After 2010, the source model of the microSelectron HDR Afterloader System was slightly modified from the previous model. Granero et al. named the modified source model "mHDR-v2r (revised model ...mHDR-v2)" and the previous model "mHDR-v2". They concluded that the dosimetric differences arising from the dimensional changes between the mHDR-v2 and mHDR-v2r designs were negligible at almost all locations (within 0.5% for r ≥ 0.25 cm), the two-dimensional anisotropy function difference between the two sources is found 2.1% at r = 1.0 cm when compared with the results of the other experimental group. To confirm this difference, we performed a full Monte Carlo simulation without energy-fluence approximation. This is useful near the radiation source where charged-particle equilibrium does not hold. The two-dimensional anisotropy function of the TG-43U1 dataset showed a few percent difference between the mHDR-v2r and mHDR-v2 sources. There was no agreement in the immediate vicinity of the source (0.10 cm and 0.25 cm), when compared to Granero et al. in mHDR-v2r sources. The differences in these two-dimensional anisotropy functions were identified.
We developed a method to detect attenuation changes during seismic wave propagation excited by precisely controlled artificial seismic sources, namely Accurately Controlled Routinely Operated Signal ...System (ACROSS), and applied it to monitor the temporal changes for in situ data collected by previous studies. Our method, together with the use of the ACROSS sources, is less susceptible to noise level changes, from which conventional methods such as envelope calculation suffer. The method utilizes the noise level that is independently estimated in the frequency domain and eliminates the influence of the noise from the observed signal. For performance testing, we applied this method to a dataset that was obtained in an experiment at Awaji Island, Japan, from 2000 to 2001. We detected a change in amplitude caused by rainfall, variation in atmospheric temperature, and coseismic ground motions. Among them, coseismic changes are of particular interest because there are limited studies on coseismic attenuation change, in contrast to many studies on coseismic velocity decrease. At the 2000 Western Tottori earthquake (
M
W
= 6.6, epicenter distance of 165 km), a sudden decrease in amplitude of up to 5% was observed. The coseismic amplitude reduction and its anisotropic characteristics, which showed a larger reduction in the direction of the major axis of velocity decrease, were consistent with the opening of fluid-filled cracks, as proposed by previous studies. The
Δ
Q
-
1
corresponding to the amplitude change gives similar values to those reported in previous studies using natural earthquakes.
Graphical Abstract
We analyze temporal variations in the travel times of both P and S waves (Vp and Vs) for 14 months at Toyohashi (central Japan) with a continuously operating vibration source that could efficiently ...produce both P and S waves. Seismic waves produced by the source, which is called the accurately controlled routinely operated signal system (ACROSS), are recorded by three nearby seismic stations, and the travel time variation at each station is estimated using the transfer function calculated from the recorded data. Long-term variations in Vp and Vs are observed and can be interpreted by the change in fluid saturation and crack density of the subsurface rocks. The variation in fluid saturation and crack density are consistent with that in the groundwater level, which is measured at the station nearest to the ACROSS. Short-term responses to rainfalls are observed at the station nearest to the ACROSS system; the interpretation of the changes in crack density and saturation is inconsistent with the ground water observation, partly owing to the initial response to rainfall. This can be interpreted as an air–water mixture within pores or cracks on a fine scale.
In this study, geodetic and seismic phenomena occurring in the subduction zone were observed with two tiltmeters that were installed in seafloor boreholes drilled in the Kumano Basin in the Nankai ...Trough, southwest Japan. We used one electrolytic-type tiltmeter and one pendulum-type tiltmeter installed 6 and 19 m below the seafloor, respectively. The two tiltmeters have been continuously operated since 2019 and 2021, respectively. The records of the two tiltmeters showed microseisms, seismic signals of normal earthquakes, and variations that correlated well with the M2 tide (tidal response). The noise environment relative to existing seafloor observatories was assessed by comparing the power spectral densities of the tiltmeters and broadband seismometers in the seismic frequency band. The two tiltmeters and the seismometers showed similar spectral peaks in the microseism band, and at lower frequencies below 10
–2
Hz, the pendulum tiltmeter had a noise level that was up to 20 dB lower than that of the broadband seismometers. The tidal responses of the tiltmeters were analyzed to reveal corresponding mechanisms because a large amplitude of the tidal response makes it difficult to detect geodetic phenomena. Considerable azimuthal dependence was observed in the NW–SE direction for both tiltmeters. The principal direction was approximately the same as the down-slope direction of the local bathymetry. This tendency was thus interpreted to be caused by the differences in the thickness of the sedimentary layer along the direction of the slope. Furthermore, the validity of the tilt measurements for the two tiltmeters was demonstrated by in-situ loading experiments, where the theoretical response of an elastic half-space medium was computed and compared with the experimental results. The results of the loading experiments can be explained using theoretical values with a set of realistic elastic moduli.
Graphical Abstract
Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive ...thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33
mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33
dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)
receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33
DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
Recently, advances in genomic technology such as RNA sequencing and genome‐wide profiling have enabled the identification of considerable numbers of non‐coding RNAs (ncRNAs). MicroRNAs have been ...studied for decades, leading to the identification of those with disease‐causing and/or protective effects in vascular disease. Although other ncRNAs such as long ncRNAs have not been fully described yet, recent studies have indicated their important functions in the development of vascular diseases. Here, we summarize the current understanding of the mechanisms and functions of ncRNAs, focusing on microRNAs, circular RNAs and long ncRNAs in vascular diseases.
Considerable numbers of non‐coding RNAs have been identified by RNA sequencing and genome‐wide profiling. These include microRNAs studied for decades and other non‐coding RNAs (ncRNAs) such as long ncRNAs. Recent studies have indicated their important functions in the development of vascular diseases. Here, we summarize the current understanding of the mechanisms and functions of these ncRNAs.
•Compared to controls, in chronic heart failure patients, skeletal muscle mass index and fat mass index decreased.•There was significant difference in serum amino acid concentration between two ...groups.•Skeletal muscle index correlated with serum amino acid concentration.
Loss of skeletal muscle mass and low nutritional status are major complications of severe chronic heart failure (CHF) and have been associated with poor prognosis. This study aimed to identify the nutritional status of outpatients with CHF based on their body composition, such as skeletal muscle index (SMI) and serum amino acid concentration.
We compared the body composition data and results of blood samples, including the serum amino acid concentration, of patients with CHF and those of controls.
No significant difference was found in total amino acid concentration between 105 patients with CHF (62% men, mean age: 71.0±11.0 years) and 106 controls (67% men, mean age: 69.1±9.4 years) (CHF: 3459.1±504.9nmol/ml, control: 3575.8±513.1nmol/ml; p=0.072). However, the concentration of essential amino acids (EAA) (CHF: 949.5±197.9nmol/ml, control: 1034.1±207.3nmol/ml; p=0.002) and branched-chain amino acid (BCAA) (CHF: 449.3±114.3nmol/ml, control: 503.9±118.2nmol/ml; p<0.001) and Fischer's ratio (CHF: 2.86±0.62, control: 3.17±0.50; p<0.001) were significantly lower in patients with CHF. Integrated analysis of these data revealed that SMI was negatively correlated with age correlation coefficient (R), −0.313; 95% confidence interval (CI), −0.514 to −0.079; p=0.010, but positively correlated with EAA concentration (R, 0.256; 95% CI, 0.017–0.467; p=0.037), BCAA concentration (R, 0.362; 95% CI, 0.134–0.554; p=0.003), and Fischer's ratio (R, 0.573; 95% CI, 0.386–0.715; p<0.001).
Serum concentrations of EAA and BCAA and Fischer's ratio were lower in patients with CHF than in controls, while SMI correlated with EAA, BCAA, and Fischer's ratio.
We discovered a secular change in the travel time of direct S-waves over a 10-year observation period by means of continuous operation of an artificial and stable seismic source, called Accurately ...Controlled Routinely Operated Signal System (ACROSS), which is deployed in the central part of Japan along the Nankai Trough. We used 13 High Sensitivity Seismograph Network Japan (Hi-net) stations around the ACROSS source to monitor the temporal variation in travel time. Green’s functions were calculated for each station daily from March 29, 2007, through October 30, 2017. Secular advance in the temporal variation in travel time was seen for the whole operation period, in addition to a steplike delay associated with the 2011 Tohoku earthquake. We estimated the rate of secular change and the amount of coseismic step by modeling the transfer function of S-waves with a linear trend and the coseismic step of the 2011 Tohoku earthquake. Distance dependences of the travel time changes can be explained as a combination of common bias and dispersion for each station, for both the secular and coseismic changes. This can be interpreted as a randomly distributed change in seismic velocity over the range of the observation region. An azimuthal dependence exists for both changes and shows larger changes in the NE–SW direction than in the NW–SE direction from the ACROSS source.
There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era.
To investigate ...the status of cancer-associated VTE in the DOAC era.
This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without.
The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66).
The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.
As heart failure (HF) progresses, ATP levels in myocardial cells decrease, and myocardial contractility also decreases. Inotropic drugs improve myocardial contractility but increase ATP consumption, ...leading to poor prognosis. Kyoto University Substance 121 (KUS121) is known to selectively inhibit the ATPase activity of valosin-containing protein, maintain cellular ATP levels, and manifest cytoprotective effects in several pathological conditions. The aim of this study is to determine the therapeutic effect of KUS121 on HF models.
Cultured cell, mouse, and canine models of HF were used to examine the therapeutic effects of KUS121. The mechanism of action of KUS121 was also examined. Administration of KUS121 to a transverse aortic constriction (TAC)-induced mouse model of HF rapidly improved the left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. In a canine model of high frequency-paced HF, administration of KUS121 also improved left ventricular contractility and decreased left ventricular end-diastolic pressure without increasing the heart rate. Long-term administration of KUS121 to a TAC-induced mouse model of HF suppressed cardiac hypertrophy and fibrosis. In H9C2 cells, KUS121 reduced ER stress. Finally, in experiments using primary cultured cardiomyocytes, KUS121 improved contractility and diastolic capacity without changing peak Ca2+ levels or contraction time. These effects were not accompanied by an increase in cyclic adenosine monophosphate or phosphorylation of phospholamban and ryanodine receptors.
KUS121 ameliorated HF by a mechanism totally different from that of conventional catecholamines. We propose that KUS121 is a promising new option for the treatment of HF.
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•KUS121 maintains intracellular ATP levels and reduces endoplasmic reticulum stress.•KUS121 improves contractility and diastolic function in heart failure.•KUS121 does not cause cardiac hypertrophy or fibrosis.•KUS121 may be a new option for the treatment of heart failure.
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