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The present study pays attention to biogas dry reforming for the purpose of producing H2. It is known that biogas contains approximately 40 vol% CO2, causing a decrease in the efficiency of power generation due to its lower heating value compared to natural gas, i.e., CH4. We suggest a hybrid system composed of a biogas dry reforming membrane reactor and a high-temperature fuel cell, i.e., a solid oxide fuel cell (SOFC). Since biogas dry reforming is an endothermic reaction, we adopt a membrane reactor, controlled by providing a non-equilibrium state via H2 separation from the reaction site. The purpose of the present study is to understand the effect of the thickness of the Pd/Cu membrane on the performance of the biogas dry reforming membrane reactor with a Pd/Cu membrane as well as a Ni/Cr catalyst. The impact of the reaction temperature, the molar ratio of CH4:CO2 and the differential pressure between the reaction chamber and the sweep chamber on the performance of the biogas dry reforming membrane reactor with the Pd/Cu membrane as well as the Ni/Cr catalyst was investigated by changing the thickness of the Pd/Cu membrane. It was revealed that we can obtain the highest concentration of H2, of 122,711 ppmV, for CH4:CO2 = 1:1 at a reaction temperature of 600 °C and a differential pressure of 0 MPa and using a Pd/Cu membrane with a thickness of 40 μm. Under these conditions, it can be concluded that the differential pressure of 0 MPa provides benefits for practical applications, especially since no power for H2 separation is necessary. Therefore, the thermal efficiency is improved, and additional equipment, e.g., a pump, is not necessary for practical applications. [ABSTRACT FROM AUTHOR]

This paper aims to study the performance of solar collectors of various sizes under different weather conditions in different Japanese cities, i.e., Kofu City, Nagoya City and Yamagata City. The heat generated by the solar collector was used to conduct a biogas dry reforming reactor for producing H2 to feed a solid oxide fuel cell (SOFC). This study revealed that the output temperature of a solar collector Tfb in April and July was higher than that in January and October irrespective of city. The optimum length of the absorber (dx) of the collector was 4 m irrespective of city. It was clarified that the Tfb in Yamagata City in January and October, i.e., winter and autumn, is lower than that in Kofu City and especially Nagoya City, which is strongly influenced by the tendency of solar intensity (I), not the velocity of the surrounding air (ua). On the other hand, the Tfb is almost the same in April and July, i.e., spring and summer, irrespective of city. The amount of produced H2 via the biogas dry reforming reactor and the power generated by the SOFC using H2 in spring and summer were higher compared to the other seasons irrespective of city. This study revealed that the highest available household number per month was 4.7, according to the investigation in this study. [ABSTRACT FROM AUTHOR]

This study proposes a combination system consisting of a biogas dry reforming reactor and a solid oxide fuel cell (SOFC). Since biogas dry reforming is an endothermic reaction, this study adopted a membrane reactor operated due to the non-equilibrium state with H2 separation from the reaction space. This study aimed to clarify the performance of the Ni/Cr/Ru catalyst using a biogas dry reforming membrane reactor. Additionally, this study also undertook a comparison of the performance of the Ni/Cr/Ru catalyst with that of the Ni/Cr catalyst. The impact of operation temperature, the molar ratio of CH4:CO2, the differential pressure between the reaction chamber and the sweep chamber, and the introduction of a sweep gas on the performance of the biogas dry reforming membrane reactor using a Pd/Cu membrane and a Ni/Cr/Ru catalyst was examined. The concentration of H2 using the Ni/Cr/Ru catalyst was greater than that using the Ni/Cr catalyst by 2871 ppmV for the molar ratio of CH4:CO2 = 1.5:1 at the reaction temperature of 600 °C and the differential pressure of 0 MPa without a sweep gas in particular. Under this condition, CH4 conversion, H2 yield, and thermal efficiency were 67.4%, 1.77 × 10−2%, and 0.241%, respectively. [ABSTRACT FROM AUTHOR]

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (n = 10), matched siblings (n = 2), and unrelated bone marrow donors (n = 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4+ T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words) [ABSTRACT FROM AUTHOR]

This comprehensive study delves into over 100 empirical articles, examining the influence of structural drivers on both internal and international migration. Employing a meta-analysis approach, we dissect these studies to pinpoint the prevalent migration drivers frequently subjected to quantitative scrutiny. Our investigation extends to scrutinizing major migration drivers in terms of their statistical impact, directional tendencies, and statistical significance. Our findings underscore that indicators such as income or GDP, education, migrant networks, gender, age, and family characteristics are the most commonly scrutinized factors shaping migration patterns. Notably, geographical distance, gender, and migrant networks emerge as highly consistent drivers, exhibiting a remarkable uniformity in both effect direction and statistical significance across the most frequently studied factors. Numerous migration drivers exhibit statistical significance roughly around 50% of the time, while several others fall considerably below this threshold. Intriguingly, we delve into the complex variations characterizing the impact of destination country GDP per capita. Our exploration reveals that articles reporting a negative effect for destination country GDP per capita are more likely to focus on irregular or asylum migration flows. However, an intriguing subset of articles that also explore asylum migration flows finds a positive effect. These nuanced disparities are further influenced by variations in sample composition, control variables, statistical models, and the operationalization of GDP per capita. In sum, our in-depth analysis sheds light on the multifaceted landscape of migration drivers, offering critical insights into both the consensus and divergence within migration research. [ABSTRACT FROM AUTHOR]

The baking industry is experiencing significant growth, primarily due to the widespread adoption of frozen dough baking. However, this process can negatively impact the fermentation ability of yeast, as freezing can induce stress in yeast cells. This study reports the molecular interplay between the ubiquitin–proteasome system and freezing stress tolerance in the yeast Saccharomyces cerevisiae. Using the proteasome inhibitor MG132, we first screened mutants with enhanced freezing stress tolerance. Three mutants showed elevated activity of the intracellular proteasome, particularly trypsin-like activity (more than threefold) and reduced sensitivity to MG132 inhibition of chymotrypsin-like activity (less than 0.125-fold). Genomic analysis of these mutants revealed mutations in the ROX1 gene, a heme-dependent repressor of hypoxic genes. Importantly, the ROX1 deletion strain displayed slightly improved freezing stress tolerance (about 1.5-fold). Comprehensive transcription analysis identified the ANB1 gene as a potential downstream target of Rox1. Overexpression of ANB1 enhanced freezing stress tolerance (about 1.5-fold) with increased the proteasome's activity, indicating that Rox1 contributes to changes in the proteasome's activity and freezing stress tolerance through the function of Anb1. The present data provide new insights into the mechanisms of freezing stress tolerance and help us improve the baking of frozen dough to produce higher-quality bread. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study of using a double-layered Cu/TiO2 and P4O10/TiO2 as photocatalysts for CO2 reduction with an extended wavelength of range light from ultraviolet light (UV) to infrared light (IR). The lights studied were UV + visible light (VIS) + IR, VIS + IR and IR only. This study also investigated the impact of the molar ratio of CO2:H2O on the CO2 reduction performance. This study revealed that the optimum molar ratio of CO2:H2O to produce CO was 1:1, irrespective of light illumination condition, which matched the theoretical molar ratio to produce CO according to the reaction scheme of CO2 reduction with H2O. Comparing the results of double-layered Cu/TiO2 and P4O10/TiO2 with those of double-layered TiO2 obtained under the UV + VIS + IR light illumination condition, the highest concentration of formed CO and the molar quantity of formed CO per unit weight of the photocatalyst increased by 281 ppmV and 0.8 μmol/g, in the case of the molar ratio of CO2:H2O = 1:1. With IR-only illumination, the highest concentration of formed CO and the molar quantity of CO formed per unit weight of the photocatalyst was 251 ppmV and 4.7 μmol/g, respectively. [ABSTRACT FROM AUTHOR]

Aim: To determine the apparent diffusion coefficient (ADC) in brain structures during the first 2 weeks of life and its relation with neurological outcome for hypoxic–ischaemic encephalopathy (HIE) in term neonates. Methods: We retrospectively evaluated 56 term‐born neonates. The ADC values were measured for 11 brain regions. The clinical outcomes at least 2 years of age were defined as normal outcome, mild disability and severe disability. The area under curves (AUCs) by ROC analysis were performed to predict the neurodevelopmental outcomes. The clinical outcomes were compared between favourable outcome and adverse outcome and also between normal outcome and unfavourable outcome. Results: Thirty‐four patients were judged as normal outcome, 10 as mild disability and 12 as severe disability. When the clinical outcomes were compared between favourable outcome and adverse outcome, the AUC on the 1st week was highest value at the thalamus. When the clinical outcomes were compared between normal outcome and unfavourable outcome, the AUC on the 1st week was highest at the thalamus. Conclusion: The ADC values in the thalamus in the 1st week can predict the neurological outcome. The ADC values in centrum semiovale on the 2nd week can be used to predict neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Although proline is the most or second most abundant amino acid in wort and grape must, it is not fully consumed by the yeast Saccharomyces cerevisiae during alcoholic fermentation, unlike other amino acids. Our previous studies showed that arginine, the third most abundant amino acid in wort, inhibits the utilization of proline in most strains of S. cerevisiae. Furthermore, we found that some non-Saccharomyces yeasts utilized proline in a specific artificial medium with arginine and proline as the only nitrogen source, but these yeasts were not suitable for beer fermentation due to their low alcohol productivity. For yeasts to be useful for brewing, they need to utilize proline and produce alcohol during fermentation. In this study, 11 S. cerevisiae strains and 10 non-Saccharomyces yeast strains in the Phaff Yeast Culture Collection were identified that utilize proline effectively. Notably, two of these S. cerevisiae strains, UCDFST 40-144 and 68-44, utilize proline and produce sufficient alcohol in the beer fermentation model used. These strains have the potential to create distinctive beer products that are specifically alcoholic but with a reduction in proline in the finished beer. [ABSTRACT FROM AUTHOR]

Since photocatalytic reactions are surface reactions, enhancing gas movement around the photocatalyst could improve photocatalytic CO2 reduction performance. A new approach using black body material to enhance the gas movement around the photocatalyst based on the natural thermosiphon movement of gases around a photocatalyst has been proposed and confirmed experimentally, but the heat-transfer mechanism of the phenomena has not yet been clarified. The aim of this study is to clarify the corresponding heat-transfer mechanism. This study calculated the temperature of the CO2/NH3 gas mixture around a P4O10/TiO2 photocatalyst using the heat-transfer formula. No difference was found between the temperature increase (Tg) from the temperature at the beginning of the CO2 reduction experiment (Tini) and the temperature of the CO2/NH3 gas mixture measured experimentally via thermocouple (Te) under the following illumination conditions: a Xe lamp with visible light (VIS) + infrared light (IR) and IR only. The heat-transfer model proposed in this study predicts Tg well under illumination from a Xe lamp with VIS + IR as well as under IR illumination only. On the other hand, the difference found between Tg and Te was as large as 10 °C under illumination from a Xe lamp with ultraviolet light (UV) + VIS + IR. [ABSTRACT FROM AUTHOR]

Purpose: X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by variants in Bruton's tyrosine kinase (BTK). XLA patients require lifelong immunoglobulin replacement therapy (IgRT). Only few XLA patients are indicated for allogeneic hematopoietic cell transplantation (HCT) because of severe complications. Accordingly, the published transplantation experience in XLA is minimal. We aimed to collect clinical data of XLA patients who received HCT in an international framework and to establish appropriate transplantation criteria and methods for XLA patients. Methods: XLA patients were recruited through a questionnaire and a literature review. The data are on patient characteristics and transplantation methods and outcomes. Results: In this study, twenty-two XLA patients who underwent HCT were recruited. The indication for HCT was recurrent or life-threatening infection in sixteen patients, malignancy in three, and other factors in three. A myeloablative conditioning, reduced toxicity myeloablative conditioning (RT-MAC), and reduced intensity conditioning (RIC) were selected in four, ten, and eight patients, respectively. Engraftment was achieved in 21 patients (95%). In all patients, 2-year overall survival (OS) and event-free survival (EFS) were 86% and 77%, respectively. In patients who received RT-MAC or RIC using treosulfan, busulfan, or melphalan, 2-year OS and EFS were 82% and 71%, respectively. Finally, twenty-one patients (95%) obtained complete or stable high-level mixed chimerism (50–95%), and the 1-year discontinuation rate of IgRT was 89%. Conclusion: Based on the concept in which IgRT is the standard treatment for XLA, HCT may be an effective and safe alternative treatment option for XLA patients, and IgRT can be discontinued following transplantation. It is ideal to perform HCT in XLA patients for whom transplantation is indicated before they develop organ damage. [ABSTRACT FROM AUTHOR]

The present study aims to analyze the performance characteristics of the biogas dry reforming process conducted in a membrane reactor using Ni/Cr catalysts and to compare these characteristics with those obtained using pure Ni catalysts. The effect of the pre-set reaction temperature, the molar ratio of CH4:CO2 and the pressure difference between the reaction chamber and the sweep chamber on the characteristics of biogas dry reforming is analyzed. In the present work, the molar ratio of the supplied CH4:CO2 is varied to 1.5:1, 1:1 and 1:1.5. In this case, CH4:CO2 = 1.5:1 simulates a biogas. The pressure difference between the reaction chamber and the sweep chamber is varied to 0 MPa, 0.010 MPa and 0.020 MPa. The reaction temperature is changed to 400 °C, 500 °C and 600 °C. It is revealed that the highest concentration of H2 is achieved using a Ni/Cr catalyst when the molar ratio of CH4:CO2 is 1.5:1 at the differential pressure of 0.010 MPa and the reaction temperature of 600 °C. Under this condition, the H2 yield, H2 selectivity and thermal efficiency are 12.8%, 17.5% and 174%, respectively. The concentration of the H2 produced using a Ni/Cr catalyst is larger than that produced using a Ni catalyst regardless of the pre-set reaction temperature, the molar ratio of CH4:CO2 and the differential pressure. [ABSTRACT FROM AUTHOR]

Proline is the most abundant amino acid in wine and beer, because the yeast Saccharomyces cerevisiae hardly assimilates proline during fermentation processes. Our previous studies showed that arginine induces endocytosis of the proline transporter Put4, resulting in inhibition of proline utilization. We here report a possible role of arginine sensing in the inhibition of proline utilization. We first found that two basic amino acids, ornithine, and lysine, inhibit proline utilization by inducing Put4 endocytosis in a manner similar to arginine, but citrulline does not. Our genetic screening revealed that the arginine transporter Can1 is involved in the inhibition of proline utilization by arginine. Intriguingly, the arginine uptake activity of Can1 was not required for the arginine‐dependent inhibition of proline utilization, suggesting that Can1 has a function beyond its commonly known function of transporting arginine. More importantly, our biochemical analyses revealed that Can1 activates signaling cascades of protein kinase A in response to extracellular arginine. Hence, we proposed that Can1 regulates proline utilization by functioning as a transceptor possessing the activity of both a transporter and receptor of arginine. Take‐away: Basic amino acids inhibit proline utilization by inducing Put4 endocytosis.Can1 is involved in the inhibition of proline utilization in yeast.Can1 is a transceptor acting as both a transporter and receptor of arginine. [ABSTRACT FROM AUTHOR]

Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals. [ABSTRACT FROM AUTHOR]

In hydrogen energy systems, the polymer electrolyte fuel cell (PEFC) is an important component. The purpose of this study is to clarify the effect of separator thickness (s.t.) in PEFC on the distributions of mass such as H2, O2, H2O and current density when PEFC is operated at 363 K and 373 K. The relative humidity (RH) of supply gases also impacts the operation. The numerical simulation (using a 3D model) with COMSOL Multiphysics has been conducted to analyze the characteristics of PEFC. It has been observed that the molar concentration of H2 using s.t. of 2.0 mm is smaller compared with the thinner s.t. cases at the initial operation temperature of a cell (Tini) = 363 K and 373 K. The molar concentration of O2 using s.t. of 2.0 mm is smaller compared with the thinner s.t. cases at Tini = 373 K, as well as the case for the RH of supply gases at the anode of 40%RH and cathode of 40%RH (A40%RH/C40%RH) irrespective of Tini. Additionally, it has been clarified that the molar concentration of H2O maintains a low value along with the gas channel at Tini = 373 K using s.t. of 1.5 mm and 1.0 mm. Moreover, it has been clarified that the current density using s.t. of 2.0 mm is the highest among the different s.t. irrespective of Tini, which is the most remarkable in the case of A40%RH&C40%RH. [ABSTRACT FROM AUTHOR]

The fruit-like aroma of two valine-derived volatiles, isobutanol and isobutyl acetate, has great impact on the flavour and taste of alcoholic beverages, including sake, a traditional Japanese alcoholic beverage. With the growing worldwide interest in sake, breeding of yeast strains with intracellular valine accumulation is a promising approach to meet a demand for sakes with a variety of flavour and taste by increasing the valine-derived aromas. We here isolated a valine-accumulating sake yeast mutant (K7-V7) and identified a novel amino acid substitution, Ala31Thr, on Ilv6, a regulatory subunit for acetohydroxy acid synthase. Expression of the Ala31Thr variant Ilv6 conferred valine accumulation on the laboratory yeast cells, leading to increased isobutanol production. Additionally, enzymatic analysis revealed that Ala31Thr substitution in Ilv6 decreased sensitivity to feedback inhibition by valine. This study demonstrated for the first time that an N-terminal arm conserved in the regulatory subunit of fungal acetohydroxy acid synthase is involved in the allosteric regulation by valine. Moreover, sake brewed with strain K7-V7 contained 1.5-fold higher levels of isobutanol and isobutyl acetate than sake brewed with the parental strain. Our findings will contribute to the brewing of distinctive sakes and the development of yeast strains with increased production of valine-derived compounds. Ala31Thr substitution in the regulatory subunit of acetohydroxy acid synthase partially removed feedback inhibition by valine and the A31T variant enabled high-level production of valine and isobutanol in yeast. [ABSTRACT FROM AUTHOR]

Aim: Clinical trials of antidepressants often fail to demonstrate their efficacy versus placebo, suggesting that patient selection based on physician ratings of depression may contribute to a high placebo response. Methods: In the CCT‐004 trial of vortioxetine, central monitoring was employed to compare physician and patient ratings of depression and anxiety at baseline and over time to identify factors contributing to a large placebo response, as well as to explore the potential of a unique patient‐rated clinical measure combining QIDS‐J and Himorogi Self‐rating Anxiety Scale (HSAS), to contribute to optimal patient selection at baseline and patient monitoring over time. Results: The CCT‐004 trial showed similar trends between the QIDS‐J and MADRS (Montgomery‐Åsberg Depression Rating Scale) ratings. It was suggested that central monitoring of the QIDS‐J and MADRS ratings of depression and anxiety symptoms helped reduce the baseline score inflation by calling the study sites' attention to discrepancies between these ratings at baseline; it also allowed these ratings to be assessed for their concordance over time. Of note, MDD patients with baseline QIDS‐J scores ≥11/HSAS ≤19 were associated with the smallest placebo response, with the effect size being larger than that for those with QIDS‐J scores ≤10/HSAS ≥20. Conclusion: The use of both physician and patient ratings of depression and anxiety symptoms at baseline and over time, as well as their central monitoring, helped minimize the baseline score inflation and optimize patient monitoring over time, and allowed the antidepressant to be evaluated for its full therapeutic potential. [ABSTRACT FROM AUTHOR]

KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy. The molecular heterogeneity of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) remains poorly characterised. Here, the authors perform multi-omics analysis for 84 ALL patients and suggest 5 distinct subgroups for risk stratification and personalised treatment.' [ABSTRACT FROM AUTHOR]

The aim of this study is to clarify the impact of the thickness of a gas diffusion layer (GDL) and a micro porous layer (MPL) on the distributions of gas, H2O, and current density in a polymer electrolyte fuel cell (PEFC) which is operated at 363 K and 373 K and with various thicknesses of polymer electrolyte membrane (PEM) as well as a relative humidity (RH) of supply gas. These investigations are carried out by numerical simulation using the 3D model with COMSOL Multiphysics. In the case of Nafion 115, which is the thicker PEM, the change in the molar concentration of H2O from the inlet to the outlet with MPL is larger than that without MPL irrespective of the thickness of GDL, Tini and RH condition. In the case of Nafion NRE-212, which is the thinner PEM, the change in the molar concentration of H2O from the inlet to the outlet is larger with MPL than that without MPL in the case of TGP-H-060 (the thicker commercial GDL), while that is smaller with MPL than that without MPL in the case of TGP-H-030 (the thinner commercial GDL). These results exhibit the same tendency as the results of the numerical simulation on the current density. [ABSTRACT FROM AUTHOR]

Background: The morphological changes in the pons and cerebellum of neonates experiencing profound asphyxia in the early period of life remain to be clarified. Purpose: To assess the changes in the size of the pons and cerebellum during the first two weeks of life in term neonates with pontine and cerebellar injury caused by hypoxic-ischemic encephalopathy in comparison with a control group. Material and Methods: Two groups were investigated: a group with pontine/cerebellar injury (PCI) (n = 10) demonstrated by magnetic resonance imaging (MRI) diffusion-weighted imaging; and a control group without PCI – focal-multifocal white matter injury and a normal pattern (n = 24). The anteroposterior diameter (APD) and height of the pons and cerebellar vermis, and the transverse width of the cerebellum were measured twice in the first and second weeks of life. Differences between the groups were analyzed statistically using paired and unpaired Student's t-test at a significance level of P < 0.05. Results: In the PCI group, the pontine APD and cerebellar vermian height were significantly decreased in the second week. An increase of pons and cerebellar size was evident during the first two weeks of life in the control groups. Conclusion: Infants with PCI and profound asphyxia show rapid decreases in pontine APD and cerebellar vermian height within the first two weeks of life. [ABSTRACT FROM AUTHOR]

Inborn errors of immunity (IEI) are caused by germline genetic mutations, resulting in defects of innate or acquired immunity. Hematopoietic cell transplantation (HCT) is indicated for curative therapy especially in patients with IEI who develop fatal opportunistic infections or severe manifestations of immune dysregulation. The first successful HCT for severe combined immunodeficiency (SCID) was reported in 1968. Since then, the indications for HCT have expanded from SCID to various non-SCID IEI. In general, HCT for IEI differs from that for other hematological malignancies in that the goal is not to eradicate certain immune cells but to achieve immune reconstitution. European Society for Blood and Marrow Transplantation/European Society for Immunodeficiencies guidelines recommend reduced-intensity conditioning to avoid treatment-related toxicity, and the optimal conditioning regimen should be considered for each IEI. We review conditioning regimens for some representative IEI disorders in Japanese and worldwide cohort studies, and future strategies for treating IEI. [ABSTRACT FROM AUTHOR]

The review of medical charts for infants having IVH confirmed by MRI disclosed that in 29 (78%) of 37 infants the presence of IVH was confirmed by US. [5] In a study of preterm neonates aged 23 to 28 gestational weeks in the United States, Bolisetty et al reported a mortality of 11% in infants without IVH and of 32% in infants with IVH. Keywords: magnetic resonance imaging; newborn; low-birth-weight infants; intraventricular hemorrhage EN magnetic resonance imaging newborn low-birth-weight infants intraventricular hemorrhage 246 250 5 09/07/22 20220701 NES 220701 Conflict of Interest None declared. Usually, grade 1 to 2 IVH is considered as mild IVH and grade 3 to 4 as severe IVH. [Extracted from the article]

The New Energy and Industry Technology Development Organization (NEDO) road map (Japan, 2017) has proposed that a polymer electrolyte fuel cell (PEFC) system, which operates at a temperature of 90 °C and 100 °C, be applied for stationary and mobility usage, respectively. This study suggests using a thin polymer electrolyte membrane (PEM) and a thin gas diffusion layer (GDL), at the same time, to achieve better power-generation performance, at a higher temperature than usual. The focus of this paper is to clarify the effect of separator thickness on the distribution of temperature at the reaction surface (Treact), with the relative humidity (RH) of the supply gasses and initial operation temperature (Tini), quantitatively. In this study, separator thickness is investigated in a system using a thin PEM and a thin GDL. Moreover, this study investigates the difference between the maximum temperature and the minimum temperature obtained from the distribution of Treact as well as the relation between the standard deviation of Treact − Tini and total voltage, to clarify the effect of separator thickness. The impact of the flow rates of the supply gases on the distribution of Treact is not large, among the investigated conditions. It is noticed that the temperature distribution is wider when a separator thickness of 2.0 mm is selected. On the other hand, it is observed that the temperature increases along with the gas flow through the gas channel, by approximately 2 °C, when using a separator thickness between 1.5 mm and 1.0 mm. The impact of the RH on the distributions of Treact − Tini is larger at Tini = 100 °C, when a separator thickness of 1.0 mm is selected. It is revealed that the wider temperature distribution provides a reduction in power-generation performance. This study proposes that the thin separators, i.e., with a thickness of 1.5 mm and 1.0 mm, are not suitable for higher temperature operation than usual. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted imaging performed shortly after brain injury has been shown to facilitate visualization of acute corticospinal tract injury known as "pre-Wallerian degeneration." Objective: The aim of this study was to determine whether diffusion restriction in the corticospinal tract and corpus callosum occurs within the first 2 weeks after birth in neonates with neonatal hypoxic–ischemic encephalopathy. Materials and methods: We enrolled a consecutive series of 66 infants diagnosed with hypoxic–ischemic encephalopathy who underwent MRI. We evaluated diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values to assess the presence of restricted diffusion in the corticospinal tract and corpus callosum. Next, we compared ADC values in the corticospinal tract and in the splenium and genu of the corpus callosum of infants with abnormal pattern on MRI with those of control infants, who showed a normal pattern on MRI. We attempted to follow all infants with hypoxic–ischemic encephalopathy until 18 months of age and assess them using a standardized neurologic examination. Results: After exclusions, we recruited 25 infants with abnormal MRI and 20 with normal MRI (controls). Among these 45 neonates, pre-Wallerian degeneration was visualized in the corticospinal tract in 10 neonates and in the corpus callosum in 12. The ADC values in the corticospinal tract in the first week were significantly lower than they were in the second week. Infants with pre-Wallerian degeneration in the corticospinal tract showed an unfavorable outcome. Conclusion: Pre-Wallerian degeneration was visualized in the corticospinal tract and corpus callosum and was associated with extensive brain injury caused by hypoxic–ischemic encephalopathy. The changes in signal were observed to evolve over time within the first 2 weeks. The clinical outcome of infants having pre-Wallerian degeneration in the corticospinal tract was unfavorable. [ABSTRACT FROM AUTHOR]

This paper argues how the study of religion in Japan influenced the nation's conduct during the Asia-Pacific War (1931–1945). Specifically, the paper addresses the wartime national indoctrination texts of Katō Totsudō 加藤咄堂 (a.k.a. Katō Yūichirō 加藤熊一郎, 1870–1949). Although Katō was not strictly a religious scholar, analyzing Katō's texts is significant in understanding the influence of religious theory and religious studies discourse on Japanese society during the war. To illustrate this point, this paper introduces previous studies that have discussed the movements of religious scholars during the war. It then clarifies the significance of discussing Katō's texts, followed by an introduction to what has been revealed about Katō so far. The paper then examines Katō's wartime texts that discuss the relationship between war, faith and the readiness to die. The East–West comparison of views of life and death used by Katō was characterized as a wartime application of comparative religion. It was intended to emphasize Japan's superiority over other countries. Such features agitated Japanese readers to proactively enter the fight to the death through spiritual mobilization in a total war system. [ABSTRACT FROM AUTHOR]

Gas movement around and/or through the photocatalyst is thought to be an inhibition factor to promote photocatalytic CO2 reduction performance. In this study, a hypothesis is put forward that the natural thermosiphon movement of gases around the photocatalyst can be improved by using black body material/surface. The black body material/surface that is placed underneath the photocatalyst in the reactor would be heated by absorbing light and then this heats up the gases to promote their movement around/through the photocatalyst. The aim of this study is to prove or disprove this hypothesis by conducting CO2 reduction performance of a TiO2 photocatalyst with NH3 under the conditions without black body material (W/O B.B.), with one black body material (W B.B.-1), and with three black body materials (W B.B.-3). The impact of molar ratio of CO2/NH3 on CO2 reduction performance is also investigated. This study revealed/proved that the hypothesis worked and that the CO2 reduction performance is promoted more with W B.B.-3 compared to that with W B.B.-1. The maximum concentration of formed CO with W B.B.-3 is two to five times as large as that under the condition W/O B.B. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. Methods: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974–2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). Results: The 10-year overall survival (OS) of the patients who received HCT in 2006–2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006–2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). Conclusion: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID. [ABSTRACT FROM AUTHOR]

Objective: There has been no previous report of diffusion restriction in the optic radiation of term neonates with hypoxic-ischemic encephalopathy. Here, using diffusion-weighted magnetic resonance imaging (MRI), we assessed diffusion restriction in the optic radiation within the first 2 weeks of life and estimated signal changes and the apparent diffusion coefficient in the optic radiation and lateral geniculate body using T1-weighted MRI. Materials and Methods: Forty-five term neonates with hypoxic-ischemic encephalopathy underwent MRI twice during the first 2 weeks of life. Diffusion-weighted imaging and apparent diffusion coefficient were used to evaluate the presence of diffusion restriction in the optic radiation and lateral geniculate body. Apparent diffusion coefficient and T1 signal changes in the optic radiation and lateral geniculate body were also compared with those in 11 control neonates showing a normal pattern on MRI. Results: Diffusion restriction in the optic radiation was observed in 29% (13/45) of the hypoxic-ischemic encephalopathy neonates at a median age of 3.5 days (range: 1-9 days). The apparent diffusion coefficient in the optic radiation of affected neonates was significantly reduced in comparison with the controls. In all neonates with optic radiation involvement, increased T1 signal intensity was observed in the optic radiation in the second week, and was also evident in in lateral geniculate body in 8 of those neonates. Conclusion: Diffusion restriction in the optic radiation is not rare among term neonates with hypoxic-ischemic encephalopathy, being visualized by diffusion-weighted imaging in the first week of life and also high-intensity T1 signal changes in the second week. This diffusion restriction in the optic radiation might be due to transsynaptic neuronal degeneration. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID). Methods: We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID. Results: The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival. Conclusions: RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID. [ABSTRACT FROM AUTHOR]

BCP-ALL of the XLA patients did not show a distinctive methylation profile. X-linked agammaglobulinemia, Bruton's tyrosine kinase, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, tumor suppressor Keywords: X-linked agammaglobulinemia; Bruton's tyrosine kinase; acute lymphoblastic leukemia; acute megakaryoblastic leukemia; tumor suppressor EN X-linked agammaglobulinemia Bruton's tyrosine kinase acute lymphoblastic leukemia acute megakaryoblastic leukemia tumor suppressor 1277 1281 5 06/18/21 20210615 NES 210615 X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in I Bruton's tyrosine kinase i ( I BTK i ). Future studies in which many patients with XLA with leukemia are enrolled may be able to clarify the more detailed characteristics of leukaemic cells in XLA. [Extracted from the article]

Most patients with homozygous or compound heterozygous pathogenic ACO2 variants present with muscular hypotonia features, namely, infantile cerebellar-retinal degeneration. Recently, two studies reported rare familial cases of ACO2 variants presenting as complex hereditary spastic paraplegia (HSP) with broad clinical spectra. Here, we report the case of a 20-year-old Japanese woman with complex HSP caused by compound heterozygous ACO2 variants, revealing a new phenotype of episodic visual loss during febrile illness. [ABSTRACT FROM AUTHOR]

The article describes the case of a four-year-old boy with a somatic RUNX1 mutation who developed atypical mucocutaneous inflammatory symptoms. Highlights include vacuolar interface dermatitis with hyperkeratosis and apoptotic keratinocytes revealed by skin biopsy from an upper arm lesion, exclusion of haematologic malignancies and myelodysplastic changes, and the use of whole-exome sequencing on leukaemic cells to characterize the tumour mutation profiling.

Ubiquitination is a key signal for endocytosis of proteins on the plasma membrane. The ubiquitin ligase Rsp5 of Saccharomyces cerevisiae , which contains an amino-terminal membrane-binding C2 domain, three substrate-recognizing tryptophan-tryptophan (WW) domains and a carboxyl-terminal catalytic homologous to the E6-AP carboxyl terminus (HECT) domain, can ubiquitinate plasma membrane proteins directing them for endocytosis. Here, we examined the roles of the C2 domain in endocytosis for the downregulation of the general amino acid permease Gap1, which is one of nitrogen-regulated permeases in S. cerevisiae. First, we constructed several rsp5 mutants producing Rsp5 variants without the C2 domain or with amino acid changes of membrane-binding lysine residues. These mutants showed defects in endocytosis of Gap1 in response to a preferred nitrogen source. Intriguingly, we found that ubiquitination of Gap1 in these mutant cells was highly similar to that in wild-type cells during endocytosis. These results indicate that the C2 domain is essential for endocytosis but not for ubiquitination of substrates such as Gap1. Moreover, genetic and biochemical analyses showed that the endocytic protein Rvs167 was ubiquitinated via Rsp5 and the C2 domain was required for efficient ubiquitination in response to a preferred nitrogen source. Here, we propose a mechanism for the C2 domain-mediated endocytosis of plasma membrane permeases. [ABSTRACT FROM AUTHOR]

The refractive index and the extinction coefficient are usually inherent (noncontrollable) material characteristics. Recently, it was reported that the reflectivity of graphene in the mid‐infrared spectral range can be modified by an external bias. This report attracted much attention, but the controllable frequency/energy range is too narrow for possible applications. In this work, it is demonstrated that the potential of graphene is not limited to mid‐infrared wavelengths, but spans a much wider range including the visible spectral range. Here, back‐gated bilayer graphene is characterized in air using spectroscopic ellipsometry with a lateral resolution in the micrometer range. By applying a back‐gate voltage, the dielectric function can be modified in a broad spectral range, including the visible spectrum. To explain the change in the dielectric function, a simplified phenomenological approach which assumes that the back‐gating‐induced change in the carrier density of graphene can be described by a modified 2D Drude model is introduced. The trend of increasing values for the dielectric function with increasing sheet charge carrier density is confirmed by theoretical calculations performed in the independent particle picture. [ABSTRACT FROM AUTHOR]

Background: Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of death and disability in infants. Magnetic resonance imaging (MRI) is valuable for predicting the outcome in high-risk neonates. The relationship of pontine and cerebellar injury to outcome has not been explored sufficiently.Purpose: To characterize MRI features of pontine and cerebellar injury and to assess the clinical outcomes of these neonates.Material and Methods: The retrospective study included 59 term neonates (25 girls) examined by MRI using 1.5-T scanner in the first two weeks of life between 2008 and 2017. Involvement of the pons and cerebellum was judged as a high signal intensity on diffusion-weighted image (DWI) and a restricted diffusion on an apparent diffusion coefficient (ADC) map.Results: Pontine involvement was observed in the dorsal portion of pons in eight neonates and cerebellar involvement was observed in dentate nucleus (n = 8), cerebellar vermis (n = 3), and hemisphere (n = 1) in 11 neonates. Combined pontine and cerebellar involvement was observed in eight neonates and only cerebellar involvement in three. The pontine and cerebellar injuries were always associated with very severe brain injury including a basal ganglia/thalamus injury pattern and a total brain injury pattern. In terms of clinical outcome, all but four lost to follow-up, had severe cerebral palsy.Conclusion: Pontine and cerebellar involvement occurred in the dorsal portion of pons and mostly dentate nucleus and was always associated with a more severe brain injury pattern as well as being predictive of major disability. [ABSTRACT FROM AUTHOR]

Sake is a traditional Japanese alcoholic beverage brewed with the yeast Saccharomyces cerevisiae. Sake taste is affected by sugars, organic acids, and amino acids. We previously isolated mutants resistant to the proline analogue azetidine-2-carboxylate derived from a diploid sake yeast strain. Some of the mutants produced a greater amount of proline in the brewed sake. One of them (strain K-9-AZC) carried a novel mutation in the PRO1 gene encoding the Gln79His variant of the γ-glutamyl kinase Pro1, a key enzyme in proline biosynthesis in S. cerevisiae. This mutation resulted in extreme desensitization to feedback inhibition by proline, leading to proline overproduction. Interestingly, sake brewed with K-9-AZC contained 3.7-fold more proline, but only 25% less succinate than sake brewed with the parent strain. Metabolome analysis suggests that the decrease in succinate was attributable to a lower level of 2-oxoglutarate, which is converted into glutamate. The approach here could be a practical method for breeding of yeast strains involved in the diversity of sake taste. [ABSTRACT FROM AUTHOR]

Proline is a predominant amino acid in grape must, but it is poorly utilized by the yeast Saccharomyces cerevisiae in wine‐making processes. This sometimes leads to a nitrogen deficiency during fermentation and proline accumulation in wine. Although the presence of other nitrogen sources under fermentation conditions is likely to interfere with proline utilization, the inhibitory mechanisms of proline utilization remain unclear. In this study, we examined the effect of arginine on proline utilization in S. cerevisiae. We first constructed a proline auxotrophic yeast strain and identified an inhibitory factor by observing the growth of cells when proline was present as a sole nitrogen source. Intriguingly, we found that arginine, and not ammonium ion, clearly inhibited the growth of proline auxotrophic cells. In addition, arginine prevented the proline consumption of wild‐type and proline auxotrophic cells, indicating that arginine is an inhibitory factor of proline utilization in yeast. Next, quantitative polymerase chain reaction (PCR) analysis showed that arginine partially repressed the expression of genes involved in proline degradation and uptake. We then observed that arginine induced the endocytosis of the proline transporters Put4 and Gap1, whereas ammonium induced the endocytosis of only Gap1. Hence, our results may involve an important mechanism for arginine‐mediated inhibition of proline utilization in yeast. The breeding of yeast that utilizes proline efficiently could be promising for the improvement of wine quality. [ABSTRACT FROM AUTHOR]

Purpose: The most severe form of profound asphyxia in neonates is now known as "total brain injury," which forms part of the clinical spectrum of hypoxic-ischemic encephalopathy (HIE). Although the magnetic resonance (MR) imaging features of total brain injury remain to be determined, a widespread hyperintensity of the supratentorial brain, known as the "white cerebrum sign," has been reported in diffusion-weighted images (DWI). Methods: We examined four neonates who developed severe profound asphyxia. Results: In the first week of life, all neonates showed the white cerebrum sign on DWI. A follow-up of these cases over a period of 1 month revealed diffuse bilateral multicystic encephalomalacia (MCE) as well as shrinkage of the basal ganglia and thalami (BG/T). These MR findings were common to all neonates, and all the neonates had severe adverse clinical outcomes. Conclusion: Neonates, who exhibit the white cerebrum sign on MR imaging due to profound asphyxia, develop major disabilities, and MCE with shrinkage of the BG/T suggests miserable outcomes. [ABSTRACT FROM AUTHOR]

High-throughput analysis revealed the unique immunoglobulin gene rearrangements in plasmacytoma-like post-transplant lymphoproliferative disorder Keywords: autoimmune disease; plasmacytoma; post-transplant lymphoproliferative disorder; X-linked inhibitor of apoptosis protein (XIAP) deficiency EN autoimmune disease plasmacytoma post-transplant lymphoproliferative disorder X-linked inhibitor of apoptosis protein (XIAP) deficiency e164 e168 5 05/19/20 20200515 NES 200515 Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ and haematopoietic stem cell transplantation (SOT, HSCT), which occurs in 1-20% of transplant recipients.[1] The majority of PTLD cells are of the B-cell type, but <5% of PTLD cells are plasma-cell type, including plasmacytoma-like lesion and plasma cell myeloma.[1] Although their worse prognosis than non-PTLD myeloma is clinically significant, only case reports and registry studies have been available.[2] In the present study, we describe the first detailed analysis of plasmacytoma-like PTLD. These findings were consistent with the lambda light-chain restriction of PTLD cells, suggesting that multiple autoantibodies produced by PTLD cells led to multiple autoimmune diseases. Four patients developed diseases within 16 months, whereas plasma cell-type PTLD usually demonstrates a delayed onset.[2] These observations suggest that autoreactive plasma cells of recipient origin could contribute to not only PTLD but also autoimmune diseases after transplantation. [Extracted from the article]

A 64-year-old woman was infected with hepatitis E virus (HEV) during chemotherapy for leukemia. By retrospective analyses of stored serum from the blood products and the patient, the source of the infection was determined to be platelet concentration (PC) transfused during chemotherapy. The partial nucleotide sequence of the HEV strain isolated from the donated PC and that from the patient's sera was identical and was subgenotype 3b. Clinical indicators such as alanine aminotransferase, HEV RNA titer, and anti-HEV antibodies in the serum were investigated from the beginning of the infection until 1 year after the termination of HEV infection. HEV RNA had propagated over 6 months and then cleared spontaneously after the completion of chemotherapy. Anti-HEV antibodies appeared in the serum just before the clearance of HEV RNA. Interestingly, HEV RNA was detected in the patient's urine, spinal fluid, and saliva. The HEV RNA titers in those samples were much lower than in the serum and feces. No renal, neurological, or salivary gland disorders appeared during the follow-up. We observed virological and biochemical progress and cure of transfusion-transmitted chronic hepatitis E in the patient despite an immunosuppressive status during and after chemotherapy against hematological malignancy. [ABSTRACT FROM AUTHOR]

Aim: The burden of major depressive disorder (MDD) in Japan is high. This study aimed to evaluate the efficacy and safety of the multimodal antidepressant vortioxetine in Japanese patients with MDD. Methods: Japanese patients aged 20–75 years with recurrent MDD and a Montgomery–Åsberg Depression Rating Scale (MADRS) score ≥ 26 were randomized to vortioxetine 10 or 20 mg or placebo in a phase‐3, double‐blind, 8‐week study. The primary end‐point was change in MADRS total score from baseline. Secondary end‐points included MADRS response and remission rates, change in Hamilton Rating Scale for Depression‐17 item (HAM‐D17) score, and other measures of depressive symptoms, including Clinical Global Impression of Severity (CGI‐S), Clinical Global Impression of Improvement (CGI‐I), and Sheehan Disability Scale (SDS). Cognitive function was assessed using Digit Symbol Substitution Test (DSST) score and Perceived Deficits Questionnaire‐5 item (PDQ‐5) score. Results: Vortioxetine 10 mg (n = 165) and 20 mg (n = 163) reduced MADRS total score by 2.66 and 3.07 points versus placebo (n = 161) after 8 weeks (P < 0.01 for each dose), respectively. MADRS response and remission rates were also significantly greater with vortioxetine than with placebo (P < 0.05 for both doses). Vortioxetine 10 and 20 mg significantly improved HAM‐D17 score, CGI‐I score, and SDS total score after 8 weeks. PDQ‐5 score was significantly improved in subjects administered vortioxetine, while DSST scores showed no significant difference. Vortioxetine was generally well tolerated. Conclusion: Vortioxetine at both the 10‐ and 20‐mg/day doses demonstrated robust antidepressant efficacy in Japanese patients with MDD, and was well tolerated over the 8‐week treatment period. [ABSTRACT FROM AUTHOR]

The Hahajima Seamount is located at the junction between the Izu–Bonin and Mariana forearc slopes in the northwest Pacific Ocean, and between the Philippine Sea Plate and the Ogasawara Plateau on the Pacific Plate. Despite numerous previous studies, the origin of the Hahajima Seamount remains controversial. Here we constrain its origin based on sedimentological and chronological analyses of shallow‐water carbonates collected from the eastern slope of the seamount. The carbonates are dominated by floatstones with numerous mollusks. Gravel‐sized bioclasts include mollusks (e.g. nerineids and rudists) and local calcareous spines and minor amounts of corals. Sand‐sized components include bioclasts of benthic foraminifers and dasycladalean algae, and non‐skeletal grains of intraclasts and peloids, with no ooids. Most of the bioclasts are bioeroded and coated with micrite envelopes. The Sr isotope ages of the samples fell into two ranges: Berriasian or Aptian (140.3 Ma or 118.3–113.2 Ma, respectively) and Coniacian to Campanian (86.5–77.2 Ma). Shallow‐water carbonates on the Hahajima Seamount are similar in lithology and Sr isotope ages to those on the Ogasawara Plateau located to the east, on the opposite side of the Izu–Bonin Trench (i.e. on the Pacific Plate). This indicates that the shallow‐water carbonates on the eastern slope of the Hahajima Seamount were not deposited in situ, but instead originated from the Ogasawara Plateau. The eastern section of this seamount can thus be interpreted as an accretionary wedge. [ABSTRACT FROM AUTHOR]