nippon Boehringer Ingelheim; personal fees from Novartis Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kowa, Teijin Pharma, Mitsubishi Tanabe Pharma, Pfizer Japan, Daiichi Sankyo, Novartis Pharma, Janssen Pharmaceutical, Pfizer Japan, Bayer Yakuhin, Otsuka Pharmaceutical, AstraZeneca, and Nippon Rinsho; and is Chairman of Japan Heart Failure Society, outside the submitted work. Dr Abe reports a grant from Konica Minolta and Daiichi Sankyo, outside the submitted work. Drs Watanabe, Yasuda, Kobayakawa, Adachi, and Tatsumi report no conflicts of interest.

Tablets are the most commonly prescribed dosage form for oral drug administration. Historically, improvement of medication adherence of tablets has been facilitated through, for example, the use of smaller tablets, distinctive shaped tablets and sugar-coated tablets. In addition, new formulation technologies such as orally disintegrating tablets (OD tablets), micro tablet-type granules, jellies, and film formulations are making it possible to create more easily ingested dosage forms. We have developed a new oral jelly coating formulation that can be applied to any sized tablet without reducing the size of the formulation. It was found that this new jelly layer formed on the tablet surface improved the tablet's slipperiness with an appropriate amount of water, while ensuring no change in the dissolution profile. In addition, the jelly layer was ensured storage stability over time without affecting the dissolution profile. Although further studies are needed, this coating technology can quickly change the tablet surface to a jelly-like state after the tablet is taken, giving the tablet the same slipperiness as if it were taken in jelly, making it easier to pass through the pharynx, and thus improving medication adherence.

It has both scientific and practical benefits to substantiate the theoretical prediction that personality (Big Five) traits systematically modulate gaze behavior in various real-world (working) situations. Nevertheless, previous methods that required controlled situations and large numbers of participants failed to incorporate real-world personality modulation analysis. One cause of this research gap is the mixed effects of individual attributes (e.g., the accumulated attributes of age, gender, and degree of measurement noise) and personality traits in gaze data. Previous studies may have used larger sample sizes to average out the possible concentration of specific individual attributes in some personality traits, and may have imposed control situations to prevent unexpected interactions between these possibly biased individual attributes and complex, realistic situations. Therefore, we generated and analyzed real-world gaze behavior where the effects of personality traits are separated out from individual attributes. In Experiment 1, we successfully provided a methodology for generating such sensor data on head and eye movements for a small sample of participants who performed realistic nonsocial (data-entry) and social (conversation) work tasks (i.e., the first contribution). In Experiment 2, we evaluated the effectiveness of generated gaze behavior for real-world personality modulation analysis. We successfully showed how openness systematically modulates the autocorrelation coefficients of sensor data, reflecting the period of head and eye movements in data-entry and conversation tasks (i.e., the second contribution). We found different openness modulations in the autocorrelation coefficients from the generated sensor data of the two tasks. These modulations could not be detected using real sensor data because of the contamination of individual attributes. In conclusion, our method is a potentially powerful tool for understanding theoretically expected, systematic situation-specific personality modulation of real-world gaze behavior., Competing Interests: JY, YT, and HO are employed by Nippon Telegraph and Telephone (NTT) Corporation. NTT signed a joint research agreement with TK and provided a research grant. NTT has pending patents (in Japan, and possibly in the United States, Europe, and China) relating to personality analysis methods., (Copyright © 2024 Yamashita, Takimoto, Oishi and Kumada.)

Myasthenia gravis (MG) is an autoimmune disease characterized by formation of autoantibodies against the nicotinic acetylcholine receptor (AChR). Some patients do not show sufficient improvement and develop adverse effects following administration of conventional immune therapy; therefore, the development of new treatments is important. Based on the concept of "selective removal of pathogenic antibodies and cells without suppression of normal immunity," we are developing a fusion protein referred to as AChR-Fc (composed of the AChR alpha subunit and Fc region of human immunoglobulin G1), which shows the following mechanisms of action: selective neutralization of AChR antibodies and cytotoxic activity against AChR antibody-producing pathogenic B cells. Treatment with AChR-Fc is a novel therapeutic approach that may be useful in the management of MG.

Aims: ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMICS) is associated with substantial mortality. As life expectancy increases, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study sought to investigate the characteristics and impact of PCI on in-hospital mortality in patients with STEMICS., Methods and Results: The Japan AMI Registry (JAMIR) is a retrospective, nationwide, real-world database. Among 46 242 patients with AMI hospitalized in 2011-2016, 2760 patients with STEMICS (median age, 72 years) were studied. We compared 2396 (86.8%) patients who underwent PCI with 364 (13.2%) patients who did not. The percentage of mechanical circulatory support use in patients with STEMICS was 69.3% and in-hospital mortality was 34.6%. Compared with patients who did not undergo PCI, patients undergoing PCI were younger and had a higher rate of intra-aortic balloon pump use. A higher proportion was male or current smokers. In-hospital mortality was significantly lower in the PCI group than in the no-PCI group (31.3% vs. 56.0%, P < 0.001). Percutaneous coronary intervention was independently associated with lower in-hospital mortality [adjusted odds ratio (OR), 0.508; 95% confidence interval (CI), 0.347-0.744]. In 789 (28.6%) patients aged ≥80 years, PCI was associated with fewer in-hospital cardiac deaths (adjusted OR, 0.524; 95% CI, 0.281-0.975), but was not associated with in-hospital mortality (adjusted OR, 0.564; 95% CI, 0.300-1.050)., Conclusion: In Japan, PCI was effective in reducing in-hospital cardiac death in elderly patients with STEMICS. Age alone should not preclude potentially beneficial invasive therapy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS., Methods: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected., Results: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm -5 ; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively., Conclusions: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

This paper provides new evidence on inequalities in resources for children age 3-4 by parental education using harmonized data from six advanced industrialized countries-United States, United Kingdom, France, Germany, Netherlands, and Japan-that represent different social welfare regime types. We analyze inequalities in two types of resources for young children-family income, and center-based child care-applying two alternative measures of parental education-highest parental education, and maternal education. We hypothesize that inequalities in resources by parental education will be less pronounced in countries where social policies are designed to be more equalizing. The results provide partial support for this hypothesis: the influence of parental education on resources for children does vary by the social policy context, although not in all cases. We also find that the measurement of parental education matters: income disparities are smaller under a maternal-only definition whereas child care disparities are larger. Moreover, the degree of divergence between the two sets of estimates differs across countries. We provide some of the first systematic evidence about how resources for young children vary depending on parents' education and the extent to which such inequalities are buffered by social policies. We find that while early inequalities are a fact of life in all six countries, the extent of those inequalities varies considerably. Moreover, the results suggest that social policy plays a role in moderating the influence of parental education on resources for children., (© 2023. The Author(s).)

Background: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension, with good results reported for residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). However, BPA is associated with complications, such as pulmonary artery perforation and vascular injury, which can lead to critical pulmonary hemorrhage requiring embolization and mechanical ventilation. Furthermore, the risk factors for occurrence of complications in BPA are unclear; therefore, this study aimed to evaluate predictors of procedural complications in BPA., Methods: In this retrospective study, we collected clinical data (patient characteristics, details of medical therapy, hemodynamic parameters, and details of the BPA procedure) from 321 consecutive sessions involving 81 patients who underwent BPA. Procedural complications were evaluated as endpoints., Results: BPA for residual PH after PEA was performed in 141 sessions (43.9 %), which involved 37 patients. Procedural complications were observed in 79 sessions (24.6 %), including severe pulmonary hemorrhage requiring embolization in 29 sessions (9.0 % of all sessions). No patients experienced severe complications requiring intubation with mechanical ventilation or extracorporeal membrane oxygenation. Age ≥ 75 years and mean pulmonary artery pressure ≥ 30 mmHg were independent predictors of procedural complications. Residual PH after PEA was a significant predictor of severe pulmonary hemorrhage requiring embolization (adjusted odds ratio, 3.048; 95 % confidence interval, 1.042-8.914, p = 0.042)., Conclusions: Older age, high pulmonary artery pressure, and residual PH after PEA increase the risk of severe pulmonary hemorrhage requiring embolization in BPA., Competing Interests: Declaration of competing interest Ryosuke Ito, Jun Yamashita, Sayo Ikeda, Yuki Nakajima, Tomohiro Kasahara, Yuichi Sasaki, Lisa Takahashi, Ikki Komatsu, Naotaka Murata, and Taishiro Chikamori are affiliated with an endowed department sponsored by Abbott Medical Japan LLC. However, these authors and others disclose no conflicts of interest related to this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The fractional flow reserve (FFR) cut-off values of 0.75 or 0.8 have been widely used; however, whether they apply to patients on hemodialysis remains unknown. We aimed to investigate the cut-off value of FFR associated with clinical outcomes in patients on hemodialysis. Using the Japanese multicenter registry, we analyzed data of patients on hemodialysis with measured FFR between January 2010 and December 2016. Survival classification and regression tree analysis for the composite primary outcome of cardiovascular mortality, myocardial infarction, and target vessel revascularization revealed a threshold FFR of 0.83. Multivariate Cox regression analyses were performed for the clinical outcomes. Additionally, the primary outcome was analyzed using propensity score matching by dividing the patients into complete and incomplete revascularization groups according to the presence of residual lesions with an FFR of ≤0.83 after the intervention. Of the 212 included patients, 112 (52.8%) had lesions with an FFR of ≤0.83. After adjusting for confounders, an FFR of ≤0.83 was associated with a higher risk for the primary outcome (adjusted hazard ratio 2.01, 95% confidence interval 1.11 to 3.66, p = 0.021). Propensity score matching showed that complete revascularization for lesions with an FFR of ≤0.83 was associated with a reduced risk for the primary outcome compared with incomplete revascularization (hazard ratio 0.38, 95% confidence interval 0.20 to 0.71, log-rank p = 0.0016). In conclusion, an FFR of ≤0.83 was an independent predictor of clinical events in patients on hemodialysis. Furthermore, complete revascularization was associated with better clinical outcomes. Thus, this population may require a distinct FFR cut-off value., Competing Interests: Declaration of Competing Interest Dr. Shiono receives lecture fees from Phillips Japan, Zeon Medical Inc., and Abbott Medical Japan. Dr. Kawase receives lecture fees from Phillips Japan, Zeon Medical Inc., Boston Scientific Corporation and Abbott Medical Japan. Dr. Yamashita is affiliated with an endowed department sponsored by Abbott Medical Japan and receives consultation fee and lecture fees from Kaneka Medix and Phillips Japan. Dr. Amano receives lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi-Sankyo, and Bristol-Myers Squibb. Dr. Tanaka receives lecture fees from Abbott Medical Japan and Daiichi-Sankyo. Dr. Akasaka receives lecture fees from Abbott Medical Japan and is Medical Advisor of Terumo Corporation. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

[Purpose] This study aimed to examine gradual changes in and relationships among preoperative and 3-month postoperative endpoints in patients with lumbar degenerative disease. [Participants and Methods] The study included 160 diagnosed with lumbar degenerative diseases who underwent surgery. Patients were divided into two groups: "good progress" and "recrudescence". Changes in the Japan Orthpedics Associations (JOA) score, JOA back pain evaluation questionnaire (JOABPEQ), and numeric rating scale (NRS) preoperatively and 3 months postoperatively, and their associations, were analyzed. [Results] Differences were found in preoperative NRS for low back pain, JOA score (other findings) at 3 months postoperatively, and NRS for low back pain at 3 months postoperatively. The causal analysis yielded paths for "daily life", "pain", and "social/psychological aspects", starting with "lumbar spine disorders". [Conclusion] The subjective symptoms, objective findings, lumbar spine dysfunction, gait dysfunction, and numbness at 3 months postoperatively yielded relevant information regarding the participants activities of daily living, pain, and social and psychological aspects, providing a perspective for monitoring postoperative patients., Competing Interests: The authors have no conflicts of interest to declare., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P <0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P <0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P <0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P =0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P =0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Opportunities for LOTE (Languages Other Than English) speakers to engage with their target language are limited, making it challenging to sustain motivation. The aim of this study is to develop and validate a scale for measuring motivational regulatory strategies among Japanese-language learners and investigate their relationship with motivational factors. This research specifically focuses on Indonesian learners of Japanese who have a non-Kanji (Chinese characters) background and are studying Japanese as a foreign language. The motivational regulatory strategies scale comprises six factors and has demonstrated adequate internal consistency and factor structure. The findings indicate a positive correlation between integrative motivation and these six strategies, suggesting that learners' integrative motivation may promote the adoption of these strategies. Furthermore, this study emphasizes the significance of the opportunity control strategy, where learners actively seek chances to expose themselves to their target language. Future research is recommended to implement the developed scale in educational settings. Conducting surveys that encompass learners from diverse cultural backgrounds and embarking on longitudinal studies should also be considered., Competing Interests: The author declares 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 Yamashita.)

Objective: This study aimed to reveal characteristic condylar movements in patients with jaw deformities., Study Design: Thirty patients with jaw deformities before surgery were enrolled and instructed to chew a cookie during 4-dimensional computed tomography (4DCT). The distance between the most anterior and posterior positions of the bilateral condyles on 4DCT images was measured and compared among patients with different skeletal classes. Correlations between the condylar protrusion and cephalometric values were also determined., Results: The distances of condylar protrusion during mastication were significantly greater in the skeletal class II group than in the skeletal class III group ( P =0.0002). Significant correlations were found between the distances of condylar protrusion during mastication and the sella-nasion-B point angle ( r =-0.442, P =0.015), A point-nasion-B point angle ( r =0.516, P =0.004), sella-nasion plane to ramus plane angle ( r =0.464, P =0.01), sella-nasion plane to occlusal plane angle ( r =0.367, P =0.047), and condylion-gonion length ( r =-0.366, P =0.048)., Conclusion: Motion analysis with 4DCT images revealed that condylar movement in patients with retrognathism was larger than in patients with mandibular prognathism. Skeletal structure was therefore correlated with condylar movement during mastication., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear., Objectives: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH., Patients/methods: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding., Results: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032)., Conclusion: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin., Competing Interests: Declaration of competing interests K.H. received personal fees from Janssen Pharmaceuticals, Bayer Yakuhin, Nippon Shinyaku, and Pfizer, outside of the submitted work. K.A. received a grant from Konica Minolta and Daiichi Sankyo, outside of the submitted work. Y. Tamura received grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical, outside of the submitted work. N.N. is member of the board of directors of the Japan Association for Medical Informatics. K. Todaka reports receiving a grant from Mochida Pharmaceutical and received a personal fee from Bayer Yakuhin, outside of the submitted work. Y. Taniguchi received grants from Janssen Pharmaceutical and Nippon Shinyak and received personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside of the submitted work. T.I. received personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside of the submitted work. I.T. received personal fees from Janssen Pharmaceutical and Nippon Shinyak and is affiliated with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, and Mochida Pharmaceutical, outside of the submitted work. J.Y. received a grant from Abbott Vascular Japan and received personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside of the submitted work. N.I. received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Bristol-Myers Squibb, outside of the submitted work. H.S. received a grant from Bayer Yakuhin and received personal fees from Actelion Pharmaceuticals Japan, Bayer Yakuhin, and Nippon Shinyaku, outside of the submitted work. T.K. reports receiving personal fees from Kaneka Medix, Abbott Medical Japan, and ACIST Japan, outside of the submitted work. M.H. received personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside of the submitted work. H.O. received grants from Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer Japan, Eisai, GlaxoSmithKline, Mochida Pharmaceutical, Janssen Pharmaceutical, and Nippon Shinyaku, and received consulting fees from Terumo, Japan Lifeline, and Century Medical and personal fees from Bayer Yakuhin, Daiichi Sankyo, Pfizer Japan, and Nippon Shinyaku, outside of the submitted work. Y.F. received grants from Actelion Pharmaceuticals Japan, Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, Pfizer Japa, and personal fees from Actelion Pharmaceuticals Japan, Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, Pfizer Japan, and Bristol-Myers Squibb, outside of the submitted work. N.T. received personal fees from Janssen Pharmaceutical, Bayer Yakuhin, and Nippon Shinyaku, outside of the submitted work. H.M. received grants from Bayer and Nippon Shinyaku; received personal fees from Bayer Yakuhin, Nippon Shinyaku, Mochida Pharmaceutical, Kaneka Medix, and Janssen Pharmaceutical, , outside of the submitted work; is a member of the board of directors or advisory committees for the International CTEPH Association and Japanese Pulmonary Circulation and Pulmonary Hypertension Society; and is a member of the data safety monitoring boards for Janssen Pharmaceutical, United Therapeutics, and Bayer. K. Fukuda received grants from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, and received personal fees from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, outside of the submitted work. H.T. received grants from Mitsubishi Tanabe Pharma, IQVIA Services Japan, Medinet, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, NEC, and Nippon Boehringer Ingelheim; received personal fees from Novartis Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kowa, Teijin Pharma, Mitsubishi Tanabe Pharma, Pfizer Japan, Daiichi Sankyo, Novartis Pharma, Janssen Pharmaceutical, Pfizer Japan, Bayer Yakuhin, Otsuka Pharmaceutical, AstraZeneca, and Nippon Rinsho, outside the submitted work; and is the chairman of the Japan Heart Failure Society. Soiken Corp accessed and verified the data. The remaining authors K. Funakoshi, S.A., S.M., K. Tatsumi, and T.O. have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Patients with acute myocardial infarction (AMI) commonly have multiple comorbidities, and some die in hospitals due to causes other than cardiac complications. However, limited information is available on noncardiac death in patients hospitalised for AMI. Therefore, the present study was performed to determine the incidence, annual trend, clinical characteristics, and predictors of in-hospital non-cardiac death in patients with AMI using the Tokyo Cardiovascular Care Unit (CCU) network registry., Methods: The registry included 38,589 consecutive patients with AMI who were admitted to the CCU between 2010 and 2019. The primary endpoint was in-hospital noncardiac death. Further, predictors of cardiac and non-cardiac death were identified., Results: The incidence of all-cause in-hospital mortality was 7.0% (n = 2700), and the proportion of mortality was 15.6% (n = 420) and 84.4% (n = 2280) for noncardiac and cardiac causes, respectively. The proportion of noncardiac deaths did not change annually over the last decade (p = 0.66). After adjusting for all variables, age, Killip classification grade, peak creatine kinase, hemoglobin, serum creatinine, and C-reactive protein were common predictors of cardiac and non-cardiac deaths. Indicators of malnutrition, such as lower body mass index (kg/m 2 ) [odds 0.94, 95%CI (0.90-0.97), p < 0.001] and serum low-density lipoprotein cholesterol level (per 10 mg/dl) [odds 0.92, 95%CI (0.89-0.96), p < 0.001] were the specific predictors for non-cardiac deaths., Conclusions: The incidence of in-hospital noncardiac death was significant in patients with AMI, accounting for 15.6% of all in-hospital mortalities. Thus, prevention and management of non-cardiac complications are vital to improve acute-phase outcomes, especially those with predictors of non-cardiac death., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures This study was funded by the Department of Cardiology, Tokyo Medical University. The Department of Cardiology at Tokyo Medical University had no role in the writing of the report or in the decision to submit the article for publication. Drs Ito, Yamashita, Nakajima, and Chikamori are affiliated with an endowed department sponsored by Abbott Medical Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: Our goal was to evaluate the combined effects of balloon pulmonary angioplasty (BPA) followed by pulmonary endarterectomy (PEA) to treat high-surgical-risk patients with chronic thromboembolic pulmonary hypertension (CTEPH)., Methods: This study included 58 patients with CTEPH who had pulmonary vascular resistance of ≥1000 dyn·s/cm5, mean pulmonary arterial pressure (mPAP) of ≥45 mmHg or mPAP of 38-44 mmHg with comorbidities. Of these, 21 patients underwent the combined therapy of BPA followed by PEA (BPA group) and 37 underwent direct PEA (non-BPA group). Preoperative and postoperative results were compared between the 2 groups. An early postoperative composite event comprised the postoperative use of extracorporeal membrane oxygenation or intra-aortic balloon pump, in-hospital death, rescue BPA, prolonged ventilation, tracheostomy, prolonged stay in the intensive care unit, deep sternal wound infection and cerebral infarction., Results: Before the first intervention (before BPA or direct PEA), patients in the BPA group had a higher mPAP than those in the non-BPA group. After undergoing BPA before PEA, the BPA group demonstrated significantly decreased mPAP and pulmonary vascular resistance (43 vs 52 mmHg, P < 0.001; 636 vs 965 dyn·s/cm5, P = 0.003, respectively) and significantly increased cardiac output (4.1 vs 3.5 l/min, P = 0.041). Notably, the number of patients with the early postoperative composite event was significantly lower in the BPA group than in the non-BPA group (4.8% vs 35.1%, P = 0.011)., Conclusions: Compared with direct PEA, the combination therapy of BPA followed by PEA can be a feasible and effective risk-reduction strategy for high-surgical-risk patients with CTEPH., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: The purpose of this study is to examine the association between physical activity and contracture in older patients confined to bed in long-term care (LTC) facilities., Methods: Patients wore ActiGraph GT3X+ for 8 hours on their wrists, and vector magnitude (VM) counts were obtained as the amount of activity. The passive range of motion (ROM) of joints was measured. The severity of ROM restriction classified, as the tertile value of the reference ROM of each joint, was scored 1-3 points. Spearman's rank correlation coefficients (Rs) were used to measure the association between the VM counts per day and ROM restrictions., Results: The sample comprised 128 patients with a mean (SD) age of 84.8 (8.8) years. The mean (SD) of VM was 84574.6 (115195.2) per day. ROM restriction was observed in most joints and movement directions. ROMs in all joints and movement directions, except wrist flexion and hip abduction, were significantly correlated with VM. Furthermore, the VM and ROM severity scores showed a significant negative correlation (Rs = -0.582, p < .0001)., Conclusions: A significant correlation between the physical activity and ROM restrictions indicates that a decrease in the amount of physical activity could be one of the causes of contracture., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare there are no conflicts of interest., (© 2023 Author(s).)

This study aimed to investigate the effect of a rehabilitation program combined with pain management targeting pain perception and activity avoidance on multifaceted outcomes in older patients with acute vertebral compression fractures (VCFs). We randomised 65 older adults with acute VCFs to either an intervention group ( n  = 32), involving usual rehabilitation combined with pain management that targeted pain perception and activity avoidance, or a control group ( n  = 33), involving only usual rehabilitation. The usual rehabilitation was initiated immediately after admission. All patients were treated conservatively. Pain management aimed to improve the patients' daily behaviour by increasing their daily activities despite pain, rather than by focusing on eliminating the pain. Pain intensity and psychological statuses such as depression, pain catastrophising, and physical activity levels were assessed on admission. Two weeks postadmission and at discharge, physical performance measures were assessed along with the above-given measurements. A significant main effect of the group was observed for the intensity of lower back pain, favouring the intervention group ( F  = 5.135, p = 0.027). At discharge, it was significantly better in the intervention group than in the control group ( p = 0.011). A time-by-group interaction emerged for magnification of the pain catastrophising scale ( p = 0.012), physical activity levels ( p < 0.001), and six-minute walking distance ( p = 0.006), all favouring the intervention group. Rehabilitation programs combined with pain management targeting pain perception and activity avoidance could be an effective conservative treatment for older patients with acute VCFs., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Hideki Kataoka et al.)

Background: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances., Methods: FFR and NHPRs were measured in 283 consecutive patients (69 ± 10 years old). Based on previously established cut-off values of the two markers (i.e. +/- = FFR ≤/> 0.80 or =NHPRs ≤/> 0.89), the study participants were divided into four groups (the + and - signs denoting "predictive of significant stenosis" and "not predictive of significant stenosis," respectively): the FFR+/NHPRs+ group (n = 124), FFR-/NHPRs+ group (n = 16), FFR+/NHPRs- group(n = 65), and FFR-/NHPRs- group (n = 78). The baPWV and ABI were also measured in all the participants, and values of <2000 cm/s and ≥1.00 of the baPWV and ABI, respectively, were considered as representing relatively less advanced atherosclerotic systemic vascular damage., Results: The prevalence of subjects with ABI ≥1.00 was higher in the FFR+/NHPRs- group than in the FFR-/NHPRs- group (p < 0.05). When the study subjects were divided into 2 groups, namely, the FFR+/NHPRs- group and the combined group, the prevalence of ABI ≥1.00 and that of baPWV <2000 cm/s were higher in the FFR+/NHPRs- group as compared with those in the combined group (p < 0.05). The results of binary logistic regression analysis demonstrated that ABI ≥1.00 was associated with a significant odds ratio (2.34, p < 0.05) for the FFR+/NHPRs- discordance., Conclusion: The FFR+/NHPRs- discordance appears to be observed in patients with relatively less advanced atherosclerotic systemic vascular damage. Thus, ABI ≥1.00 may be a marker of the presence of the FFR+/NHPRs- discordance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Oral lichen planus (OLP) is a type of chronic and refractory stomatitis characterized by abnormal keratinization, which is often painful. There is no consensus regarding treatment options for OLP, particularly in the presence of pain. The current study protocol focuses on the short-term efficacy and long-term safety of an ibuprofen gargle for pain management in patients with OLP. Patients ( n = 24) with painful OLP will be enrolled. During a crossover study period, patients in the ibuprofen-placebo (IP) group will receive an ibuprofen gargle (0.6%) on day 1, a placebo gargle on day 2, and an ibuprofen gargle on days 3-5 at least once daily. Patients in the placebo-ibuprofen (PI) group will receive a placebo gargle on day 1, an ibuprofen gargle on day 2, and an ibuprofen gargle on days 3-5 at least once daily. The primary endpoint of the crossover study period is the change in pain level as measured by a visual analogue scale score from before gargle administration to 5 min after gargle administration on days 1 and 2. The primary endpoint of the long-term extension study is assessment of long-term safety. The results of this study may support existing evidence regarding the effectiveness of ibuprofen rinses in treating OLP.

Background: Recent retrospective investigations have suggested that optical coherence tomography (OCT) enables the diagnosis of underlying acute coronary syndrome (ACS) causes such as plaque rupture, plaque erosion, and calcified nodule. The relationships of these etiologies with clinical outcomes, and the clinical utility of OCT-guided primary percutaneous coronary intervention (PCI) are not systematically studied in real-world ACS treatment settings., Methods: The TACTICS registry is an investigator-initiated, prospective, multicenter, observational study to be conducted at 21 hospitals in Japan. A total of 700 patients with ACS (symptom onset within 24 h) undergoing OCT-guided primary PCI will be enrolled. The primary endpoint of the study is to identify the underlying causes of ACS using OCT-defined morphological assessment of the culprit lesion. The key secondary clinical endpoints are hazard ratios of the composite of cardiovascular death, non-fatal myocardial infarction, heart failure, or ischemia-driven revascularization in patients with underlying etiologies at the 12- and 24-month follow-ups. The feasibility of OCT-guided primary PCI for ACS will be assessed by the achievement rates of optimal post-procedural results and safety endpoints., Conclusion: The TACTICS registry will provide an overview of the underlying causes of ACS using OCT, and will reveal any difference in clinical outcomes depending on the underlying causes. The registry will also inform on the feasibility of OCT-guided primary PCI for patients with ACS., Competing Interests: Declaration of competing interest Masahiko Ochiai, lecture fee – Abbott Medical Japan LLC., Asahi Intecc, Boston Scientific, and Terumo; Hiromasa Otake, lecture fee - Abbott Medical Japan LLC. and Terumo; Toshiro Shinke, personal fees and research grant - Abbot Japan LLC. The rest of the authors have none to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Understanding temporally attention fluctuations can benefit scientific knowledge and real-life applications. Temporal attention studies have typically used the reaction time (RT), which can be measured only after a target presentation, as an index of attention level. We have proposed the Micro-Pupillary Unrest Index (M-PUI) based on pupillary fluctuation amplitude to estimate RT before the target presentation. However, the kind of temporal attention effects that the M-PUI reflects remains unclear. We examined if the M-PUI shows two types of temporal attention effects initially reported for RTs in the variable foreperiod tasks: the variable foreperiod effect (FP effect) and the sequential effect (SE effect). The FP effect refers to a decrease in the RT due to an increase in the foreperiod of the current trial, whereas the SE effect refers to an increase in the RT in the early part of the foreperiod of the current trial due to an increase in the foreperiod of the previous trial. We used a simple reaction task with the medium-term variable foreperiods (Psychomotor Vigilance Task) and found that the M-PUI primarily reflects the FP effect. Inter-individual analyses showed that the FP effect on the M-PUI, unlike other eye movement indices, is correlated with the FP effect on RT. These results suggest that the M-PUI is a potentially powerful tool for investigating temporal attention fluctuations for a partly unpredictable target., Competing Interests: The authors have read the journal’s policy and have the following competing interests: The authors, JY, HT, MY, KM, and HO, are paid employees of NTT. NTT has signed a joint research agreement with TK and provided a research grant. The authors would like to declare the following patents/patent applications associated with this research: PCT/JP2020/043246 and PCT/JP2021/008837. NTT has a pending patent (in Japan, and possibly in the United States, Europe, and China) for estimating task performance using the amplitude of pupillary fluctuations. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The mortality rate of acute myocardial infarction (AMI) has improved dramatically because of reperfusion therapy during the last 40 years; however, recent temporal trends for AMI have not been fully clarified in Japan., Objectives: The purpose of this study was to elucidate the temporary trend in in-hospital mortality and treatment of AMI for the last decade in the Tokyo Metropolitan area., Methods: We enrolled 30,553 patients from the Tokyo Cardiovascular Care Unit Network Registry, diagnosed with AMI from 2007 to 2016, as part of an ongoing, multicenter, cohort study. We analyzed the temporal trends in basic characteristics, treatment, and in-hospital mortality of AMI., Results: The overall emergency percutaneous coronary intervention (PCI) rate significantly increased ( P  < 0.001). In particular, it remarkably increased in patients older than 80 years of age (58.3% to 70.3%, P  < 0.001) and patients with Killip III or IV (Killip III, 46.9% to 65.7%; Killip IV, 65.2% to 76.6%, P  < 0.001 for both). The crude and age-adjusted in-hospital mortality remained low (5.2% to 8.2% and 3.4% to 5.5%, respectively) and significantly decreased during the decade ( P  < 0.001). The in-hospital mortality remarkably decreased in patients older than 80 years of age (17.3% to 12.7%, P  < 0.001) and in those with cardiogenic shock (38.5% to 27.3%, P  < 0.001)., Conclusions: This large cohort study from Tokyo revealed that in-hospital mortality of AMI significantly decreased with the increase in emergency percutaneous coronary intervention rate over the decade, particularly for high-risk patients such as older patients and those with cardiogenic shock., Competing Interests: The Tokyo CCU network database for this study was financially supported by the Tokyo Metropolitan Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Rationale: Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) rarely causes cholesterol crystal embolism (CCE). In our case, the histological findings suggested that the onset of CCE occurred at different time points in different organs., Patient Concerns: A 72-year-old Japanese woman with HCC underwent TACE. After TACE, serum creatinine level and eosinophil count gradually increased. Three months later, she was admitted to our department with a fever and back pain., Diagnosis: Laboratory examinations showed sepsis with disseminated intravascular coagulation. She was treated with antimicrobial agents and anticoagulants, but died of multiple organ failure., Interventions: An autopsy was performed to examine the cause of multiple organ failure after 3 months of TACE., Outcomes: A mixture of both chronic phase emboli with intimal thickening and fibrosis and acute phase emboli with inflammatory cell infiltration were observed in the small intestine. Moreover, multiple intravascular cholesterol fissures were observed in the kidney, stomach, duodenum, colon, pancreas, and spleen, which were the vascular dominant organs of the celiac artery and superior mesenteric artery. These histological findings suggested that cholesterol crystals were continuously disseminated after TACE., Lessons: TACE for HCC may cause progressive CCE and damage in multiple organs. When progressive renal dysfunction, eosinophilia, or multiple organ dysfunction is observed after TACE, the CCE should be suspected., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Older adults who require nursing care have joint contractures characterized by limited range of motion (ROM). The present study investigated age-related muscle changes using ultrasonography and the relationship between ROM and muscle changes in older adults. Twenty-two healthy young adults (mean age: 23.3 y) and 60 hospitalized older adults (mean age: 86.1 y) participated. ROM of hip abduction was measured using a goniometer. Echo intensity (EI), reflecting interstitial fibrous tissue or fat within adductor longus (ADDl) was measured using B-mode ultrasonography, and strain ratio (SR), reflecting ADDl stiffness, was measured by strain elastography. The Mann-Whitney U-test and Spearman's correlation test were used for analysis. The ROM and SR of older adults were significantly lower than those of young adults (both p values <0.001). The EI was significantly higher in older adults than in young adults (p < 0.001). In older adults, the SR was moderately correlated with ROM (ρ = 0.49, p < 0.001). In conclusion, limited ROM and increase in interstitial fibrous tissue or fat and stiffness occur with aging, and the SR measured by strain elastography is useful for investigating the effect of muscle stiffness on the ROM of hospitalized older adults., Competing Interests: Conflict of interest disclosure The authors have no conflicts of interest with respect to this study., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Gene therapy, cell therapy and vaccine research have led to an increased use of qPCR/ddPCR in bioanalytical laboratories. CROs are progressively undertaking the development and validation of qPCR and ddPCR assays. Currently, however, there is limited regulatory guidance for the use of qPCR and a complete lack of any regulatory guidelines for the use of the newer ddPCR to support regulated bioanalysis. Hence, the Global CRO Council in Bioanalysis (GCC) has issued this White Paper to provide; 1) a consensus on the different validation parameters required to support qPCR/ddPCR assays; 2) a harmonized approach to their validation and 3) a consistent development of standard operating procedures (SOPs) for all the bioanalytical laboratories using these techniques.

Background: Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents., Methods and results: This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis., Conclusions: The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.

Background: Acute myocardial infarction (AMI) patients with low body mass index (BMI) exhibit worse clinical outcomes than obese patients; however, to our knowledge, no prospective, nationwide study has assessed the effect of BMI on the clinical outcomes of AMI patients., Methods and results: In this multi-center, prospective, nationwide Japanese trial, 2,373 AMI patients who underwent emergent percutaneous coronary intervention within 12 h of onset from the Japanese AMI Registry (JAMIR) were identified. Patients were divided into the following 4 groups based on their BMI at admission: Q1 group (BMI <18.5 kg/m 2 , n=133), Q2 group (18.5≤BMI<25.0 kg/m 2 , n=1,424), Q3 group (25.0≤BMI<30.0 kg/m 2 , n=672), and Q4 group (30.0 kg/m 2 ≤BMI, n=144). The primary endpoint was all-cause death, and the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. The median follow-up period was 358 days. Q1 patients were older and had lower prevalence of coronary risk factors. Q1 patients also had higher all-cause mortality and higher incidence of secondary endpoints than normal-weight or obese AMI patients. Multivariate analysis showed that low BMI (Q1 group) was an independent predictor for primary endpoint., Conclusions: AMI patients with low BMI had fewer coronary risk factors but worse clinical outcomes than normal-weight or obese patients.

Taste bud cells are renewed throughout life in a process requiring innervation. Recently, we reported that R-spondin substitutes for neuronal input for taste cell regeneration. R-spondin amplifies WNT signaling by interacting with stem-cell-expressed E3 ubiquitin ligases RNF43/ZNRF3 (negative regulators of WNT signaling) and G-protein-coupled receptors LGR4/5/6 (positive regulators of WNT signaling). Therefore, we hypothesized that RNF43/ZNRF3 may serve as a brake, controlled by gustatory neuron-produced R-spondin, for regulating taste tissue homeostasis. Here, we show that mice deficient for Rnf43/Znrf3 in KRT5-expressing epithelial stem/progenitor cells (RZ dKO) exhibited taste cell hyperplasia; in stark contrast, epithelial tissue on the tongue degenerated. WNT signaling blockade substantially reversed all these effects in RZ dKO mice. Furthermore, innervation becomes dispensable for taste cell renewal in RZ dKO mice. We thus demonstrate important but distinct functions of RNF43/ZNRF3 in regulating taste versus lingual epithelial tissue homeostasis., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)