Search

Abstract JSNS $$^2$$ 2 (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) is an experiment that searches for sterile neutrinos via the observation of $$\bar{\nu }_{\mu } \rightarrow \bar{\nu }_{e}$$ ν ¯ μ → ν ¯ e appearance oscillations using muon decay-at-rest neutrinos. The JSNS $$^2$$ 2 experiment performed data taking from 2021. In this manuscript, a study of the accidental background is presented. The rate of the accidental background is ( $$9.29\pm 0.39) \times 10^{-8}$$ 9.29 ± 0.39 ) × 10 - 8 /spill with 0.75 MW beam power and comparable to the expected number of signal events.

Abstract Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With $$40\,\textrm{t}$$ 40 t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ( $$0\upnu \upbeta \upbeta $$ 0 ν β β ), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We present here the results of simulations performed to determine the production rate of $${}^{137}$$ 137 Xe, the most crucial isotope in the search for $$0\upnu \upbeta \upbeta $$ 0 ν β β of $${}^{136}$$ 136 Xe. Additionally, we explore the contribution that other muon-induced spallation products, such as other unstable xenon isotopes and tritium, may have on the cosmogenic background.

Abstract Spin–orbit coupling forms the physical basis for quantum materials with non-trivial topology and potential spintronics applications. The Rashba interaction is a textbook model of spin–orbit interactions, with charge carriers undergoing linear, isotropic spin-splitting in momentum space. Recently, non-centrosymmetric semiconductors in the family BiTeX (X = Cl, Br, I) have been identified as exemplary Rashba materials due to the strong splitting of their bulk bands, yet a detailed investigation of their spin textures, and their relationships to local crystal symmetry, is currently lacking. We perform high-efficiency spin-resolved photoemission spectroscopy to directly image the spin texture of surface states of BiTeCl, and we find dramatic deviations from idealized behavior, including a reversal of the spin-polarization near the Fermi level. We show that this behavior can be described by higher-order contributions to the canonical Rashba model with the surface states localized to individual trilayers of the crystal. Due to the prominence of these effects near the Fermi level, they should have a strong impact on the spin-dependent transport of carriers.

For precision machining such as slicing and grooving of hard and brittle materials, wire tools with electroplated diamond abrasives have been widely used. Slicing with electroplated diamond wire tools, in particular, is quickly becoming a common method for machining hard materials. Many studies have been published on the machining properties of electroplated diamond wire tools. However, there are very few reports on the tool wear of wire tools. In particular, the influence of work material on the machining and wear characteristics of electroplated diamond wire tools is still unclear. Fundamental grooving experiments are used to investigate the effect of the workpiece’s material properties on the grooving characteristics and the wear characteristics of the wire tool. Two types of ceramics, alumina (Al2O3) and zirconia (ZrO2), were used as work materials in this study. The grooving experiments revealed that the workpiece material affects the machining characteristics. Alumina, which is brittle, was found to be more machinable than zirconia, which has a high toughness for the same hardness. The wear of the electroplated diamond wire tools, on the other hand, showed no significant difference.

Abstract JSNS $$^2$$ 2 (J-PARC Sterile Neutrino Search at J-PARC Spallation Neutron Source) is an experiment that is searching for sterile neutrinos via the observation of $${\bar{\nu }}_{\mu } \rightarrow {\bar{\nu }}_{e}$$ ν ¯ μ → ν ¯ e appearance oscillations using muon decay-at-rest neutrinos. Before dedicated data taking in the first-half of 2021, we performed a commissioning run for 10 days in June 2020. Using the data obtained in this commissioning run, in this paper, we present an estimate of the correlated background which imitates the $${\bar{\nu }}_{e}$$ ν ¯ e signal in a sterile neutrino search. In addition, in order to demonstrate future prospects of the JSNS $$^2$$ 2 experiment, possible pulse shape discrimination improvements towards reducing cosmic ray induced fast neutron background are described.

A spectroscopic system with multiple viewing chords was developed for QUEST (Q-shu University Experiment with Steady-State Spherical Tokamak) to measure the spatial distribution of ion toroidal velocities in discharges sustained by electron cyclotron resonance heating (ECH). Twenty-four viewing chords were aligned in the midplane and C III emission line spectra were measured for three types of ECH discharge under different magnetic field configurations. By applying an inversion method to the measured spectra, we evaluated the radial distributions of C2+ ion emissivity, temperature, and toroidal velocity. The error in the evaluated velocity was estimated to be less than 5 km/s. It was found that the velocity depends on the magnetic field configuration.

The van der Waals ferromagnet Cr_{2}Ge_{2}Te_{6} (CGT) has a two-dimensional crystal structure where each layer is stacked through van der Waals force. We have investigated the nature of the ferromagnetism and the weak perpendicular magnetic anisotropy (PMA) of CGT by means of x-ray absorption spectroscopy and x-ray magnetic circular dichroism (XMCD) studies of CGT single crystals. The XMCD spectra at the Cr L_{2,3} edge for different magnetic field directions were analyzed on the basis of the cluster-model multiplet calculation. The Cr valence is confirmed to be 3+ and the orbital magnetic moment is found to be nearly quenched, as expected for the high-spin t_{2g}^{3} configuration of the Cr^{3+} ion. A large (∼0.2 eV) trigonal crystal-field splitting of the t_{2g} level caused by the distortion of the CrTe_{6} octahedron has been revealed, while the single-ion anisotropy (SIA) of the Cr atom is found to have a sign opposite to the observed PMA and too weak compared to the reported anisotropy energy. The present result suggests that anisotropic exchange coupling between the Cr atoms through the ligand Te 5p orbitals having strong spin-orbit coupling has to be invoked to explain the weak PMA of CGT, as in the case of the strong PMA of CrI_{3}.

This study reports the effects of the parameters of a vibration-based impact mode piezoelectric power generator. First, an evaluation of the effects of the impact parameters, the mass, and the impact velocity is presented. It is found that the output voltage of the piezoelectric device in impact mode is directly proportional to the velocity, whereas the output power is equal to a quadratic function of the same variable. For the same impact momentum, the effect of the velocity in generating a higher peak output is dominant compared with the mass. Second, the vibration-based impact mode piezoelectric power generator is discussed. The experimental results show that a wider operating frequency bandwidth of the output power can be achieved with the preloading configuration. However, regarding magnitude, due to the high velocity of impact, the configuration with a gap between the tip and the piezoelectric device produces a higher output.

Based on the "Preliminary report of comparative studies on the Agrico-Pastoral People in the South Western Eurasia", the results obtained by the research group from the Plant Germplasm Institute, Fac. Agr., Kyoto University are briefly presented. Collections and preliminary evaluations were made on Triticum monococcum, T. aestivum, Hordeum vulgare, Secale cereale, Avena sativa, Panicum milliaceum, Agropyron ssp., and weeds (Bromus secalinus, Lolium temulentum) associated with grain fields.

Aims: The purposes of the present study were to clarify the normal variation and to determine the normal reference values of diffusion tensor (DT) parameters (mean diffusivity [MD] and fractional anisotropy [FA]) of the spinal cord in single-shot fast spin-echo-based sequence at 3.0-Tesla (3T). Materials and Methods: Thirty healthy subjects (mean age = 44.2 years, range = 20-72 years) were enrolled for this study. Mean values of MD and FA in six spinal levels (C2/3, C3/4, C4/5, C5/6, C6/7, and C7/Th1) were measured. Mean values, variances, and distributions of the MD and FA in each spinal level were analyzed. Age-dependent change of MD and FA as well as correlation between MD and FA was also analyzed. Results: At all spinal levels, the values can be considered to be Gaussian distribution in MD but not in FA. A significant statistical negative correlation was observed between aging and the values of MD (r = 0.429, P = 0.018), but insignificant between the values of FA (P = 0.234). A slight significant statistical negative correlation was observed between the values of MD and FA (r = 0.156, P = 0.037). One way repeated measures analysis of variance indicated the significant difference between the spinal levels in both MD (P = 0.003) and FA (P < 0.0001). Conclusions: The analyzed data in the present study would be helpful for comparison when investigating the spinal condition of spinal disorders.

In order to investigate the mechanism of ferromagnetic ordering in the new n-type magnetic semiconductor (In,Fe)As codoped with Be, we have performed x-ray absorption spectroscopy and x-ray magnetic circular dichroism (XMCD) studies of ferromagnetic and paramagnetic samples. The spectral line shapes suggest that the ferromagnetism is intrinsic, originating from Fe atoms incorporated into the zinc-blende-type InAs lattice. The magnetization curves of Femeasured byXMCDwere well reproduced by the superposition of a Langevin function representing superparamagnetic (SPM) behavior of nanoscale ferromagnetic domains and a T-linear function representing Curie-Weiss paramagnetism even much above the Curie temperatures. The data at 20 K showed a deviation from the Langevin behavior, suggesting a gradual establishment of macroscopic ferromagnetism on lowering temperature. The existence of nanoscale ferromagnetic domains indicated by the SPM behavior suggests spatial fluctuations of Fe concentration on the nanoscale. [ABSTRACT FROM AUTHOR]

The performance of a new structure plasma display panel (PDP) cell with counter sustain electrodes was diagnosed by optical emission and laser absorption spectroscopic measurements of the spatiotemporal behaviours of the microplasma. Two different types of panels were prepared: one with sustain electrodes only and the other with additional data and auxiliary electrodes on the rear and front plates. By using cells of the former type, the basic performance was measured as the dependences on the Xe concentration in Ne, the total pressure and the applied sustain voltage. It was seen that a higher Xe concentration was advantageous for the luminous efficiency although the required minimum sustain voltage became larger. By using the latter type of cell, the effects of driving schemes were investigated by varying the applied potentials onto the auxiliary and data electrodes. It was found that the role of the auxiliary electrode is remarkable; the discharge expands largely in the cell when the voltage and the width of the pulses applied to the auxiliary electrode are optimized to be 200 V and 0.3 µs, respectively, while the data electrode is grounded. The production efficiency of Xe atoms in the metastable (1s5) and resonance (1s4) states was derived from the measured absolute densities normalized by the input power per cell and the decay rates of those densities. The vacuum ultraviolet emission efficiency estimated from the results was compared between the tested conditions, and a noticeable improvement was recognized in the optimized condition, about 40% larger than a conventional driving condition without additional pulses. It was also seen that this cell structure is potentially superior in luminous efficiency to the conventional coplanar structure currently used in commercial PDPs. [ABSTRACT FROM AUTHOR]

Most of the attention currently focused on endocrine-active chemicals is directed to their effects on the development of offspring exposed to them in utero or during the neonatal period. Pregnant Crj:CD(SD)IGS rats were given ethinyl estradiol (EE) orally in doses of 0.5-50 μg/kg/day from gestational day 7 to postnatal day 18, and their offspring were examined for its effects. Our previous study according to a similar protocol demonstrated the occurrence of cleft phallus in the female offspring exposed to 50 μg/kg of EE in utero and during the lactation period. The present study was designed to assess (1) the reproducibility of the induction of cleft phallus, (2) the fertility of female rats with cleft phallus, and (3) whether any delayed effects, possibly delayed anovulation, were induced. At 50 μg/kg cleft phallus was observed in almost all of the female offspring, and slight retardation of body weight gain was detected in both sexes. At 15-17 weeks of age the animals with cleft phallus could copulate and had fertility comparable to the control group. At 6 months of age, on the other hand, 6/8 of the female offspring at 50 μg/kg exhibited abnormal cyclicity, including persistent estrus, and histological examination revealed follicular cysts and absence of corpora lutea in the ovaries of the rats with persistent estrus. These findings are consistent with delayed anovulation syndrome. The results suggest that observation of cyclicity at 6 months old is able to detect possible delayed ovarian dysfunction induced by perinatal exposure to chemicals. [ABSTRACT FROM AUTHOR]

We report on the low-threshold operation of membrane buried heterostructure distributed feedback laser arrays. 45 devices were fabricated on a wafer covering a wide wavelength range of 75 nm. The lowest threshold pump power as low as 0.64 mW along with the submode suppression-ratio of over 30 dB at two times the threshold were successfully obtained at room-temperature continuous-wave condition. [ABSTRACT FROM PUBLISHER]

We report two types of site-selective metal deposition methods based on colloidal crystal templating. We discuss in particular the controllability of the morphology and crystallinity of Au nanodots depending of the choice of method. [ABSTRACT FROM AUTHOR]

Feed and water efficiency are important traits to improve beef cattle production’s economic and environmental sustainability. This study evaluated residual feed intake (RFI) and residual water intake (RWI) and their relationship with performance, ingestive behavior, and carcass traits in Caracu beef cattle. The data were analyzed using a generalized linear model with least squares means. The ingestive behavior, performance, and carcass traits were influenced by sex (p < 0.05). Males showed higher dry matter intake (DMI), average daily gain (ADG), mid-test metabolic weight (BW0.75), rib eye area, and rump fat thickness than females, besides spending more time drinking and eating. Low RFI animals exhibited higher DMI than high RFI animals. Low RWI animals ingested 3.89 L/d of water further than high RWI animals. The interaction between sex and RWI influenced the DMI, BW0.75, and backfat thickness. The ingestive behavior of low and high RFI animals was similar, although high RWI animals visited a smaller number of drinkers than low RWI animals. Water intake positively affects productive efficiency, and the combined use of RWI and RFI may help improve the selection of more efficient animals contributing to reducing the costs of beef cattle production and improving environmental sustainability.

The inclusion of plant extracts that contain secondary compounds with the potential to modulate rumen fermentation and improve animal performance has gained attention in recent years. The aim of this study was to evaluate the effect of the inclusion of yerba mate extract (Ilex paraguariensis ST. Hilaire) (YME) on the ruminal parameters. Eight castrated cattle were divided into four groups, a control without YME (0%) and three treatment groups with 0.5, 1 and 2% inclusion of YME in the dry matter. The inclusion of YME did not show differences in ruminal methane emissions (CH4), and total apparent digestibility (p = 0.54). Likewise, YME did not modify ruminal pH, but positively affected NH3-N, which decreased linearly as the extract level in the diet increased (p = 0.01). No short chain fatty acids (SCFA) were influenced by YME, except isovaleric acid (p = 0.01), which showed a lower concentration in the inclusion of 2% YME. Our results show that up to 2% YME does not affect digestibility, ruminal fermentation parameters, or the concentration of short-chain fatty acids in the rumen.

The present study aimed to investigate whether different lines of a composite breed (5/8 Charolais × 3/8 Zebu), formed at different times, and genetically improved, would result in differences in animal performance, enteric methane emissions, and carcass traits. Forty-six Canchim steers (15 months, 280 ± 33 kg liveweight) from three different lines were used: old, new, and their cross. These three breed lines were considered the treatments (arranged in four randomized blocks based on initial liveweight) and were evaluated under grazing and feedlot conditions in relation to the performance and emission of enteric methane. During the grazing period, the new line was found to be superior to the old only in relation to the average daily liveweight gain (0.692 vs. 0.547 kg/day), and with no differences in relation to the cross line (0.692 vs. 0.620). In the feedlot finishing phase, only the average daily liveweight gain was significantly higher in the new line compared to the cross and old line (1.44 vs. 1.32 and 1.23 kg/day). The new and cross lines demonstrated higher dry matter intake when compared to the old line (10.25 and 10.42 vs. 9.11 kg/day), with the crossline animals demonstrating the best feed conversion. The new line showed higher enteric methane emissions compared to the old line (178 vs. 156 g/day). The line had an effect on the carcass dressing of the animals, with greater fat thickness in carcasses from the new and cross lines than the old line (4.4 and 3.8 vs. 3.2 mm). Canchim cattle selected for improved productive performance characteristics does not guarantee animals with lower methane emissions under grazing conditions; while in feedlots, can lead to increased daily feed consumption, and hence, to higher emissions of methane.

Systemic lupus erythematosus (SLE) is a chronic disease with multiple pathologies that can affect every organ system of the body including central nervous system. Intracerebral aneurysms and subarachnoid hemorrhage (SAH) are one of comparatively rarer manifestations of central nervous system SLE. Here we present a case of known SLE complicated by the rupture of intra cerebral aneurysm at basilar artery tip which was successfully treated with endovascular coiling. Keywords: cerebral aneurysm, endovascular surgery, SAH, SLE

: Background Sufficient analgesia for cancer pain is sometimes difficult to achieve with conventional treatments. We aimed at investigating the analgesic efficacy and safety of intrathecal betamethasone in patients with uncontrollable cancer pain. : Methods Betamethasone 1 mg mixed with saline was injected into the lumbar intrathecal space once a week in 10 patients with persistent cancer pain in the lower half of the body. During the 4-week study period, the analgesic efficacy and adverse effects related to intrathecal betamethasone were observed. : Results Long-lasting analgesia (mean numerical pain score =5) for 7 days, after immediate analgesia within 10 min, was obtained without the need to increase the morphine dose in 5 of 10 patients. In almost all of the patients, not only pain, but also uncomfortable symptoms were improved. Adverse effects related to neurotoxicity of intrathecal betamethasone, such as sensory and motor dysfunctions, were not observed in any patients. : Conclusion When conventional cancer pain treatments are not successful, intrathecal betamethasone may be useful, as it probably induces long-lasting analgesia without adverse effects and improves activities of daily living, especially in patients with vertebral bone metastases. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer., Methods: The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed., Results: Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM., Conclusion: CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT., (© 2024 Wiley Periodicals LLC.)

Developing non-contact, non-destructive monitoring methods for marine life is crucial for sustainable resource management. Recent monitoring technologies and machine learning analysis advancements have enhanced underwater image and acoustic data acquisition. Systems to obtain 3D acoustic data from beneath the seafloor are being developed; however, manual analysis of large 3D datasets is challenging. Therefore, an automatic method for analyzing benthic resource distribution is needed. This study developed a system to estimate benthic resource distribution non-destructively by combining high-precision habitat data acquisition using high-frequency ultrasonic waves and prediction models based on a 3D convolutional neural network (3D-CNN). The system estimated the distribution of asari clams (Ruditapes philippinarum) in Lake Hamana, Japan. Clam presence and count were successfully estimated in a voxel with an ROC-AUC of 0.9 and a macro-average ROC-AUC of 0.8, respectively. This system visualized clam distribution and estimated numbers, demonstrating its effectiveness for quantifying marine resources beneath the seafloor., (© 2024. The Author(s).)

Background: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018., Methods: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021., Results: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories., Conclusions: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan., (© 2024 The Japanese Urological Association.)

Land plants have evolved a hydrophobic cuticle on the surface of aerial organs as an adaptation to ensure survival in terrestrial environments. Cuticle is mainly composed of lipids, namely cutin and intracuticular wax, with epicuticular wax deposited on plant surface. The composition and permeability of cuticle have a large influence on its ability to protect plants against drought stress. However, the regulatory mechanisms underlying cuticular wax biosynthesis in response to drought stress have not been fully elucidated. Here, we identified three AP2/ERF transcription factors (DREB26/ERF12, ERF13 and ERF14) involved in the regulation of water permeability of the plant surface. Transmission electron microscopy revealed thicker cuticle on the leaves of DREB26-overexpressing (DREB26OX) plants, and thinner cuticle on the leaves of transgenic plants expressing SRDX repression domain-fused DREB26 (DREB26SR). Genes involved in cuticular wax formation were upregulated in DREB26OX and downregulated in DREB26SR. The levels of very-long chain (VLC) alkanes, which are a major wax component, increased in DREB26OX leaves and decreased in DREB26SR leaves. Under dehydration stress, water loss was reduced in DREB26OX and increased in DREB26SR. The erf12/13/14 triple mutant showed delayed growth, decreased leaf water content, and reduced drought-inducible VLC alkane accumulation. Taken together, our results indicate that the DREB26/ERF12 and its closed family members, ERF13 and ERF14, play an important role in cuticular wax biosynthesis in response to drought stress. The complex transcriptional cascade involved in the regulation of cuticular wax biosynthesis under drought stress conditions is discussed., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Aim: To assess the preoperative disease characteristics and indications for living donor liver transplantation (LDLT), complications, patient survival, and prognosis after LDLT for fibropolycystic liver disease (FLD) in children., Methods: We undertook a cross-sectional survey of patients who underwent LDLT for FLD between January 2002 and December 2020., Results: A total of 35 patients (22 male and 13 female individuals) with FLD were included in this study, of whom 19 (54.3%) had isolated congenital hepatic fibrosis and 16 (45.6%) had Caroli syndrome. Refractory gastrointestinal bleeding was the most frequent symptom related to the indication for LDLT, being found in 48.6% of our patients, followed by uncontrollable cholangitis and ascites. The median age at the time of LDLT was 8.1 years old. Of the 27 patients presenting with renal involvement, 13 patients required kidney transplantation (KT). Overall, the renal function after LDLT decreased regardless of renal involvement; however, patients with renal involvement had a significantly lower estimated glomerular filtration rate than those without renal involvement throughout the course of this study (p < 0.01). The 5-year overall patient survival rate was 97.1%. Two patients died with a median follow-up of 8.9 years after LDLT; one died due to sepsis 2 weeks after simultaneous liver-kidney transplantation and the other committed suicide 10 years after LDLT., Conclusion: The prognosis of the pediatric patients who underwent LDLT for FLD was excellent. However, an individualized treatment approach based on the status of the renal function and liver disease is important, as a certain proportion of patients require KT., (© 2024 Japan Society of Hepatology.)

Aim: Sarcopenia has been with a decrease in masseter muscle (MM) thickness in high-risk older populations. However, the relationship between sarcopenia and determinants of MM volume (MMV) in the general elderly population remains unclear., Method: In a cross-sectional study of 1,484 older adults in Tokyo, we evaluated MMV using 3D MRI scanning, appendicular skeletal muscle mass (ASMM), handgrip strength, dietary intake, smoking, insulin-like growth factor 1 (IGF-1) levels, and the ACTN3 R577X polymorphism. Participants were divided into quintiles based on MMV (Q1-5)., Results: Participants in our study had a mean age of 73.0 ± 5.3 years and their MMV (Men: 35.3 ± 7.8 mL, Women: 25.0 ± 5.1 mL) was significantly higher in men than in women. A significant association between MMV and sarcopenia was observed, with the lowest quintile (Q1) showing a higher risk compared to the highest quintile (Q5) in both sexes. Body mass index (BMI) and age were independent determinants of ASMM in both sexes, whereas BMI, but interestingly not age, was a determinant of MMV. Moreover, IGF-1 was positively correlated with MMV in both sexes; smoking was negatively correlated with MMV in women. The ACTN3 577XX genotype was only associated with smaller MMV in men., Conclusion: Low MMV increased the risk of sarcopenia, particularly in men. BMI and age strongly influenced ASMM, while MMV was only weakly associated with BMI and not with age. Notably, IGF-1 level was positively associated with MMV only, and ACTN3 genotype was associated to reduced MMV only in men., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: There have been only a few cases showing the efficacy of pembrolizumab on granulocyte-colony - stimulating factor (G-CSF)-producing non-small-cell lung cancer (NSCLC) with high programmed cell death ligand 1 (PD-L1) expression. Herein, we report the first case showing the efficacy of pembrolizumab for G-CSF-producing NSCLC with high PD-L1 expression, although the patient had factors indicative of poor pembrolizumab efficacy, such as poor performance status (PS) due to the tumor-induced inflammation and corticosteroids administration., Case Presentation: A 77-year-old woman was diagnosed with G-CSF-producing NSCLC-not otherwise specified, classified as clinical stage IVB, T2N3M1c. She had fever and her PS was 3, and her C-reactive protein (CRP) was 6.47 mg/dL due to inflammation by a G-CSF-producing tumor. Thus, we initiated the administration of dexamethasone (3.3 mg/day). Her fever abated the next day, and CRP dropped to 3.22 mg/dL after 4 days. Driver mutations were negative, and PD-L1, tumor proportion score, was highly expressed at 100%. Thus, pembrolizumab was started. Subsequently, the white blood cell count decreased, and the tumor shrank, indicating a partial response. After three cycles of pembrolizumab therapy, the anorexia improved, and she was discharged. The patient developed sclerosing cholangitis after discharge. Therefore, the pembrolizumab treatment was discontinued. The primary lesion was enlarged, indicating progressive disease. However, the patient and her family did not want additional treatment. Finally, her progression-free survival and overall survival were 6 and 7 months, respectively., Conclusion: Pembrolizumab may be effective against G-CSF-producing NSCLC with high PD-L1 expression. Corticosteroids seemed to inhibit inflammation induced by the tumor, and exert the efficacy of pembrolizumab., Competing Interests: Takeshi Masuda reports personal fee from Daiichi-Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Kyowa Kirin Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., and AstraZeneca K.K. outside the submitted work. Kakuhiro Yamaguchi reports honoraria from Ono Pharmaceutical Co., Ltd., outside the submitted work. Shinjiro Sakamoto reports honoraria from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., and Novartis Pharma K.K. outside the submitted work. Yasushi Horimasu reports honoraria from Nippon Boehringer Ingelheim Co., Ltd., outside the submitted work. Taku Nakashima reports honoraria from AstraZeneca K.K. and Chugai Pharmaceutical Co., Ltd., outside the submitted work. Noboru Hattori reports honoraria from AstraZeneca K.K., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted work. No other disclosures are reported., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The delivery of mRNA molecules to organs beyond the liver is valuable for therapeutic applications. Functionalized lipid nanoparticles (LNPs) using exogenous mechanisms can regulate in vivo mRNA expression profiles from hepatocytes to extrahepatic tissues but lead to process complexity and cost escalation. Here, we report that mRNA expression gradually shifts from the liver to the spleen in an ionizable lipid tail length-dependent manner. Remarkably, this simple chemical strategy held true even when different ionizable lipid head structures were employed. As a potential mechanism underlying this discovery, our data suggest that 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC) is enriched on the surface of mRNA/LNPs with short-tail lipids. This feature limits their interaction with biological components, avoiding their rapid hepatic clearance. We also show that spleen-targeting LNPs loaded with SARS-CoV-2 receptor-binding domain (RBD) mRNA can efficiently induce immune responses and neutralize activity following intramuscular vaccination priming and boosting.

Objectives: The frozen elephant trunk (FET) technique is effective for treating extended aortic arch aneurysms. This study compares hand-made and factory-made devices in this context., Methods: A retrospective case-control study was conducted on 68 patients who underwent FET for distal aortic arch aneurysm at our institution. We used two different types of devices: hand-made stent graft in group Z (17 cases, 25.0%) and a commercialized stent graft in group J (51 cases, 75.0%). The study compared demographic characteristics and the outcomes between the two groups., Results: In-hospital mortality was equivalent in both groups (5.9%). Spinal cord injury rates were 5.9% in group Z and 3.9% in group J. Group Z had a higher rate of aortic events (55.9% vs 96.9%, p  < 0.001) and more frequent stent migration. The number of cases with aneurysm diameter shrinkage was lower in group Z. The landing zone angle at insertion influenced aneurysm changes, being 17.6 degrees in shrink cases and 26.7 degrees in unchanged or enlarged cases ( p  = 0.045)., Conclusions: FROZENIX device notably reduced incidences of postoperative complications compared to hand-made prostheses. Factors such as insertion angle and stent size, rather than changes in the landing zone angle, appeared to influence aneurysm shrinkage. The use of FROZENIX in TARFET procedures has shown benefits in reducing complications and improving long-term prognosis, taking into account the landing zone angle., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia, is usually observed in children and infants, although more recently adult-onset nesidioblastosis has also been described. We present a case of nesidioblastosis in a 78-year-old man that was detected by 111In-pentetreotide single photon emission computed tomography (SPECT/CT). The patient was transferred to our hospital's emergency department in a hypoglycemic coma. Dynamic enhanced CT could detect no lesion in the pancreas, but an 111In-pentetreotide SPECT/CT scan performed after a similar episode four weeks later showed increased focal uptake at the head of the pancreas. The results of a selective arterial calcium injection test were negative. After careful consideration and discussion among colleagues, surgical intervention was selected, and a pancreaticoduodenectomy was performed. On histology, there were elevated numbers of Langerhans islets in the pancreatic head, and the islets themselves appeared enlarged. Hypertrophic β-cells comprised the majority, but α-cells, δ-cells and pancreatic polypeptide were also detected in the islets. Based on the histopathological results and repeated hyperinsulinemic hypoglycemic crises, the patient was finally diagnosed with adult-onset nesidioblastosis. He had no hypoglycemic symptoms during outpatient follow-up examination. Since 111In-pentetreotide SPECT/CT may be able to detect nesidioblastosis, clinicians should consider this relatively new-modality examination when encountering such cases., Competing Interests: No potential conflict of interest relevant to this article was reported.

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69 + in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions., 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. Published by Elsevier Inc.)

To resolve the critical donor shortage worldwide, enlarging the potential donor pool to include expanded criteria donors is necessary. Despite numerous attempts to establish new preservation solutions, no dramatic innovation has occurred since University of Wisconsin (UW) solution displaced Euro Collins' solution; UW solution remains the global gold standard. We previously developed a heavy water (D 2 O)-containing organ storage solution, Dsol, which is effective for livers subjected to extended cold storage (CS), and reported its effectiveness. Dsol is a modified UW solution; however, the substances or conditions that exhibit a synergistic or additive effect with D 2 O are unclear. Here we made UWD solution by removing hydroxyethyl starch (HES) from and adding 30%-D 2 O to UW solution, and compared the effects of these solutions. After 48 hours of CS, the livers were reperfused at 37 °C on an isolated perfused rat liver apparatus, and their perfusion kinetics, functions, and injuries were compared. In the UW group, portal vein resistance significantly increased and the oxygen consumption rate and bile production decreased; in contrast, these changes were suppressed in the UWD group. Organ expansion and liver damage progressed in both groups. These results confirmed that the removal of HES from and addition of D 2 O to the UW solution reduced CS-induced cellular function impairments and microcirculatory disorders. However, to reduce injury during reperfusion after CS, it is necessary to provide conditions that inhibit injury progression after reperfusion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Moto Fukai reports financial support was provided by Japan Society for the Promotion of Science. Tsuyoshi Shimamura reports financial support was provided by Japan Society for the Promotion of Science. Moto Fukai reports a relationship with Japan Society for the Promotion of Science that includes: funding grants. Tsuyoshi Shimamura reports a relationship with Japan Society for the Promotion of Science that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The postoperative prognosis of patients with interstitial lung disease (ILD) and lung cancer is poor. Recently, the ILD-gender-age-physiology (GAP) index was identified as a clinical prognostic factor for patients with ILD. This study investigated the ILD-GAP index and oncological factors regarding postoperative outcomes., Methods: We retrospectively reviewed 87 lung cancer patients with comorbid ILD who underwent curative resection at our institution between April 2005 and December 2019. Short-term postoperative outcomes and overall survival (OS) based on the ILD-GAP index were examined. OS rates after surgery were calculated using the Kaplan-Meier method, and group differences were analyzed using the Log-Rank test. Univariate and multivariate analyses for OS were performed using the Cox regression model., Results: Multivariate analyses revealed ILD-GAP index ≥ 4 [Hazard ratio, 3.349; 95% confidence interval 1.375-8.155; P = 0.008] as a factor associated with OS. In the ILD-GAP index ≥ 4 group, no deaths occurred from primary lung cancer, with respiratory-related deaths being the most common, and exacerbation of ILD was more frequent (P = 0.007). Regarding perioperative results, a significant difference was observed in 90-day mortality (2.7% vs. 23.0% [P = 0.022]), and more patients required home oxygen therapy (14.9% vs. 69.2% [P < 0.001]) in the ILD-GAP index ≥ 4 group., Conclusions: An ILD-GAP index ≥ 4 indicated a poor prognostic factor for patients with surgically treated lung cancer. Careful consideration of surgical indications is essential for patients with an ILD-GAP index ≥ 4., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: This study estimated an individual's genetic liability to cardiometabolic risk factors by polygenic risk score (PRS) construction and examined whether high cardiorespiratory fitness (CRF) modifies the association between PRS and cardiometabolic risk factors., Methods: This cross-sectional study enrolled 1296 Japanese adults aged ≥40 yr. The PRS for each cardiometabolic trait (blood lipids, glucose, hypertension, and obesity) was calculated using the LDpred2 and clumping and thresholding methods. Participants were divided into low-, intermediate-, and high-PRS groups according to PRS tertiles for each trait. CRF was quantified as peak oxygen uptake (V̇O 2peak ) per kilogram body weight. Participants were divided into low-, intermediate-, and high-CRF groups according to the tertile V̇O 2peak value., Results: Linear regression analysis revealed a significant interaction between PRS for triglyceride (PRS TG ) and CRF groups on serum TG levels regardless of the PRS calculation method, and the association between PRS TG and TG levels was attenuated in the high-CRF group. Logistic regression analysis revealed a significant sub-additive interaction between LDpred2 PRS TG and CRF on the prevalence of high TG, indicating that high CRF attenuated the genetic predisposition to high TG. Furthermore, a significant sub-additive interaction between PRS for body mass index and CRF on obesity was detected regardless of the PRS calculation method. These significant interaction effects on high TG and obesity were diminished in the sensitivity analysis using V̇O 2peak per kilogram fat-free mass as the CRF index. Effects of PRSs for other cardiometabolic traits were not significantly attenuated in the high-CRF group regardless of PRS calculation methods., Conclusions: The findings of the present study suggest that individuals with high CRF overcome the genetic predisposition to high TG levels and obesity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Objective: To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study, a prospective observational study for Japanese patients, initiated in 2010., Patients and Methods: At the beginning, inclusion criteria were initially low-risk patients, prostate-specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow-up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments., Results: As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64-73) years, 5.3 (4.5-6.6) ng/mL, 0.15 (0.12-0.17) ng/mL, and 1 (1-2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re-biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re-biopsies were 29%, 30%, 35% and 25%, respectively. The 1-, 5- and 10-year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer., Conclusion: Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded., (© 2024 BJU International.)

Background: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies., Methods: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS)., Results: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone., Conclusions: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan., Methods: This multicenter prospective observational cohort study enrolled men aged 50-80 years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20 ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6 months and every 3 months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2 years and pathological progression on repeat biopsy., Results: Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70 years, 6.5 ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7 years. At 1 year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15 years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy., Conclusion: Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein ( GCKR ) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences., Methods: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65-84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters., Results: Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity., Conclusion: The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR -related metabolic outcomes., (© The Author(s), 2024.)

A 63-year-old Japanese female presented with fever. Computed tomography showed multiple nodules in both lungs. Corticosteroids and antibiotics were administered to treat suspected organizing and bacterial pneumonia, resulting in no improvement and respiratory failure worsened. Surgical lung biopsy revealed infiltration of CD3, CD56, Granzyme B, and EBV-encoded RNA-ISH-positive atypical lymphocytes. She was diagnosed with primary pulmonary extranodal NK/T-cell lymphoma (ENKL) and died two months after diagnosis with only a temporary effectiveness of chemotherapy. We should consider the possibility of ENKL and perform prompt and appropriate biopsy for early diagnosis in cases where empiric therapy is ineffective for suspected pneumonia., 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. No conflicts of interest., (© 2024 The Authors.)

Valve-sparing aortic root replacement is not widely performed due to technical requirements. The Florida sleeve technique (FST) is a new technique for aortic root remodeling with the preservation of the aortic valve without aortic root wall resection and coronary artery reconstruction. We successfully treated with the FST for a Marfan syndrome patient with an aortic root aneurysm and aortic valve insufficiency. We believe that this technique is very suitable for cases with moderately enlarged aortic roots. It could reduce surgical risks and prevent dilatation of the aortic root through coverage with a graft for a long time., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Objectives: To examine the effects of distractor sounds presented to the contralateral ear on speech intelligibility in patients with listening difficulties without apparent peripheral pathology and in control participants., Design: This study examined and analyzed 15 control participants (age range, 22 to 30 years) without any complaints of listening difficulties and 15 patients (age range, 15 to 33 years) diagnosed as having listening difficulties without apparent peripheral pathology in the outpatient clinic of the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital. Speech intelligibility for 50 Japanese monosyllables presented to the right ear was examined under the following three different conditions: "without contralateral sound," "with continuous white noise in the contralateral ear," and "with music stimuli in the contralateral ear.", Results: The results indicated the following: (1) speech intelligibility was significantly worse in the patient group with contralateral music stimuli and noise stimuli; (2) speech intelligibility was significantly worse with contralateral music stimuli than with contralateral noise stimuli in the patient group; (3) there was no significant difference in speech intelligibility among three contralateral masking conditions (without contra-stimuli, with contra-noise, and with contra-music) in the control group, although average and median values of speech intelligibility tended to be worse with contralateral music stimuli than without contralateral stimuli., Conclusions: Significantly larger masking effects due to a contralateral distractor sound observed in patients with listening difficulties without apparent peripheral pathology may suggest the possible involvement of masking mechanisms other than the energetic masking mechanism occurring in the periphery in these patients. In addition, it was also shown that the masking effect is more pronounced with real environmental sounds, that is, music with lyrics, than with continuous steady noise, which is often used as a masker for speech-in-noise testing in clinical trials. In other words, it should be noted that a speech-in-noise test using such steady noise may underestimate the degree of listening problems of patients with listening difficulties in their daily lives, and a speech-in-noise test using a masker such as music and/or speech sounds could make listening problems more obvious in patients with listening difficulties., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although bone marrow-derived cells with high aldehyde dehydrogenase activity (ALDH br ) have shown therapeutic potential against various diseases in animal studies, clinical trials have failed to show concurrent findings. We aimed to clarify the optimal conditions for the efficacy of ALDH br cells by using a murine bleomycin-induced pulmonary fibrosis model., Methods: We intravenously transferred male or female donor C57BL/6 mice-derived ALDH br cells into recipient C57BL/6 mice under various conditions, and used mCherry-expressing mice as a donor to trace the transferred ALDH br cells., Results: Pulmonary fibrosis improved significantly when (1) female-derived, not male-derived, and (2) lineage (Lin)-negative, not lineage-positive, ALDH br cells were transferred during the (3) fibrotic, not inflammatory, phase. Consistent with the RNA-sequencing results, female-derived Lin - /ALDH br cells were more resistant to oxidative stress than male-derived cells in vitro, and transferred female-derived Lin - /ALDH br cells were more viable than male-derived cells in the fibrotic lung. The mechanism underlying the antifibrotic effects of Lin - /ALDH br cells was strongly associated with reduction of oxidative stress., Conclusions: Our results indicated that Lin - /ALDH br cell therapy could ameliorate pulmonary fibrosis by reducing oxidative stress and suggested that their efficacy was mediated by sex-related differences. Thus, sex-awareness strategies may be important for clinical application of bone marrow ALDH br cells as a therapeutic tool., (© 2024. The Author(s).)

Intraspecific variation in specialized metabolites plays a crucial role in the adaptive response to diverse environments. Two major subspecies, japonica and indica, are observed in Asian cultivated rice (Oryza sativa L.). Previously, we identified (3R)-β-tyrosine, a novel nonproteinogenic β-amino acid in plants, along with the enzyme tyrosine aminomutase (TAM1), which is required for β-tyrosine biosynthesis, in the japonica cultivar Nipponbare. Notably, TAM1 and β-tyrosine were preferentially distributed in japonica cultivars compared with indica cultivars. Considering its phytotoxicity and antimicrobial activity, intraspecific variation in β-tyrosine may contribute to the defensive potential of japonica rice. Investigation of the evolutionary trajectory of TAM1 and β-tyrosine should enhance our understanding of the evolution of rice defense. However, their distribution patterns in O. rufipogon, the direct ancestor of O. sativa, remain unclear. Therefore, in this study, we extensively examined TAM1 presence/absence and β-tyrosine content in 110 genetically and geographically diverse O. rufipogon accessions and revealed that they are characteristically observed in the ancestral subpopulation of japonica rice, while being absent or slightly accumulated in other subpopulations. Thus, we conclude that TAM1 and β-tyrosine in japonica rice are likely derived from its ancestral subpopulation. Furthermore, the high and low TAM1 possession rates and β-tyrosine content in japonica and indica rice, respectively, could be attributed to distribution patterns of TAM1 and β-tyrosine in their ancestral subpopulations. This study provides fundamental insights into the evolution of rice defense.

In treating aortic root diseases, the Bentall procedure offers reliable and stable results. However, it requires a prosthetic valved conduit, which presents inherent challenges due to the need for anticoagulation. The Ozaki procedure, which uses pericardium for aortic valve neocuspidization, is an alternative to prosthetic valves and does not need anticoagulation. We developed a surgical technique combining the Bentall and Ozaki procedures to treat patients with aortic root disease, which we describe in this article. Because the risk of bleeding due to anticoagulation after prosthetic valve replacement was a concern, we combined the Bentall and Ozaki procedures with a graft conduit using bovine pericardial patch neocuspidization. Postoperative echocardiography showed a competent aortic valve with no regurgitation. We believe that this novel procedure provides hope for a more adaptable and patient-friendly option., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Amikacin  liposome inhalation suspension (ALIS) improved sputum culture conversion rate at 6 months for patients with refractory Mycobacterium avium complex pulmonary disease (MAC-PD) in an international phase 3 trial. Patient characteristics and chest high-resolution CT (HRCT) findings associated with ALIS effectiveness are poorly documented., Objective: We aimed to clarify ALIS effectiveness for refractory MAC-PD at 6 months, elucidating associated patient characteristics and chest CT findings., Methods: We reviewed medical records of 12 patients with refractory MAC-PD for whom ALIS treatment was initiated at Toho University Omori Medical Center from November 2021 through September 2022. All patients demonstrated treatment persistence for at least 3 months. They were divided into culture conversion and non-conversion groups using sputum culture conversion status after 6-month ALIS treatment initiation. Clinical and radiological characteristics were compared., Results: Seven of the 12 patients (58.3%) achieved sputum culture conversion within 6 months. The culture conversion group had shorter pre-ALIS initiation treatment duration [21 months (16-25) vs. 62 months (32-69); p = 0.045]; lower cavitary lesion incidence on HRCT (28.6% vs. 100%; p = 0.028); and fewer clarithromycin (CLA)-resistant strains [0/7 (0%) vs. 3/5 (60%); p = 0.045]. Chest HRCT findings improved in 4 of 7 (57.1%) and 1 of 5 (20%) patients in the culture conversion and non-conversion groups, respectively., Conclusion: ALIS facilitated sputum culture conversion within 6 months in 58.3% of patients with refractory MAC-PD. Sputum culture conversion was significantly more frequent for CLA-susceptible strains and patients with fewer cavitary lesions. Improved CT findings after ALIS did not always correspond to sputum culture conversion., (© 2024. The Author(s).)

The prognosis of anti-glomerular basement membrane (anti-GBM) nephritis, often accompanied by the presence of antineutrophil cytoplasmic antibodies (ANCA), is poor, and even with aggressive therapeutic approaches, kidney replacement therapy (KRT) is typically required. Here, we present a case of necrotizing crescentic glomerulonephritis in a patient double-seropositive for anti-GBM antibodies and ANCA who successfully achieved dialysis independence following aggressive treatment, including avacopan. The patient was a 77-year-old woman with rapidly progressive glomerulonephritis and double seropositivity for myeloperoxidase-ANCA and anti-GBM antibodies. A kidney biopsy revealed diffuse cellular crescents with necrosis and immunoglobin (Ig)G1 and IgG3 positivity on immunofluorescence staining, leading to a histological diagnosis of anti-glomerular basement membrane nephritis. Our treatment approach involved a novel combination of glucocorticoids, rituximab, low-dose cyclophosphamide, and plasma exchange complemented by avacopan. Temporary hemodialysis was required, and the patient successfully discontinued dialysis after 12 sessions despite a poor histological prognosis. This case underscores the significance of considering aggressive therapeutic strategies, including avacopan, for severe anti-GBM nephritis, even in the absence of lung involvement, to avert the need for KRT., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)