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Masaki Tago,1 Risa Hirata,1 Hiromizu Takahashi,2 Shun Yamashita,1,3 Masayuki Nogi,4,5 Kiyoshi Shikino,6 Yosuke Sasaki,7 Takashi Watari,8 Taro Shimizu9 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan; 3Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, Japan; 4Hospitalist Division, The Queen’s Medical Center, Honolulu, HI, USA; 5Department of General Internal Medicine, Kameda Medical Center, Chiba, Japan; 6Department of General Medicine, Chiba University Hospital, Chiba, Japan; 7Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 8General Medicine Center, Shimane University Hospital, Shimane, Japan; 9Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpAbstract: Hospital Medicine in the United States has achieved significant progress in the accumulation of evidence. This development has influenced the increasing societal demand for General Medicine in Japan. Generalists in Japan actively engage in a wide range of interdisciplinary clinical practices, education, and management. Furthermore, Generalists have also contributed to advances in research. However, there is limited evidence regarding the benefits of General Medicine in Japan in all these areas, with most of the evidence derived from single-center studies. In Japan, the roles of Generalists are diverse, and the comprehensive definition of General Medicine makes it difficult to clearly delineate its scope. This results in an inadequate accumulation of evidence regarding the benefits of General Medicine, potentially making it less attractive to the public and younger physicians. Therefore, it is necessary to categorize General Medicine and collect clear evidence regarding its benefits.Keywords: classification, evidence, general medicine

Aims: Congestive heart failure (HF) is a common complication in patients with acute myocardial infarction (AMI). The estimated plasma volume status [ePVS = (100 - haematocrit)/haemoglobin] is used as the blood plasma volume index to determine the presence of congestion in patients with HF. However, the clinical impact of ePVS at discharge in patients with AMI remains unclear. This study aimed to investigate whether ePVS at discharge could determine the long-term prognosis in patients with AMI., Methods and Results: We retrospectively identified patients with AMI with ePVS measured at discharge between January 2012 and December 2020. The primary endpoint was post-discharge all-cause death. The patients were divided into two groups according to an ePVS cut-off value of 5.5%, which is commonly used in HF. In total, 1012 patients with AMI were included. The median age was 70 years (range, 61-78 years), and 76.4% of the patients were male. The ePVS > 5.5% (high-ePVS) group included 365 patients (36.1%), and the all-cause mortality rate in the total cohort was 17.7%. The log-rank test revealed that the high-ePVS group had a significantly higher rate of all-cause death than the ePVS ≤ 5.5% (low-ePVS) group (P < 0.001). Multivariate Cox proportional hazards model analysis revealed that high ePVS was associated with post-discharge all-cause death, independent of other risk factors (hazard ratio = 1.879; 95% confidence interval = 1.343-2.629, P < 0.001)., Conclusions: High ePVS at discharge was independently associated with high post-discharge all-cause mortality in patients with AMI. Our study suggests that ePVS at discharge in patients with AMI could serve as a novel prognostic marker., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Dehydration of a cellulose nanofiber (CNF)/water dispersion requires large amounts of energy and time due to the high hydrophilicities and high specific surface areas of the CNFs. Various dehydration methods have been proposed for CNF/water dispersions; however, an efficient dehydration method for individually dispersed CNFs is needed. Here, electrodeposition of CNFs was evaluated as a dehydration method. Electrodeposition at a DC voltage of 10 V on a 0.2 wt% CNF/water dispersion resulted in a concentration of ∼1.58 wt% in 1 h. The dehydration energy efficiency was ∼300 times greater than that of dehydration by evaporation. The concentrated CNF hydrogels recovered after electrodeposition were redispersed with a simple neutralization process, and clear transparent films were obtained by drying after redispersion. This work provides a new method for dehydration and reuse of individually dispersed CNF/water dispersions and provides new insights into control of the hierarchical structures of CNFs by electrodeposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hypochloremia has been suggested as a strong marker of mortality in hospitalized patients with heart failure (HF). This study aimed to clarify whether incorporating hypochloremia into pre-existing prognostic models improved the performance of the models., Methods: We tested the prognostic value of hypochloremia (<97 mEq/L) measured at discharge in hospitalized patients with HF registered in the REALITY-AHF and NARA-HF studies. The primary outcome was 1-year mortality after discharge., Results: Among 2496 patients with HF, 316 (12.6 %) had hypochloremia at the time of discharge, and 387 (15.5 %) deaths were observed within 1 year of discharge. The presence of hypochloremia was strongly associated with higher 1-year mortality compared to those without hypochloremia (log-rank: p < 0.001), and this association remained even after adjustment for the Get With the Guideline-HF risk model (GWTG-HF), anemia, New York Heart Association (NYHA) classification, and log-brain natriuretic peptide (BNP) [hazard ratio (HR) 1.64; p < 0.001]. Furthermore, adding hypochloremia to the prediction model composed of GWTG-HF + anemia + NYHA class + log-BNP yielded a numerically larger area under the curve (0.740 vs 0.749; p = 0.059) and significant improvement in net reclassification (0.159, p = 0.010)., Conclusions: Incorporating the presence of hypochloremia at discharge into pre-existing risk prediction models provides incremental prognostic information for hospitalized patients with HF., Competing Interests: Declaration of competing interest Dr. Yuya Matsue is affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Keisuke Kida received honoraria from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. Dr. Takahiro Okumura received research honoraria from Ono Yakuhin, Otsuka, Novartis, and Astrazeneca and research grants from Ono Yakuhin, Amgen Astellas, Pfizer, Alnylam, and Alexion (not in connection with the submitted work). Dr. Yoshihiko Saito received research funds from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Actelion Pharmaceuticals Japan Ltd., Kyowa Kirin Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nihon Medi-Physics Co., Ltd., and Fuji Yakuhin Co., Ltd.; research expenses from Roche Diagnostics K.K., Otsuka Pharmaceutical Co., Ltd., Terumo Corporation, Kowa Company, Abbott Medical Japan LLC, Alnylam Japan K.K., and CMIC Holdings Co., Ltd.; speakers' bureau/honorarium from Alnylam Japan K.K., AstraZeneca K.K., Amicus Therapeutics, Inc., Amgen K.K. Edwards Lifesciences Corporation, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Tsumura & Co., Toa Eiyo Ltd., Nippon Shinyaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bayer Yakuhin Ltd., Mochida Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K.; consultation fees from AstraZeneca K.K., Novartis Pharma K.K., and Nippon Boehringer Ingelheim Co., Ltd.; and other remuneration (supervisor) from Towa Pharmaceutical Co., Ltd. The other authors have nothing to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hospitalists may work in a variety of clinical settings to manage COVID-19 cases. However, the extent of their involvement in COVID-19 care is unknown, particularly in hospitals without infectious disease (ID) specialists., Methods: This study aimed to confirm whether hospitalists provided COVID-19 management in various clinical settings when ID specialists were unavailable. We conducted a multicenter cross-sectional study using a web-based questionnaire. The participants were full-time hospitalists working in Japanese academic community-based hospitals. The study period was from 15 January 2021 to 15 February 2021, during Japan's third wave of the COVID-19 pandemic. The primary outcome was the rate of hospitalists participating in COVID-19 inpatient management in hospitals with or without ID specialists., Results: ID specialists were absent in 31% of small hospitals (those with fewer than 249 registered beds), but only 4% of large hospitals ( p  < 0.001). Hospitalists were more likely to manage both COVID-19 inpatient care and emergency department care in hospitals without than with hospitals with ID specialists (76 versus 56% ( p  = 0.01) and 90 versus 73% ( p  = 0.01), respectively). After adjusting for confounders by multivariate analysis, hospitalists who worked in hospitals without ID specialists had higher odds of participating in COVID-19 inpatient care than those who worked in hospitals with such specialists (adjusted odds ratio: 3.0, 95% CI: 1.2-7.4)., Conclusion: Hospitalists were more likely to provide COVID-19 inpatient care in various clinical settings in hospitals without ID specialists.

Tuberculous peritonitis (TB peritonitis) is one of the most challenging forms of extrapulmonary TB to diagnose. While tumor markers can be elevated in patients with TB peritonitis, FDG-PET/CT can aid in distinguishing TB peritonitis from malignancies, if an apron-like omentum pattern is seen. Laparoscopy is crucial for accurate and early diagnosis., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A 2 B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort., Methods and Results: We examined the 2-year mortality in relation to the A 2 B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A 2 B score was determined by assigning points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10-11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A 2 B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A 2 B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively)., Conclusions: The A 2 B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

Introduction: Basic fibroblast growth factor (bFGF, FGF2) and integrin α6β1 are important for maintaining the pluripotency of human pluripotent stem cells (hPSCs). Although bFGF-integrin binding contributes to biofunctions in cancer cells, the relationship in hPSCs remains unclear., Methods: To investigate the relationship between bFGF and integrin in human induced pluripotent stem cells (hiPSCs), we generated recombinant human bFGF wild-type and mutant proteins, that do not bind to integrin, FGFR, or both. We then cultured hiPSCs with these recombinant bFGF proteins. To evaluate the abilities of recombinant bFGF proteins in maintaining hPSC properties, pluripotent markers, ERK activity, and focal adhesion structure were analyzed through flow cytometry, immunofluorescence (IF), and immunoblotting (IB)., Result: We identified an interaction between bFGF and integrin α6β1 in vitro and in hiPSCs. The integrin non-binding mutant was incapable of inducing the hPSC properties, such as proliferation, ERK activity, and large focal adhesions at the edges of hiPSC colonies. Signaling induced by bFGF-FGFR binding was essential during the first 24 h after cell seeding for maintaining the properties of hPSCs, followed by a shift towards intracellular signaling via the bFGF-integrin interaction. The mixture of the two bFGF mutants also failed to maintain hPSC properties, indicating that bFGF binds to both FGFR and integrin., Conclusion: Our study demonstrates that the integrin-bFGF-FGFR ternary complex maintains the properties of hPSCs via intracellular signaling, providing insights into the functional crosstalk between bFGF and integrins in hiPSCs., Competing Interests: K. S. is a co-founder and shareholder of Matrixome, Inc. Y.T. holds a position as a Project Leader at Matrixome Inc., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Background: Several guidelines recommend the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to diagnose heart failure (HF); however, no screening criteria for measuring NT-proBNP in asymptomatic patients exist. We develop/validate a clinical prediction model for elevated NT-proBNP to support clinical outpatient decision-making., Methods: In this multicenter cohort study, we used a derivation cohort (24 facilities) from 2017 to 2021 and a validation cohort at one facility from 2020 to 2021. Patients were aged ≥65 years with at least one risk factor of HF. The primary endpoint was NT-proBNP ≥125 pg/mL. The final model was selected using backward stepwise logistic regression analysis. Diagnostic performance was evaluated for sensitivity and specificity, the area under the curve (AUC), and calibration. In total, 1645 patients (derivation cohort, n = 837; validation cohort, n = 808) were included, of whom 378 (23.0 %) had NT-proBNP ≥125 pg/mL. Body mass index, age, systolic blood pressure, estimated glomerular filtration rate, cardiothoracic ratio, and heart disease were used as predictors and aggregated into a BASE-CH score of 0-11 points., Results: Internal validation resulted in an AUC of 0.74 and an external validation AUC of 0.70., Conclusions: Based on available clinical and laboratory variables, we developed and validated a new risk score to predict NT-proBNP ≥125 pg/mL in patients at risk for HF or with pre-HF., Competing Interests: Declaration of competing interest Saito Y. received research funds from Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Bristol-Myers Squibb Company, Actelion Pharmaceuticals Japan Ltd., Kyowa Kirin Co., Ltd., Kowa Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Teijin Pharma Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nihon Medi-Physics Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., and Fuji Yakuhin Co., Ltd.; research expenses from Novartis Pharma K.K., Roche Diagnostics K.K., Amgen Inc., Bayer Yakuhin, Ltd., Astellas Pharma Inc., and Actelion Pharmaceuticals Japan Ltd.; speakers' bureau/honorarium from Alnylam Japan K.K., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Tsumura & Co., Teijin Pharma Ltd., Toa Eiyo Ltd., Nippon Shinyaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bayer Yakuhin Ltd., Pfizer Japan Inc., Bristol-Myers Squibb Company, and Mochida Pharmaceutical Co., Ltd.; and consultation fees from Ono Pharmaceutical Co., Ltd. and Novartis Pharma K.K. Masuda I. received research funds from Astra Zeneca K.K., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Nippon Boehringer Ingelheim Co., Mitsubishi Tanabe Pharma Co., Ltd.,Daiichi Sankyo Co., Ltd., Kowa Company, Ltd., MSD K.K., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., Novartis Pharma K.K., Teijin Pharma Ltd., Otsuka Pharmaceutical Co., Ltd.; and manuscript fees from OMRON HEALTHCARE Co., Ltd. The other authors have no financial conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Elastic carbon aerogels show great potential for various applications but are often hindered by structure-derived fatigue failure, weak elasticity with low compressibility, and low stress and height retention. Herein, we demonstrate a super-elastic and fatigue-resistant nanochitin-derived carbon honeycomb with honeycomb-like anisotropic microstructures and carbon-based molecular structures, which was tailored by optimizing the nanochitin concentrations and carbonization temperatures. The carbon honeycomb fabricated at a nanochitin concentration of 1.0 wt % and a carbonization temperature of 900 °C demonstrated anisotropic honeycomb channels, nanofibrous network channel walls with few cracks, and weak interactions between the carbonized nanochitin, which afforded high compressibility with up to 90% strain and complete recovery. In particular, the carbon honeycomb provided good fatigue resistance with high stress and height retentions of 87 and 94%, respectively, after more than 10,000 compression cycles at 90% strain. Moreover, the tailored anisotropic honeycomb channels and molecular structures endowed the carbon honeycomb with elasticity even under severe conditions, such as exposure to flame (approximately 1000 °C) and liquid nitrogen (approximately -196 °C). Owing to these properties, the nanochitin-derived carbon honeycomb could act as a high-sensitivity pressure sensor for a wide working pressure range of 0-185.5 kPa and ultrawide temperature range of -196-600 °C. This study can provide a promising route to develop all-biomass-derived, super-elastic, and fatigue-resistant carbon materials for pressure sensing under harsh conditions and for versatile electronic applications.

Water containing low amounts of cellulose nanofiber (CNF) is widely used as a thickening agent owing to its three unique properties: high transparency, viscosity, and controllable viscosity based on the shear rate. CNF dry powders are used to reduce the transportation and storage costs or expand applications as a thickening agent. Herein, the preparation of CNF dry powders that can be used to obtain redispersions while maintaining the aforementioned properties is reported. In this regard, the dehydration and vaporization procedures for a CNF water dispersion without using additives are discussed. When dry powders are prepared by removing water by boiling, their redispersions do not exhibit all their unique properties because of dense aggregations. However, when their redispersions are vigorously stirred to break the dense aggregations, they become transparent, although they do not recover their initial viscosity. Freeze-dried powders recover all their initial properties after redispersion. Nevertheless, their large volume does not reduce the transportation and storage costs. When the liquid is evaporated from the solvent-exchanged CNF organogels, their redispersions also fully recover all their properties. Furthermore, the evaporative dry powders with dense small volumes and good handling contribute to reducing the transportation and storage costs., (© 2023 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Optically transparent materials that are air permeable have potentially numerous applications, including in wearable devices. From the perspective of sustainable development, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibers with widths of 3-4 nm have attracted considerable attention as starting materials for the preparation of clearly transparent nanofiber paper (denoted as conventional nanopaper). However, conventional nanopaper that is prepared from a water dispersion of TEMPO-oxidized cellulose nanofibers by direct drying exhibits poor air permeability owing to its densely packed layered structure. In this study, we prepared a clearly transparent and air-permeable nanopaper by applying filtration-based solvent exchange from high-surface-tension water to low-surface-tension ethanol and hexane, followed by drying under continuous vacuum filtration. The resulting hexane-exchanged nanopaper had a porous structure with individually dispersed and thin nanofiber networks and interlayer pore spaces. Owing to the tailored porous structures, the hexane-exchanged nanopaper provides similar clear transparency (total light transmittance and haze at 600 nm: 92.9% and 7.22%, respectively) and 10 6 times higher air permeability (7.8 × 10 6 mL μm m -2 day -1 kPa -1 ) compared to the conventional nanopaper. This study will facilitate the development of clearly transparent and air-permeable nanopapers to extend their functional applications., Competing Interests: The authors declare no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Remarkable progress has been made in the development of carbonized chitin nanofiber materials for various functional applications, including solar thermal heating, owing to their N- and O-doped carbon structures and sustainable nature. Carbonization is a fascinating process for the functionalization of chitin nanofiber materials. However, conventional carbonization techniques require harmful reagents, high-temperature treatment, and time-consuming processes. Although CO 2 laser irradiation has progressed as a facile and second-scale high-speed carbonization process, CO 2 -laser-carbonized chitin nanofiber materials and their applications have not yet been explored. Herein, we demonstrate the CO 2 -laser-induced carbonization of chitin nanofiber paper (denoted as chitin nanopaper) and investigate the solar thermal heating performance of the CO 2 -laser-carbonized chitin nanopaper. While the original chitin nanopaper was inevitably burned out by CO 2 laser irradiation, CO 2 -laser-induced carbonization of the chitin nanopaper was achieved by pretreatment with calcium chloride as a combustion inhibitor. The CO 2 -laser-carbonized chitin nanopaper exhibits excellent solar thermal heating performance; its equilibrium surface temperature under 1 sun irradiation is 77.7 °C, which is higher than those of the commercial nanocarbon films and the conventionally carbonized bionanofiber papers. This study paves the way for the high-speed fabrication of carbonized chitin nanofiber materials and their application in solar thermal heating toward the effective utilization of solar energy as heat., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients., Methods and Results: We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m 2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups., Conclusions: ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups)., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Risk stratification is important in patients with acute heart failure (AHF), and a simple risk score that accurately predicts mortality is needed. The aim of this study is to develop a user-friendly risk-prediction model using a machine-learning method., Methods: A machine-learning-based risk model using least absolute shrinkage and selection operator (LASSO) regression was developed by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF), and its performance was externally validated in the validation cohort (NARA-HF) and compared with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry risk (ADHERE)., Results: In-hospital deaths in the derivation and validation cohorts were 76 (5.1 %) and 61 (4.9 %), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4 V-RS). Even though 4 V-RS comprised fewer variables, in the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; p = 0.059) and a significant improvement in net reclassification (0.359; 95 % CI, 0.10-0.67; p = 0.006). 4 V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p = 0.426) and net reclassification (0.176; 95 % CI, -0.08-0.43; p = 0.178)., Conclusions: The 4 V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF., Competing Interests: Declaration of competing interest Dr. Yuya Matsue is affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Keisuke Kida received honorariums from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. Dr. Takahiro Okumura received research honoraria from Ono Yakuhin, Otsuka, Novartis, and Astrazeneca and research grants from Ono Yakuhin, Amgen Astellas, Pfizer, Alnylam, and Alexion (not in connection with the submitted work). Dr. Yoshihiko Saito received research funds from Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Actelion Pharmaceuticals Japan Ltd., Kyowa Kirin Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nihon Medi-Physics Co., Ltd., Fuji Yakuhin Co., Ltd.; research expences from Roche Diagnostics K.K., Otsuka Pharmaceutical Co., Ltd., Terumo Corporation, Kowa Company, Abbott Medical Japan LLC, Alnylam Japan K.K. Cmic Holdings Co., Ltd.; Speakers' bureau/honorarium from Alnylam Japan K.K., AstraZeneca K.K., Amicus Therapeutics, Inc., Amgen K.K. Edwards Lifesciences Corporation, Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Kowa Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Tsumura & Co., Toa Eiyo Ltd., Nippon Shinyaku Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Bayer Yakuhin Ltd., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.; Consultation fees from AstraZeneca K.K., Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd.; Other remuneration (supervisor) from Towa Pharmaceutical Co., Ltd. The other authors have nothing to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sustainable biomass-derived carbons have attracted research interest because of their ability to effectively absorb and convert solar light to thermal energy, a phenomenon known as solar thermal heating. Although their carbon-based molecular and nanoporous structures should be customized to achieve enhanced solar thermal heating performance, such customization has insufficiently progressed. In this study, we transformed a chitin nanofiber/water dispersion into paper, referred to as chitin nanopaper, with subwavelength nanoporous structures by spatially controlled drying, followed by temperature-controlled carbonization without any pretreatment to customize the carbon-based molecular structures. The optimal carbonization temperature for enhancing the solar absorption and solar thermal heating performance of the chitin nanopaper was determined to be 400 °C. Furthermore, we observed that the nitrogen component, which afforded nitrogen-doped carbon structures, and the high morphological stability of chitin nanofibers against carbonization, which maintained subwavelength nanoporous structures even after carbonization, contributed to the improved solar absorption of the carbonized chitin nanopaper. The carbonized chitin nanopaper exhibited a higher solar thermal heating performance than the carbonized cellulose nanopaper and commercial nanocarbon materials, thus demonstrating significant potential as an excellent solar thermal material.

Background: Hypochloremia is a risk factor for poor outcomes in patients with acute heart failure (AHF). However, the changes in serum chloride levels during decongestion therapy and their impact on prognosis remain unknown., Methods: In total, 2798 patients with AHF were retrospectively studied and divided into four groups according to their admission and discharge serum chloride levels: (1) normochloremia (n=2,192, 78%); (2) treatment-associated hypochloremia, defined as admission normochloremia with a subsequent decrease (<98 mEq/L) during hospitalization (n=335, 12%); (3) resolved hypochloremia, defined as admission hypochloremia that disappeared at discharge (n=128, 5%); (4) persistent hypochloremia, defined as chloride <98 mEq/L at admission and discharge (n = 143, 5%). The primary outcome was all-cause death, and the secondary outcomes were cardiovascular death and a composite of cardiovascular death and rehospitalization for heart failure after discharge., Results: The mean age was 76 ± 12 years and 1584 (57%) patients were men. The mean left ventricular ejection fraction was 46 ± 16%. During a median follow-up period of 365 days, persistent hypochloremia was associated with an increased risk of all-cause death (adjusted hazard ratio [95% confidence interval]: 2.27 [1.53-3.37], p < 0.001), cardiovascular death (2.38 [1.46-3.87], p < 0.001), and a composite of cardiovascular death and heart failure rehospitalization (1.47 [1.06-2.06], p = 0.022). However, the outcomes were comparable between patients with resolved hypochloremia and normochloremia., Conclusions: Persistent hypochloremia was associated with worse clinical outcomes, while resolved hypochloremia and normochloremia showed a comparable prognosis. Changes in serum chloride levels can help identify patients with poor prognoses and can be used to determine subsequent treatment strategies., Competing Interests: Declaration of Competing Interest Dr. Kagiyama is affiliated with and receives a salary from a department funded by Philips Healthcare; Asahi KASEI Corporation; Inter Reha Co., Ltd.; and Toho Holdings Co., Ltd. based on collaborative research agreements. Dr. Kida received honorariums from Daichi Sankyo Co., Ono Pharmaceutical Co., Ltd., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd. Dr. Matsue received an honorarium from Otsuka Pharmaceutical Co, Novartis Japan, Bayer Inc., and AstraZeneca, and collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co and EN Otsuka Pharmaceutical Co., Ltd., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, P <0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; P <0.001]). Conclusions The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.

Background: Mitral annular calcification (MAC) is increasingly observed in elderly population. The purpose of this study was to investigate incidence of MAC and its association with mitral valvular disease (MVD)., Methods: A total of 13,483 consecutive patients who underwent echocardiography were enrolled. MAC was defined as an echo-dense, shelf-like structure with an irregular, lumpy appearance involving the mitral valve annulus, with acoustic shadowing. Prevalence of MAC and its association with significant mitral stenosis (MS) or mitral regurgitation (MR) were studied. Significant (≥moderate) MS was defined as mean transmitral valvular pressure gradient > 5 mm Hg and significant MR was defined as ≥moderate MR based on quantitative or semi-quantitative Doppler methods., Results: MAC was present in 1881 of 13,483 patients (14%). Patients with MAC (MAC group) was older and more female gender than those without MAC (non-MAC group). Significant MS was present in 2.2% of MAC and in .6% of the non-MAC group (p < 0.0001). Significant MR was present in 11.9% of MAC and in 5.0% of the non-MAC group (p < 0.0001). Co-existence of MAC and aortic valve replacement (AVR) was associated with increased prevalence of MVD (MS:11.4%, MR:17.2%, respectively)., Conclusion: MAC was present in 14% of the patients and was associated with significant MVD. Co-existence of MAC and AVR may increase the risk of MVD., (© 2021 Wiley Periodicals LLC.)

The orientation control and the formation of hierarchical structures of nanoscale components, such as bionanofibers and nanosheets, have attracted considerable research interest with the aim of achieving sophisticated functional materials. Herein, we report a simple and flexible strategy for constructing sophisticated hierarchical structures through electrophoretic and electrochemical deposition. Cellulose nanofibers (CNFs), which are used as model materials, are deposited on an anode in an aqueous dispersion and seamlessly oriented from horizontal to vertical relatively to the electrode by adjusting the applied voltage between the electrodes. The oriented CNF hydrogels not only exhibit anisotropic mechanical properties but also form complex orientations and hierarchical structures, such as cartilage- and plant stem-like configurations in response to electrode shape and applied voltage. This simple and flexible technique is expected to be applicable to various materials and contribute to a wide range of fields that include biomimicry, functional nanomaterials, and sustainable and functional moldings.

Background: Hospitalist turnover is exceedingly high, placing financial burdens on hospital medicine groups (HMGs). Following training, many begin their employment in medicine as early-career hospitalists, the majority being millennials., Objective: To understand what elements influence millennial hospitalists' recruitment and retention., Design: We developed a survey that asked participants to rate the level of importance of 18 elements (4-point Likert scale) in their decision to choose or remain at an HMG., Participants: The survey was electronically distributed to hospitalists born in or after 1982 across 7 HMGs in the USA., Main Measures: Elements were grouped into four major categories: culture of practice, work-life balance, financial considerations, and career advancement. We calculated the means for all 18 elements reported as important across the sample. We then calculated means by averaging elements within each category. We used unpaired t-tests to compare differences in means for categories for choosing vs. remaining at an HMG., Key Results: One hundred forty-four of 235 hospitalists (61%) responded to the survey. 49.6% were females. Culture of practice category was the most frequently rated as important for choosing (mean 96%, SD 12%) and remaining (mean 96%, SD 13%) at an HMG. The category least frequently rated as important for both choosing (mean 69%, SD 35%) and remaining (mean 76%, SD 32%) at an HMG was career advancement. There were no significant differences between respondent gender, race, or parental status and ratings of elements for choosing or remaining with HMGs., Conclusion: Culture of practice at an HMG may be highly important in influencing millennial hospitalists' decision to choose and stay at an HMG. HMGs can implement strategies to create a millennial-friendly culture which may help improve recruitment and retention., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45-0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF., (© 2022. The Author(s).)

Semiconducting nanomaterials with 3D network structures exhibit various fascinating properties such as electrical conduction, high permeability, and large surface areas, which are beneficial for adsorption, separation, and sensing applications. However, research on these materials is substantially restricted by the limited trans-scalability of their structural design and tunability of electrical conductivity. To overcome this challenge, a pyrolyzed cellulose nanofiber paper (CNP) semiconductor with a 3D network structure is proposed. Its nano-micro-macro trans-scale structural design is achieved by a combination of iodine-mediated morphology-retaining pyrolysis with spatially controlled drying of a cellulose nanofiber dispersion and paper-crafting techniques, such as microembossing, origami , and kirigami . The electrical conduction of this semiconductor is widely and systematically tuned, via the temperature-controlled progressive pyrolysis of CNP, from insulating (10 12 Ω cm) to quasimetallic (10 -2 Ω cm), which considerably exceeds that attained in other previously reported nanomaterials with 3D networks. The pyrolyzed CNP semiconductor provides not only the tailorable functionality for applications ranging from water-vapor-selective sensors to enzymatic biofuel cell electrodes but also the designability of macroscopic device configurations for stretchable and wearable applications. This study provides a pathway to realize structurally and functionally designable semiconducting nanomaterials and all-nanocellulose semiconducting technology for diverse electronics.

Aims: Acute heart failure (AHF) is a clinical syndrome with a poor prognosis and a major public health concern worldwide. The aim of this study was to investigate whether carperitide administration improves the 1 year prognosis of patients with AHF and to check whether there is an optimal dose of the drug., Methods and Results: We analysed the data of COOPERATE-HF-J (the Consortium for Pooled Data Analysis regarding Hospitalized Patients with Heart Failure in Japan), combining two cohorts (NARA-HF and REALITY-AHF), which included 2435 patients with acute decompensated heart failure. The patients were divided into no carperitide (NO-ANP, n = 1098); very low-dose carperitide (VLD-ANP, <0.02 μg/kg/min, n = 593); and low-dose carperitide groups (LD-ANP, ≥0.02 μg/kg/min, n = 744). The primary endpoint was cardiovascular mortality within 1 year after admission. The secondary endpoints were all-cause mortality and rehospitalization due to worsening heart failure within 1 year after admission. The median carperitide doses in the VLD-ANP and LD-ANP groups were 0.013 and 0.025 μg/kg/min, respectively. Kaplan-Meier analysis showed that cardiovascular mortality and all-cause mortality were significantly lower in the LD-ANP group than in the NO-ANP and VLD-ANP groups (P < 0.001 and P = 0.002, respectively). Multivariable Cox regression analysis for cardiovascular and all-cause mortality revealed that LD-ANP was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission, even after adjusting other covariates (hazard ratio: 0.696 and 0.791, 95% confidence interval: 0.513-0.944 and 0.628-0.997, P = 0.020 and 0.047, respectively)., Conclusions: Low-dose carperitide was significantly associated with lower cardiovascular and all-cause mortality within 1 year after admission. Our results suggest the necessity for well-designed randomized controlled trials to determine the doses of carperitide that could improve clinical outcomes in patients with AHF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as <98 mmol/L. The external validation and comparison of model performance were performed in an independent group of 1,256 patients with AHF (validation cohort). All models were tested for in-hospital mortality. Hypochloremia was observed in 9.4% and 12.2% of the derivation and validation cohorts, respectively. Hypochloremia was an independent predictor of in-hospital mortality in the derivation cohort (odds ratio 2.02; p = 0.028). In the validation cohort, the GWTG-HF, GWTG-BNP, and GWTG-BNP-Cl risk scores demonstrated good discrimination (area under the curve: 0.742, 0.749, and 0.763, respectively). However, the GWTG-BNP-Cl risk score was more reliable than the GWTG-HF and GWTG-BNP risk scores in risk reclassification (net reclassification improvement: 0.491 and 0.408, respectively; p <0.01 for both). Moreover, this score demonstrated a good calibration of the GWTG-BNP-Cl model (Hosmer-Lemeshow test: p = 0.479). In conclusion, incorporating hypochloremia into the preexisting risk model improves the model performance., Competing Interests: Disclosures Dr. Yuya Matsue is affiliated to a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi and received an honorarium from Otsuka Pharmaceutical Co and Novartis Japan. Dr. Takahiro Okumura received research grants from Ono Pharmaceutical Co., Ltd., Bayer Pharmaceutical Co., Ltd., Daiichi-Sankyo Pharma Inc., and Amgen Astellas BioPharma K.K. outside the submitted work, and received honorariums from Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., and Medtronic Japan Co., Ltd. The other authors have no conlicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biomass-derived three-dimensional (3D) porous nanocarbons have attracted much attention due to their high surface area, permeability, electrical conductivity, and renewability, which are beneficial for various electronic applications, including energy storage. Cellulose, the most abundant and renewable carbohydrate polymer on earth, is a promising precursor to fabricate 3D porous nanocarbons by pyrolysis. However, the pyrolysis of cellulosic materials inevitably causes drastic carbon loss and volume shrinkage. Thus, polydopamine doping prior to the pyrolysis of cellulose nanofiber paper is proposed to fabricate the 3D porous nanocarbons with improved yield and volume retention. Our results show that a small amount of polydopamine (4.3 wt%) improves carbon yield and volume retention after pyrolysis at 700 °C from 16.8 to 26.4% and 15.0 to 19.6%, respectively. The pyrolyzed polydopamine-doped cellulose nanofiber paper has a larger specific surface area and electrical conductivity than cellulose nanofiber paper that without polydopamine. Owing to these features, it also affords a good specific capacitance up to 200 F g -1 as a supercapacitor electrode, which is higher than the recently reported cellulose-derived nanocarbons. This method provides a pathway for the effective fabrication of high-performance cellulose-derived 3D porous nanocarbons.

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group ( P <0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P =0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m 2 , interaction P =0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.

Rationale: Malignant infiltration accounts for 0.5% of acute liver failure cases, with non-Hodgkin's lymphoma the predominant cause. Adult T-cell lymphoma/leukemia (ATLL) is a rarer source of acute hepatitis, with only 3 cases reported and all resulting in immediate deterioration with death. ATLL rises from human T-lymphocytic virus-1 (HTLV-1), commonly found in Japan (southern and northern islands), the Caribbean, Central and South America, intertropical Africa, Romania, and northern Iran. In Micronesia, HTLV-1 infection amongst native-born is absent or exceedingly rare., Patient Concerns: A 77-year-old Marshallese man presented to the emergency department with a 1-week history of generalized weakness, fatigue, and nausea. The physical exam revealed a cervical papulonodular exanthem and scleral icterus., Diagnosis: Laboratory studies were remarkable for aspartate-aminotransferase of 230 IU/L (reference range [RR]: 0-40), alanine-aminotransferase of 227 IU/L (RR: 0-41), alkaline phosphatase of 133 IU/L (RR: 35-129), and total bilirubin of 4.7 mg/dL (RR: 0-1.2), supporting acute liver injury. Platelet count was 11.6x104/μL (RR: 15.1-42.4 × 104), hemoglobin was 13.8 g/dL (RR: 13.7-17.5), and white blood cell count was 7570/μL (RR: 3800-10,800) with 81.8% neutrophils (RR: 34.0-72.0) and 10.4% lymphocytes (RR: 12.0-44.0). The peripheral blood smear demonstrated abnormal lymphocytes with occasional flower cell morphology. HTLV-1/2 antibody tested positive. The skin and liver biopsies confirmed atypical T-cell infiltrate. The diagnosis of ATLL was established., Interventions: The patient elected for palliative chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP). He began antiviral treatment with zidovudine 250 mg bis in die (BID) indefinitely. Ursodiol and cholestyramine were added for his hyperbilirubinemia., Outcomes: Four weeks from admission, the patient returned to near baseline functional status and was discharged home., Lessons: This case highlights that ATLL can initially present as isolated acute hepatitis, and how careful examination of peripheral blood-smear may elucidate hepatitis etiology. We also present support for utilizing ursodiol with cholestyramine for treating a hyperbilirubinemia. Moreover, unlike prior reports of ATLL presenting as liver dysfunction, combined antiviral and CVP chemotherapy was effective in this case. Lastly, there are seldom demographic reports of HTLV-1 infection from the Micronesian area, and our case represents the first indexed case of HTLV-1-associated-ATLL presenting as acute liver failure in a Marshallese patient., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR., Competing Interests: None., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Chitin, a natural polysaccharide polymer, forms highly crystalline nanofibers and is expected to have sophisticated engineering applications. In particular, for development of next-generation heat-transfer and heat-insulating materials, analysis of the thermal conductivity is important, but the thermal conductivity properties of chitin nanofiber materials have not been reported. The thermal conductivity properties of chitin nanofiber materials are difficult to elucidate without excluding the effect of adsorbed water and analyzing the influence of surface amino groups. In this study, we aimed to accurately evaluate the thermal conductivity properties of chitin nanofiber films by changing the content of surface amino groups and measuring the thermal diffusivity under dry conditions. Chitin and deacetylated-chitin nanofiber films with surface deacetylation of 5.8% and 25.1% showed in-plane thermal conductivity of 0.82 and 0.73 W/mK, respectively. Taking into account that the films had similar crystalline structures and almost the same moisture contents, the difference in the thermal conductivity was concluded to only depend on the amino group content on the fiber surfaces. Our methodology for measuring the thermal diffusivity under conditioned humidity will pave the way for more accurate analysis of the thermal conductivity performance of hydrophilic materials.

Objective: Pulmonary arterial hypertension is characterized by abnormal proliferation of pulmonary artery smooth muscle cells and vascular remodeling, which leads to right ventricular (RV) failure. Bsg (Basigin) is a transmembrane glycoprotein that promotes myofibroblast differentiation, cell proliferation, and matrix metalloproteinase activation. CyPA (cyclophilin A) binds to its receptor Bsg and promotes pulmonary artery smooth muscle cell proliferation and inflammatory cell recruitment. We previously reported that Bsg promotes cardiac fibrosis and failure in the left ventricle in response to pressure-overload in mice. However, the roles of Bsg and CyPA in RV failure remain to be elucidated. Approach and Results: First, we found that protein levels of Bsg and CyPA were upregulated in the heart of hypoxia-induced pulmonary hypertension (PH) in mice and monocrotaline-induced PH in rats. Furthermore, cardiomyocyte-specific Bsg-overexpressing mice showed exacerbated RV hypertrophy, fibrosis, and dysfunction compared with their littermates under chronic hypoxia and pulmonary artery banding. Treatment with celastrol, which we identified as a suppressor of Bsg and CyPA by drug screening, decreased proliferation, reactive oxygen species, and inflammatory cytokines in pulmonary artery smooth muscle cells. Furthermore, celastrol treatment ameliorated RV systolic pressure, hypertrophy, fibrosis, and dysfunction in hypoxia-induced PH in mice and SU5416/hypoxia-induced PH in rats with reduced Bsg, CyPA, and inflammatory cytokines in the hearts and lungs., Conclusions: These results indicate that elevated Bsg in pressure-overloaded RV exacerbates RV dysfunction and that celastrol ameliorates RV dysfunction in PH model animals by suppressing Bsg and its ligand CyPA. Thus, celastrol can be a novel drug for PH and RV failure that targets Bsg and CyPA. Graphic Abstract: A graphic abstract is available for this article.

We propose a new methodology for direct evaluation of the degree of fibrillation of fibrillating pulp suspensions through the pixel-resolved retardation distribution. Through simple normalization by just injecting a pulp suspension with a certain concentration into a quartz flow channel with a constant cross-sectional shape, the degree of fibrillation (i.e., the degree of bundling of cellulose molecular chains) can be directly mapped by the retardation gradation, reflecting locally high retardation (pulp fibers), smaller retardation (balloons on fibrillating pulps), and much smaller retardation close to water (dispersed nanofibers). Both the average retardation and standard deviation are found to be the direct indicators of the degree of fibrillation. We envision that the proposed methodology will become the future standard for determining the degree of fibrillation by the retardation distribution, and it will pave the way for more precise control of pulp fibrillation and more sophisticated applications of cellulose nanofiber suspensions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Iron is an essential trace element in the body. However, in heart failure (HF), iron is only recognized as the cause of anemia. Actually, iron itself affects myocardial exercise tolerance and cardiac function via mitochondrial function. Therefore, it is necessary to clarify the pathological significance of iron in acute HF, irrespective of concomitant anemia. We investigated the impact of serum iron level at discharge on the prognosis of 615 patients emergently admitted with acute decompensated HF (ADHF). Patients were divided into two groups according to the median level of serum iron (62 µg/dL). The endpoint was the composite outcome, which included all-cause mortality and readmission for HF. During the mean follow-up period of 32.1 months, there were 333 events. Kaplan-Meier analysis showed that the incidence of the composite outcome was significantly higher in the Low iron group (P < 0.0001). In the multivariate analysis adjusted with factors including hemoglobin and ferritin levels, low serum iron was an independent predictor for the composite outcome (hazard ratio, 1.500; 95% confidence interval, 1.128-1.976; P = 0.0044). Low serum iron was an independent predictor of poor prognosis in ADHF, irrespective of hemoglobin or ferritin level, providing a new concept that iron may play a role in the pathophysiology of ADHF via non-hematopoietic roles.

As a renewable nanomaterial, transparent nanopaper is one of the promising materials for electronic devices. Although conventional evaporation drying method endows nanopaper with superior optical properties, the long fabrication time limits its widely use. In this work, we propose a multi-stage drying method to achieve high-speed fabrication of clear transparent nanopaper. Drying experiments reveal that nanopaper's drying process can be separated into two periods. For the conventional single-stage evaporation drying, the drying condition is kept the same. In our newly proposed multi-stage drying, the relative humidity (RH), which is the key parameter for both drying time and haze, is set differently during these two periods. Applying this method in a humidity-controllable environmental chamber, the drying time can be shortened by 35% (from 11.7 h to 7.6 h) while maintaining the same haze level as that from single-stage drying. For a conventional humidity-uncontrollable oven, a special air flow system is added. The air flow system enables decrease of RH by removing water vapor at the water/air interface during the earlier period, thus fabricating clear transparent nanopaper in a relatively short time. Therefore, this humidity-controlled multi-stage drying method will help reduce the manufacturing time and encourage the widespread use of future nanopaper-based flexible electronics.

Background: Takotsubo cardiomyopathy (TC) is characterized as a transient segmental cardiac dysfunction mimicking acute coronary syndrome triggered by emotional or physical stress. Although neurological disorders, infection, malignant diseases, trauma and surgery are known triggers for the development of TC, role of cardiac diseases as underlying conditions for the development of TC is uncertain. The aim of this study was to investigate incidence and clinical characteristics of TC among critically ill cardiac disease patients and to verify that TC may coexist with other cardiac diseases., Methods: Between November, 2015 and September, 2017, 862 echocardiographic examinations were recorded from 413 patients who were admitted to the CCU. All echo images, electrocardiograms as well as medical records were reviewed. TC was diagnosed according to the modified Mayo criteria., Results: Takotsubo cardiomyopathy was diagnosed in 29 of 413 patients (7%). TC was a primary diagnosis in 18 patients (group P) and the other 11 patients (group S) were not diagnosed as TC during the CCU stay. Primary diagnosis of these patients was acute myocardial infarction (n = 5), acute decompensated heart failure (two aortic stenosis, one cardiac amyloidosis, and two tachycardia induced cardiomyopathy), and ventricular tachycardia (n = 1)., Conclusion: Takotsubo cardiomyopathy may develop in critically ill cardiac diseases but are often underdiagnosed. Careful echocardiographic examination is needed to unveil these "hidden" TC.

It is essential to build multiaxis oriented nanocellulose films in the plane for developing thermal or optical management films. However, using conventional orientation techniques, it is difficult to align nanocelluloses in multiple directions within the plane of single films rather than in the thickness direction like the chiral nematic structure. In this study, we developed the liquid-phase three-dimensional (3D) patterning technique by combining wet spinning and 3D printing. Using this technique, we produced a checkered film with multiaxis oriented nanocelluloses. This film showed similar retardation levels, but with orthogonal molecular axis orientations in each checkered domain as programmed. The thermal transport was enhanced in the domain with the oriented pattern parallel to the heat flow. This liquid-phase 3D patterning technique could pave the way for bottom-up design of differently aligned nanocellulose films to develop sophisticated optical and thermal materials.