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Abstract The target‐cell limited model, which is one of the mathematical modeling approaches providing a quantitative understanding of viral dynamics, has been applied to describe viral RNA profiles of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in previous studies. However, these models have been developed mainly using patient data from the early phase of the pandemic. Furthermore, no reports focused on the profiles of the viral titer. In this study, the dynamics of both viral RNA and viral titer were characterized using data reflecting the current clinical situation in which the Omicron variant has become epidemic and vaccines for SARS‐CoV‐2 have become available. Consecutive data for 5212 viral RNA levels and 5216 viral titers were obtained from 720 patients with coronavirus disease 2019 (COVID‐19) in a phase II/III study for ensitrelvir. Our model assumed that productively infected cells would produce only infectious viruses, which could be transformed into non‐infectious viruses, and has been used to describe the dynamics of both viral RNA levels and viral titer. The time from infection to symptom onset (tinf) of unvaccinated patients was estimated to be 3.0 days, which was shorter than that of the vaccinated patients. The immune‐related parameter as a power function for the vaccinated patients was 1.1 times stronger than that for the unvaccinated patients. Our model allows the prediction of the viral dynamics in patients with COVID‐19 from the time of infection to symptom onset. Vaccination status was identified as a factor influencing tinf and the immune function.

Lebrikizumab has previously demonstrated efficacy in Phase 3 trials: ADvocate1 and ADvocate2 (as monotherapy), ADhere, and ADhere-J (in combination with topical corticosteroids). Here, the impact of lebrikizumab combined with low- to mid-potency topical corticosteroids on patient-reported outcomes at 16 weeks in Japanese patients with moderate-to-severe atopic dermatitis is evaluated. Eligible patients (n = 286) were randomized 2:2:3 to receive placebo+ topical corticosteroids, 250 mg lebrikizumab every 4 weeks (LEBQ4W+topical corticosteroids, 500 mg loading dose at baseline), or 250 mg lebrikizumab every 2 weeks (LEBQ2W+ topical corticosteroids, 500 mg loading dose at baseline and Week 2) by subcutaneous injection. All PRO endpoints for the study were met; patients in the lebrikizumab in combination with topical corticosteroids groups demonstrated statistically significant and clinically meaningful improvements compared with placebo in combination with topical corticosteroids in Skin Pain NRS, DLQI, POEM, WPAI-AD, and SCORAD scales. Lebrikizumab combined with topical corticosteroids compared with placebo+topical corticosteroids improved patient-reported outcomes in Japanese patients with moderate-to-severe atopic dermatitis.

Abstract Introduction Ensitrelvir, a novel oral inhibitor of 3C-like protease of SARS-CoV-2, shows efficacy and safety in participants with mild to moderate COVID-19. Since urinary recovery of ensitrelvir ranged from 12.9% to 21.8% across dose groups given 20–1000 mg in a single-ascending dose study, renal excretion contributes to the elimination of ensitrelvir. Therefore, the effect of renal impairment on the pharmacokinetics and safety of ensitrelvir needed to be evaluated. Methods This study (NCT05363215) was a phase 1, open-label, nonrandomized, parallel-group study. The effect of renal function on the pharmacokinetics of ensitrelvir was investigated. Ensitrelvir was administered as a single dose of 375 mg to participants with normal renal function and those with mild, moderate, and severe renal impairment. The participants with normal renal function were matched to each participant with moderate renal impairment with respect to sex, age, and body mass index. The unbound fractions in plasma after administration of ensitrelvir were also evaluated. For the safety assessment, the nature, frequency, and severity of treatment-emergent adverse events were evaluated and recorded. Results The plasma concentrations of participants with renal impairment were higher than those of participants with normal renal function. The ratios (90% confidence intervals) of the area under the plasma concentration-time curve from 0 to infinity (AUC0–inf) in participants with mild, moderate, and severe renal impairment compared to normal renal function were 1.4374 (1.1716–1.7636), 1.4885 (1.1883–1.8646), and 1.6021 (1.2782–2.0080), respectively. The plasma protein-unbound fraction was similar regardless of the plasma ensitrelvir concentration or renal function. Ensitrelvir was well tolerated in participants with mild to severe renal impairment and normal renal function. Conclusion Ensitrelvir was well tolerated by participants with renal impairment. There was no clinically meaningful increase on exposure to ensitrelvir in participants with renal impairment, indicating that no dose adjustment would be required due to renal function.

Exploration of novel resistive switching materials attracts attention to achieve neuromorphic computing that can surpass the limit of the current Von-Neumann computing for the time of Internet of Things (IoT). Battery materials priorly used to serve as an electrode or electrolyte have demonstrated metal-insulator transitions upon an electrical biasing due to resulting compositional change, which is desirable property for future resistive switching devices. For example, it has been suggested that solid-state electrolyte amorphous lithium lanthanum titanate (a-LLTO) changes in electronic conductivity depending on oxygen content. In this work, switching behavior of a-LLTO was investigated at both bulk- and nano-scale by employing a range of voltage sweep techniques, ultimately establishing a stable and optimal operating condition within the voltage window of − 3.5 V to 3.5 V. This voltage range effectively balances the desirable trait of a substantial resistance change by three orders of magnitude with the imperative avoidance of LLTO decomposition. Experiment and computation with different LLTO composition shows that LLTO has two distinct conductivity states due to Ti reduction. The distribution of these two states is discussed using simplified binary model, implying the conductive filament growth during low resistance state. Consequently, our study deepens understanding of LLTO electronic properties and encourages the interdisciplinary application of battery materials for resistive switching devices.

Abstract Aim This phase 1 study assessed the pharmacokinetics, safety, and tolerability of zuranolone in Japanese and White healthy adults, and Japanese healthy elderly subjects. Methods This single‐center study consisted of three parts. In Part A (randomized, double‐blind), the safety, tolerability, and pharmacokinetics of single dose and 7‐day consecutive multiple doses of zuranolone 10, 20, and 30 mg and placebo were assessed in 36 Japanese adults, 24 White adults, and 12 Japanese elderly (aged 65–75 years) subjects. In Part B (randomized, open‐label, crossover), the effect of food intake on the pharmacokinetics and safety of single‐dose zuranolone 30 mg was evaluated in 12 Japanese adults. In Part C (randomized, double‐blind, crossover), the effects of single‐dose zuranolone 10 and 30 mg and placebo on electroencephalography parameters were evaluated in eight Japanese adults. Results Single and multiple doses of zuranolone were safe and well tolerated in all subjects. Linear pharmacokinetics were observed in the studied dose range. Time to steady‐state plasma concentration was within 72 h for Japanese and White adults. Pharmacokinetic profiles were comparable between Japanese and White adults and between Japanese adults and Japanese elderly subjects. Plasma exposures of zuranolone were greater in the fed versus fasted state. Single‐dose zuranolone 30 mg increased low‐beta electroencephalography power. Conclusion In healthy Japanese subjects, zuranolone was well tolerated; pharmacokinetic profile was unaffected by ethnicity or age; plasma exposures were greater in the fed state. The increased low‐beta electroencephalography power with the 30‐mg dose is consistent with γ‐aminobutyric acid receptor type A activation by zuranolone.

We demonstrated an ultrafast time-resolved measurement method operating at the single-photon level and employing a two-color comb-based asynchronous optical sampling (ASOPS) setup. We harnessed the two-color ASOPS photon counting approach to achieve long-term averaging of the ultralow intensity signal with a synchronized optical trigger signal, which minimizes residual timing jitter between the two combs. A pulse-width limited picosecond cross-correlation signal was successfully obtained with a power level of

Free-space optical (FSO) communications can offer high-capacity transmission owing to the properties of the laser beams. However, performance degradation caused by atmospheric turbulence is an urgent issue. Recently, the application of polar codes, which can provide capacity-achieving error-correcting performance with low computational cost for decoding, to FSO communications has been studied. However, long-distance and real-field experiments have not been conducted in these studies. To the best of our knowledge, this study is the first to present the experimental results of polar-coded transmission over 7.8-km FSO links. Using experimental data, we investigated the performance of polar codes over atmospheric channels, including their superiority to regular low-density parity-check codes. We expect that our results will offer a path toward the application of polar codes in high-speed optical communication networks including satellites.

Abstract Platelets are produced by hematopoietic stem cells via megakaryocytes in the bone marrow and play a critical role in hemostasis. The aim of this study was to develop a new platelet model based on the thrombopoiesis and platelet life‐cycle by a quantitative systems pharmacology modeling approach, which could describe changes in platelet count profiles in platelet‐related diseases and drug intervention. The proposed platelet model consists of 44 components. The model was applied to thrombopoiesis of a thrombopoietin receptor agonist, lusutrombopag. It could well describe the observed platelet count profiles after administration of lusutrombopag for both healthy subjects and patients with chronic liver disease and thrombocytopenia. This model should be useful for understanding the disease progression of platelet‐related conditions, such as thrombocytopenia and for predicting platelet count profiles in various disease situations related to platelets and drug administration in drug development.

Epoxides are essential precursors for epoxy resins and other chemical products. In this study, we investigated whether electrochemically oxidizing carbonate ions could produce percarbonate to promote an epoxidation reaction in the presence of appropriate metal catalysts, although Tanaka and co-workers had already completed a separate study in which the electrochemical oxidation of chloride ions was used to produce hypochlorite ions for electrochemical epoxidation. We found that epoxides could be obtained from styrene derivatives in the presence of metal complexes, including manganese(III) and oxidovanadium(IV) porphyrin complexes and manganese salen complexes, using a boron-doped diamond as the anode. After considering various complexes as potential catalysts, we found that manganese salen complexes showed better performance in terms of epoxide yield. Furthermore, the substituent effect of the manganese salen complex was also investigated, and it was found that the highest epoxide yields were obtained when Jacobsen’s catalyst was used. Although there is still room for improving the yields, this study has shown that the in situ electrochemical generation of percarbonate ions is a promising method for the electrochemical epoxidation of alkenes.

Conventional optical synthesis, the manipulation of the phase and amplitude of spectral components to produce an optical pulse in different temporal modes, is revolutionizing ultrafast optical science and metrology. These technologies rely on the Fourier transform of light fields between time and frequency domains in one-dimensional space. However, within this treatment, it is impossible to incorporate the quantum correlation among photons. Here, we expand the Fourier synthesis into high-dimensional space to deal with the quantum correlation and carry out an experimental demonstration by manipulating the two-photon probability distribution of a biphoton in two-dimensional time and frequency space. As a potential application, we show the manipulation of a heralded single-photon wave packet, which is never explained by the conventional one-dimensional Fourier optics. Our approach opens up a new pathway to tailor the temporal characteristics of a photon wave packet with high-dimensional quantum-mechanical treatment. We anticipate that such high-dimensional treatment of light in time and frequency domains could bridge the research fields between quantum optics and ultrafast optical measurements.

The original form of the regulatory focus theory has proposed that persons with a promotional focus regard the existence of positive outcomes as important, whereas persons with a prevention focus regard the absence of negative outcomes as important. However, more recently, the theory has been extended to claim that the former group of persons s outcomes cognitively, whereas the latter evaluates the same outcomes more emotionally. Employing the extended version of regulatory focus theory, this study hypothesized that eWOM receivers with the promotional focus would be likely to avoid recommended products, eWOM receivers with the prevention focus would be more likely to adopt them, in contrast with previous research that has hypothesized that all eWOM receivers would avoid recommended products. To test this hypothesis, ANOVA was conducted using a dataset from a consumer experiment. Consequently, our hypothesis was supported.

In this study drag calculations were performed for an airplane cruising at transonic speed in a flow-field using two far-field methods. Subjected flow-fields in the calculations were computational fluid dynamics (CFD) results of Reynolds-averaged Navier–Stokes simulation (RANS) around a wing. The objectives were to establish effective means to utilize far-field drag methods and wake flow phenomena as well as report pseudo total enthalpy which peculiarly appeared in the CFD simulation results. The drag calculation was completed using four wake integration equations. The first originated from the equation of the momentum conservation law itself, the second was based on enthalpy variation, the third was based on entropy variation, and the last was a method for induced drag calculation. Drag values resulting from the integrations were compared to those via a near-field method commonly used in CFD. Through the computation and comparison of wake integration drag values, it was proved that the both far-field methods were able to predict a comparably accurate drag value compared to that of the near-field method. In addition, strange inappropriate total enthalpy (pseudo total enthalpy) generation was found in some regions where a flying airplane never affects flow behavior. In the wake integrations, the pseudo total enthalpy generation seems to compensate for the drag value via the first equation. The pseudo total enthalpy generation depends on far-field boundary locations. In summary, wake integrations are promising to provide useful information for accurate drag prediction.

Light incident upon molecules triggers fundamental processes in diverse systems present in nature. However, under natural conditions such as sunlight illumination, it is impossible to assign known times for photon arrival due to continuous pumping, and therefore the photoinduced processes cannot be easily investigated. In this work, we demonstrate theoretically that the characteristics of sunlight photons, such as photon number statistics and spectral distribution, can be emulated through a quantum entangled photon pair generated with parametric down-conversion (PDC). We show that the average photon number of sunlight in a specific frequency spectrum, e.g., the visible light, can be reconstructed by adjusting the PDC crystal length and pump frequency, and thereby the molecular dynamics induced by the pseudo-sunlight can be investigated. The entanglement time, which is the hallmark of quantum entangled photons, can serve as a control knob to resolve the photon arrival times, enabling investigations on real-time dynamics triggered by pseudo-sunlight photons.

Background: Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis. Methods: In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100 mg EMIQ or a placebo for 8 weeks, starting 4 weeks prior to the onset of pollen release. Subjective symptoms, ADL scores and the usage of drugs were recorded daily, and the QOL score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum levels of IgE and flavonoids. Results: During the entire study period, ocular symptom + medication score for the EMIQ group was significantly lower (p < 0.05) than that of the placebo group. When limited to the period, ocular symptom scores (p < 0.05, weeks 5–6), and ocular congestion scores (p < 0.05, weeks 5–6) for the EMIQ group was significantly lower than that for the placebo group while other scores for the EMIQ group, such as ocular itching scores (p = 0.09, weeks 4–5), lacrimation scores (p = 0.07, weeks 5–6), and ocular congestion scores (p = 0.06, weeks 45), all tended to be lower. However no significant differences were found in nasal symptoms between the two groups. Serum concentrations of IgE were not significantly downregulated but the serum concentrations of quercetin and its derivatives were elevated significantly by the intake of EMIQ. Conclusions: Intake of the quercetin glycoside EMIQ proved to be effective for the relief of ocular symptoms caused by Japanese cedar pollinosis.