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BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigators choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

We present a case of pulmonary metastasis originating from renal angiomyolipoma (AML), as evidenced by whole-exome sequencing (WES) analysis. Although AML predominantly arises in the kidneys, it can emerge in various body parts, making it important to distinguish between multicentric development and metastasis. However, previous studies have not distinguished between these conditions. Our case features an 82-year-old woman with a history of renal AML who presented with multiple, randomly distributed, bilateral pulmonary nodules of varying size and pure fat densities. The patient's condition followed a benign course over 10 years. Through WES, we discovered shared mutations in pulmonary lesions that were absent in the patient's blood, including a pathological mutation in TSC2, suggesting a metastatic origin from renal AML. Knowledge of the pulmonary manifestations of AML and their distinctive imaging findings can help radiologists and clinicians diagnose and manage patients with similar presentations.

Abstract Background Anterior knee pain due to patellar maltracking following total knee arthroplasty (TKA) reduces patients’ satisfaction. This study aimed to determine the patellofemoral pressure (PFP) in patients with favorable patellar tracking (FT) and impaired patellar tracking (IT) following TKA, the factors causing patellar maltracking, and the effect of lateral retinacular release (LRR) on patients with IT. Methods Forty-four patients with varus knee osteoarthritis undergoing cruciate-retaining TKA were enrolled. After component implantation, patients with a separation of ≥ 2 mm of the patellar medial facet from the medial femoral trochlea throughout knee range of motion were classified into the IT group; meanwhile, the others were classified into the FT group. PFP was measured intraoperatively in three phases: (1) with the resurfaced patella (RP); (2) with the resurfaced patella and knee (RPK); and (3) when LRR was performed in IT (post-LRR). The PFPs at 0°, 90°, 120°, and 135° knee flexion were compared between FT and IT using the Mann–Whitney U test. Pairwise comparison of the PFP in IT between RPK and post-LRR was performed using the Wilcoxon signed-rank test. Correlations between PFP and pre- and postoperative radiographic parameters, such as hip–knee–ankle angle, lateral distal femoral angle, medial proximal tibial angle, anterior femoral offset, Insall–Salvati ratio (ISR), patellar tilt, and patellar resection angle (PRA), were evaluated using Spearman’s rank correlation coefficients. Results High lateral PFP in the knee flexion position led to patellar maltracking. Patients with IT (n = 24) had higher lateral and lower medial PFP than did patients with FT (n = 20) at 90°, 120°, and 135° knee flexion in RP and RPK. LRR in IT reduced the lateral PFP in the knee flexion position. PRA and ISR were correlated with the lateral PFP at no less than 90° in RP and RPK. Conclusions This study demonstrated that internal rotational patellar resection, which resulted in a thick medial patellar remnant and a thin lateral counterpart, and patella alta were the causative factors of high lateral PFP, which induced patellar maltracking after TKA. Surgeons should avoid internal rotational patellar resection to achieve FT and perform LRR in patients with patellar maltracking.

Abstract Engineered spin-electric coupling enables spin qubits in semiconductor nanostructures to be manipulated efficiently and addressed individually. While synthetic spin-orbit coupling using a micromagnet is widely investigated for driving and entangling qubits based on single spins in silicon, the baseband control of encoded spin qubits with a micromagnet in isotopically purified silicon has been less well investigated. Here, we demonstrate fast singlet-triplet qubit oscillation (~100 MHz) in a gate-defined double quantum dot in 28Si/SiGe with an on-chip micromagnet with which we show the oscillation quality factor of an encoded spin qubit exceeding 580. The coherence time T 2* is analyzed as a function of potential detuning and an external magnetic field. In weak magnetic fields, the coherence is limited by frequency-independent noise whose time scale is faster than the typical data acquisition time of ~100 ms, which limits the T 2* below 1 μs in the ergodic limit. We present evidence of sizable and coherent coupling of the qubit with the spin states of a nearby quantum dot, demonstrating that appropriate spin-electric coupling may enable a charge-based two-qubit gate in a (1,1) charge configuration.

Abstract Background Interference with activities of daily living can negatively impact maternal practices both physically and psychologically. This study aimed to explore the patterns of interference with activities of daily living and perineal pain among Japanese women until 1 month postpartum. Furthermore, we aimed to describe how both perineal pain and delivery-related factors were associated with interference with activities of daily living. Methods This study was part of a larger prospective longitudinal study conducted at five maternity hospitals in Japan. The participants were 293 women who had full-term vaginal deliveries and singleton infants. Participants self-evaluated their perineal pain and interference with activities of daily living using a 100 mm visual analogue scale and ‘behaviour that interferes with daily life scale’ at day 1, day 5, and 1 month postpartum. We used a linear mixed model to calculate the fixed-effects parameter estimates and their 95% confidence intervals. Interference with activities of daily living, which included difficulty sitting, difficulty moving, and difficulties with excretion and cleanliness, were set as the dependent variables. Results The final analysis included 184 participants with a mean age of 31.5±4.5 years. Perineal pain and the three sub-scales of interference with activities of daily living reduced from day 1 to 5 postpartum, and further from day 5 to 1 month postpartum (perineal pain, p

Speeding is a significant global issue, with disparities in speed and safety outcomes between low- and middle-income countries (LMICs) and high-income countries (HICs). This study aims to address speed research gaps in LMICs by examining the prevalence of self-reported speeding and factors influencing drivers’ speeding behavior using the Theory of Planned Behavior (TPB). An online survey involving 387 anonymous drivers was conducted in Yaoundé. Results showed that all drivers reported exceeding speed limits, with 81% exceeding them by 5 km/h, 12% by 10 km/h, and 7% by more than 10 km/h in urban areas. On highways, 54% reported exceeding the limit by more than 10 km/h. Age, driver’s license, and gender showed significant associations with speed limit non-compliance. This study’s results suggest that the TPB can be useful in assessing speeding behavior, as the inclusion of TPB variables led to a more than 50% proportionate increase in speeding behavior variance. Structural equation modeling revealed attitude towards speeding as the strongest predictor of speeding intention, along with certain demographics indirectly influencing speeding behavior through speeding intention. Perceived behavioral control and speeding intention directly influenced speeding behavior. These findings emphasize the potential of interventions targeting attitude, intentions, and perceived behavioral control to modify speeding behavior and improve road safety.

Abstract Aim To investigate changes in the clinical characteristics of patients who abused benzodiazepine receptor agonists (BZRA) or over‐the‐counter (OTC) drugs before and after COVID‐19 based on the 2018 and 2022 data of the “Nationwide Psychiatric Hospital (NPH) Survey on Drug‐related Psychiatric Disorders.” Method A total of 446 and 155 cases, and 435 and 273 cases, who mainly abused BZRAs or OTC drugs, respectively, were extracted from the database of the two NPH Surveys. Demographic variables, education, employment, criminal record, drug use during the previous year, psychiatric diagnosis, and types of abused drugs were compared between 2018 and 2022. Result A comparison of BZRA abusers revealed a decreased number of users during the previous year and an increase in the comorbidity rate of other disorders (F3 and F4 in ICD‐10) in 2022. Etizolam, flunitrazepam, triazolam, and zolpidem were used most in both years, with an increase in zolpidem and a decrease in triazolam in 2022. A comparison of OTC drug abusers revealed a higher proportion of women and young patients in 2022. An increase in the comorbidity rate of F3 and F9 and a significant increase in the use of dextromethorphan products were observed in 2022, although codeine products were in the majority in both years. Conclusion By comparing NPH Surveys before and after the COVID‐19 pandemic, both BZRA abusers and OTC drug abusers present complex pathologies, requiring tailor‐made treatment. The younger OTC drug abusers were particularly evident among women, and the abuse of dextromethorphan‐containing OTC drugs has increased alarmingly.

Verticillium dahliae is a soilborne fungal pathogen that causes disease on many economically important crops. Based on the resistance or susceptibility of differential cultivars in tomato, isolates of V. dahliae are divided into three races. Avirulence (avr) genes within the genomes of the three races have also been identified. However, the functional role of the avr gene in race 3 isolates of V. dahliae has not been characterized. In this study, bioinformatics analysis showed that VdR3e, a cysteine-rich secreted protein encoded by the gene characterizing race 3 in V. dahliae, was likely obtained by horizontal gene transfer from the fungal genus Bipolaris. We demonstrate that VdR3e causes cell death by triggering multiple defense responses. In addition, VdR3e localized at the periphery of the plant cell and triggered immunity depending on its subcellular localization and the cell membrane receptor BAK1. Furthermore, VdR3e is a virulence factor and shows differential pathogenicity in race 3-resistant and -susceptible hosts. These results suggest that VdR3e is a virulence factor that can also interact with BAK1 as a pathogen-associated molecular pattern (PAMP) to trigger immune responses. IMPORTANCE Based on the gene-for-gene model, research on the function of avirulence genes and resistance genes has had an unparalleled impact on breeding for resistance in most crops against individual pathogens. The soilborne fungal pathogen, Verticillium dahliae, is a major pathogen on many economically important crops. Currently, avr genes of the three races in V. dahliae have been identified, but the function of avr gene representing race 3 has not been described. We investigated the characteristics of VdR3e-mediated immunity and demonstrated that VdR3e acts as a PAMP to activate a variety of plant defense responses and induce plant cell death. We also demonstrated that the role of VdR3e in pathogenicity was host dependent. This is the first study to describe the immune and virulence functions of the avr gene from race 3 in V. dahliae, and we provide support for the identification of genes mediating resistance against race 3.

Abstract This paper proposes a nanoparticle‐based atomic switch network memristive device, capable of both volatile and nonvolatile switching operations, which have not been previously reported for this material. The operational modes can be determined by altering the compliance current, demonstrating high stability over 100 cycles. Analysis of the conduction mechanism using I–V curves reveals switching characteristics consistent with space‐charge‐limited current conduction during the set process and ohmic behavior in the reset state. Furthermore, this study analyzes these dual‐operational modes in devices with varying electrode spacings. The results indicate that a wider spacing necessitated a higher compliance current for the volatile‐to‐nonvolatile transition, underscoring the significance of interconnection. These findings facilitate the integration of neuron and synapse functions within a single atomic switch network device, thereby advancing neuromorphic systems.

Background The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low‐risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era. Methods and Results The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry‐2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30‐day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan‐Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out‐of‐hospital pulmonary embolism were treated at home. The cumulative 30‐day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log‐rank P

Abstract Background In the phase 3 EMPOWER‐Cervical 1/GOG‐3016/ENGOT‐cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first‐line platinum‐based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Methods Patients were enrolled regardless of programmed cell death‐ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single‐agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow‐up was 13.6 (6.0–25.3) versus 18.2 (6.0–38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0‐not evaluable) and 9.4 (5.4–14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43–1.68). Median PFS (95% CI) was 4.0 (1.4–8.2) versus 3.7 (1.8–4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50–1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44–13.99). Incidence of treatment‐emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. Discussion While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6‐month shorter median duration of follow‐up versus the overall study population.

Cadherin 23 (CDH23) is one of the most common genes responsible for hereditary hearing loss; a mutation of CDH23 can cause a wide range of symptoms depending on the variant. In this study, an iPSC line was generated from a patient with late-onset, progressive high frequency hearing loss caused by c.[719C > T];[6085C > T]:p.[P240L];[R2029W] compound heterozygous variants of CDH23. The cells were confirmed to have a normal karyotype, express markers of pluripotency, and have tri-embryonic differentiation potential. This disease-specific iPSC line will further the construction of disease models and the elucidation of the pathophysiology of CDH23 mutations.

In Yaoundé, Cameroon, where walking dominates transport modes, pedestrian safety remains an issue as pedestrians account for a fair share of road traffic casualties, partly due to the lack of walking policies and pedestrian facilities safety data, hindering targeted intervention. This study used a pedestrian safety index (PSI) and the Global Walkability Index (GWI) to investigate 12 road segments frequented by diverse pedestrian groups. Indexes were graded from E—lowest to A—highest and analyzed using description and rank correlation. Main safety issues included lack of adequate and accessible sidewalks, bollards, pedestrian crossings, signage, shade, and street lighting. Only one segment (R7) achieved grade C, while the remainder scored D or E, indicating poor pedestrian safety conditions and an unpleasant walking experience. The correlation coefficient (0.69) between the PSI and GWI at a 99% significance level validated the safety assessment, providing confidence in the results. A seven-year (2024–2030) safety strategy is proposed to improve all roads to grade B. This strategy contains several interventions, including engineering improvement, which have been proven effective. This study offers evidence for city officials to improve pedestrian safety and informs walking policies and the implementation of upcoming projects. Future research should quantify the recommendations’ benefits and validate indexes with crash or conflict data.

Distracted driving is a major cause of road traffic crashes in Yaoundé. This is partly due to the scarcity of enforcement and a lack of evidence and investigation using the distraction safety performance indicator (SPI), hindering evidence-based interventions. This study aimed to address this evidence gap by evaluating the distraction SPI using a proven methodology. Data on distracted driving (handheld mobile device; interaction; eating/smoking/drinking) were collected from roadside observations on 36 randomly selected road sections carefully spread to cover the city. SPIs were computed and weighted with traffic volume to ensure the representativeness of the values. A total of 41,004 drivers were observed (38,248 in cars; 1116 in vans; 977 in trucks; 663 in buses). The prevalence of distracted driving in Yaoundé is 13.69% for the three distractions type combined. The prevalence is 7.84% for interaction, 4.89% for handled mobile device usage and 0.96% for eating/smoking/drinking. Leveraging these insights, a seven year (2024–2030) fighting strategy aimed at halving the prevalence was developed. The strategy contains interventions including legislation/enforcement, which have been proven to be effective. This study, pioneered in Yaoundé, provides stakeholders with evidence of the issue and measures to implement and can also be used when developing a road safety strategy. Future research should consider investigation at national level.

Abstract Background To examine whether the "Effectiveness of Guideline for Dissemination and Education in psychiatric treatment (EGIUDE)" project affects the rate of prescriptions of hypnotic medication and the type of hypnotic medications prescribed among psychiatrists, for schizophrenia and major depressive disorder in Japan. Methods The EGUIDE project is a nationwide prospective study of evidence-based clinical guidelines for schizophrenia and major depressive disorder in Japan. From 2016 to 2021, clinical and prescribing data from patients discharged from hospitals participating in the EGUIDE project were used to examine hypnotic medication prescriptions The prescribing rate of hypnotics and the prescribing rate of each type of hypnotic (benzodiazepine receptor agonist, nonbenzodiazepine receptor agonist, melatonin receptor agonist, and orexin receptor antagonist) were compared among patients who had been prescribed medication by psychiatrists participating in the EGUIDE project and patients who had been prescribed medication by nonparticipating psychiatrists. Multivariate logistic regression analysis was performed to examine the effect of the EGUIDE project on the prescription of hypnotic medications. Results A total of 12,161 patients with schizophrenia and 6,167 patients with major depressive disorder were included. Psychiatrists participating in the EGUIDE project significantly reduced the rate of prescribing hypnotic medication and benzodiazepine receptor agonists for both schizophrenia (P

Abstract To investigate the association between hereditary hearing loss and vestibular function, we compared vestibular function and symptoms among patients with GJB2, SLC26A4, and CDH23 variants. Thirty-nine patients with sensory neural hearing loss (11 males and 28 females) with biallelic pathogenic variants in either GJB2, SLC26A4, or CDH23 were included in this study (13 GJB2, 15 SLC26A4, and 11 CDH23). The patients were examined using caloric testing and cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP). We also compared vestibular function and symptoms between patients with these gene variants and 78 normal-hearing ears without vestibular symptoms as controls. The frequency of semicircular canal hypofunction in caloric testing was higher in patients with SLC26A4 variants (47%) than in those with GJB2 (0%) and CDH23 variants (27%). According to the cVEMP results, 69% of patients with GJB2 variants had saccular hypofunction, a significantly higher proportion than in those carrying other variants (SLC26A4, 20%; CDH23, 18%). In oVEMP, which reflects utricular function, no difference was observed in the frequency of hypofunction among the three genes (GJB2, 15%; SLC26A4, 40%; and CDH23, 36%). Hence, discernable trends indicate vestibular dysfunction associated with each gene.

The present study describes an improvement of damping performance of a mechanical tensioner driven by friction force at the power spring interface, used for the timing chain system for an internal combustion engine. The mechanical tensioner consists of a power spring subjected to face-to-face contact with a reciprocal motion and a leaf spring to apply the reaction load. The concave and convex surface texture was fabricated with an electrochemical etching on the power spring surfaces. Since the reaction load is affected by the friction force at the power spring interface, the damping performance is evaluated from a hysteresis loop resulting in the reaction load and the plunger displacement trajectory. Superior stabilization of the reaction load and a remarkable decrease of the wear loss including the restriction of the oxidation was found on the convex textured tensioner in lubricated condition. The tensioner performance was also evaluated in staved lubricating conditions. Results showed that the change of the reaction load of the convex textured tensioner was small just before the stiction occurrence. In contrast, the reaction load of the concave textured tensioner increased with the increase in the number of cycles. Therefore, the applicability of the convex surface texture to the power spring surface of the tensioner was confirmed. It was also estimated that the discharge of the wear debris is an important factor in maintaining the tensioner performance.

Abstract The MYO7A gene is known to be responsible for both syndromic hearing loss (Usher syndrome type1B:USH1B) and non-syndromic hearing loss including autosomal dominant and autosomal recessive inheritance (DFNA11, DFNB2). However, the prevalence and detailed clinical features of MYO7A-associated hearing loss across a large population remain unclear. In this study, we conducted next-generation sequencing analysis for a large cohort of 10,042 Japanese hearing loss patients. As a result, 137 patients were identified with MYO7A-associated hearing loss so that the prevalence among Japanese hearing loss patients was 1.36%. We identified 70 disease-causing candidate variants in this study, with 36 of them being novel variants. All variants identified in autosomal dominant cases were missense or in-frame deletion variants. Among the autosomal recessive cases, all patients had at least one missense variant. On the other hand, in patients with Usher syndrome, almost half of the patients carried biallelic null variants (nonsense, splicing, and frameshift variants). Most of the autosomal dominant cases showed late-onset progressive hearing loss. On the other hand, cases with autosomal recessive inheritance or Usher syndrome showed congenital or early-onset hearing loss. The visual symptoms in the Usher syndrome cases developed between age 5–15, and the condition was diagnosed at about 6–15 years of age.

Abstract Aim The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case–control sample. Method Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP‐CNVs) in PRKN and examined their association with SCZ and ASD. Results In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP‐CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP‐CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early‐onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. Conclusion The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.

Abstract Objective To examine the clinical characteristics of over‐the‐counter (OTC) drug abusers in psychiatric practice in Japan. Method We examined the attributes, ICD‐10 subcategory, and comorbid mental disorders of patients who mainly abuse OTC products and compared the clinical characteristics of single product and multiple products abusers, using the database of the “2022 Nationwide Mental Hospital Survey of Drug‐related Disorders.” Results Among the 2468 subjects included in this survey, 273 (11.1%) used OTC products as main drugs. Of these, 209 (78.3%) and 58 (21.7%) were classified into the single product group and the multiple products group, respectively. Six were excluded for unknown ingredients. By comparing these groups, we found that many of the multiple products group consisted of young women who were recently treated for drug problems. Many subjects in the group also had a short treatment period. No differences were observed between the groups regarding the ICD‐10 F1 subcategory, but many subjects in the multiple products group fulfilled the criteria of F6 “disorders of adult personality and behavior.” Conclusion OTC products are easily accessible drugs of abuse for young women in Japan. The results of this study indicate the necessity to reconsider the educational approach for preventing drug abuse, which has focused on illicit drugs. The study also indicates that some OTC products, which contain ingredients banned overseas due to their harmful effects, are still sold in Japan and that abusers for those products exist. Measures by the government are considered urgently needed.

Abstract The MEG II experiment, based at the Paul Scherrer Institut in Switzerland, reports the result of a search for the decay $$\upmu ^+ \rightarrow {\textrm{e}}^+ \upgamma $$ μ + → e + γ from data taken in the first physics run in 2021. No excess of events over the expected background is observed, yielding an upper limit on the branching ratio of $${\mathcal {B}} (\upmu ^+ \rightarrow {\textrm{e}}^+ \upgamma ) < 7.5 \times 10^{-13}$$ B ( μ + → e + γ ) < 7.5 × 10 - 13 (90% CL). The combination of this result and the limit obtained by MEG gives $${\mathcal {B}} (\upmu ^+ \rightarrow {\textrm{e}}^+ \upgamma ) < 3.1 \times 10^{-13}$$ B ( μ + → e + γ ) < 3.1 × 10 - 13 (90% CL), which is the most stringent limit to date. A ten-fold larger sample of data is being collected during the years 2022–2023, and data-taking will continue in the coming years.

Multicrystalline materials play a crucial role in our society. However, their microstructure is complicated, and there is no universal approach to achieving high performance. Therefore, a methodology is necessary to answer the fundamental question of how we should design and create microstructures. ‘Multicrystalline informatics’ is an innovative approach that combines experimental, theoretical, computational, and data sciences. This approach helps us understand complex phenomena in multicrystalline materials and improve their performance. The paper covers various original research bases of multicrystalline informatics, such as the three-dimensional visualization of crystal defects in multicrystalline materials, the machine learning model for predicting crystal orientation distribution, network analysis of multicrystalline structures, computational methods using artificial neural network interatomic potentials, and so on. The integration of these research bases proves to be useful in understanding unexplained phenomena in complex multicrystalline materials. The paper also presents examples of efficient optimization of the growth process of high-quality materials with the aid of informatics, as well as prospects for extending the methodology to other materials.

Background There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long‐term outcomes from the warfarin era to the DOAC era. Methods and Results We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010–2014) and Registry 2: 5197 patients in the DOAC era (2015–2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P