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Introduction: This study evaluated constipation, including reduced bowel movement frequency and difficult defecation, in patients with isolated rapid eye movement sleep behavior disorder (IRBD), which is prodromal Parkinson's disease (PD) or dementia with Lewy bodies (DLB) in middle-aged and older adults., Methods: We used a validated Japanese version of the Constipation Assessment Scale (CAS-J) to evaluate bowel habits over 1 month in 117 men aged 50-86 years and 34 women aged 56-86 years with video-polysomnography-confirmed IRBD and 22 controls. Furthermore, we performed a longitudinal assessment of outcomes at follow-up visits., Results: The CAS-J score was higher in the 22 IRBD patients than in 22 age- and gender-matched paired controls. In 151 IRBD patients, the CAS-J score was higher for women than for men. At baseline, the CAS-J score was similar between patients who developed PD and DLB, but the three IRBD patients who developed multiple system atrophy had a low CAS-J score. Those with constipation (CAS-J score ≥ 2) converted to PD or DLB in a significantly shorter time duration (i.e., time frame for phenoconversion) than those with CAS-J score < 2 (log-rank test, p < 0.001). When adjusted for age and gender, Cox hazards analysis revealed that the CAS-J score significantly predicted phenoconversion to PD or DLB (hazard ratio: 5.9, 95 % confidence interval: 1.8-19.1, p = 0.003)., Conclusions: Constipation, i.e., reduced bowel movement frequency and difficult defecation, was common in middle-aged and elderly patients with IRBD, and CAS-J score predicted phenoconversion to PD or DLB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

An earthquake with a moment magnitude of 7.5 (Mw) struck the northern Noto Peninsula, Ishikawa Prefecture, Japan, at 16:10 local time on January 1, 2024. This earthquake triggered a tsunami that propagated along the coastline of Ishikawa, Toyama, and Niigata Prefectures facing the Sea of Japan and significantly damaged coastal communities and infrastructure. Approximately 70 researchers from 23 universities or other institutes throughout Japan formed a joint research group to conduct a post-tsunami survey along a 340 km stretch of the coast. Based on the watermarks and traces of the tsunami, the inundation and run-up heights were surveyed using total stations, automatic optical levels, laser range finders, and a real-time kinematic (RTK) Global Navigation Satellite System (GNSS). The tidal correction was adjusted using astronomical tidal tables. In total, 303 survey records have been compiled, generating the NP2024TS (Noto Peninsula 2024 Tsunami Survey) dataset. This dataset provides comprehensive information on the inundation and run-up heights of the tsunami, which is useful for understanding tsunami characteristics and validating numerical tsunami models., (© 2024. The Author(s).)

Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFβ1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nakajima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a key component for next-generation wireless communications (6 G and beyond), terahertz (THz) electronic oscillators are being actively developed. Precise and dynamic phase control of ultrafast THz waveforms is essential for high-speed beam steering and high-capacity data transmission. However, measurement and control of such ultrafast dynamic process is beyond the scope of electronics due to the limited bandwidth of the electronic equipment. Here we surpass this limit by applying photonic technology. Using a femtosecond laser, we generate offset-free THz pulses to phase-lock the electronic oscillators based on resonant tunneling diode. This enables us to perform phase-resolved measurement of the emitted THz electric field waveform in time-domain with sub-cycle time resolution. Ultrafast dynamic response such as anti-phase locking behaviour is observed, which is distinct from in-phase stimulated emission observed in laser oscillators. We also show that the dynamics follows the universal synchronization theory for limit cycle oscillators. This provides a basic guideline for dynamic phase control of THz electronic oscillators, enabling many key performance indicators to be achieved in the new era of 6 G and beyond., (© 2024. The Author(s).)

Background: This study investigated whether the chronic use of adaptive servo-ventilation (ASV) reduces all-cause mortality and the rate of urgent rehospitalization in patients with heart failure (HF)., Methods and results: This multicenter prospective observational study enrolled patients hospitalized for HF in Japan between 2019 and 2020 who were treated either with or without ASV therapy. Of 845 patients, 110 (13%) received chronic ASV at hospital discharge. The primary outcome was a composite of all-cause death and urgent rehospitalization for HF, and was observed in 272 patients over a 1-year follow-up. Following 1:3 sequential propensity score matching, 384 patients were included in the subsequent analysis. The median time to the primary outcome was significantly shorter in the ASV than in non-ASV group (19.7 vs. 34.4 weeks; P=0.013). In contrast, there was no significant difference in the all-cause mortality event-free rate between the 2 groups., Conclusions: Chronic use of ASV did not impact all-cause mortality in patients experiencing recurrent admissions for HF.

White adipose tissue (WAT) is critical for whole-body energy metabolism, and its dysfunction leads to various metabolic disorders. In recent years, many studies have suggested that impaired mitochondria may contribute to obesity-related decline in adipose tissue function, but the detailed mechanisms remain unclear. To investigate these mechanisms, we carried out a comprehensive analysis of WAT from mice with diet-induced obesity. We discovered the transcription factor Parkin interactive substrate (PARIS or ZNF746), which suppresses the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key regulator of mitochondrial biogenesis, to be accumulated in adipose progenitor cells from obese mice. Furthermore, we demonstrated that 3T3-L1 preadipocytes with overexpression of PARIS protein exhibited decreased mitochondrial biogenesis and impaired adipogenesis. Our results suggest that the accumulation of PARIS protein may be a novel component in the pathogenesis of obesity-related dysfunction in WAT., (© 2023. The Author(s).)

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m 2 with azilsartan vs 1.4 mL/m 2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required., (© 2023. The Author(s).)

Background: Myostatin is a negative regulator of skeletal muscle mass. On the other hand, growth differentiation factor (GDF)-15 is associated with lower muscle strength and muscle mass. We investigated the relationship between serum GDF-15, myostatin, and sarcopenia in patients receiving cardiovascular surgery through a ROC curve and a multivariate regression analysis., Methods: Skeletal muscle mass index (SMI) by bioelectrical impedance analysis, hand-grip strength, knee extension strength, and walking speed were measured. Preoperative serum GDF-15 and myostatin levels were determined by ELISA. The sarcopenia index could be expressed as: -0.0042 × [myostatin] + 0.0007 × [GDF-15] + 0.0890 × age + 1.4030 × sex - 0.2679 × body mass index (BMI) - 2.1186. A ROC curve was plotted to identify the optimal cutoff level of the sarcopenia index to detect sarcopenia., Results: 120 patients receiving cardiovascular surgery were included in the study. SMI, hand-grip strength, knee extension strength, and walking speed inversely correlated with GDF-15, but positively correlated with myostatin. In the multivariate stepwise regression analysis, SMI was a determinant of myostatin, and both GDF-15 and myostatin were determinants of SMI and muscle thickness, even after adjustment for age, sex, and BMI. A ROC curve showed that the sarcopenia index was a determinant of sarcopenia (cutoff value -1.0634, area under the curve 0.901, sensitivity 96.9%, specificity 70.9%)., Conclusion: GDF-15 and myostatin are associated with skeletal muscle volume in patients receiving cardiovascular surgery, but these associations are different. The sarcopenia index calculated from GDF-15 and myostatin levels may be a biomarker of sarcopenia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: Recent reports have shown laparoscopic gastric devascularization and splenectomy (Hassab's procedure) to be a safe and effective treatment for esophagogastric varices with portal hypertension. However, the long-term postoperative results remain unclear., Methods: Between 2009 and 2015, 17 patients with portal hypertension and esophagogastric varices underwent laparoscopic Hassab's procedure at our institution. Two patients were lost to long-term follow-up (at least 2 years) and excluded. The remaining 15 patients' data and endoscopic findings were retrospectively reviewed., Results: The median postoperative follow-up period was 56 months. The median spleen volume, operation time, blood loss, and length of postoperative hospital stay were 651 (320-1,265) mL, 305 (275-547) minutes, 347 (24-1,131) mL, and 20 (8-41) days, respectively. According to the endoscopic findings 1 year after surgery, the esophagogastric varices disappeared in three patients and improved in 12 patients. The median platelet count was significantly higher 1 year after surgery (19.7 × 10 4 /dL) than before surgery (5.5 × 10 4 /dL) (P < .001) and remained stable 2 years after surgery. Two patients died of liver disease. The remaining 13 patients, with a median postoperative follow-up of 57 months, were alive without bleeding from esophagogastric varices., Conclusion: Laparoscopic Hassab's procedure is a feasible treatment for esophagogastric varices with portal hypertension in terms of both short- and long-term results., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Adiponectin (APN), a major adipokine secreted from white adipose tissue, prevents inflammation and improves insulin sensitivity. APN exists as distinct multimeric complexes with different physiological activities, including low, middle and high molecular weight complexes (LMW, MMW and HMW, respectively) in peripheral blood. Caloric restriction (CR), an intervention that suppresses aging-related pathophysiological changes and extends lifespan, reportedly elevates the expression levels of Adipoq (encoding APN) and total circulating APN. Circulating APN levels have generally been measured using ELISA, but ELISA fails to directly and separately detect APN multimeric complexes other than HMW. Here, we aimed to evaluate the association of aging and CR with oligomerization of APN in rodent models, using immunoblotting to distinguish multimeric complexes based on molecular sizes. In mice, aging elevated plasma levels of HMW and MMW, while CR only elevated HMW. In contrast, LMW and monomeric APN levels were unchanged, suggesting that aging and CR can induce the assembly of APN oligomers in adipocytes. In rats, plasma levels of all multimeric complexes and monomeric APN were not significantly changed by aging or CR. Collectively, levels of circulating APN in mice were consistent with previous findings, whereas those of rats were partially inconsistent, probably because of experimental differences. Moreover, aging reduced Adipoq mRNA levels in mice and rats, while CR prevented this reduction only in rats. Such a discrepancy between Adipoq expression and circulating APN levels may be attributed to proteasomal regulation in adipocytes or tissue accumulation of APN. In conclusion, this study provides new findings of aging- and CR-related changes of each APN multimeric complex and underscores the importance of qualitative approaches for a greater understanding of physiological changes in APN., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Optical frequency combs in the terahertz frequency range are long-awaited frequency standards for spectroscopy of molecules and high-speed wireless communications. However, a terahertz frequency comb based on a low-cost, energy-efficient, and room-temperature-operating device remains unavailable especially in the frequency range of 0.1 to 3 THz. In this paper, we show that the resonant-tunneling-diode (RTD) oscillator can be passively mode-locked by optical feedback and generate a terahertz frequency comb. The standard deviation of the spacing between the comb lines, i.e., the repetition frequency, is reduced to less than 420 mHz by applying external bias modulation. A simulation model successfully reproduces the mode-locking behavior by including the nonlinear capacitance of RTD and multiple optical feedback. Since the mode-locked RTD oscillator is a simple semiconductor device that operates at room temperature and covers the frequency range of 0.1 to 2 THz (potentially up to 3 THz), it can be used as a frequency standard for future terahertz sensing and wireless communications., (© 2022. The Author(s).)

In this work, we present a simple method to improve the spatial uniformity of two-dimensional electro-optical imaging of terahertz (THz) beams. In this system, near-field THz images are captured by fully illuminating a sample using conventional optical microscope objectives. Unfortunately, due to the linear relationship between the optical probe power and the measured THz electric field, any spatial variation in probe intensity translates directly into a variation of the recorded THz electric field. Using a single normalized background frame information map as a calibration tool prior to recording a sequence of THz images, we show a full recovery of a two-dimensional flat field for various combinations of magnification factors. Our results suggest that the implementation of dynamic intensity profile correction is a promising avenue for real-time electro-optical imaging of THz beams.

Background: The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol., Methods and Results: The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group., Conclusions: Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Sanwa Kagaku Kenkyusho Co., Ltd. provided funding for this study in the form of a research grant awarded to the Dokkyo Medical University. The authors would like to declare the following marketed products associated with this research: Uriadec Tablets by Sanwa Kagaku Kenkyusho Co., Ltd., or Topiloric Tablets by Fuji Yakuhin Co., Ltd. as topiroxostat and Zyloric tablets by Pfizer Japan Inc. and its generic drug as allopurinol. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other patents, products in development or marketed products associated with this research to declare.

The tsunami caused by the Tonga submarine volcanic eruption that occurred at 13:15 Japan Time (JST) on January 15, 2022, exposed a blind spot in Japan's tsunami monitoring and warning system, which was established in 1952 for local tsunamis and expanded to distant tsunamis after the 1960 Chile tsunami. This paper summarizes how the warning system responded to the unprecedented tsunami, the actual evacuation process, and the damage it caused in Japan. Initially, the tsunami from the volcanic eruption was expected to arrive at approximately midnight with amplitudes of less than 20 cm. However, a series of short waves arrived at approximately 21:00, a few hours earlier than expected. The early arrival of these sea waves coincided with a rapid increase in atmospheric pressure; then, the short-period component was predominant, and the wave height was amplified while forming wave groups. After a 1.2 m tsunami was observed in Amami City in southern Japan at 23:55 JST, the Japan Meteorological Agency issued a tsunami warning/advisory. The tsunami continued, and all advisories were cleared at 14:00 JST on January 16. Information about this tsunami and the response to it are summarized here, including the characteristics and issues of the actual tsunami evacuation situation in each region. There were no casualties, but the issues that emerged included difficulty evacuating on a winter night and traffic congestion due to evacuation by car and under the conditions of the COVID-19 pandemic. In the coastal area, damage to fishing boats and aquaculture facilities was reported due to the flow of the tsunami. In addition, damage to aquaculture facilities, including those producing oysters, scallops, seaweed and other marine products, decreased the supply of marine products, and the economic impact is likely to increase in the future., Competing Interests: Conflict of interestThe authors have not disclosed any competing interests., (© The Author(s) 2022.)