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Abstract The domain of psychiatric drug development is currently witnessing a notable transformation, with a paramount emphasis on targeting nonmonoamine receptors and exploring inventive mechanisms of action. This paper presents an overview of the ongoing advancements in antipsychotic and antidepressant drug development. Historically, antipsychotics predominantly targeted dopamine receptors, but there is now an escalating interest in drugs that act on alternative receptors, exemplified by the TAAR1 receptor. One noteworthy candidate is Ulotaront (SEP‐363856), an agent acting as a TAAR1 agonist with 5‐HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side‐effects. Similarly, MIN‐101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)‐approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor‐positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK‐653 (NBI‐1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric modulation, respectively. This paper underscores the transformative potential of these novel drug candidates in psychiatric treatment and their ability to address cases that were previously treatment‐resistant. By focusing on nonmonoamine receptors and introducing innovative mechanisms, these drugs offer a promising prospect of improved outcomes for individuals suffering from schizophrenia and MDD. Thus, sustained attention and dedication to the development of such drugs are essential to augmenting the therapeutic options available for psychiatric patients.

To investigate the Mo release behavior and its influence on the oxidation of UO2/mixed oxide (MOX) fuel, the oxidation and evaporation (O&E) behaviors of Mo powders and their influencing mechanisms with respect to oxygen partial pressure around powders (pO2s) were researched by using a thermogravimetric analysis technique under Ar-0.1 % O2, Ar-1.0 % O2, and Ar-1.5 % O2 atmospheres in the temperature range from 1473 to 1673 K. The study results reveal that Mo O&E could quickly consume oxygen, substantially decreasing pO2s. This decrease in pO2s facilitates the attainment of an oxygen mass balance by enhancing the diffusion rate of O2(g) towards the powder surfaces and decelerating the O&E rates of the powders. Subsequently, the oxygen consumption rate with respect to Mo release (FO-con) and the potential oxidation rate of UO2 nuclear fuels (FO-ads) under the typical accident conditions created in VERCORS were estimated using the latest analytical model of Mo and the existing fuel oxidation model, respectively. The results demonstrate that, as accident proceeds, FO-con has the potential to surpass FO-ads, thereby retarding the oxidation of nuclear fuel.

Laughter has a protective effect on human health. The spread of coronavirus disease 2019 (COVID-19) has changed opportunities for face-to-face communication and might decrease opportunities for laughter. This cross-sectional study aimed to investigate whether the decrease in face-to-face communication during the COVID-19 pandemic is associated with a decrease in laughter. Additionally, we investigated whether an increase in online communication mitigates this association. Data from the “Japan COVID-19 and Society Internet Survey (JACSIS),” conducted between August and September 2020, were used. Participants aged 15–79 years were included in this study. The outcome was a decrease in laughter before the onset of the COVID-19 pandemic. The explanatory variables were decreased face-to-face communication with friends and increased online communication (text message, telephone, and video contact). Causal mediation analysis was used to calculate prevalence ratios (PRs) and 95 % confidence intervals (CIs) of the controlled direct effects of increased online communication. Furthermore, the proportions eliminated (PEs) by an increase in online communication were calculated. Among the 25,482 participants, 40.4 % had decreased face-to-face communication and 21.4 % had a decreased frequency of laughter. After adjusting for confounders, a decrease in face-to-face communication was significantly associated with a decrease in laughter (PR = 1.62, 95 %CI = 1.55–1.70). PEs for decrease in laughter were 27.2 % (95 %CI = –2.0 to 56.4) for text-based communication, 36.1 % (95 %CI = 12.3–59.8) for telephone-based communication, and 28.6 % (95 %CI = 0.6–56.6) for video-based communication. Although a decrease in face-to-face communication was associated with a decrease in laughter during the COVID-19 pandemic, online communication, particularly telephone-based communication, mitigated this association.

Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs).Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6 weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated.Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns.Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC.

This study investigates the impact of different control strategies on the performance of a single desiccant wheel dehumidifier with a heat recovery in real-world applications. A method to minimize the performance fluctuation as an effect of dynamic system performance response is proposed. First, the effect of regeneration heat input (Qin) changes on the system performance of the above dehumidifier was clarified. Second, the performance behavior was examined in response to transient conditions for different operation modes and was used to determine the most effective operation mode. Qin was assumed to change over time, which would influence the regeneration temperature and airflow velocity. The results showed that fluctuating Qin reduces the dehumidification capacity (ΔX) and coefficient of regeneration performance (COPreg). Therefore, a rotational control speed was implemented in the optimum operation mode, which was effective in preventing the system performance decline and accelerated the emergence of the rotational speed control effect.

Abstract The chemical order and disorder of solids have a decisive influence on the material properties. There are numerous materials exhibiting chemical order/disorder of atoms with similar X-ray atomic scattering factors and similar neutron scattering lengths. It is difficult to investigate such order/disorder hidden in the data obtained from conventional diffraction methods. Herein, we quantitatively determined the Mo/Nb order in the high ion conductor Ba7Nb4MoO20 by a technique combining resonant X-ray diffraction, solid-state nuclear magnetic resonance (NMR) and first-principle calculations. NMR provided direct evidence that Mo atoms occupy only the M2 site near the intrinsically oxygen-deficient ion-conducting layer. Resonant X-ray diffraction determined the occupancy factors of Mo atoms at the M2 and other sites to be 0.50 and 0.00, respectively. These findings provide a basis for the development of ion conductors. This combined technique would open a new avenue for in-depth investigation of the hidden chemical order/disorder in materials.

ABSTRACT: Objectives: The association between toothbrushing and coronavirus disease 2019 (COVID-19) infections is unknown. The aim of this study was to test the hypothesis that the change in time and frequency of toothbrushing is associated with having COVID-19 symptoms. Methods: In this 8-month retrospective cohort study, we used the data from the Japan COVID-19 and Society Internet Survey (JACSIS; N = 22,366), which was conducted between August and September 2020. The logistic regression analyses were used to calculate the odds ratios (ORs) of having the 3 main COVID-19 symptoms (high fever, cough, and taste and smell disorder). Confounders were age, sex, educational attainment, equivalised income level, self-rated health, health literacy, and living area. Results: The mean age of the participants was 49 years (SD = ±17.3), and 49.2% were male. Overall 2704 (12.1%) participants changed (increased or decreased) the time and frequency of toothbrushing, whilst 19,662 (87.9%) did not change. Only 60 participants (0.3%) had the 3 main COVID-19 symptoms. All logistic regression models showed that those who had a change in time and frequency of toothbrushing had higher odds of having the 3 main COVID-19 symptoms compared to those who had unchanged time and frequency of toothbrushing. The ORs ranged from 6.00 (95% confidence interval [CI], 3.60–9.99) in the crude model to 4.08 (95% CI, 2.38–6.98) in the fully adjusted model. Conclusions: The change in time and frequency of toothbrushing from before to after the COVID-19 pandemic was associated with having the 3 main COVID-19 symptoms.

Introduction Regressed germ cell tumors are a rare disease commonly diagnosed with metastatic symptoms without local symptoms in the testis. Case presentation A 33‐year‐old man with azoospermia was referred to our hospital. His right testis was slightly swollen, and ultrasonography revealed hypoechogenicity of the right testis with decreased blood flow. Right high orchiectomy was performed. Pathologically, the seminiferous tubules were absent or highly atrophied with vitrification degeneration; however, no neoplastic lesion was confirmed. One‐month post‐surgery, the patient noticed a mass in the left supraclavicular fossa, of which a biopsy revealed seminoma. The patient was diagnosed with a regressed germ cell tumor and underwent systemic chemotherapy. Conclusion We reported the first case of a regressed germ cell tumor discovered due to complaints of azoospermia.

Abstract Background No clear evidence exists regarding the effects of the different periods and magnitude of spread of the COVID‐19 infection on cancer treatments. This study investigated the effects of the different periods and magnitude of COVID‐19 infection spread on in‐hospital cancer operations. Methods Medical claims data from 17 hospitals where in‐hospital operations for patients with malignant neoplasms were performed between 1 April 2017 and 31 March 2021 in Yamagata were extracted and analyzed. The critical time points as exposure used to evaluate the impact of different COVID‐19 infection spread periods on cancer operations were (1) April 2020 (emergency declaration introduced by the government) and (2) December 2020 (the second wave). From April to November 2020 and December 2020 to March 21, the number of confirmed COVID‐19 cases was 130 and 840, respectively. The 17 hospitals were classified into intervention or control groups based on whether in‐hospital treatments for patients with COVID‐19 were provided. Results The interrupted time series analysis reported that the difference in the trend of pre‐COVID‐19 and postsecond wave (March 2020 to December 2020) periods was statistically significant between groups, with 50.67 fewer operations (95% confidence interval [CI] = 12.19–89.15) performed per month in the intervention group compared with the control group. Moreover, the immediate change in the number of operations in April 2020 (beginning of the first wave) was statistically significant between groups, with 80.14 operations (95% CI = 39.62–120.67) less immediately after the first wave in the intervention group compared with the control group. Conclusion Our findings suggest that a statement of emergency by the government and the COVID‐19 infection spread are both associated with the number of cancer operations performed in the Yamagata prefecture during the COVID‐19 pandemic.

Abstract Background To evaluate whether urine laminin‐γ2 monomer (Ln‐γ2m) offers a useful biomarker for patients with non‐muscle‐invasive bladder cancer (NMIBC). Methods Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln‐γ2m was prospectively measured and accuracy was analyzed. Receiver operating characteristic (ROC) curves were determined and area under the ROC curve (AUC) was calculated for urine Ln‐γ2m, and compared to those of traditional urine tumor markers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytology. The net benefits of combining urine markers were analyzed by decision curve analysis. Results Mean urine Ln‐γ2m was significantly higher in NMIBC than in BD or HD. The AUC for urine Ln‐γ2m was significantly higher than those for urine NMP22, BTA or cytology when comparing NMIBC with HD. In patients with low‐grade NMIBC, the AUC for urine Ln‐γ2m was higher than the AUCs for NMP22, BTA or cytology. A net benefit of combined examination using urine Ln‐γ2m/uCRN with NMP22 was demonstrated. Conclusion These results suggest urine Ln‐γ2m as a potentially useful biomarker for NMIBC, particularly in cases of low‐grade cancer.

Recent research has shown that the Default Mode Network (DMN) typically exhibits increased activation during processing of social and personal information but shows deactivation during working memory (WM) tasks. Previously, we reported the Frontal Parietal Network (FPN) and DMN showed coactivation during task preparation whereas the DMN exhibited deactivation during task execution in working memory tasks. Aging research has shown that older adults exhibited decreased functional connectivity in the DMN relative to younger adults. Here, we investigated whether age-related cognitive decline is related to a reduced relationship between the FPN and DMN using a working memory task during the execution period. First, we replicated our previous finding that the FPN and DMN showed coactivation during the preparation period, whereas the DMN showed deactivation during the execution period. The older adults showed reduced DMN activity during task preparation and reduced deactivation during task execution; however, they exhibited a higher magnitude of activation in the FPN than the young individuals during task execution. Functional connectivity analyses showed that the elderly group, compared to the young group, showed weaker correlations within the FPN and the DMN, weaker positive correlations between the FPN and DMN during task preparation, and weaker negative correlations between the FPN and DMN during execution. The results suggest that cognitive decline in the older adults might be related to reduced connectivity within the DMN as well as between the FPN and DMN.

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and an essential mediator of energy metabolism. The redox balance between NAD+ and NADH affects various diseases, cell differentiation, and aging, and in recent years there has been a growing need for measurement techniques with improved accuracy. However, NAD(H) measurements, representing both NAD+ and NADH, have been limited by the compound’s properties. We achieved highly sensitive simultaneous measurement of NAD+ and NADH under non-ion pairing, mobile phase conditions of water, or methanol containing 5 mM ammonium acetate. These were achieved using a simple pre-treatment and 7-min analysis time. Use of the stable isotope 13C5-NAD+ as an internal standard enabled validation close to BMV criteria and demonstrated the robustness of NAD(H) determination. Measurements using this method showed that brain NAD(H) levels correlate strongly with plasma NAD(H) levels in the same mouse, indicating that NAD(H) concentrations in brain tissue are reflected in plasma. As NAD(H) is involved in various neurodegenerative diseases and cerebral ischemia, as well as brain diseases such as mitochondrial myopathies, monitoring changes in NADH levels in plasma after drug administration will be useful for development of future diagnostics and therapeutics.

Non-aqueous Li–O2 batteries offer an extremely high energy density, but suffer from high overvoltage on charge and poor cycle characteristics. In the past decade, soluble redox mediators (RMs) have been utilized to reduce the charge overvoltage. However, the use of RMs inhibits the effective decomposition of Li2O2 due to the shuttling of RMs between the cathode and anode. In this study, 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO), which was previously proposed as an RM, was immobilized on the electrode surface by immersing carbon paper in a solution of the synthesized 4-(N-(3-triethoxysilyl-propyl) carbamoyloxy)-2,2,6,6-tetramethyl-1-piperidinoxyl (TESPCP), followed by a heat treatment. Charge–discharge testing of Li–O2 batteries using the TEMPO-immobilized cathode with a Li anode exhibited a charge plateau of about 3.7 V, indicating that the immobilized TEMPO could react electrochemically as a redox mediator. No overcharge behavior was observed in the cell, suggesting the RM shuttling effect was suppressed. Furthermore, SEM and XPS analyses of the cathode surface confirmed that no Li2O2 residues remained on the cathode after charging, unlike the control sample that utilized soluble RMs. These results indicate that a TEMPO-immobilized cathode can successfully mitigate RM shuttling while maintaining the benefits of RMs, allowing effective decomposition of Li2O2, during charging without leading to overcharging.

Abstract Peptidoglycan for elongation in Escherichia coli is synthesized by the Rod complex, which includes RodZ. Although various mutant strains of the Rod complex have been isolated, the relationship between the activity of the Rod complex and the overall physical and chemical structures of the peptidoglycan have not been reported. We constructed a RodZ mutant, termed RMR, and analyzed the growth rate, morphology, and other characteristics of cells producing the Rod complexes containing RMR. The growth and morphology of RMR cells were abnormal, and we isolated suppressor mutants from RMR cells. Most of the suppressor mutations were found in components of the Rod complex, suggesting that these suppressor mutations increase the integrity and/or the activity of the Rod complex. We purified peptidoglycan from wild‐type, RMR, and suppressor mutant cells and observed their structures in detail. We found that the peptidoglycan purified from RMR cells had many large holes and different compositions of muropeptides from those of WT cells. The Rod complex may be a determinant not only for the whole shape of peptidoglycan but also for its highly dense structure to support the mechanical strength of the cell wall.

To planarize semiconductor materials such as gallium nitride (GaN) and silicon carbide with high efficiency, we developed a polarization method that combines ultraviolet irradiation and an abrasive-free polishing method known as catalyst-referred etching (CARE). In this method, the substrate surface is photoelectrochemically oxidized, thus improving the removal rate. Accordingly, an atomically well-ordered surface was obtained at a removal rate 100 times higher than that of the conventional CARE method without ultraviolet irradiation. However, in some cases, for GaN substrates with a high oxygen impurity concentration area, the oxidation rate is nonuniform on the substrate surface, resulting in the formation of a rough surface. In this study, we propose the application of a positive bias to the GaN substrate to suppress the oxidation rate fluctuation. In the positive bias state, the width of the depletion layer generated at the interface of GaN and the etchant becomes uniform on the entire surface regardless of crystallographic fluctuation, thereby achieving a uniform oxidation rate. When only 3.0 V was applied, the oxidation rate was uniform; thus, a flat GaN surface without the footprint originating from crystallographic fluctuations was obtained.