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Background: Approximately 10% of hypertrophic cardiomyopathy (HCM) patients have left ventricular systolic dysfunction (end-stage HCM) leading to severe heart-failure; however, risk stratification to identify patients at risk of progressing to end-stage HCM remains insufficient., Objectives: In this study, the authors sought to elucidate whether the coexistence of other cardiovascular disease (CVD)-related variants is associated with progression to end-stage HCM in patients with HCM harboring pathogenic or likely pathogenic (P/LP) sarcomeric variants., Methods: The authors performed genetic analysis of 83 CVD-related genes in HCM patients from a Japanese multicenter cohort. P/LP variants in 8 major sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL2, MYL3, and ACTC1) definitive for HCM were defined as "sarcomeric variants." In addition, P/LP variants associated with other CVDs, such as dilated cardiomyopathy and arrhythmogenic cardiomyopathy, were referred to as "other CVD-related variants.", Results: Among 394 HCM patients, 139 carried P/LP sarcomeric variants: 11 (7.9%) carried other CVD-related variants, 6 (4.3%) multiple sarcomeric variants, and 122 (87.8%) single sarcomeric variants. In a multivariable Cox regression analysis, presence of multiple sarcomeric variants (adjusted HR [aHR]: 3.35 [95% CI: 1.25-8.95]; P = 0.016) and coexistence of other CVD-related variants (aHR: 2.80 [95% CI: 1.16-6.78]; P = 0.022) were independently associated with progression to end-stage HCM. Coexisting other CVD-related variants were also associated with heart failure events (aHR: 2.75 [95% CI: 1.27-5.94]; P = 0.010)., Conclusions: Approximately 8% of sarcomeric HCM patients carried other CVD-related variants, which were associated with progression to end-stage HCM and heart failure events. Comprehensive surveillance of CVD-related variants within sarcomeric HCM patients contributes to risk stratification and understanding of mechanisms underlying end-stage HCM., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from SENSHIN Medical Research Foundation (to Dr Ko and Dr Nomura), Japan Foundation for Applied Enzymology (to Dr Ko and Dr Nomura), Kanae Foundation for the Promotion of Medical Science (to Dr Nomura), Merck Sharp & Dohme Life Science Foundation (to Dr Ko and Dr Nomura), Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to Dr Ko), Tokyo Biomedical Research Foundation (to Dr Nomura), Astellas Foundation for Research on Metabolic Disorders (to Dr Nomura), Novartis Foundation (Japan) for the Promotion of Science (to Dr Nomura), Japanese Circulation Society (to Dr Ko and Dr Nomura), Takeda Science Foundation (to Dr Ko and Dr Nomura), Cell Science Research Foundation (to Dr Nomura), Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Dr Nomura), Japan Heart Foundation (to Dr Ko), Daiichi Sankyo Foundation of Life Science (to Dr Nomura), a Grant-in-Aid for Scientific Research (A) (to Dr Nomura), a Grant-in-Aid for Scientific Research (S) (to Dr Komuro), UTEC-UTokyo FSI Research Grant Program (to Dr Nomura), JST FOREST Program (grant number JPMJFR210U) (to Dr Nomura), Japan Agency for Medical Research and Development (AMED) (JP18km0405209, JP21ek0109543, JP21ek0109569, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011, JP23tm0724607, JP23gm4010020, JP223fa627011, JP23tm0524009, JP23tm0524004, JP23jf0126003, JP24ek0109755, and JP24ek0210205) (to Dr Nomura and Dr Komuro), and JP23ek0109600h0002 (to Dr Ko). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization., Objectives: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA)., Methods: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort., Results: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA., Conclusions: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow Inc. The company performed the computational fluid dynamics, and artificial intelligence quantitative coronary plaque analysis but was not involved in the study design, collection, analysis, and interpretation of data; the writing of this paper; or the decision to submit it for publication. Dr Koo has received institutional research grants from Abbott, Philips, and HeartFlow Inc. Dr Nam has received institutional research grants from Abbott and Genoss. Dr Merkely has received direct personal payments for speaker fees or studies from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Medtronic, and Novartis and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr de Bruyne has received institutional unrestricted research grants from Abbott, Boston Scientific, and Biotronik; has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE, Bayer, Philips, HeartFlow Inc, Edwards Life Sciences, Sanofi, and Omega Pharma. Dr Ko has equity in Artrya and has received honoraria from Medtronic, Abbott Vascular, and Canon Medical. Dr Leipsic is a consultant for and holds stock options in HeartFlow Inc and modest personal core lab fees from Arineta. Dr Shah has received honoraria as a speaker for HeartFlow Inc. Dr Bax has received unrestricted research grants from Abbott and Edwards Lifesciences to the Department of Cardiology, Leiden University Medical Center, the Netherlands. Dr Shaw has received honoraria from HeartFlow Inc and Elucid Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Trabectedin is an antineoplastic drug used to treat soft tissue sarcomas. Trabectedin is mainly infused from the central venous port (CVP) because trabectedin leakage causes serious skin and soft tissue complications. Characteristic sterile inflammation has recently been reported after infusion of trabectedin from the CVP. Here, we report a case of sterile inflammation along a tunneled catheter pathway after trabectedin infusion from the CVP, with residual postinflammatory changes even after CVP removal. A 57-year-old man with myxoid liposarcoma developed skin erythema, swelling, and induration along a tunneled catheter pathway of the CVP after 16 cycles of trabectedin infusion through the CVP. The patient was diagnosed with sterile inflammation because various tests were negative for infection. The CVP was removed because the increasing injection resistance made trabectedin infusion difficult. The catheter firmly adhered to the surrounding tissue during removal. The induration and pigmentation along the catheter persisted for 4 months after CVP removal., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood., Methods: One hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis., Results: In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV., Conclusions: In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epidermal keratinocytes, forming the outermost layer of the human body, serve as a crucial barrier against diverse external stressors such as ultraviolet radiation. Proper keratinocyte differentiation and effective responses to external stimuli are pivotal for maintaining barrier integrity. Heat is one such stimulus that triggers the synthesis of heat shock proteins (HSPs) when cells are exposed to temperatures above 42 °C. Additionally, activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) occurs at 42 °C. Here, we explore the interplay between TRPV1 signaling and HSP induction in human keratinocytes. Both heat and capsaicin, a TRPV1 agonist, induce expression of HSP27, HSP70, and HSP90 in keratinocytes. Interestingly, pharmacological inhibition of TRPV1 attenuates heat-induced HSP27 expression, but not that of HSP70 or HSP90. Furthermore, both heat and capsaicin stimulation result in distinct phosphorylation patterns of heat shock factor 1 (HSF1), with phosphorylation at serine 326 being a common feature. Notably, genetic manipulation to mimic dephosphorylation of HSF1 at serine 326 reduces HSP27 levels. Additionally, ΔNp63, a key regulator of epidermal differentiation, negatively modulates HSP27 expression independently of HSF1 phosphorylation status. While heat stimulation has no effect on ΔNp63 expression, capsaicin reduces its levels. The precise role of TRPV1 signaling in keratinocytes warrants further investigation for a comprehensive understanding of its impact on barrier function., 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.)

Background: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP., Materials and Methods: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response., Results: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively)., Conclusion: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Coronary angiography-derived radial wall strain (RWS) is a newly developed index that can be readily accessed and describes the biomechanical features of a lesion., Objectives: The authors sought to investigate the association of RWS with fractional flow reserve (FFR) and high-risk plaque (HRP), and their relative prognostic implications., Methods: We included 484 vessels (351 patients) deferred after FFR measurement with available RWS data and coronary computed tomography angiography. On coronary computed tomography angiography, HRP was defined as a lesion with both minimum lumen area <4 mm 2 and plaque burden ≥70%. The primary outcome was target vessel failure (TVF), a composite of target vessel revascularization, target vessel myocardial infarction, or cardiac death., Results: The mean FFR and RWS max were 0.89 ± 0.07 and 11.2% ± 2.5%, respectively, whereas 27.7% of lesions had HRP, 15.1% had FFR ≤0.80. An increase in RWS max was associated with a higher risk of FFR ≤0.80 and HRP, which was consistent after adjustment for clinical or angiographic characteristics (all P < 0.05). An increment of RWS max was related to a higher risk of TVF (HR: 1.23 [95% CI: 1.03-1.47]; P = 0.022) with an optimal cutoff of 14.25%. RWS max >14% was a predictor of TVF after adjustment for FFR or HRP components (all P < 0.05) and showed a direct prognostic effect on TVF, not mediated by FFR ≤0.80 or HRP in the mediation analysis. When high RWS max was added to FFR ≤0.80 or HRP, there were increasing outcome trends (all P for trend <0.001)., Conclusions: RWS was associated with coronary physiology and plaque morphology but showed independent prognostic significance., Competing Interests: Funding Support and Author Disclosures Dr Doh has received research grants from Philips Volcano. Dr Koo has received institutional research grants from Abbott Vascular and Philips Volcano. Dr Tu is the cofounder of, has received research grants from, and has been a consultant for Pulse Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The definition of progressive pulmonary fibrosis is based on a 1-year lung function decline., Objectives: To evaluate the epidemiology and clinical relevance of 1-year lung function decline in sarcoidosis., Methods: A retrospective observational study at a general sarcoidosis clinic., Results: Of the 198 patients, 42 (18.4 %) had a 1-year lung function decline (absolute 12-month decline in percentage predicted forced vital capacity [%FVC] of ≥5 % or percentage predicted diffusion capacity for carbon monoxide [%DLCO] of ≥10 %). A 1-year lung function decline was associated with a 2-year lung function decline (a relative 24-month decline in %FVC of ≥10 % or %DLCO of ≥15 %), which occurred in 13 (7.4 %) of the 175 patients with 24-month follow-up results. A 1-year lung function decline was not associated with survival; a 2-year lung function decline predicted mortality., Conclusions: Compared with a 24-month decline, a 12-month decline in lung function did not predict worse survival in sarcoidosis., Competing Interests: Conflict of interest Kiminobu Tanizawa received a research grant from the FUJIFILM Corporation; Tomohiro Handa received a research grant from the FUJIFILM Corporation and belongs to an endowed department sponsored by Teijin Pharma Ltd; Sonoko Nagai has no conflicts of interest; Kohei Ikezoe received a research grant from the FUJIFILM Corporation; Takeshi Kubo has no conflicts of interest; Takafumi Yokomatsu has no conflicts of interest; Seigen Ueda has no conflicts of interest; Yasutaka Fushimi has no conflicts of interest; Shumpei Ogino has no conflicts of interest; Kizuku Watanabe has no conflicts of interest; Yoshinari Nakatsuka belonged to an endowed department sponsored by Philips Respironics, Teijin Pharma Ltd., Fukuda Denshi Inc., and Fukuda Lifetec Keiji; Toyohiro Hirai received a research grant from the FUJIFILM Corporation; and Takateru Izumi has no conflicts of interest., (© 2023 Published by Elsevier B.V. on behalf of The Japanese Respiratory Society.)

Objectives: The present study investigates the diagnosis and prediction of COVID-19 based on clinical symptoms, and corresponding difference between the Delta- and Omicron-dominant periods, using data collected at polymerase chain reaction (PCR) centers in Hiroshima Prefecture, Japan., Methods: Data was collected using a J-SPEED-style COVID-19 standard data collection form. The analysis was done in two directions: calculating the likelihood ratio that clinical symptoms will manifest in "infected" versus "non-infected" individuals and calculating the diagnostic odds ratio (OR) of infection for those who have symptoms compared to those without symptoms., Results: COVID-19 was more strongly associated with smell and taste disorders during the Delta-dominant period, and muscle pain during the Omicron-dominant period. An age-specific analysis of likelihood and diagnostic ORs found cold-like symptoms had the lowest ability to diagnose COVID-19, and the lowest predictability of COVID-19 with children during both periods. The likelihood and diagnostic ORs of other symptoms for COVID-19 were highest in adults and lowest in those over 65., Conclusion: Symptoms are an important indicator of COVID-19, but the association between specific symptoms and COVID-19 is dependent on the dominant variant of the virus., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A glucagon-like peptide-1 receptor agonist (GLP-1RA) has recently been established as a pharmacological option for the treatment of type 2 diabetes. Recent studies have demonstrated the molecular role of GLP-1R in skeletal muscle homeostasis; however, the therapeutic efficacy of semaglutide, a GLP-1RA, on skeletal muscle atrophy in chronic liver disease (CLD) under diabetic conditions remains unclear. In the present study, semaglutide effectively inhibited psoas muscle atrophy and suppressed declines in grip strength in a diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-fed diabetic KK-A y mouse model. Moreover, semaglutide inhibited ubiquitin-proteosome-mediated skeletal muscle proteolysis and promoted myogenesis in palmitic acid (PA)-stimulated C2C12 murine myocytes. Mechanistically, this effect of semaglutide on skeletal muscle atrophy was mediated by multiple functional pathways. First, semaglutide protected against hepatic injury in mice accompanied by increased production of insulin-like growth factor 1 and reduced accumulation of reactive oxygen species (ROS). These effects were associated with decreased proinflammatory cytokines and ROS accumulation, leading to the suppression of ubiquitin-proteosome muscle degradation. Moreover, semaglutide inhibited the amino acid starvation-related stress signaling that was activated under chronic liver injury, resulting in the recovery of the mammalian target of rapamycin activity in the skeletal muscle of DDC-diet fed KK-A y mice. Second, semaglutide improved skeletal muscle atrophy by directly stimulating GLP-1R in myocytes. Semaglutide induced cAMP-mediated activation of PKA and AKT, enhanced mitochondrial biogenesis, and reduced ROS accumulation, thereby resulting in inhibition of NF-κB/myostatin-mediated ubiquitin-proteosome degradation and the augmentation of heat-shock factor-1-mediated myogenesis. Collectively, semaglutide may have potential as a new therapeutic strategy for CLD-related skeletal muscle wasting., 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 © 2023 Elsevier B.V. All rights reserved.)

Mpox virus is known to be transmissible from the onset of clinical manifestations. We report the first case in Japan of a man who contracted mpox through close contact with an individual with pre-symptomatic infection. Given that transmission before symptom onset has recently been reported from various countries, the importance of prophylaxis for reducing the risk of infection and controlling the disease should be emphasized., Competing Interests: Declaration of competing interest None., (Copyright © 2023 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: Limited information on anticancer therapy for super-elderly patients with non-small-cell lung cancer is available. Immune checkpoint inhibitors offer long-term survival to elderly patients aged ≥65 years with non-small-cell lung cancer. However, the efficacy and safety of immune checkpoint inhibitors in more elderly patients are not well understood., Methods: We retrospectively evaluated the efficacy and safety of immune checkpoint inhibitors in patients aged ≥85 years with advanced non-small-cell lung cancer at nine centers using the Okayama Lung Cancer Study Group-Immunotherapy Database., Results: Among 531 patients who received immune checkpoint inhibitors, 16 were aged ≥85 years (median, 86.5 years; range, 85-93 years). Many had high programmed death-ligand 1 expression and received pembrolizumab as first-line therapy. The objective response rate, median progression-free survival, and median survival time were 25% (95% confidence interval: 1-49), 2.8 months (95% confidence interval: 1.7-4.5), and not reached (95% confidence interval: 4.7-not reached), respectively. Moreover, the 4-year overall survival rate was 60.8% (95% confidence interval: 29.3-81.7), and a long-lasting effect of immune checkpoint inhibitors was observed even in patients aged ≥85 years. The incidence of immune-related and grade ≥3 immune-related adverse events was 32% and 6%, respectively., Conclusions: The effect and toxicity of immune checkpoint inhibitors for patients aged ≥85 years were acceptable. Immune checkpoint inhibitors may be a treatment option for patients aged ≥85 years., Competing Interests: Conflict of Interest T. Kubo received honoraria from Bristol-Myers Squibb, Taiho Pharmaceutical, Kyowa Hakko Kirin, AstraZeneca, Ono Pharmaceutical, Nippon Kayaku, Chugai Pharma, MSD, Pfizer, Lilly, Novartis, Boehringer Ingelheim, and Towa Pharmaceutical; E. Ichihara received honoraria from AstraZeneca K·K., Novartis, Janssen Pharmaceutical K·K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K·K., Pfizer, Bristol-Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Boehringer Ingelheim; K. Hotta received research funding from MSD, AstraZeneca K·K., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K·K., and Bristol-Myers Squibb Co. Ltd.; Y. Maeda received honoraria from AstraZeneca K·K., Astellas Pharma Inc.Astellas Pharma, Amgen K·K., AbbVie GK, Eisai Co., Ltd, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sanofi K.K., Celgene Corporation, Bristol-Myers Squibb K·K., CSL BehringCSL Behring K·K., Daiichi Sankyo Company, Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Ltd., Terumo Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K·K., Pfizer Japan Inc., Mundipharma K·K., Human Life CORD Japan Inc., Meiji Seika Pharma Co., Ltd., Janssen Pharmaceutical K·K., and Yakult Honsha Co., Ltd. and research funding from Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., AstraZeneca K·K., Astellas Pharma, Novartis Pharma K·K., Janssen Pharmaceutical K·K., and Mundipharma K.K. and scholarship donations from Astellas Pharma, Asahi Kasei Pharma Corporation, Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., TAIHO Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Japan Blood Products Organization, and Nippon Shinyaku Co., Ltd.; K. Kiura received consulting fees from Daiichi Sankyo Co., Ltd., Nippon Kayaku Co., Ltd., and Nipro Corporation and honoraria from AstraZeneca K·K., Eli Lilly Japan K·K., Novartis International AG, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Pfizer Japan Inc., Ono Pharmaceutical Co., Ltd. Bristol-Myers Squibb K·K., MSD K·K., Boehringer Ingelheim Co., Ltd. Daiichi Sankyo Co., Ltd., Merck Biopharma Co., Ltd, Nippon Kayaku Co., Ltd., and Takeda Pharmaceutical Co., Ltd. and research funding from Merck Biopharma Co., Ltd, KYORIN Pharmaceutical Co., Ltd., Pfizer Japan Inc., MSD K.K., Boehringer Ingelheim Co., Ltd., Shionogi & Co., Ltd., Nippon Kayaku Co., Ltd., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., TEIJIN Pharma Ltd., Novartis International AG, and Takeda Pharmaceutical Co., Ltd. The other authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Particle packed columns used for liquid chromatography (LC) can suppress a column internal band broadening (hereinafter referred to as band broadening) by packing monodisperse particles homogenously. However, a quantitative evaluation for the effects of particle shape and packed state on band broadening needs to be more investigated. In this study, we fabricated a model of particle packed bed using microfluid LC columns that have pillar array structure prepared by microfabrication technology, evaluating how structural factors inside of a column affect its band broadening. At first, microfluid LC columns was prepared using Si-quartz glass (Si-Q column) for the optimization of LC measurement system. Through the evaluation, it showed 11.6 times higher pressure tolerance compared to that of PDMS-soda lime glass (PDMS-g column). Then, an optimized LC measurement system was constructed using a microfluidic LC column made of Si-Q column, and it was confirmed that the measurement error was small enough and the LC measurement could be performed with high repeatability. Additionally, the effect of a distribution of structural size on band broadening was evaluated. It was confirmed that wide distribution of the structural size provided large band broadening in actual measurements. Comparing two columns having different structural log-normal distributions of 0 and 0.22 showed approximately 1.8 times difference in both real LC measurement. Lastly, the relationship between packed state and band broadening was evaluated. As packed state, we employed void arrangement and structural arrangement in the columns. Different location arrangements of 50 and 100 µm pillar sizes afforded different band broadening. Well-homogenized array showed approximately two times worse band broadening compared to that of delocalized array. Based on these results, the developed packed bed of particles model was able to evaluate the relation between structural factors and band broadening., 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 © 2023. Published by Elsevier B.V.)

The fat-augmented latissimus dorsi myocutaneous flap can overcome the volume insufficiency of latissimus dorsi flaps by immediate fat grafting into the flap. When breast skin supplementation is unnecessary, latissimus dorsi flaps can be harvested as a muscle flap to avoid an additional back incision. Here, we compared the efficacy of fat-augmented latissimus dorsi myocutaneous and muscle flaps in total breast reconstruction. We retrospectively reviewed 94 cases of unilateral total breast reconstruction using fat-augmented latissimus dorsi flaps (muscle: 40, myocutaneous: 54) at our hospital from September 2017 to March 2022. The muscle flap group had a significantly shorter operative time than the myocutaneous flap group (p < 0.0001). Mastectomy specimen weight did not differ between the 2 groups, but total flap weight in the muscle flap group was significantly lower (p < 0.0001). Conversely, total fat graft volume, fat graft volume to the latissimus dorsi flap, and fat graft volume to the pectoralis major muscle were significantly greater in the muscle flap group (p < 0.0001, p < 0.0001, and p = 0.02, respectively). The percentage of cases requiring additional fat grafting was significantly higher in the muscle flap group, but postoperative esthetic evaluation did not significantly differ between the 2 groups. Both groups scored high on each BREAST-Q item, but the muscle flap group scored significantly higher for "Satisfaction with Back." Although the frequency of additional fat grafting was higher than with fat-augmented latissimus dorsi myocutaneous flaps, total breast reconstruction with fat-augmented latissimus dorsi muscle flaps is a viable technique with a short operative time and high patient satisfaction., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acts as a sensor under oxidative stress, leading to induction of various biological responses. Given that mitogen-activated protein kinase (MAPK) signaling pathways mediate cellular responses to a wide variety of stimuli, including oxidative stress, here, we aimed to elucidate whether a cross-talk cascade between GAPDH and MAPKs occurs under oxidative stress. Of the three typical MAPKs investigated-extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase (JNK)-we found that hydrogen peroxide (H 2 O 2 )-induced JNK activation is significantly reduced in HEK293 cells treated with small-interfering (si)RNA targeting GAPDH. Co-immunoprecipitation with a GAPDH antibody further revealed protein-protein interactions between GAPDH and JNK in H 2 O 2 -stmulated cells. Notably, both JNK activation and these interactions depend on oxidation of the active-site cysteine (Cys152) in GAPDH, as demonstrated by rescue experiments with either exogenous wild-type GAPDH or the cysteine-substituted mutant (C152A) in endogenous GAPDH-knockdown HEK293 cells. Moreover, H 2 O 2 -induced translocation of Bcl-2-associated X protein (Bax) into mitochondria, which occurs downstream of JNK activation, is attenuated by endogenous GAPDH knockdown in HEK293 cells. These results suggest a novel role for GAPDH in the JNK signaling pathway under oxidative stress., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We applied a novel measure of average lifespan shortened (ALSS) to examine changes in lifespan among patients who died of cancer over a 10-year period from 2006 to 2016 in 20 selected high-income countries from North America, Europe, Asia, and Oceania., Methods: We retrieved cancer deaths in each country from the World Health Organization mortality database. We calculated ALSS as a ratio of years of life lost to the expected lifespan among patients who died from cancer., Results: Between 2006 and 2016, we observed modest changes in ALSS for overall cancer deaths over the study in many countries. The changes in the ALSS over time due to any cancer ranged between -1.7 and +0.4 percentage points (pps) among men and between -1.9 and +0.6 pps among women. Across countries, overall cancer deaths led to an average loss between 16% and 22% of their lifespan in men, and between 18% and 24% in women. Across cancer sites, patients who died of central nervous system cancers, for instance, lost a large proportion of their lifespan., Conclusions: In this study, we demonstrated the use of ALSS across selected high-income countries, which enables population-level assessment of premature mortality among cancer patients over time., (Copyright © 2023. Published by Elsevier Inc.)

Optical coherence tomography (OCT) is an intravascular imaging technique that uses near-infrared light. OCT provides high-resolution cross-sectional images of coronary arteries and enables tissue characterization of atherosclerotic plaques. OCT can identify plaque rupture, plaque erosion, and calcified nodule in culprit lesions of acute coronary syndrome. OCT can also detect important morphologic features of vulnerable plaques such as thin fibrous caps, large lipid cores, macrophages accumulation, intraplaque microvasculature, cholesterol crystals, healed plaques, and intraplaque hemorrhage., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Limited data are available regarding therapies for hypertrophic cardiomyopathy (HCM). This study assessed the prevalence, clinical characteristics, and treatment patterns of HCM in Japan., Methods: This retrospective database study analyzed data from 438 hospitals in the Japan Medical Data Vision database from 2016 to 2020. We identified 3913 patients (15 %) with obstructive HCM (oHCM) and 21,714 patients (85 %) with nonobstructive HCM (nHCM)., Results: The estimated total number of patients with oHCM and nHCM in 2020 among Japanese hospitals was 8500 and 43,500, respectively. The prevalence of oHCM and nHCM steadily increased by 27 % and 12 %, respectively, from 2016 to 2020, with a 1:5.2 ratio of oHCM to nHCM in 2020. The mean age of the oHCM and nHCM populations was 72 and 70 years, respectively, and comorbidities included atrial fibrillation (AF) (oHCM, 33.8 %; nHCM, 32.2 %), other arrythmia (30.1 %; 27.6 %), and stroke (16.6 %; 16.4 %). Furthermore, 45.0 % of oHCM and 37.7 % of nHCM patients had undergone at least one hospitalization. A substantial number of HCM patients aged between 20 and 59 years reported AF (oHCM, 17-37 %; nHCM, 4-24 %) and stroke (oHCM, 0-12 %; nHCM, 3-10 %). β-blockers (oHCM, 64.0 %; nHCM, 42.1 %) were the most frequently prescribed treatment, followed by Na channel blockers (29.5 %; 5.7 %), calcium channel blockers (18.1 %; 8.8 %), direct oral anticoagulants (14.5 %; 15.2 %), and warfarin (11.0 %; 11.4 %)., Conclusions: This study provides important information on the current epidemiological and clinical characteristics of HCM in Japan., Competing Interests: Declaration of competing interest Naoki Terasaka, Dionysis Spanopoulos, and Hidetaka Miyagoshi are employees of Bristol Myers Squibb. Toru Kubo and Hiroaki Kitaoka have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients., Method: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination., Results: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded., Conclusion: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely., 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 © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The current state of knowledge related to disease management of heart failure (HF) and information coordination practices provided by non-physician healthcare professionals such as nurses and therapists working at home-visit nursing stations in Japan are not well known., Methods: A questionnaire survey of healthcare professionals working at home-visit nursing stations was conducted in Kochi Prefecture. Data collected from 151 nurses and therapists were analyzed., Results: Regarding the basic characteristics of the respondents, the majority were in their 30s and 40s, and approximately 75 % were nurses. In terms of HF knowledge, 53.7 % of respondents said that they "knew" about the New York Heart Association classification. A total of 40.0 % of respondents said that they were "aware of the existence of the HF handbook", and only 29.3 % of respondents said that they "knew" the classification of HF stages. When they were asked about their level of satisfaction related to all medical information provided by the hospital and hospital wards, no one was "very satisfied", and the most common response (66.2 %) was "not very satisfied". In the essential medical information that respondents wanted to obtain from hospitals and hospitals wards for managing HF patients at home, "medication at discharge", "current medical history", "fluid intake and restrictions", "symptoms, signs, and response to exacerbation", and "ideal body weight" were the top five contents., Conclusion: In the cross-sectional study targeted healthcare professionals working at home-visit nursing stations in Kochi Prefecture, the current state of knowledge related to HF and information coordination practices among healthcare professionals were not fully satisfactory in HF management. It is necessary to increase educational opportunities regarding HF for them and further promote information sharing., Competing Interests: Declaration of competing interest The authors have no conflict of interest with a company, organization, or institution to be disclosed., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A severe negative energy balance and high circulating free fatty acids (FFA) in postpartum cows impair fertility. The lipotoxicity of FFA has been shown to decrease the quality of bovine oocytes in vitro. Therefore, excess FFA in cells is converted to triacylglycerol (TAG), a non-toxic form, to avoid lipotoxicity. We recently reported that the TAG content in oocytes was higher in postpartum lactating cows subjected to grazing management than in heifers (Theriogenology 176: 174-182, 2021). The present study investigated the compositions of the energy metabolism-related lipids, FFA and TAG, in the plasma and oocytes of cows at different lactation stages under indoor intensive feeding management in order to obtain insights into lipotoxicity in oocytes, particularly those in early postpartum cows. Blood and oocytes were collected from 20 lactating cows categorized into the following lactation groups: 20-30 days in milk (DIM) (n = 5), 40-50 DIM (n = 5), 60-80 DIM (n = 5), and 130-160 DIM (n = 5). Daily energy balance data were obtained for 3 weeks prior to oocyte collection using the ovum pick up (OPU) method. The contents and compositions of FFA and TAG in plasma and oocytes were analyzed using liquid chromatography-mass spectrometry. As expected, plasma FFA was high at 20-30 DIM, decreased by 50 DIM, and was maintained at a low level for the remainder of the experimental period. Similar changes were observed in oocyte FFA and TAG with DIM as plasma FFA. Oocyte FFA positively correlated with plasma FFA (P < 0.05), but negatively correlated with the mean energy balance 1 and 21 days before OPU (P < 0.05). Relationships were noted between the composition and content of FFA in plasma and oocytes, with the FFA 16:1/16:0 and 18:1/18:0 ratios positively correlating with the total amount of FFA (P < 0.05). Elevated oocyte FFA in cows in the early postpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity. Furthermore, the present results implied that the severe negative energy balance in the previous few weeks was closely related to increases in oocyte FFA, which supports the importance of long-term cow feeding management for preserving the quality of oocytes in the early postpartum period. The present results provide insights into the effects of high circulating FFA on the fertility of postpartum cows., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)